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Abstract This review provides a comprehensive analysis of apoptotic signaling pathways in the context of bone metastatic lung cancer, emphasizing the intricate molecular mechanisms and microenvironmental influences. Beginning with an overview of apoptosis in cancer, the paper explores the specific molecular characteristics of bone metastatic lung cancer, highlighting alterations in apoptotic pathways. Focused discussions delve into key apoptotic signaling pathways, including the intrinsic and extrinsic pathways, and the roles of critical molecular players such as Bcl-2 family proteins and caspases. Microenvironmental factors, such as the tumor microenvironment, extracellular matrix interactions, and immune cell involvement, are examined in depth. The review also addresses experimental approaches and techniques employed in studying apoptotic signaling, paving the way for a discussion on current therapeutic strategies, their limitations, and future prospects. This synthesis contributes a holistic understanding of apoptosis in bone metastatic lung cancer, offering insights for potential therapeutic advancements.

Abstract Aims Herein, we examined the correlation between platelet/high-density lipoprotein cholesterol ratio (PHR) and symptoms of depression among United States adults. Methods Data acquired from the 2007–2018 National Health and Nutrition Examination Survey, involving individuals ≥ 20 years of age, with available PHR and depression diagnosis information. We employed weighted uni- and multivariable logistic regression analyses to assess the distinct correlation between PHR and depressive symptoms. Additionally, we conducted subgroup, interaction, and restricted cubic spline analyses. Results In all, 28,098 subjects were recruited for analysis, with 8.04% depression status and 19.31 ± 0.11 mean PHR value. Depressive symptoms increased with higher quartiles of PHR. Following fully confounder adjustments in model 2, participants with the largest PHR quartiles exhibited a 53% (OR: 1.53, 95%CI: 1.00–2.33, P = 0.05) raised depressive symptoms, relative to participants with least PHR quartiles. Based on the two-piece-wise regression, the breakpoint was PHR = 23.76, and a positive association was more evident when PHR

Breast cancer (BC) is one of the primary causes of death in women worldwide. The challenges associated with adverse outcomes have increased significantly, and the identification of novel therapeutic targets has become increasingly urgent. Regulated cell death (RCD) refers to a type of cell death that can be regulated by several different biomacromolecules, which is distinctive from accidental cell death (ACD). In recent years, apoptosis, a representative RCD pathway, has gained significance as a target for BC medications. However, tumor cells exhibit avoidance of apoptosis and result in treatment resistance, which emphasizes further studies devoted to alternative cell death processes, namely necroptosis, pyroptosis, and ferroptosis. Here, in this review, we focus on summarizing the crucial signaling pathways of these RCD in BC. We further discuss the molecular mechanism and potentiality in clinical application of several prospective drugs, nanoparticles, and other small compounds targeting different RCD subroutines of BC. We also discuss the benefits of modulating RCD processes on drug resistance and the advantages of combining RCD modulators with conventional treatments in BC. This review will deepen our understanding of the relationship between RCD and BC, and shed new light on future directions to attack cancer vulnerabilities with RCD modulators for therapeutic purposes.

Objective(s): Endoscopic thyroidectomy, such as axillary, areola and transoral approaches, offer the advantage of a good cosmetic outcome, but it requires a wider dissection field compared to open thyroidectomy. Recently, chest-collarbone approach thyroidectomy has been widely developed in China because of its shorter anatomical route compared to other endoscopic approaches. This study retrospectively evaluated endoscopic thyroidectomy via chest-collarbone approach in patients with thyroid nodules to determine its feasibility. Methods: A total of 46 patients with thyroid disease who underwent endoscopic thyroidectomy between January 2022 and December 2022 were enrolled in the study and randomly matched to patients with thyroid disease who underwent open thyroidectomy at the same time based on nodule size and pathology. Postoperative bleeding, hoarseness situation, hospital stay, postoperative drainage volume, laryngeal nerve palsy, hypoparathyroidism and wound infection were assessed in both groups. Results: Forty-four patients underwent endoscopic thyroidectomy successfully and two patients changed to open thyroidectomy. The amount of postoperative drainage for the endoscopic thyroidectomy group was 102.78 ± 28.04 mL, and which was 71.91 ± 19.20 for open thyroidectomy group (p

