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Abstract Background Neoadjuvant chemotherapy (NAC) is an effective treatment for locally advanced breast cancer (BC). However, there are no effective biomarkers for evaluating its efficacy. CDR1-AS, well known for its important role in tumorigenesis, is a famous circular RNA involved in the chemosensitivity of cancers other than BC. However, the predictive role of CDR1-AS in the efficacy and prognosis of NAC for BC has not been fully elucidated. We herein aimed to clarify this role. Methods The present study included patients treated with paclitaxel-cisplatin-based NAC. The expression of CDR1-AS was detected by real-time quantitative reverse transcription polymerase chain reaction testing. The predictive value of CDR1-AS expression was examined in pathological complete response (pCR) after NAC using logistic regression analysis. The relationship between CDR1-AS expression and survival was demonstrated using the Kaplan–Meier method, and tested by log-rank test and Cox proportional hazards regression model. Results The present study enrolled 106 patients with BC. Multivariate logistic regression analysis revealed that CDR1-AS expression was an independent predictive factor for pCR (odds ratio [OR] = 0.244; 95% confidence interval [CI] 0.081–0.732; p = 0.012). Furthermore, pCR benefits with low CDR1-AS expression were observed across all subgroups. The Kaplan–Meier curves and log-rank test suggested that the CDR1-AS high-expression group showed significantly better disease-free survival (DFS; log-rank p = 0.022) and relapse-free survival (RFS; log-rank p = 0.012) than the CDR1-AS low-expression group. Multivariate analysis revealed that CDR1-AS expression was an independent prognostic factor for DFS (adjusted HR = 0.177; 95% CI 0.034–0.928, p = 0.041), RFS (adjusted HR = 0.061; 95% CI 0.006–0.643, p = 0.020), and distant disease-free survival (adjusted HR = 0.061; 95% CI 0.006–0.972, p = 0.047). Conclusions CDR1-AS may be a potential novel predictive biomarker of pCR and survival benefit in patients with locally advanced BC receiving NAC. This may help identify specific chemosensitive individuals and build personalized treatment strategies.

Abstract Background and objective Breast cancer is a leading cause of morbidity and mortality among women worldwide. This study aimed to assess the global burden of breast cancer and identify attributable risk factors across 204 countries and territories from 1990 to 2021. Methods Using data from the Global Burden of Disease Study 2021, we analyzed the incidence, mortality, disability-adjusted life years (DALYs), and risk factors associated with breast cancer. We obtained and analyzed the age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALYs rate from 1990 to 2021. We assessed geographical variations and the impact of the Socio-demographic Index (SDI) using regression analysis and stratification by SDI quintiles. Additionally, we estimated the risk factors attributable to breast cancer deaths and DALYs using the comparative risk assessment framework of the GBD study. Results Globally, breast cancer incident cases increased from 875,657 in 1990 to 2,121,564 in 2021. The ASIR rose from 16.42 to 26.88 per 100,000 (95% CI: 1.54–1.60). High SDI regions showed the highest ASIR (66.89 per 100,000 in 2021), while Low SDI regions had the lowest (6.99 per 100,000 in 2021). The global ASDR decreased from 10.42 to 8.54 per 100,000, and the age-standardized DALYs rate decreased from 313.36 to 261.5 per 100,000 between 1990 and 2021. However, these improvements were not uniform across SDI regions. Risk factors included high body-mass index, alcohol use, tobacco, and high fasting plasma glucose, with variations across SDI regions. Conclusion The global burden of breast cancer has increased significantly from 1990 to 2021, with disparities observed across SDI regions. While high SDI areas show improvements in mortality and DALYs, lower SDI regions face increasing burdens. Targeted interventions addressing modifiable risk factors and improving healthcare access in less developed regions are crucial for reducing the global impact of breast cancer.

Abstract Breast cancer is the most common diagnosed cancer, the HER2-positive subtype account for 15% of all breast cancer. HER2-targeted therapy is the mainstay treatment for HER2-positive breast cancer. Cuproptosis is a novel form of programmed cell death, and is caused by mitochondrial lipoylation and destabilization of iron-sulfur proteins triggered by copper, which was considered as a key player in various biological processes. However, the roles of cuproptosis-related genes in HER2-positive breast cancer remain largely unknown. In the present study, we constructed a prognostic prediction model of HER2-positive breast cancer patients using TCGA database. Dysregulated genes for cells resistant to HER2-targeted therapy were analyzed in the GEO dataset. KEGG pathway, GO enrichment and GSEA was performed respectively. The immune landscape of DLAT was analyzed by CIBERSORT algorithm and TIDE algorithm. HER2-positive breast cancer patients with high CRGs risk score showed shorter OS. DLAT was downregulated and correlated with better survival of HER2-positive breast cancer patients (HR = 3.30, p = 0.022). High expressed DLAT was associated with resistant to HER2-targeted therapy. Knocking down DLAT with siRNA increased sensitivity of breast cancer to trastuzumab. KEGG pathway and GO enrichment of DEGs indicated that DLAT participates in various pathways correlated with organelle fission, chromosome segregation, nuclear division, hormone-mediated signaling pathway, regulation of intracellular estrogen receptor signaling pathway, condensed chromosome and PPAR signaling pathway. There was a negative correlation between TIDE and DLAT expression (r = − 0.292, p

ObjectiveTo evaluate the value of refined extracapsular anatomy combined with carbon nanoparticle suspension tracing technology for protecting parathyroid function and the thoroughness of lymph node dissection in the central region during endoscopic thyroid cancer surgery.Patients and methodsRetrospective clinical data analysis was performed on 108 patients who underwent endoscopic thyroid cancer surgery at the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from November 2019 to November 2022. Before surgery, thyroid function tests, color Doppler ultrasounds and neck-enhanced CT scans were performed on all patients. Cytopathological diagnosis obtained via ultrasound-guided fine-needle aspiration served as confirmation for the primary diagnosis. It was determined whether to perform a total thyroidectomy or a hemithyroidectomy (HT) together with preventive unilateral (ipsilateral) central neck dissection. Follow-up times were 1 to 34 months.ResultsTransient neuromuscular symptoms were present in 3.70% (4/108) cases, with no permanent neuromuscular symptoms or permanent hypoparathyroidism. Regarding transient hypoparathyroidism, the patients recovered after three months and did not need long-term calcium supplementation. The number of harvested LNs (mean± SD) was 5.54 ± 3.84, with ≤5 in 57.41% (62/108) and >5 in 42.59% (46/108) cases. The number of patients with metastatic LNs was 37.96% (41/108), with ≤2 in 65.85% (27/41) and >2 in 34.15% (14/41) cases.ConclusionsFine extracapsular anatomy combined with carbon nanoparticle suspension tracing is effective in endoscopic thyroid cancer surgery. It can improve the thoroughness of prophylactic central neck dissection and recognition of the parathyroid gland and avoid parathyroid injury and other complications to effectively protect parathyroid function.

