Exploring the supplementary potential of all-trans retinoic acid with methotrexate in rheumatoid arthritis: modulation of synovial cell apoptosis and autophagy.

OBJECTIVES: The imbalance between apoptosis and proliferation in fibroblast-like synoviocytes (FLSs) plays a key role in the pathogenesis of rheumatoid arthritis (RA). This study aims to investigate the potential of all-trans retinoic acid (ATRA) as a supplementary therapeutic agent alongside methotrexate (MTX) for RA, by examining its ability to inhibit synovial cell proliferation and enhance apoptosis through the ROS-JNK signalling pathway. METHODS: The viability, apoptosis, and autophagy levels of human rheumatoid arthritis fibroblast-like synovial cells (HFLS-RA) were evaluated, while ROS generation was measured through the DCFH-DA fluorescence microplate assay. Western blotting was used to analyse the expression levels of JNK signalling pathway-related proteins. To assess therapeutic potential in vivo, a collagen-induced arthritis (CIA) model was established in Wistar rats. RESULTS: Small doses of MTX did not significantly affect the viability of HFLS-RAs or induce apoptosis. However, when ATRA was added to the treatment, the therapy markedly inhibited cell proliferation and induced apoptosis and excessive autophagy. Mechanistically, ATRA activated the ROS/JNK signalling pathway in HFLS-RAs. ROS scavengers and JNK inhibitors significantly attenuated ATRA-induced apoptosis and autophagy. In vivo, the combination therapy demonstrated a remarkable enhancement of the anti-arthritic efficacy in CIA rats. CONCLUSIONS: The ability of ATRA to inhibit proliferation in RA FLSs through autophagy and apoptosis underscores its potential as a supplementary therapeutic agent alongside MTX for RA, particularly when compared to the limited impact of MTX on these processes. This combined strategy holds promise for enhancing therapeutic outcomes and warrants further investigation in the management of RA.

Valorization of Lignocellulose with One-Step Acidified Monophasic Phenoxyethanol Fractionation.

Effective fractionation of lignocelluosic biomass and subsequent valorization of all three major components under mild conditions were achieved. Pretreatment with acidified monophasic phenoxyethanol (EPH) efficiently removed 92.6 % lignin and 80 % xylan from poplar at 110 °C in 60 min, yielding high-value EPH-xyloside, EPH-modified lignin (EPHL), and a solid residue nearly purely composed of carbohydrates. After removing the grafted acetyl groups using 1 % NaOH at 50 °C, the highest enzymatic digestibility reached 92.3 %. EPHL could be recovered in high yield and purity with an uncondensed structure, while xylose was converted to EPH-xyloside, a potential precursor in biomedical industries. Additionally, the acidified monophasic EPH solvent could effectively fractionate biomass from species other than hardwood, achieving over 70 % delignification from recalcitrant pinewood under the same mild conditions, demonstrating the high potential of monophasic EPH pretreatment.

Precise execution of personalized surgical planning using three-dimensional printed guide template in severe and complex adult spinal deformity patients requiring three-column osteotomy: a retrospective, comparative matched-cohort study.