Objective: Composite Dietary Antioxidant Index (CDAI) values serve as a summary of an individual's combined dietary antioxidant intake. Although specific antioxidants are known to reduce thyroid damage from oxidative stress, the relationship between the CDAI and thyroid function remains uncertain. The purpose of this study was thus to investigate this relationship in greater detail while focusing on a representative American adult population. Methods: A total of 6,860 subjects from the 2007–2012 NHANES cohort were included in this study. Associations between CDAI values and thyroid function were evaluated with weighted linear regression models and smoothed curve fitting. Subgroup analyses were also performed. Results: The weighted mean (SD) values for variables analyzed in this study included a CDAI of 0.13 (0.06), serum free T4 (FT4) levels of 0.80 (0.01) ng/dL, and serum total T4 (TT4) levels of 7.80 (0.03) ug/dL. Lower CDAI values were found to be associated with higher levels of FT4 and TT4 using both unadjusted and adjusted models that accounted for relevant confounders (adjusted model, FT4 β = −0.003, p = 0.005; TT4 β = −0.035, p

AimsThe primary objective of this study was to investigate the relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR) and the prevalence of nephrolithiasis within the adult population of the United States.MethodsThe data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2018. The analysis included a non-pregnant population aged 20 years or older, providing proper PHR index and nephrolithiasis data. The research utilized subgroup analyses and weighted univariate and multivariable logistic regression to evaluate the independent association between the PHR and the susceptibility to nephrolithiasis.ResultsThe study comprised 30,899 participants with an average PHR value of 19.30 ± 0.11. The overall prevalence rate of nephrolithiasis was estimated at 9.98% with an increase in the higher PHR tertiles (T1, 8.49%; T2, 10.11%; T3, 11.38%, P < 0.0001). An elevated PHR level was closely linked with a higher susceptibility to nephrolithiasis. Compared with patients in T1, and after adjusting for potential confounders in model 2, the corresponding odds ratio for nephrolithiasis in T3 was 1.48 (95% CI: 1.06 to 2.08), with a P-value = 0.02. The results of the interaction tests revealed a significant impact of chronic kidney disease on the relationship between PHR and nephrolithiasis. Furthermore, the restricted cubic spline analyses exhibited a positive, non-linear correlation between PHR and the risk of nephrolithiasis.ConclusionA convenient biomarker, the PHR, was independently associated with nephrolithiasis and could be a novel biomarker in predicting occurrence in clinical decision.

Thermoelectric generator (TEG) with improved performance is a promising technology in power supply and energy harvesting. Existing studies primarily adopt constant material properties to investigate TEG performance. However, thermoelectric (TE) material properties are subjected to considerable variations with temperature. Thus, reasonable doubts have risen concerning the influence level of temperature-dependent material properties on TEG performance. To solve this problem, an efficient and a comprehensive one-dimensional numerical model is developed to fully consider the third-order polynomial temperature-dependent thermal conductivity, Seebeck coefficient, and electrical resistivity. Control volume and finite difference algorithms are compared, and experiments are conducted to verify the developed numerical model. The temperature distribution along the TE leg obviously differs from the parabolic shape, which is a classic temperature distribution under the assumption of constant material properties. Insights find that the local change rate of thermal conductivity and Thomson effect are the essential reasons for the abovementioned phenomenon. It has been found that Thomson heat is released in the part of the leg near the cold-end, whereas it is absorbed in the remaining parts of the leg near the hot-end. The electric power on the basis of constant material properties is confirmed to be accurate enough by the developed numerical model, but the parabolic shape of the TE efficiency can be only obtained when temperature-dependent material properties are considered. Furthermore, it is wise to improve the TE efficiency by structural optimization. The present work provides an efficient and a comprehensive one-dimensional numerical model to include temperature-dependent material properties. New insights into the temperature and heat flux distribution, Thomson influence, and structural optimization potential are also presented for the in-depth understanding of the TE conversion process.