[Introduction] In order to realize the real-time reconstruction of plasma shape and position in tokamak, a visible light edge reconstruction algorithm based on fully connected neural network is proposed based on the analysis of camera calibration algorithm. [Method] The function of the algorithm was to establish the corresponding relationship between the pixel coordinate system and the tokamak coordinate system, and then realize the plasma visible light edge reconstruction. [Result] On the basis of the algorithm, few-shot learning is added to further improve the reconstruction algorithm of fully connected neural network. [Conclusion] Experimental results show that the algorithm can accurately reconstruct the plasma visible light edge, and also meet the real-time requirements of the system.

[Introduction] As an important design improvement to cope with the station black out (SBO) accident, the advanced secondary passive residual heat removal (ASP) system is based on the closed natural circulation of secondary side of the steam generator (SG), can effectively remove the residual heat of the reactor core in the case of total loss of feedwater. [Method] Based on full-scope simulator (FSS),the paper introduced the SBO superimposed SBO diesel engine failure and ASG pneumatic pump failure accident conditions on the simulator platform , and verified the influence of the ASP system for the primary and secondary loops of nuclear plants in accident conditions by using the simulation method. [Result] The simulation results we obtained demonstrate that after the ASP system was put into operation, the residual heat of the core was effectively removed. After 4 hours , the water level of the SG recover to 8.6 m, the pressure of the SG dropped to 1.2 MPa（a）, the core outlet temperature dropped to about 209 ℃, and the margin of core saturation temperature is greater than 20 ℃, there is no risk of meltdown of the core, and the accident is in a controllable state. [Conclusion] The ASP system meets the requirements of the design conditions, and can realize the long-term and effective removal of the residual heat of the reactor core.

Abstract Background Triple negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and lack of effective treatment target. Here we screened differentially expressed lncRNAs through bioinformatics analysis and identified CARMN as a downregulated lncRNA which is lowest expressed in TNBC. We aimed to identify the potential role and molecular mechanisms of CARMN in TNBC. Methods Predictive value of CARMN was explored in breast cancer cohorts. TNBC cell lines with CARMN overexpression or CARMN silence and were used for in vitro and in vivo experiments. RNA-seq of CARMN overexpressed cells was performed for exploring downstream of CARMN. Results CARMN is downregulated at different phase of malignant transformation of breast tissue. CARMN can predict both better prognosis and higher response rate of cisplatin-based neoadjuvant chemotherapy in breast cancer. A nomogram is built to predict cisplatin-based chemotherapy response in breast cancer. Through in vitro and in vivo studies, we confirmed CARMN can also inhibit tumorigenesis and enhance sensitivity to cisplatin in TNBC cells. RNA-seq and further experiments revealed CARMN can inhibit DNA replication. MCM5, an important DNA replication initiation factor, is the most downregulated gene in DNA replication pathway following CARMN overexpression. We confirmed CARMN can produce miR143-3p from its exon5 which is DROSHA and DICER dependent, resulting binding and decrease of MCM5. Moreover, suppressing miR143-3p can weaken function of CARMN in suppressing tumorigenesis and promoting chemosensitivity. Conclusions Our results indicated lncRNA CARMN is a predictive biomarker of better prognosis and enhanced cisplatin sensitivity in TNBC. CARMN is the host gene of miR143-3p which downregulates MCM5, causing inhibited DNA replication.

Cancer occurrence and development are closely related to the environment. Aryl hydrocarbon receptor (AhR) is an important receptor mediating the toxic effects of many environmental compounds, and is also involved in regulating tumor cell migration. Glioblastoma is the most malignant glioma and exhibits high motility, but the effects of AhR on the migration of glioblastoma are still unclear. We aimed to understand the role of AhR in the migration of this type of tumor cell and to explore the underlying molecular mechanism. In cultured human neuroblastoma cells (U87), we found that AhR overexpression or knockdown increased or suppressed the migration ability of U87 cells, respectively. Furthermore, inhibition of basal activation of the AhR pathway suppressed migration ability, suggesting a positive correlation between endogenous activity of the AhR pathway and cell migration. When the AhR pathway was activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 6-formyl [3,2-b] carbazole (FICZ), the migration of U87 cells was inhibited by inducing the expression of a tumor suppressor, IL24, which is a downstream responsive gene of AhR activation. Moreover, a similar AhR-IL24-dependent mechanism for migration inhibition of TCDD was documented in a breast cancer cell line and a lung cancer cell line. This study demonstrated that AhR plays important roles in regulating the migration of glioblastoma, and the induction of the AhR-IL24 axis mediates the inhibition of migration in response to TCDD or FICZ treatment.