BACKGROUND: The surgical treatment of severe and complex adult spinal deformity (ASD) commonly required three-column osteotomy (3-CO), which was technically demanding with high risk of neurological deficit. Personalized three dimensional (3D)-printed guide template based on preoperative planning has been gradually applied in 3-CO procedure. The purpose of this study was to compare the efficacy, safety, and precision of 3D-printed osteotomy guide template and free-hand technique in the treatment of severe and complex ASD patients requiring 3-CO. METHODS: This was a single-centre retrospective comparative cohort study of patients with severe and complex ASD (Cobb angle of scoliosis > 80° with flexibility < 25% or focal kyphosis > 90°) who underwent posterior spinal fusion and 3-CO between January 2020 to January 2023, with a minimum 12 months follow-up. Personalized computer-assisted three-dimensional osteotomy simulation was performed for all recruited patients, who were further divided into template and non-template groups based on the application of 3D-printed osteotomy guide template according to the surgical planning. Patients in the two groups were age- and gender- propensity-matched. The radiographic parameters, postoperative neurological deficit, and precision of osteotomy execution were compared between groups. RESULTS: A total of 40 patients (age 36.53 ± 11.98 years) were retrospectively recruited, with 20 patients in each group. The preoperative focal kyphosis (FK) was 92.72° ± 36.77° in the template group and 93.47° ± 33.91° in the non-template group, with a main curve Cobb angle of 63.35° (15.00°, 92.25°) and 64.00° (20.25°, 99.20°), respectively. Following the correction surgery, there were no significant differences in postoperative FK, postoperative main curve Cobb angle, correction rate of FK (54.20% vs. 51.94%, P = 0.738), and correction rate of main curve Cobb angle (72.41% vs. 61.33%, P = 0.101) between the groups. However, the match ratio of execution to simulation osteotomy angle was significantly greater in the template group than the non-template group (coronal: 89.90% vs. 74.50%, P < 0.001; sagittal: 90.45% vs. 80.35%, P < 0.001). The operating time (ORT) was significantly shorter (359.25 ± 57.79 min vs. 398.90 ± 59.48 min, P = 0.039) and the incidence of postoperative neurological deficit (5.0% vs. 35.0%, P = 0.018) was significantly lower in the template group than the non-template group. CONCLUSION: Performing 3-CO with the assistance of personalized 3D-printed guide template could increase the precision of execution, decrease the risk of postoperative neurological deficit, and shorten the ORT in the correction surgery for severe and complex ASD. The personalized osteotomy guide had the advantages of 3D insight of the case-specific anatomy, identification of osteotomy location, and translation of the surgical planning or simulation to the real surgical site.

Unconventional Band Structure via Combined Molecular Orbital and Lattice Symmetries in a Surface-Confined Metallated Graphdiyne Sheet.

Graphyne (GY) and graphdiyne (GDY)-based monolayers represent the next generation 2D carbon-rich materials with tunable structures and properties surpassing those of graphene. However, the detection of band formation in atomically thin GY/GDY analogues has been challenging, as both long-range order and atomic precision have to be fulfilled in the system. The present work reports direct evidence of band formation in on-surface synthesized metallated Ag-GDY sheets with mesoscopic (≈1 µm) regularity. Employing scanning tunneling and angle-resolved photoemission spectroscopies, energy-dependent transitions of real-space electronic states above the Fermi level and formation of the valence band are respectively observed. Furthermore, density functional theory (DFT) calculations corroborate the observations and reveal that doubly degenerate frontier molecular orbitals on a honeycomb lattice give rise to flat, Dirac and Kagome bands close to the Fermi level. DFT modeling also indicates an intrinsic band gap for the pristine sheet material, which is retained for a bilayer with h-BN, whereas adsorption-induced in-gap electronic states evolve at the synthesis platform with Ag-GDY decorating the (111) facet of silver. These results illustrate the tremendous potential for engineering novel band structures via molecular orbital and lattice symmetries in atomically precise 2D carbon materials.

Impact of HER2 status on clinicopathological characteristics and pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer.

PURPOSE: HER2-low triple-negative breast cancer (TNBC) accounted for up to 34%-39% of primary TNBC and 22.2%-32% of metastatic TNBC. Our study aims to explore the relationship between HER2 expression and clinicopathological characteristics, analyze the impact of HER2 expression on the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in TNBC. METHODS: This study involved 191 patients with TNBC who underwent operation after NAC from October 2021 to August 2022. Clinicopathological characteristics and the frequency of pCR were compared between HER2-low and HER2-0 TNBC. RESULTS: 42.2% (81/191) patients in our cohort were HER2-low. They exhibited differences in menopausal status, body mass index (BMI), androgen receptor (AR) expression, and histological grade (P < 0.05). Particularly, in HER2-low TNBC, AR was associated with tumor size, lymph node metastase, histological grade, and the incidence of multifocal disease (P < 0.05). The total pCR rate of entire cohor was 39.8%. Tumor size (P = 0.025), AR status (P = 0.033) and histological grade (P = 0.007) were significantly associated with the pCR rate of them, while the HER2 status did not exert a similar association. The multivariate analysis revealed that BMI (P = 0.004) and histological grade (P < 0.001) were associated with pCR of HER2-low TNBC, while tumor size (P = 0.034) and AR (P = 0.034) were associated with pCR of HER2-0 TNBC, respectively. CONCLUSIONS: In our cohort, HER2-low TNBC patients exhibits specific clinical characteristics and response features to NAC.

U2AF2-SNORA68 promotes triple-negative breast cancer stemness through the translocation of RPL23 from nucleoplasm to nucleolus and c-Myc expression.