Mounting evidence indicates that inhibition of microglial activation and neuronal pyroptosis plays important roles in brain function recovery after subarachnoid hemorrhage (SAH). LDC7559 is a newly discovered gasdermin D (GSDMD) inhibitor. Previous studies have demonstrated that LDC7559 could inhibit microglial proliferation and pyroptosis. However, the beneficial effects of LDC7559 on SAH remain obscure. Based on this background, we investigated the potential role and the mechanism of LDC7559 on SAH-induced brain damage both in vivo and in vitro. The findings revealed that microglial activation and neuronal pyroptosis were evidently increased after SAH, which could be markedly suppressed by LDC7559 both in vivo and in vitro. Meanwhile, LDC7559 treatment reduced neuronal apoptosis and improved behavior function. Mechanistically, LDC7559 decreased the levels of GSDMD and cleaved GSDMD after SAH. In contrast, nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation by nigericin increased GSDMD-mediated pyroptosis and abated the beneficial effects of LDC7559 on SAH-induced brain damage. However, LDC7559 treatment did not significantly affect the expression of NLRP3 after SAH. Taken together, LDC7559 might suppress neuronal pyroptosis and microglial activation after SAH by inhibiting GSDMD, thereby promoting brain functional recovery.

ObjectiveSleep disturbance is a common problem in the general population. Sleep deprivation or dysfunction can have profound health consequences. However, how sleep duration is associated with thyroid function remains unclear. This study was thus developed to examine the association between sleep duration and thyroid function in the US adult population.MethodsA total of 8102 participants from the NHANES 2007-2012 dataset were included in this study. Weighted data analyses were conducted, and the link between sleep duration and thyroid function was probed using linear regression models with smoothed curve fitting. Stratified analyses were also performed.ResultsWeighted mean (standard deviation) values for study variables were as follows: sleep duration 6.85 (0.02) hours, thyroid-stimulating hormone (TSH) 1.86 (0.03) mIU/ml, serum free T3 3.20 (0. 01) pg/mL, serum free T4 0.80 (0.01) ng/dL, serum total T3 115.12 (0.64) ng/dL, serum total T4 7.81 (0.04) ug/dL, TPOAb 16.20 (1.53) IU/mL, TgAb 5.75 (0.73) IU/mL, and Tg 15.11 (0.46) ng/mL. In unadjusted analyses, increased sleep duration was associated with higher serum TSH levels and decreased FT3 levels. After adjustment for potential confounders, a significant negative relationship was detected between sleep duration and FT3 levels in participants with ≤7 hours of sleep. When sleep duration exceeded 7 hours, no significant changes in FT3 levels were observed after further increases in sleep duration.ConclusionIncreased sleep duration was related to decreased FT3 levels, primarily at short sleep durations, and this correlation was no longer evident when participants reached the recommended healthy sleep duration.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection caused the pandemic of coronavirus disease 2019 (COVID-19). Gastrointestinal (GI) involvement is common among patients with COVID-19, and GI symptoms can appear earlier than respiratory symptoms. Except for direct infectious effects, patients infected with SARS-CoV-2 are at risk of complications requiring gastroenterological management. Diarrhea is the most common GI symptom in patients with COVID-19 and occurs in up to half of them. Other GI symptoms, such as anorexia, discomfort, nausea, abdominal pain, loss of taste sensation, and vomiting, have been reported. GI symptoms are associated with a poor prognosis. Fecal viral excretion may have clinical significance because of the possible fecal–oral transmission of infection. In the present narrative review article, six different aspects of studies published to date are summarized as follows: GI manifestations of COVID-19, the roles of fecal–oral transmission, poor prognosis of GI symptoms; abnormal abdominal imaging findings, COVID-19 in patients with irritable bowel disease, and prevention and control of SARS-CoV-2 infection in the digestive endoscopy room. Timely understanding of the association between COVID-19 and the digestive system and effective preventive measures are critical to improve this disease and help clinicians take appropriate measures to mitigate further transmission.