Hypoxia-induced chemotherapy resistance is the main hindrance for solid tumor treatment. Hypoxia inducible factor-1α (HIF1α), an adaptive gene of hypoxia condition, played an important role in affecting chemotherapy sensitivity for many cancer types and various therapeutic regimens. This study focused on the impact of HIF1α on predicting response and survival of taxane-based neoadjuvant therapy (NAT) for breast cancer (BC) patients and the concrete mechanism that HIF1α mediated paclitaxel chemo-insensitivity. We evaluated HIF1α expression immunohistochemically from biopsies of 108 BC patients receiving paclitaxel–cisplatin NAT. Univariate and multivariate logistic regression analysis revealed that high HIF1α expression led to lower rate of pathological complete response (pCR) and worse prognosis. Analysis of GEO datasets also indicated negative association between HIF1α expression and response of taxane-based NAT in BC patients. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of differential expression genes (DEGs) in different HIF1α expression groups from TCGA database showed that HIF1α participated in interleukin 17 (IL-17) signaling pathway. Correlation analysis suggested that HIF1α was positively related to the IL-17 pathway. CXC motif chemokine ligand 10 (CXCL10) was the only DEG in the IL-17 pathway inversely relating to NAT response. Experiments in vitro verified that HIF1α/IL-17 pathway influences paclitaxel sensitivity to BC cells. Correlation analysis between HIF1α/IL-17A/CXCL10 and infiltration of immune cells in BC uncovered that high expression of all the above three genes were positively correlated to neutrophil infiltration in BC. Collectively, our findings shed novel insight into the mechanism of chemotherapy resistance and implied that HIF1α inhibitor may be a promising drug combined with traditional chemotherapeutic drug to increase the chemotherapy efficacy.

Background: Recent evidence shows that inducing ferroptosis may improve efficacy of tumor therapy. However, ferroptosis-related genes have been little studied in patients with breast cancer especially in the neoadjuvant setting. ACSL4 and GPX4 have been well established as the positive and negative regulator of ferroptosis, respectively. This study aimed to explore the predictive value of ACSL4 and GPX4 for patients with breast cancer administered neoadjuvant chemotherapy. Methods: This study included patients treated with paclitaxel-cisplatin-based neoadjuvant chemotherapy. Immunohistochemistry staining of ACSL4 and GPX4 was carried out on the core needle biopsy specimens. Logistic regression was performed to explore the predictive biomarkers of pathological complete response (pCR). Survival analyses were examined by log-rank test and Cox proportional hazard regression. Findings: A total of 199 patients were included for the analyses. Both ACSL4 expression and ACSL4/GPX4 combination status could serve as independent predictive factors for pCR. The interaction for pCR was observed between ACSL4 and clinical tumor stage. Besides, ACSL4 expression, GPX4 expression, and their combination status were independent prognostic factors for disease-free survival. Analyses of the Kaplan-Meier Plotter database suggested that higher ACSL4 expression is related to better overall survival, and higher GPX4 expression is related to better distant metastasis-free survival. Pathway analyses revealed that ACSL4 and GPX4 might function in crucial pathways including apoptosis, autophagy, cell adhesion, lipid metabolism, etc. Interpretation: This study revealed the critical value of ACSL4 and GPX4 serving as novel predictive and prognostic biomarkers for patients with breast cancer receiving neoadjuvant chemotherapy. It might be a novel strategy to induce ferroptosis to promote chemosensitivity. Future studies are required to elucidate the potential mechanisms. Funding: This work was supported by Shanghai Natural Science Foundation [grant number 19ZR1431100], Clinical Research Plan of Shanghai Hospital Development Center [grant numbers SHDC2020CR3003A, 16CR3065B, and 12016231], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Youth Medical Talents - Specialist Program [grant number 2018-15], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Outstanding Youth Medical Talents [grant number 2018-16], Shanghai Collaborative Innovation Center for Translational Medicine [grant number TM201908], Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University [grant numbers YG2017QN49, ZH2018QNA42, and YG2019QNA28], Nurturing Fund of Renji Hospital [grant numbers PYMDT-002, PY2018-IIC-01, PY2018-III-15, and PYIII20-09], Science and Technology Commission of Shanghai Municipality [grant numbers 20DZ2201600 and 15JC1402700], and Shanghai Municipal Key Clinical Specialty.

Abstract Background Zinc finger E-box binding homeobox 1 (ZEB1) is a molecule involved in the progression of epithelial-to-mesenchymal transition (EMT) in various kinds of cancers. Here, we aimed to determine whether the expression of the ZEB1 protein is related to the response of patients to neoadjuvant therapy as well as their survival outcome. Methods Immunohistochemistry (IHC) was performed on paraffin-embedded tumor samples from core needle biopsy before neoadjuvant therapy (NAT). Univariate and multivariate logistic regression analyses were used to analyze the associations between the protein expression of ZEB1 and the pathological complete response (pCR) outcome. Kaplan–Meier plots and log-rank tests were used to compare disease-free survival (DFS) between groups. A Cox proportional hazards model was used to calculate the adjusted hazard ratio (HR) with a 95% confidential interval (95% CI). Results A total of 75 patients were included in the IHC test. High ZEB1 protein expression was associated with a low pCR rate in both univariate (OR = 0.260, 95% CI 0.082–0.829, p = 0.023) and multivariate (OR = 0.074, 95% CI 0.011–0.475, p = 0.006) logistic regression analyses. High ZEB1 protein expression was also associated with a short DFS according to both the log-rank test (p = 0.023) and Cox proportional hazard model (HR = 9.025, 95% CI 1.024–79.519, p = 0.048). In hormone receptor positive (HorR-positive) patients, high ZEB1 protein expression was also associated with a lower pCR (OR = 0.054, 95% CI 0.007–0.422, p = 0.005) and a poorer DFS (HR = 10.516, 95% CI 1.171–94.435, p = 0.036) compared with low ZEB1 protein expression. In HER2-overexpressing patients, ZEB1 protein expression was also associated with poor survival (p = 0.042). Conclusions Our results showed that high ZEB1 protein expression was a negative predictive marker of pCR and DFS in neoadjuvant therapy in breast cancer patients and in HorR-positive and HER2-overexpressing subgroups. Trial registration NCT, NCT02199418. Registered 24 July 2014—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02199418?term=NCT02199418&rank=1. NCT, NCT 02221999. Registered 21 August 2014—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02221999?term=NCT02221999&rank=1