BACKGROUND: Small nucleolar RNAs (snoRNAs) play key roles in ribosome biosynthesis. However, the mechanism by which snoRNAs regulate cancer stemness remains to be fully elucidated. METHODS: SNORA68 expression was evaluated in breast cancer tissues by in situ hybridization and qRT‒PCR. Proliferation, migration, apoptosis and stemness analyses were used to determine the role of SNORA68 in carcinogenesis and stemness maintenance. Mechanistically, RNA pull-down, RNA immunoprecipitation (RIP), cell fractionation and coimmunoprecipitation assays were conducted. RESULTS: SNORA68 exhibited high expression in triple-negative breast cancer (TNBC) and was significantly correlated with tumor size (P = 0.048), ki-67 level (P = 0.037), and TNM stage (P = 0.015). The plasma SNORA68 concentration was significantly lower in patients who achieved clinical benefit. The SNORA68-high patients had significantly shorter disease-free survival (DFS) (P = 0.036). Functionally, SNORA68 was found to promote the cell stemness and carcinogenesis of TNBC in vitro and in vivo. Furthermore, elevated SNORA68 expression led to increased nucleolar RPL23 expression and retained RPL23 in the nucleolus by binding U2AF2. RPL23 in the nucleolus subsequently upregulated c-Myc expression. This pathway was validated using a xenograft model. CONCLUSION: U2AF2-SNORA68 promotes TNBC stemness by retaining RPL23 in the nucleolus and increasing c-Myc expression, which provides new insight into the regulatory mechanism of stemness.

Development and classification of autonomous vehicle's ambiguous driving scenario.

Human drivers are gradually being replaced by highly automated driving systems, and this trend is expected to persist. The response of autonomous vehicles to Ambiguous Driving Scenarios (ADS) is crucial for legal and safety reasons. Our research focuses on establishing a robust framework for developing ADS in autonomous vehicles and classifying them based on AV user perceptions. To achieve this, we conducted extensive literature reviews, in-depth interviews with industry experts, a comprehensive questionnaire survey, and factor analysis. We created 28 diverse ambiguous driving scenarios and examined 548 AV users' perspectives on moral, ethical, legal, utility, and safety aspects. Based on the results, we grouped ADS, with all of them having the highest user perception of safety. We classified these scenarios where autonomous vehicles yield to others as moral, bottleneck scenarios as ethical, cross-over scenarios as legal, and scenarios where vehicles come to a halt as utility-related. Additionally, this study is expected to make a valuable contribution to the field of self-driving cars by presenting new perspectives on policy and algorithm development, aiming to improve the safety and convenience of autonomous driving.

Cellular senescence in chronic lung diseases from newborns to the elderly: An update literature review.

The role of cellular senescence in age-related diseases has been fully recognized. In various age-related-chronic lung diseases, the function of alveolar epithelial cells (AECs) is impaired and alveolar regeneration disorders, especially in bronchopulmonary dysplasia，pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), cancer, etc. Except for age-related-chronic lung diseases, an increasing number of studies are exploring the role of cellular senescence in developmental chronic lung diseases, which typically originate in childhood and even in the neonatal period. This review provides an overview of cellular senescence and lung diseases from newborns to the elderly, attempting to draw attention to the relationship between cellular senescence and developmental lung diseases.

Urban green and blue infrastructure: unveiling the spatiotemporal impact on carbon emissions in China's Yangtze River Delta.

Blue-green infrastructure (BGI) plays a crucial role in regulating urban carbon cycles. Nonetheless, the spatiotemporal effect of BGI on carbon emissions has not received extensive attention. This study used the Yangtze River Delta (YRD) region as the study area and quantified the landscape patterns of BGI. Using a spatiotemporal geographically weighted regression model, we analyzed the impact of evolving spatiotemporal characteristics of BGI on carbon emissions. Additionally, we constructed a spatiotemporal weight matrix using the Moran index ratio to examine the spillover effects of BGI among different regions. Our results show that the aggregation effect of carbon emissions in the YRD region is gradually increasing while BGI has a dynamic impact on carbon emissions. In terms of spatial and temporal spillovers, under the influence of economic connections between regions, patch fragmentation and distance exert a persistent positive influence on carbon emissions, while shape complexity has a negative impact, with area and layout characteristics showing no significant effects. However, area and patch distance have a persistent positive influence on carbon emissions in adjacent areas, while shape complexity exhibits a negative impact. Therefore, optimizing urban BGI through a regional synergistic governance system is important to promote low-carbon urban development.