Abstract Background Glioma is a common type of brain tumor and is classified as low and high grades according to morphology and molecules. Growing evidence has proved that long non-coding RNAs (lncRNAs) play pivotal roles in numerous tumors or diseases including glioma. Proteasome 20S subunit alpha 3 antisense RNA 1 (PSMA3-AS1), as a member of lncRNAs, has been disclosed to play a tumor-promoting role in cancer progression. However, the role of PSMA3-AS1 in glioma remains unknown. Therefore, we concentrated on researching the regulatory mechanism of PSMA3-AS1 in glioma. Methods PSMA3-AS1 expression was detected using RT-qPCR. Functional assays were performed to measure the effects of PSMA3-AS1 on glioma progression. After that, ENCORI ( http://starbase.sysu.edu.cn/ ) database was used to predict potential genes that could bind to PSMA3-AS1, and miR-411-3p was chosen for further studies. The interaction among PSMA3-AS1, miR-411-3p and homeobox A10 (HOXA10) were confirmed through mechanism assays. Results PSMA3-AS1 was verified to be up-regulated in glioma cells and promote glioma progression. Furthermore, PSMA3-AS1 could act as a competitive endogenous RNA (ceRNA) for miR-411-3p to regulate HOXA10 and thus affecting glioma progression. Conclusion PSMA3-AS1 stimulated glioma progression via the miR-411-3p/HOXA10 pathway, which might offer a novel insight for the therapy and treatment of glioma.

Objectives To investigate the relationship between high-molecular-weight cytokeratin (34βE12) and clinicopathological parameters (including HER-2, Ki67 and steroid receptors) in breast cancer to determine its usefulness as a prognostic marker. Methods In this retrospective study, the expression level 34βE12 was assessed in surgically resected breast cancer specimens by immunohistochemical staining. Data were correlated with the patients’ clinicopathological parameters. Results Of the 348 breast cancer tissue samples, 232 (67%) showed positive expression of 34βE12. There were statistically significant differences between the positive and negative 34βE12 expression groups in tumour size, lymph node involvement, oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status. There were no differences between groups in age, tumour grade, or Ki67 status. In addition, patients who were positive for 34βE12 had significantly extended overall survival. In multivariate analysis, the expression level of 34βE12 was found to be a significant independent prognostic factor. Conclusion These results suggest that positive 34βE12 expression is associated with a favourable outcome in breast cancer and so may be a useful prognostic factor. Further studies are required to confirm these results.

Many studies in recent years have focused on social image understanding due to the increasing number of shared images from social networks and online communities. However, previous work in social image understanding fails to learn an effective feature representation because of a large amount of missing and irrelevant tags, though matrix completion techniques are frequently utilized for this purpose. Autoencoder models have been validated to be effective in learning latent low-dimensional representations in unsupervised learning. In this paper, we propose a new social image understanding model based on deep autoencoders, which can learn the shared latent codes of social images and tags as supervision information in the deep autoencoders. First, social images are extracted with multi-modal features, which provide a comprehensive characterization to image semantic understanding. And, the social image understanding problems are transformed into the problem of minimizing an optimization objective. Second, multi-layered autoencoders with weak supervision integration are employed to learn an efficient low-dimensional representation from the multi-view feature sources that can make up the semantic gap between image features and tags through minimizing the problem formulation. Finally, we design a new balanced loss function based on binary cross entropy, in which we address highly sparse inputs for a better optimization performance. The extensive experiments on several real-world social image datasets confirm the effectiveness and robustness of the proposed model compared with the state-of-the-art methods.