ObjectiveLinc00665 is a novel long non-coding RNA that can promote the progression of breast cancer, but its value in predicting the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer has not been reported. We aim to analyze the correlation between Linc00665 expression and pathological complete response (pCR) in breast cancer patients.Materials and MethodsThe present study examined the predictive role of Linc00665 expression in pCR after NAC using both univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to evaluate the performance of Linc00665 in predicting pCR. The Kyoto Encyclopedia of Gene and Genome (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) were also conducted to determine the biological processes where Linc00665 may participate in.ResultsThe present study study totally enrolled 102 breast cancer patients. The univariate analysis showed that Linc00665 level, human epidermal growth factor receptor 2 (HER2) status and hormone receptor (HR) status were correlated with pCR. The multivariate analysis showed that Linc00665 expression was an independent predictor of pCR (OR = 0.351, 95% CI: 0.125–0.936, P = 0.040), especially in patients with HR-positive/HER2-negative subtype (OR = 0.272, 95% CI: 0.104–0.664, P = 0.005). The KEGG analysis indicated that Linc00665 may be involved in drug metabolism. The GSEA analysis revealed that Linc00665 is correlated to DNA damage repair.ConclusionLinc00665 may be a potential novel predictive biomarker for breast cancer in NAC, especially for HR-positive/HER2-negative patients.

Background: EPIC1 is an oncogenic long non-coding ribonucleic acid (RNA) that promotes cell growth and cell-cycle progression and inhibits apoptosis in several cancer cell lines. However, clinical studies on EPIC1 in breast cancer, specifically in the neoadjuvant setting, are relatively few. Methods: Patients treated with weekly paclitaxel–cisplatin-based neoadjuvant chemotherapy after core-needle biopsy were included in the study. Real-time quantitative polymerase chain reaction assays were performed to detect EPIC1 expression. Results: Among all patients included in this study ( n = 111), higher EPIC1 expression was associated with estrogen receptor negativity, human epidermal growth factor receptor 2 positivity, higher Ki67 index, and higher histologic grade. Multivariate analysis suggested that EPIC1 expression was an independent predictive factor for pathological complete response, with a significant interaction between EPIC1 expression and age. The Kaplan–Meier Plotter dataset suggested that the EPIC1 high-expression group showed a worse 10-year distant metastasis-free survival and post-progression survival when compared with the EPIC1 low-expression group. The Cancer Genome Atlas dataset suggested that the overall survival in the EPIC1 high-expression group was inferior to that in the EPIC1 low-expression group, specifically in hormone receptor (HorR)-positive patients and patients aged

Dioxin exposure is reported to affect nervous system development and increase the risk of neurodegenerative diseases. Generally, dioxin exerts its neurotoxicity via aryl hydrocarbon receptor (AhR). Neurofilament (NF) light (NFL) protein is a biomarker for both neuronal differentiation and neurodegeneration and its expression is controlled by the mitogen-activated protein kinase (MAPK) pathway. However, the effects of dioxin on NFL expression and involved mechanisms are incompletely understood. We aimed to investigate the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on NFL expression and elucidate the underlining signaling pathways and their potential crosstalk, specifically between MAPK and AhR pathway. We employed primary cultured rat cortical neurons to evaluate the effect of TCDD exposure on NFL expression. We also used nerve growth factor (NGF)-treated PC12 cells with specific inhibitors to investigate the involvement of and potential crosstalk between the MAPK pathway and the AhR pathway in mediating the effects of TCDD on NFL expression. After TCDD exposure, NFL mRNA and protein levels were upregulated in cultured neurons. NFL protein was preferentially found in the cell body compared with neurites of the cultured neurons. In PC12 cells, TCDD enhanced both NGF-induced NFL expression and phosphorylation of ERK1/2 and p38. The addition of MAPK-pathway inhibitors (PD98059 and SB230580) partially blocked the TCDD-induced NFL upregulation. CH223191, an AhR antagonist, reversed the upregulation of NFL and phosphorylation of ERK1/2 and p38 induced by TCDD. This study demonstrated TCDD-induced upregulation of NFL in cultured neurons, with protein retained in the cell body. TCDD action was dependent on activation of AhR and MAPK, while crosstalk was found between these two signaling pathways.

“Conventional chemotherapy-photothermal therapy combination has limited efficacy in drug resistant cancers. Here they develop Copper-palladium tetrapod nanoparticles to overcome these challenges and show them to work in synergy with autophagy inhibitors to treat drug resistant cancers”

Abstract Background The financial burden of cancers has profound effects and there is a clear need to explore the issue from different perspectives and for different population groups. This study aimed at investigating inpatient cancer care (ICC) burden in Anhui, a typical inland province of China. Methods The study collected data through a household survey conducted during April to November, 2014 using cluster-randomized sampling and a structured questionnaire administered face-to-face by trained interviewers. Results The survey covered 60,678 urban and rural residents and 318 person-times of ICC during the past year. Age-adjusted annual person-times and days of ICC per thousand population added up to 4.24 and 76.78 respectively and urban residents showed significantly greater admission rates and length of stay than that of rural ones. Total ICC expenditures accounted for 13.30 % of all that of inpatient care for the whole population. Per-case direct and indirect costs of all types of cancers were estimated as 10365.1 and 929.9 RMB. Per-case total cost on ICC at township hospitals was 2142.3 RMB and at province level hospitals, 17133.0 RMB. Significant variations in per-case ICC expenditures also existed between patients with different household income and type of medical insurance systems, but patients suffering from different types of cancers. Out-of-pocket payment due to ICC turned out to be catastrophic for 20.6 % of all cancer patients and 65.2 % for other medical insurance, 45.6 % for enrollees of urban and rural medical insurance, 43.2 % for the 65 to 74 years old. Multi regression revealed statistically significant association between ICC costs and education, reimbursement ratio, household income and level of hospital. Conclusions Cancers characterize low incidence, moderate service use and high expenses. There exist substantial differences between subgroups and part of these variations cannot be explained by pathological factors. ICC expenses are catastrophic in nature to a large part of patients. There is a clear need for more effectively regulating cancer-related medical practices and service seeking behaviors.