The small nucleolar RNA SNORA51 enhances breast cancer stem cell-like properties via the RPL3/NPM1/c-MYC pathway.

Breast cancer stem cells (BCSCs) are key players in carcinogenesis and development. Small nucleolar RNAs (snoRNAs) seem to have a crucial influence on regulating stem cell-like properties in various cancers, but the underlying mechanism in breast cancer has not been determined. In this study, we first found that the expression of SNORA51 might be strongly and positively related to BCSCs-like properties. SNORA51 expression was assessed in breast cancer tissues (n = 158 patients) by in situ hybridization. Colony formation, cell counting kit-8, and sphere formation assays were used to detect cell proliferation and self-renewal, respectively. Wound healing and transwell assays were used to detect cell migration. Coimmunoprecipitation and molecular docking were used to determine the underlying mechanism through which SNORA51 regulates BCSCs-like properties. High SNORA51 expression was associated with a worse prognosis, overall survival, and disease-free survival, in 158 breast cancer patients and was also closely related to lymph node status, ER status, the Ki-67 index, histological grade, and TNM stage. Further analysis proved that SNORA51 could enhance and maintain stem cell-like properties, including cell proliferation, self-renewal, and migration, in breast cancer. Moreover, high SNORA51 expression could reduce nucleolar RPL3 expression, induce changes in the expression of NPM1 in the nucleolus and nucleoplasm, and ultimately increase c-MYC expression. Taken together, our findings demonstrated that SNORA51 could enhance BCSCs-like properties via the RPL3/NPM1/c-MYC pathway both in vitro and in vivo. Therefore, SNORA51 might be a significant biomarker and potential therapeutic target and might even provide a new viewpoint on the regulatory mechanism of snoRNAs in breast cancer or other malignant tumors.

Effects of food-grade iron(III) oxide nanoparticles on cecal digesta- and mucosa-associated microbiota and short-chain fatty acids in rats.

Although iron(III) oxide nanoparticles (IONPs) are widely used in diverse applications ranging from food to biomedicine, the effects of IONPs on different locations of gut microbiota and short-chain fatty acids (SCFAs) are unclear. So, a subacute repeated oral toxicity study on Sprague Dawley (SD) rats was performed, administering low (50 mg/kg·bw), medium (100 mg/kg·bw), and high (200 mg/kg·bw) doses of IONPs. In this study, we found that a high dose of IONPs increased animal weight, and 16S rRNA sequencing revealed that IONPs caused intestinal flora disorders in both the cecal digesta- and mucosa-associated microbiota. However, only high-dose IONP exposure changed the abundance and composition of the mucosa-associated microbiota. IONPs increased the relative abundances of Firmicutes, Ruminococcaceae_UCG-014, Ruminiclostridium_9, Romboutsia, and Bilophila and decreased the relative abundance of Bifidobacterium, and many of these microorganisms are associated with weight gain, obesity, inflammation, diabetes, and mucosal damage. Functional analysis showed that changes in the gut microbiota induced by a high dose of IONPs were mainly related to metabolism, infection, immune, and endocrine disease functions. IONPs significantly elevated the levels of valeric, isobutyric, and isovaleric acid, promoting the absorption of iron. This is the first description of intestinal microbiota dysbiosis in SD rats caused by IONPs, and the effects and mechanisms of action of IONPs on intestinal and host health need to be further studied and confirmed.

All-trans retinoic acid alleviates collagen-induced arthritis and promotes intestinal homeostasis.

All-trans retinoic acid (ATRA) has emerged as a promising adjunctive treatment for rheumatoid arthritis. However, the mechanism by which ATRA mitigates arthritis remains unclear. In this study, we aimed to explore ATRA alleviation of arthritis and the role of ATRA in regulating intestinal homeostasis. Thus, we established a collagen-induced arthritis (CIA) model in Wistar rats. After 6 weeks of ATRA treatment, the arthritis index of CIA rats decreased, synovial inflammation was alleviated, and the disruption of Th17/Treg differentiation in peripheral blood was reversed. Additionally, the Th17/Treg ratio in the mesenteric lymph nodes decreased and the expression of Foxp3 mRNA increased and that of IL-17 mRNA decreased in the colon and ileum. Microscopically, we observed reduced intestinal inflammation. Transmission electron microscopy revealed that ATRA could repair tight junctions, which was accompanied by an increase in the expression of Claudin-1, Occludin and ZO-1. Moreover, ATRA regulated the composition of the gut microbiota, as was characterized based on the reduced abundance of Desulfobacterota and the increased abundance of Lactobacillus. In conclusion, ATRA demonstrates the potential to alleviate arthritis in CIA rats, which might be correlated with modulating the gut microbiota and regulating the intestinal immune response. Our findings provide novel insights into ATRA-mediated alleviation of arthritis.