Esophageal squamous cell cancer with distant metastases has a poor prognosis. The metastatic sites usually involve the liver, bones, and lungs. Treatment of metastatic disease is essentially palliative and based on chemoradiotherapy. A 57-year-old man with a solitary metastatic mass of 82 × 58 mm in the left liver was treated on 19 October 2012. Irinotecan and cisplatin combination chemotherapy and nimotuzumab targeted therapy were administered. The liver metastatic mass was treated by stereotactic Gamma Knife radiosurgery. Complete remission of the primary disease and hepatic lesion was achieved, and no local or distant recurrence was found during the 7-year follow-up. Because extrahepatic lesions were ruled out and the local disease was completely locoregionally controlled, the use of stereotactic Gamma Knife radiosurgery to remove the hepatic lesion was justified and produced a reasonable outcome.

The entry of a metallic foreign body into the thyroid gland via the esophagus is a rare occurrence, with no previously reported cases. We present a 42-year-old woman who was admitted to hospital with right-sided neck pain, reporting that she had inadvertently swallowed a fish bone. She underwent laryngoscopy, which showed no fish bone in the throat, and no obvious bleeding in the bilateral tonsils and pear-shaped fossa. X-ray examination showed a needle-shaped foreign body in the neck, and a computed tomography scan of her neck showed a 0.1-cm diameter, 2.0-cm long foreign body in the right thyroid. She underwent emergency surgery and a needle of the corresponding size was found in the thyroid gland. This case demonstrates the importance of adequate preoperative assessment and an appropriate surgical approach for thyroid metallic foreign bodies.

Low-speed two-stroke marine diesel engines dominate the modern global long-distance transportation market; with the increasingly stringent regulations, the combustion and emissions of these engines is gaining intense interest. The primary objective of the present study was to understand the effects of air-fuel mixing by pilot injection strategy on the combustion and emission characteristics of the marine diesel engines through a numerical study. Specifically, a computational fluid dynamic (CFD) model was established and validated by experimental data for a typical low-speed two-stroke marine diesel engine. The combustion parameters under different stages were analyzed, including mean in-cylinder temperature and pressure, indicated thermal efficiency (ITE), indicated specific fuel consumption (ISFC), and distribution of fuel-air mixture. Results indicated that, due to the premixing effect, the pilot injection produced unburned soot from the main injection’s ignition as well as decrease the intervals between the middle and final stages of combustion, thus raising the in-cylinder temperature. The interaction between the reduction of soot particles resulted from the increased temperature, and the decrease of the stage intervals led to lower overall boundary heat loss, which improved the effective thermal efficiency. The pilot injection timing and quality, respectively, showed quadratic and linear impact modes on engine performance and emissions.

Managed pressure drilling (MPD) is a drilling technique used to address the narrow density window under complex geological environments. It has widespread applications in the exploration and exploitation of oil and gas, both onshore and offshore. In this study, to achieve effective control of the downhole pressure to ensure safety, a gas−liquid two-phase flow model based on the drift flux model is developed to describe the characteristics of transient multiphase flow in the wellbore. The advection upwind splitting method (AUSM) numerical scheme is used to assist with calculation and analysis, and the monotonic upwind scheme for conservation laws (MUSCLs) technique with second-order precision is adopted in combination with the Van Leer slope limiter to improve precision. Relevant data sourced from prior literature are used to validate the suggested model, the results of which reveal an excellent statistical consistency. Further, the influences of various parameters in a field application, including backpressure, density, and mass flow, are analyzed. Over the course of later-stage drilling, a combination of wellhead backpressure and displacement is recommended to exercise control.