Abstract Renewable energy is essential for power system decarbonization, but extended and unexpected periods of extremely low wind and solar resources (i.e., wind and solar droughts) pose a threat to reliability. The challenge is further exacerbated if shortages of the two occur simultaneously or if they affect neighboring grids simultaneously. Here we present a framework to characterize these events and propose three metrics to comprehensively assess renewable energy quality: resource availability, variability, and extremeness. An examination of long-term data across a vast geographical region shows a strong spatial correlation and temporal coincidence of renewable energy droughts. It also finds a lack of sites that excel in all three quality attributes, which presents a trilemma to investors, system planners, and policymakers. These findings underscore the significance of considering factors beyond mere resource availability and contribute to developing informed strategies for the reliable and sustainable deployment of variable energy resources.

Abstract Sports injuries often arise from improper scheduling of exercise loads, and timely assessment of these loads is essential for minimizing injury risk. This article investigates the validity of using changes in pupillary light reflex (PLR) during dynamic aerobic training as a novel approach to evaluating exercise load. Dynamic aerobic training was conducted on a power bicycle for 15 min. With a 3-minute interval as the demarcation line, PLR measurement was performed before training and heart rate was recorded throughout the process. The Rating of Perceived Exertion (RPE) scale invented by Borg was used for scoring before training and after training. The normal distribution of data was confirmed through the Shapiro-Wilk test. Pearson correlation analysis was used to quantify the correlation between variables. The Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) analysis were used to determine the indicators of exercise load. The optimal threshold of the indicators was calculated through the Youden index to evaluate sensitivity and specificity. Thirty male second-tier athletes with a mean age of 23.66 ± 2.21 years, a mean height of 175.3 ± 6.5 cm, and a mean weight of 68.99 ± 10.35 kg participated in this study. Based on the RPE scale results, it was confirmed that the 15-minute dynamic aerobic exercise successfully elicited varying levels of perceived exertion among the athletes. The findings of this study indicate significant changes in PLR and heart rate (HR) with increasing exercise duration and external load. There were strong correlations between RPE and maximum constriction velocity (MCV) (|r| = 0.8309, p

Abstract Cellular communication network factor 2 (CCN2) is a secreted extracellular matrix-associated protein, and its aberrantly increased expression has been implicated in a diversity of diseases involving pathological processes of fibrosis, chronic inflammation, or tissue injury, which has promoted the evaluation of CCN2 as therapeutic targets for multiple disorders. However, human phenotypes associated with CCN2 deficiency have remained enigmatic; variants in CCN2 have not yet been associated with a human phenotype. Here, we collected families diagnosed with spondyloepimetaphyseal dysplasia (SEMD), and screened candidate pathogenic genes for families without known genetic causes using next-generation sequencing. We identified a monoallelic variant in signal peptide of CCN2 (NM_001901.2: c.65 G > C [p.Arg22Pro]) as the cause of SEMD in 14 subjects presenting with different degree of short stature, premature osteoarthritis, and osteoporosis. Affected subjects showed decreased serum CCN2 levels. Cell lines harboring the variant displayed decreased amount of CCN2 proteins in culture medium and an increased intracellular retention, indicating impaired protein secretion. And the variant weakened the stimulation effect of CCN2 on osteogenesis of bone marrow mesenchymal stem cells. Zebrafish ccn2a knockout model and osteoblast lineage-specific Ccn2-deficient mice (Ccn2 fl/fl ;Prx1 Cre ) partially recapitulated the phenotypes including low bone mass observed in affected subjects. Pathological mechanism implicated in the skeletal abnormality in Ccn2 fl/fl ;Prx1 Cre mice involved decreased bone formation, increased bone resorption, and abnormal growth plate formation. Collectively, our study indicate that monoallelic variants in CCN2 lead to a human inherited skeletal dysplasia, and highlight the critical role of CCN2 in osteogenesis in human.

Abstract Background In sepsis, the relationship between lymphocyte counts and patient outcomes is complex. Lymphocytopenia and lymphocytosis significantly influence survival, illustrating the dual functionality of lymphocytes in responding to infections. This study investigates this complex interaction, focusing on how variations in lymphocyte counts correlate with all-cause hospital mortality among sepsis patients. Methods This retrospective cohort study analyzed data from two extensive critical care databases: the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV 2.0) from Beth Israel Deaconess Medical Center, Boston, Massachusetts, and the eICU Collaborative Research Database (eICU-CRD), which was Multi-center database from over 200 hospitals across the United States conducted by Philips eICU Research Institute. We included adult patients aged 18 years and older who met the Sepsis-3 criteria, characterized by documented or suspected infection and a Sequential Organ Failure Assessment (SOFA) score of 2 or higher. Sepsis patients were categorized into quartiles based on lymphocyte counts. The primary outcome was all-cause mortality in the hospital, with 90 and 60-day all-cause mortality as the secondary outcomes. Univariable and multivariable Cox proportional hazard regressions were utilized to assess lymphocyte counts' impact on hospital mortality. An adjusted restricted cubic spline (RCS) analysis was performed to elucidate this relationship further. Subgroup analyses were also conducted to explore the association across various comorbidity groups among sepsis and septic shock patients. Results Our study included 37,054 patients, with an observed in-hospital mortality rate of 16.6%. Univariable and multivariable Cox proportional hazard regression models showed that lymphocyte counts were independently associated with in-hospital mortality (HR = 1.04, P

Abstract To reduce system complexity and bridge the interface between electronic and photonic circuits, there is a high demand for a non-volatile memory that can be accessed both electrically and optically. However, practical solutions are still lacking when considering the potential for large-scale complementary metal-oxide semiconductor compatible integration. Here, we present an experimental demonstration of a non-volatile photonic-electronic memory based on a 3-dimensional monolithic integrated ferroelectric-silicon ring resonator. We successfully demonstrate programming and erasing the memory using both electrical and optical methods, assisted by optical-to-electrical-to-optical conversion. The memory cell exhibits a high optical extinction ratio of 6.6 dB at a low working voltage of 5 V and an endurance of 4 × 104 cycles. Furthermore, the multi-level storage capability is analyzed in detail, revealing stable performance with a raw bit-error-rate smaller than 5.9 × 10−2. This ground-breaking work could be a key technology enabler for future hybrid electronic-photonic systems, targeting a wide range of applications such as photonic interconnect, high-speed data communication, and neuromorphic computing.