Effects of the Chinese Heart-Healthy Diet (Sichuan Cuisine Version) on the 10-year CVD risk and vascular age: a randomised controlled feeding trial.

Sichuan cuisine was previously fitted into the Chinese Heart-Healthy Diet (CHH) trial to verify the antihypertensive effect. Whether the modified Sichuan diet lessens cardiovascular disease (CVD) is not fully explored. We aimed to estimate the effects of the Sichuan version of CHH diet (CHH diet-SC) on the 10-year risk of CVD and vascular age. A single-blinded randomised controlled feeding trial was conducted. General CVD prediction model was used in manners of intention-to-treat and per-protocol set. After a 7-d run-in period, fifty-three participants with pre- and grade I hypertension from local communities were randomised and provided with either CHH diet-SC (n 27) or a control diet (n 26) for 4 weeks. Mean absolute and relative estimated CVD risks were reduced by 4·5 % and 27·9 % in the CHH diet-SC group, and the between-group relative risk reduction was 19·5 % (P < 0·001) using linear mixed-effects models. The sensitivity analysis with datasets and models showed consistent results, and pre-specified factors were not associated with the intervention effects. The vascular age of CHH-SC group was theoretically 4·4 years younger than that of the control group after intervention. Compared with a typical diet, adopting the CHH diet-SC over 1 month significantly reduced 10-year CVD risks and vascular ages among local adults with mild hypertension.

Shaping the future of chronic disease management: Insights into patient needs for AI-based homecare systems.

BACKGROUND: The rising demand for healthcare resources, especially in chronic disease management, has elevated the importance of Artificial Intelligence (AI) in healthcare. While AI-based homecare systems are being developed, the perspectives of chronic patients, who are one of the primary beneficiaries and risk bearers of these technologies, remain largely under-researched. While recent research has highlighted the importance of AI-based homecare systems, the current understanding of patients' desired designs and features is still limited. OBJECTIVE: This paper explores chronic patients' perspectives regarding AI-based homecare systems, an area currently underrepresented in research. We aim to identify the factors influencing their decision to use such systems, elucidate the potential roles of government and other concerned authorities, and provide feedback to AI developers to enhance adoption, system design, and usability and improve the overall healthcare experiences of chronic patients. METHOD: A web-based open-ended questionnaire was designed to gather the perspectives of chronic patients about AI-based homecare systems. In total, responses from 181 participants were collected. Using Krippendorff's clustering technique, an inductive thematic analysis was performed to identify the main themes and their respective subthemes. RESULT: Through rigorous coding and thematic analysis of the collected responses, we identified four major themes further segmented into thirteen subthemes. These four primary themes were: 1) "Personalized Design", emphasizing the need for patients to manage their health condition better through personalized and educational resources and user-friendly interfaces; 2) "Emotional & Social Support", underscoring the desire for AI systems to facilitate social connectivity and provide emotional support to improve the well-being of chronic patients at home; 3) "System Integration & Proactive Care", addressing the importance of seamless communication, proactive patient monitoring and integration with existing healthcare platforms; and 4) "Ethics & Regulation", prioritizing ethical guidelines, regulatory compliance, and affordability in the design. CONCLUSION: This study has offered significant insights into the needs and expectations of chronic patients regarding AI-based home care systems. 'The findings highlight the importance of personalized and accessible care, emotional and social support, seamless system integration, proactive care, and ethical considerations in designing and implementing such systems. By aligning the design and operation of these systems with the lived experiences and expectations of patients, we can better ensure their acceptance and effectiveness.