In this work, a methodology for characterizing reservoir pore pressure and permeability during underbalanced drilling of horizontal wells was presented. The methodology utilizes a transient multiphase wellbore flow model that is extended with a transient well influx analytical model during underbalanced drilling of horizontal wells. The effects of the density behavior of drilling fluid and wellbore heat transfer are considered in our wellbore flow model. Based on Kneissl’s methodology, an improved method with a different testing procedure was used to estimate the reservoir pore pressure by introducing fluctuations in the bottom hole pressure. To acquire timely basic data for reservoir characterization, a dedicated fully automated control real-time data monitoring system was established. The methodology is applied to a realistic case, and the results indicate that the estimated reservoir pore pressure and permeability fit well to the truth values from well test after drilling. The results also show that the real-time data monitoring system is operational and can provide accurate and complete data set in real time for reservoir characterization. The methodology can handle reservoir characterization during underbalanced drilling of horizontal wells.

Breast cancer is the most prevalent neoplasm affecting women globally, of which a notable proportion of cases are triple-negative breast cancer (TNBC). However, there are limited curative treatment options for patients with TNBC, despite advancements in the field. Amino acids and amino acid transporters serve vital roles in the regulation of tumor metabolism. Notably, cystine and cysteine can interconvert via a redox reaction, with cysteine exerting control on cell survival and growth and exogenous cystine serving a crucial role in the proliferation of numerous types of cancers. Breast cancer has been reported to disrupt the cystine/cysteine metabolism pathway, as cystine and cysteine transporters affect the development and growth of tumors. The present review aims to provide a comprehensive overview of the metabolic pathways involving cystine and cysteine in normal and TNBC cells. Furthermore, the roles of cystine and cysteine transporters in TNBC progression and metastasis and their potential as therapeutic targets for treatment of TNBC are evaluated. [ABSTRACT FROM AUTHOR]

ABSTRACT Fungal pathogens are underappreciated causes of significant morbidity and mortality worldwide. In previous studies, we determined that a heat-killed, Cryptococcus neoformans fbp1-deficient strain (HK-fbp1) is a potent vaccine candidate. We determined that vaccination with HK-fbp1 confers protective immunity against lethal Cryptococcosis in an interferon γ (IFNγ)-dependent manner. In this study, we set out to uncover cellular sources and relevant targets of the protective effects of IFNγ in response to the HK-fbp1 vaccine. We found that early IFNγ production peaks at day 3 and that monocytes and neutrophils are important sources of this cytokine after vaccination. Neutralization of IFNγ at day 3 results in impaired CCR2+ monocyte recruitment and reduced differentiation into monocyte-derived dendritic cells (Mo-DC). In turn, depletion of CCR2+ cells prior to immunization results in impaired activation of IFNγ-producing CD4 and CD8 T cells. Thus, monocytes are important targets of innate IFNγ and help promote further IFNγ production by lymphocytes. We employed monocyte-fate mapper and conditional STAT1 knockout mice to uncover that STAT1 activation in CD11c+ cells, including alveolar macrophages, Mo-DCs, and monocyte-derived macrophages (Mo-Mac) is essential for HK-fbp1 vaccine-induced protection. Altogether, our aggregate findings suggest critical roles for innate cells as orchestrators of vaccine-induced protection against Cryptococcus infection.IMPORTANCEThe number of patients susceptible to invasive fungal infections across the world continues to rise at an alarming pace yet current antifungal drugs are often inadequate. Immune-based interventions and novel antifungal vaccines hold the promise of significantly improving patient outcomes. In previous studies, we identified a Cryptococcus neoformans mutant strain (Fbp1-deficient) as a potent, heat-inactivated vaccine candidate capable of inducing homologous and heterologous antifungal protection. In this study, we used a combination of methods together with a cohort of conditional knockout mouse strains to interrogate the roles of innate cells in the orchestration of vaccine-induced antifungal protection. We uncovered novel roles for neutrophils and monocytes as coordinators of a STAT1-dependent cascade of responses that mediate vaccine-induced protection against invasive cryptococcosis. This new knowledge will help guide the future development of much-needed antifungal vaccines.