PurposePregnant women with a diagnosis of differentiated thyroid cancer (DTC) were potentially high-risk but largely ignored study population. We aimed to explore whether gestational thyrotropin levels were associated with progression of DTC.MethodsWe conducted a retrospective cohort study at Peking University Third Hospital in Beijing, China from January 2012 to December 2022. We included pregnant women with a pre-pregnancy DTC managed by active surveillance (under-surveillance DTC) or surgical treatment (after-surgery DTC). Dynamic changes of gestational thyrotropin levels across multiple time points were characterized by both statistical (average level, change instability, longitudinal trajectory) and clinical (thyroid dysfunction, thyrotropin suppression, and achievement of thyrotropin suppression target) indicators. Outcomes were clinician-validated progression of DTC, measured separately for patients under surveillance (tumor enlargement or lymph node metastasis) and those after surgery (≥ 3 mm growth in the size of existing metastatic foci, development of new lymph node metastases, ≥ 2 mm growth in the size of existing cancer foci in the contralateral thyroid, or biochemical progression).ResultsAmong 43 and 118 patients with under-surveillance and after-surgery DTC, we observed no evidence of associations between any of the quantitative or clinical indicators of gestational thyrotropin levels and progression-free survival, after a median of 2.63 (IQR: 0.90-4.73) and 4.22 (2.53-6.02) year follow-up, respectively (all P values > 0.05).ConclusionsGestational thyrotropin levels appeared to play a minor role in the progression of under-surveillance or after-surgery DTC. Clinicians might focus on the risk of adverse pregnancy outcomes when optimizing thyrotropin levels for pregnant women with a diagnosis of DTC.

ObjectiveThis study aims to explore the association of methyltransferase-like protein 3 (METTL3) expression with severity of coronary artery stenosis in patients with coronary heart disease (CHD).MethodsA total of 100 patients administrated in the Fourth Affiliated Hospital of China Medical University between October 2022 and June 2023 with primary symptoms of chest pain or tightness, or cardiac discomfort, and who underwent coronary angiography for a definitive diagnosis, were included in the study. The baseline characteristics, including TG, TC, LDL-C, HDL-C, uric acid and past history were recorded. Peripheral blood samples were collected to assess the expression levels of METTL3, YT521-B homology domains 1 (YTHDF1), YT521-B homology domains 2 (YTHDF2), and YT521-B homology domains 3 (YTHDF3) using the PCR method. Relative expression levels of METTL3 protein were determined by Western blotting. Correlation analysis were conducted to evaluate the relationship between METTL3/YTHDF1 gene expression and clinical data. Receiver operating characteristic (ROC) curve analysis was employed to assess the predictive value of METTL3 and YTHDF1 for CHD. Binary logistic regression was used to determine whether the expression of METTL3 and YTHDF1 in peripheral blood were risk factors for CHD.ResultsThe study found no significant differences in baseline characteristics between CHD patients and controls, except for length of stay, Lymphocytes, Neutrophils, AST, HDL-C and modified Gensini score. The gene expression levels of METTL3 and YTHDF1 were significantly higher in CHD patients compared to controls (p 0.052. The AUC for YTHDF1 in CHD was 0.623, with a sensitivity of 47.4% and a specificity of 74.4% at a cut-off value of >0.027. Binary logistic regression revealed that only increased METTL3 expression in peripheral blood was an independent risk factor for CHD (p

BackgroundDifferentiated thyroid cancer (DTC) has been increasingly common in women of reproductive age. However, the evidence remains mixed regarding the association of DTC with adverse pregnancy outcomes in pregnant women previously diagnosed with DTC.MethodsWe conducted a retrospective cohort study in the Peking University Third Hospital in Beijing, China between January 2012 and December 2022. We included singleton-pregnancy women with a pre-pregnancy DTC managed by surgical treatment (after-surgery DTC) or active surveillance (under-surveillance DTC). To reduce the confounding effects, we adopted a propensity score to match the after-surgery and under-surveillance DTC groups with the non-DTC group, respectively, on age, parity, gravidity, pre-pregnancy weight, height, and Hashimoto's thyroiditis. We used conditional logistics regressions, separately for the after-surgery and under-surveillance DTC groups, to estimate the adjusted associations of DTC with both the composite of adverse pregnancy outcomes and the specific mother-, neonate-, and placenta-related pregnancy outcomes.ResultsAfter the propensity-score matching, the DTC and non-DTC groups were comparable in the measured confounders. In the after-surgery DTC group (n = 204), the risk of the composite or specific adverse pregnancy outcomes was not significantly different from that of the matched, non-DTC groups (n = 816; P > 0.05), and the results showed no evidence of difference across different maternal thyroid dysfunctions, gestational thyrotropin levels, and other pre-specified subgroup variables. We observed broadly similar results in the under-surveillance DTC group (n = 37), except that the risk of preterm birth, preeclampsia, and delivering the low-birth-weight births was higher than that of the matched, non-DTC group [n = 148; OR (95% CI): 4.79 (1.31, 17.59); 4.00 (1.16, 13.82); 6.67 (1.59, 27.90)].ConclusionsDTC was not associated with adverse pregnancy outcomes in pregnant women previously treated for DTC. However, more evidence is urgently needed for pregnant women with under-surveillance DTC, which finding will be clinically significant in individualizing prenatal care.

Abstract In response to the Paris Agreement, a growing number of countries, 123 in total, have committed to carbon reduction targets. While existing research has assessed various policies’ effectiveness in achieving these targets, the potential of the act of goal-setting itself as a policy instrument has been underexplored. Here we leveraged a comprehensive panel dataset spanning 163 countries from 2011 to 2022 and employed a rigorous difference-in-difference model. Empirical findings reveal that both proposing carbon reduction targets and setting higher targets effectively reduce emissions intensity. The mechanism driving the impact of carbon reduction targets on CO2 emissions centers on the level of education, rather than renewable energy capacity, requiring further investigation to the mechanism. Subsequent analysis establishes connections between target levels and renewable energy capacity. Our results advocate for dynamic updates of carbon reduction targets aligned with renewable energy capacity when formulating climate objectives.