Evaluation of bone mineral density in adolescent idiopathic scoliosis using a three-dimensional finite element model: a retrospective study.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is often accompanied by osteopenia and osteoporosis, which can cause serious complications. The aim of this study was to determine the specific bone mineral density (BMD) of each vertebral body in patients with AIS using biomechanical finite element modeling based on three-dimensional (3D) reconstruction. METHODS: This retrospective study involved 56 patients with AIS. Computed tomography (CT) and radiography were performed. Spinal vertebrae were segmented from the spinal CT images of patients with AIS to reconstruct 3D vertebral models. The vertebral models were meshed into tetrahedral finite elements to assess the BMD. RESULTS: The mean main curve Cobb angle was 88.6 ± 36.7°, and the mean kyphosis angle was 36.8 ± 31.5°. The mean BMD of the global spine was 0.83 ± 0.15 g/cm2. The highest BMD was measured on the concave side of the apex (0.98 ± 0.16 g/cm2). Apical vertebral BMD was negatively correlated with age and height (r = - 0.490, p = 0.009 and r = - 0.478, p = 0.043, respectively). There were no significant differences in BMD values between the concave and convex sides (p > 0.05). CONCLUSIONS: The 3D finite element modeling of BMD in patients with AIS is a reliable and accurate BMD measurement method. Using this method, the overall BMD of patients with AIS was shown to gradually decrease from the top to the bottom of the spine. Our findings provide valuable insights for surgical planning, choice of screw trajectories, and additional biomechanical analyzes using finite element models in the context of scoliosis.

Case Report: Non-negligible Epstein-Barr virus-associated posttransplant lymphoproliferative disorders in a lung transplant recipient.

Background: Posttransplant lymphoproliferative disorders (PTLDs) are uncommon but serious complications in patients following solid organ transplantation. Primary Epstein-Barr virus (EBV) infection is a risk factor for the development of PTLD, especially early-onset PTLD, in EBV-negative recipients. To date, however, there are no specific guidelines on the threshold of EBV-DNA load for therapeutic intervention, the source for measurement (e.g., blood, bronchoalveolar fluid), or the use of antiviral agents as prophylaxis for early PTLD prevention in EBV-mismatched patients. Methods: The present study describes a 56-year-old male lung transplant recipient diagnosed with EBV-associated PTLD. Results: This patient had a history of invasive fungal disease and Mucor and Aspergillus fumigatus infections in the early post-transplant period, necessitating antifungal therapy throughout the course of the disease. The patient was EBV-positive 15 days after transplantation, with lung CT showing multiple bilateral nodules of varying sizes beginning 98 days after transplantation. A lung biopsy showed PTLD, and next-generation sequencing (NGS) revealed EBV. This patient, however, did not receive any antiviral therapy for early PTLD prevention or any PTLD-related treatment. He died 204 days after lung transplantation. Conclusion: The present study describes a lung transplant recipient who developed EBV-associated PTLD, a non-negligible disease, after solid organ transplantation. Monitoring EBV-DNA load is important, as a sudden increase may be a sensitive indicator of PTLD. An earlier diagnosis may increase the likelihood of successful treatment.

Activation of kappa opioid receptor (KOR) inhibits estrogen receptor (ER)-positive breast cancer through the KOR-ER-XBP1 pathway.

Opioids are commonly used in patients with breast cancer (BC), both for perioperative analgesia and for the relief of chronic cancer pain. Studies have suggested a potential association of opioid receptors (ORs) with the prognosis of BC patients. However, the exact roles of different ORs remain poorly understood. In this study, we found that κ opioid receptor (KOR) was the only OR (among the four types of ORs) that was significantly decreased in BC tumor tissues compared with peritumoral normal tissues. In addition, decreased expression of KOR correlated with poor clinical outcomes in patients with estrogen receptor (ER)-positive BC. In vitro studies confirmed the anti-tumor effects of KOR agonists in ER-positive MCF-7 and T47D cells by showing that activation of KOR significantly inhibited cellular proliferation and promoted apoptosis. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction network (PPI) analysis, we found that KOR-ER-XBP1 was the potential downstream signaling pathway mediating the anti-tumor effects of KOR agonist. Finally, the role of XBP1 was confirmed as KOR activation-induced increase in the proliferative and monoclonal formation abilities of ER-positive BC cells were both significantly abolished after silencing of XBP1. These findings provide us a better understanding of the roles of different ORs in BC, identifying KOR agonists as better opioids than traditional µ opioid receptor (MOR) agonists for providing analgesia in ER-positive BC patients owing to their association with better prognosis.

Evaluation of Pulmonary Function After Halo-Pelvic Traction for Severe and Rigid Kyphoscoliosis Utilizing CT with 3D Reconstruction.

BACKGROUND: The purpose of the present study was to evaluate changes in pulmonary function, caused by preoperative halo-pelvic traction (HPT) for the treatment of extremely severe and rigid kyphoscoliosis, with use of 3-dimensional computed tomography (3D-CT) reconstruction and pulmonary function tests (PFTs). METHODS: Twenty-eight patients with severe and rigid scoliosis (Cobb angle, >100°) underwent preoperative HPT and staged posterior spinal fusion. CT, radiographic assessment, and PFT were performed during pre-traction and post-traction visits. The changes in total lung volume were evaluated with use of 3D-CT reconstruction, and the changes in pulmonary function were evaluated with PFTs at each time point. Differences were analyzed with use of 2-tailed paired Student t tests, and correlations were analyzed with use of Spearman rank tests. RESULTS: None of the patients had pulmonary complications during traction, and all radiographic spinal measurements improved significantly after HPT. The main Cobb angle was corrected from 143.30° ± 20.85° to 62.97° ± 10.83° between the pre-traction and post-traction evaluations. Additionally, the C7-S1 distance was lengthened from 280.48 ± 39.99 to 421.26 ± 32.08 mm between the pre-traction and post-traction evaluations. Furthermore, 3D lung reconstruction demonstrated a notable increase in total lung volume (TLV) (from 1.30 ± 0.25 to 1.83 ± 0.37 L) and maximum lung height (from 176.96 ± 27.44 to 202.31 ± 32.45 mm) between the pre-traction and post-traction evaluations. Moreover, PFTs showed that total lung capacity (TLC) improved between the pre-traction and post-traction evaluations (from 2.06 ± 0.32 to 2.98 ± 0.82 L) and that the changes in T1-T12 distance and maximum lung height were correlated with changes in TLV (p = 0.0288 and p = 0.0007, respectively). CONCLUSIONS: The application of HPT is a safe and effective method for improving pulmonary function in patients with extremely severe and rigid scoliosis before fusion surgery. The TLV as measured with CT-based reconstruction was greatly increased after HPT, mainly because of the changes in thoracic height. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Suppression of Secondary Electron Emission from Nickel Surface by Graphene Composites Based on First-Principles Method.

Secondary electron emission (SEE) is a fundamental phenomenon of particle/surface interaction, and the multipactor effect induced by SEE can result in disastrous impacts on the performance of microwave devices. To suppress the SEE-induced multipactor, an Ni (111) surface covered with a monolayer of graphene was proposed and studied theoretically via the density functional theory (DFT) method. The calculation results indicated that redistribution of the electron density at the graphene/Ni (111) interface led to variations in the work function and the probability of SEE. To validate the theoretical results, experiments were performed to analyze secondary electron yield (SEY). The measurements showed a significant decrease in the SEY on an Ni (111) surface covered with a monolayer of graphene, accompanied by a decrease in the work function, which is consistent with the statistical evidence of a strong correlation between the work function and SEY of metals. A discussion was given on explaining the experimental phenomenon using theoretical calculation results, where the empty orbitals lead to an electron trapping effect, thereby reducing SEY.

Carbon intensity of global crude oil trading and market policy implications.

The energy mix transition has accelerated the need for more accurate emissions reporting throughout the petroleum supply chain. Despite increasing environmental regulations and pressure for emissions disclosure, the low resolution of existing carbon footprint assessment does not account for the complexity of crude oil trading. The lack of source crude traceability has led to poor visibility into the "well-to-refinery-entrance" carbon intensities at the level of granular pathways between producers and destination markets. Using high-fidelity datasets, optimization algorithms to facilitate supply chain traceability and bottom-up, physics-based emission estimators, we show that the variability in global "well-to-refinery-entrance" carbon intensities at the level of crude trade pathways is significant: 4.2-214.1 kg-CO2-equivalent/barrel with a volume-weighted average of 50.5 kg-CO2-equivalent/barrel. Coupled with oil supply forecasts under 1.5 °C scenarios up to 2050, this variability translates to additional CO2-equivalent savings of 1.5-6.1 Gigatons that could be realized solely by prioritizing low-carbon supply chain pathways without other capital-intensive mitigation measures.