Abstract. Background:. Differentiated thyroid cancer (DTC) is commonly diagnosed in women of child-bearing age, but whether pregnancy influences the prognosis of DTC remains controversial. This study aimed to summarize existing evidence regarding the association of pregnancy with recurrence risk in patients previously treated for DTC. Methods:. We searched PubMed, Embase, Web of Science, Cochrane, and Scopus based on the prespecified protocol registered at PROSPERO (CRD42022367896). After study selection, two researchers independently extracted data from the included studies. For quantitative data synthesis, we used random-effects meta-analysis models to pool the proportion of recurrence (for pregnant women only) and odds ratio (OR; comparing the risk of recurrence between the pregnancy group and the nonpregnancy group), respectively. Then we conducted subgroup analyses to explore whether risk of recurrence differed by response to therapy status or duration of follow-up time. We also assessed quality of the included studies. Results:. A total of ten studies were included. The sample size ranged from 8 to 235, with participants’ age at pregnancy or delivery ranging from 28 to 35 years. The follow-up time varied from 0.1 to 36.0 years. The pooled proportion of recurrence in all pregnant patients was 0.13 (95% confidence intervals [CI]: 0.06–0.25; I2: 0.58). Among six included studies reporting response to therapy status before pregnancy, we observed a trend for increasingly higher risk of recurrence from excellent, indeterminate, and biochemically incomplete to structurally incomplete response to therapy (Ptrend 0.05) or the OR of recurrence in studies with a comparison group (P >0.05). Two included studies that focused on patients with distant metastasis also did not show a significant difference in disease recurrence between pregnancy and nonpregnancy groups (OR: 0.51 [95% CI: 0.14–1.87; I2: 59%]). Conclusion:. In general, pregnancy appears to have a minimal association with the disease recurrence of DTC with initial treatment. Clinicians should pay more attention to progression of DTC among pregnant women with biochemical and/or structural persistence. Registration:. PROSPERO, https://www.crd.york.ac.uk/PROSPERO/; No. CRD42022367896.

Abstract Background This study aimed to develop and validate an interpretable machine-learning model that utilizes clinical features and inflammatory biomarkers to predict the risk of in-hospital mortality in critically ill patients suffering from sepsis. Methods We enrolled all patients diagnosed with sepsis in the Medical Information Mart for Intensive Care IV (MIMIC-IV, v.2.0), eICU Collaborative Research Care (eICU-CRD 2.0), and the Amsterdam University Medical Centers databases (AmsterdamUMCdb 1.0.2). LASSO regression was employed for feature selection. Seven machine-learning methods were applied to develop prognostic models. The optimal model was chosen based on its accuracy, F1 score and area under curve (AUC) in the validation cohort. Moreover, we utilized the SHapley Additive exPlanations (SHAP) method to elucidate the effects of the features attributed to the model and analyze how individual features affect the model’s output. Finally, Spearman correlation analysis examined the associations among continuous predictor variables. Restricted cubic splines (RCS) explored potential non-linear relationships between continuous risk factors and in-hospital mortality. Results 3535 patients with sepsis were eligible for participation in this study. The median age of the participants was 66 years (IQR, 55–77 years), and 56% were male. After selection, 12 of the 45 clinical parameters collected on the first day after ICU admission remained associated with prognosis and were used to develop machine-learning models. Among seven constructed models, the eXtreme Gradient Boosting (XGBoost) model achieved the best performance, with an AUC of 0.94 and an F1 score of 0.937 in the validation cohort. Feature importance analysis revealed that Age, AST, invasive ventilation treatment, and serum urea nitrogen (BUN) were the top four features of the XGBoost model with the most significant impact. Inflammatory biomarkers may have prognostic value. Furthermore, SHAP force analysis illustrated how the constructed model visualized the prediction of the model. Conclusions This study demonstrated the potential of machine-learning approaches for early prediction of outcomes in patients with sepsis. The SHAP method could improve the interoperability of machine-learning models and help clinicians better understand the reasoning behind the outcome.

At present, the research on NbC/Fe cluster-reinforced steel-based composite has been proofread, but little attention has been paid to the effect of Nb/C ratio on composites. The effects of different Nb/C ratio (Nb/C = 1:0.5 and 1:1) on the microstructure and mechanical properties of the composites were studied by in situ hot pressing sintering, and the internal mechanism is explained by the method of first-principles. For Nb/C = 1:0.5, the transition-zone Laves phase Nb2C, NbC/iron-poor zone, and NbC/iron-rich zone were formed on the outside of the Nb particles. When the Nb/C atomic ratio increased to 1:1, the Nb atoms reacted completely to form NbC, and Nb2C was minimized. For Nb/C = 1:1, the deflections of the three- and five-layer composites increased by 112.34 % and 56.79 %, respectively, compared with those of the corresponding layers of T10 steel. The strengthening mechanism of the composite is load transfer, and the toughening mechanism is crack deflection and “delamination cracking”. A first-principles approach showed that the NbC chemical bonds were mainly strong Nb–C covalent bonds, Nb–Nb metallic bonds, and some Nb–C ionic bonds. The chemical bonding of Nb2C comprised Nb–C covalent bonds, strong Nb–Nb metallic bonds, and a large number of Nb–C antibonding states. The advantages of NbC in terms of its thermodynamic and mechanical properties have also been determined.

The effective detection of organic amines is particularly important for environmental protection and human health. Herein, according to hard and soft acid base theory, a novel three-dimensional (3D) butterfly shaped Eu4(OH)2 cluster-based metal–organic framework with Lewis basic triazole sites, {[Eu4(taip)4(ox)(OH)2(H2O)4]·3H2O}n (1) (H2taip = 5-(1,2,4-triazol-1-yl) isophthalic acid, H2ox = oxalic acid), was successfully synthesized under solvothermal conditions, and was characterized by single crystal X-ray diffraction, powder X-ray diffraction, elemental analysis, infrared spectroscopy and thermogravimetric analysis. Structural analysis reveals that compound 1 is a 3D net constructed from butterfly shaped Eu4(OH)2 clusters and contains isosceles triangular channels with dimensions of 8.84 × 8.84 × 8.63 Å3, which shows an unprecedented 8-connected topology with a Schläfli symbol {36·418·53·6}. Fluorescence experiments of compound 1 show sensitive luminescence quenching responses to organic amines such as diethylamine (DEA), trimethylamine (TMA), triethylamine (TEA), ethylenediamine (EDA) and aniline, and the quenching constants (KSV) decrease in the following order: EDA > DEA > TMA > TEA > aniline. The fluorescence quenching responses may be attributed to the energy gap between the LUMO energy values of H2taip and organic amines, which hinders the transfer of excited state energy to the emission state of Eu3+ and results in luminescence quenching. The fluorescence lifetimes of compound 1 in ethanol and organic anilines indicate that the fluorescence recognition process of organic amines was static. [ABSTRACT FROM AUTHOR]

Background: Out-of-hospital cardiac arrest (OHCA) is a major public health problem. Acute respiratory distress syndrome (ARDS) is a common condition in OHCA patients. We investigated the relationship between the expression of programmed death-1 (PD-1) related molecules and the development and prognosis of ARDS. Methods: Between January 2021 and December 2023, post-resuscitated patients were screened for eligibility in the study. PD-1 related molecules expression was measured by flow cytometry at 48 h of admission in patients with OHCA. The prognostic variables were the development of ARDS during hospitalization and the 28-day patient mortality rate. We analyzed the relationship between the expression of PD-1-related molecules and the development of secondary ARDS in OHCA patients, and assessed the correlation of this expression with the prognosis of ARDS patients. Results: In total, 107 consecutive OHCA patients were enrolled in this study. The median age of the enrolled patients was 60 years, with an age range of 53 to 67 years, and 71 % were male. Among the cardiac arrest patients, 44.8 % had a cardiac etiology, 30.8 % were witnessed, 17.8 % received bystander CPR, and 66.4 % had an initial rhythm of asystole. Our results showed that only monocyte ligand programmed death ligand-1 (PD-L1) expression was significantly elevated in the ARDS group of OHCA patients (P

Objective: This research aims to investigate the prognosis value using the time-weighted average neutrophil-to-lymphocyte ratio (TWA-NLR) for predicting all-cause hospital mortality among sepsis patients. Data were analyzed through the use of the eICU Collaborative Research Database (eICU-CRD 2.0) as well as Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2). Methods: Septic patients from both eICU-CRD 2.0 as well as MIMIC-IV 2.2 databases were included. The neutrophil-to-lymphocyte ratios (NLR) were available for analysis, utilizing complete blood counts obtained on days one, four, and seven following ICU admission. The TWA-NLR was computed at the end of the seven days, and patients were then stratified based on TWA-NLR thresholds. 90-day all-cause mortality during hospitalization was the primary objective, with 60-day all-cause hospital mortality as a secondary objective. The correlation between TWA-NLR and sepsis patients' primary outcome was analyzed using univariable and multivariable Cox proportional hazard regressions. A restricted cubic spline (RCS) analysis was conducted in an attempt to confirm this association further, and subgroup analyses were employed to evaluate the correlation across various comorbidity groups. Results: 3921 patients were included from the eICU-CRD 2.0, and the hospital mortality rate was 20.8 %. Both multivariable as well as univariable Cox proportional hazard regression analyses revealed that TWA-NLR was independently correlated with 90-day all-cause hospital mortality, yielding a hazard ratio (HR) of 1.02 (95 % CI 1.01–1.02, P-value10.5) and lower (≤10.5) TWA-NLR cohorts. A significantly decreased incidence of 90-day all-cause hospital mortality (HR = 0.56, 95 % CI 0.48–0.64, P-value

Xijiao Huojiu (Xijiao), an ancient Chinese rice wine (ACRW), is produced using traditional methods, which involve biological-ageing-like process and result in distinctive sensory profiles. However, its aroma composition is still unclear. In this study, the aroma characteristics of three samples with varying ageing times were examined. Xijiao_SCT, with a short cellar time, exhibited a strong fruity and floral aroma and a less grain-like aroma. Conversely, Xijiao_LCT, which had a long cellar time, had a deep cocoa- and caramel-like aroma. A total of 27 key odorants that greatly influenced the aroma characteristics of Xijiao were identified. Comparative studies were used to identify 12 key odorants that distinguish Xijiao from modern Chinese rice wine (MCRW) and grape wines (GW). Additionally, 13 dominant latent ageing markers differentiated Xijiao_SCT from Xijiao_LCT. Our results suggested that ACRW and MCRW have overlapping but distinct volatile metabolomic profiles, highlighting the characteristics of ACRW during ageing process.

Worldwide, the prevalence of obesity and diabetes have increased, with heart disease being their leading cause of death. Traditionally, the management of obesity and diabetes has focused mainly on weight reduction and controlling high blood glucose. Unfortunately, despite these efforts, poor medication management predisposes these patients to heart failure. One instigator for the development of heart failure is how cardiac tissue utilizes different sources of fuel for energy. In this regard, the heart switches from using various substrates, to predominantly using fatty acids (FA). This transformation to using FA as an exclusive source of energy is helpful in the initial stages of the disease. However, over the progression of diabetes this has grave end results. This is because toxic by-products are produced by overuse of FA, which weaken heart function (heart disease). Lipoprotein lipase (LPL) is responsible for regulating FA delivery to the heart, and its function during diabetes has not been completely revealed. In this review, the mechanisms by which LPL regulates fuel utilization by the heart in control conditions and following diabetes will be discussed in an attempt to identify new targets for therapeutic intervention. Currently, as treatment options to directly target diabetic heart disease are scarce, research on LPL may assist in drug development that exclusively targets fuel utilization by the heart and lipid accumulation in macrophages to help delay, prevent, or treat cardiac failure, and provide long-term management of this condition during diabetes.