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Abstract Background No standard has been established for the clinical target volume (CTV) margins of lymph nodes (LNs) in patients with non-small-cell lung cancer (NSCLC) receiving chemotherapy or chemotherapy combined with immunotherapy followed by radiotherapy. This study aimed to discuss the CTV range of NSCLC after chemotherapy or chemotherapy combined with immunotherapy by observing the microscopic extent of tumor spread beyond the LN capsule. Methods We retrospectively analyzed the data of 240 patients with stage II and III NSCLC who underwent surgery without neoadjuvant therapy, with neoadjuvant chemotherapy (NAC), or with NAC combined with immunotherapy (NACI). We measured the maximal distance of extracapsular extension (ECE) using a digital microscope, analyzed the correlation between clinicopathological features and ECE distance, and determined the CTV margins of metastatic LN under different treatment methods. Results The ECE distance differed significantly among the three groups (p

BackgroundSalvia miltiorrhiza and ligustrazine injection (SML) is a type of traditional Chinese medicine injection, which has been considered a promising adjunctive therapy treatment for acute cerebral infarction (ACI). Although there have been positive reports on the treatment of SML, there is still controversy over its exact efficacy and safety in ACI patients. In this study, a systematic review was conducted on randomized controlled trials (RCTs) of SML for the treatment of ACI to evaluate its clinical efficacy and safety.MethodFrom the establishment of the database until May 2023, all randomized controlled trials related to SML and ACI were collected from the Cochrane Library, Web of Science, Embase, Medline, PubMed, CSJD, Wanfang database, CBM and CNKI. This systematic review and meta-analysis were strictly conducted in accordance with the PRISMA statement. The reported outcomes including overall response (ORR), National Institutes of Health Stroke Scale (NIHSS), hemorrheology indexes, activity of daily living (ADL) and adverse events were in detail investigated.ResultsAn analysis was conducted on the relevant data of 3869 ACI patients from 38 trials. The results indicated that the combination of conventional treatment and SML can significantly improve the ORR of patients (RR = 1.23, 95% CI = 1.20–1.27, P < 0.00001), neurological status (NIHSS, MD = −4.35, 95% CI = −5.15–3.54, P < 0.00001) and ADL (Barthel Index score, MD = 10.27, 95% CI = 7.75–12.79, P < 0.00001) compared with regular treatment alone. After the combined therapy, the hemorheology of ACI patients also significantly improved (P < 0.05). There is no significant difference in the frequency of adverse events between the two groups (RR = 1.49, 95% CI = 0.91–2.46, P = 0.11).ConclusionThe evidence from the meta-analysis suggested that the combination of conventional therapy and SML is safer and more effective than conventional therapy alone in treating ACI. However, due to the limitations of this analysis, such as regional bias and publication bias, the above conclusions need to be further verified by prospective, high-quality and multicenter clinical trials.

Abstract Natural answer generation is in a very clear practical significance and strong application background, which can be widely used in the field of knowledge services such as community question answering and intelligent customer service. Traditional knowledge question answering is to provide precise answer entities and neglect the defects; namely, users hope to receive a complete natural answer. In this research, we propose a novel attention-based recurrent neural network for natural answer generation, which is enhanced with multi-level copying mechanisms and question-aware loss. To generate natural answers that conform to grammar, we leverage multi-level copying mechanisms and the prediction mechanism which can copy semantic units and predict common words. Moreover, considering the problem that the generated natural answer does not match the user question, question-aware loss is introduced to make the generated target answer sequences correspond to the question. Experiments on three response generation tasks show our model to be superior in quality while being more parallelizable and requiring significantly less time to train. Our model achieves 0.727 BLEU on the SimpleQuestions response generation task, improving over the existing best results by over 0.007 BLEU. Our model has scored a significant enhancement on naturalness with up to 0.05 more than best performing baseline. The simulation results show that our method can generate grammatical and contextual natural answers according to user needs.

Infantile Epileptic Spasm Syndrome (IESS) is a group of infantile spasm syndromes of various etiologies that typically present in early infancy, predispose to refractory epilepsy, and leave intellectual disability. Ketogenic diet therapy (KDT) is a non-pharmacologic treatment modality for medically refractory IESS. Recent scientific evidence supported the efficacy, safety, and tolerability of KDT for the treatment of IESS. KDT not only reduces the frequency of seizures in infants with IESS, but also improve their cognition and long-term prognosis. Recently, it has also received increasing attention as a potential treatment for neurological disorders. This reviewed the recent research progress of KDTs for the treatment of IESS, and discussed the different types and the mechanisms of KDTs, the expansion of KDT applications, the influencing factors, and future research issues.

ObjectiveThis study aimed to explore the combination effects of prenatal exposure to environment tobacco smoke (ETS) and nutrients supplement during pregnancy on childhood obesity in preschoolers.MethodsA cross-sectional study was conducted with 58,814 child-mother dyads from 235 kindergartens in Longhua District of Shenzhen, China in 2021. A self-administered structured questionnaire was completed by mothers to collect socio-demographic characteristics, prenatal ETS exposure, and nutrients supplement in pregnancy, and preschoolers' heights and weights were measured at the same time. After controlling for potential confounding variables, logistic regression models and cross-analyses were used to examine the independent and combination effects of maternal prenatal ETS exposure and nutrients supplementation during pregnancy on obesity in preschool children.ResultsThe results of our study showed that prenatal ETS exposure increased the risk of childhood obesity (AOR = 1.22, 95% CI = 1.11–1.34) in preschoolers. In addition, risk of childhood obesity was significantly higher when mothers didn't take supplements of multivitamins (AOR = 1.12, 95% CI = 1.05–1.20), folic acid (AOR = 1.23, 95% CI = 1.10–1.37) and iron (AOR = 1.11, 95% CI = 1.04–1.19) during pregnancy. The cross-over analysis showed that the combination of prenatal ETS exposure with mothers taking no multivitamins (AOR = 1.40, 95% CI = 1.21–1.62), no folic acid (AOR = 1.55, 95% CI = 1.12–2.14) and no iron (AOR = 1.38, 95% CI = 1.19–1.59) during pregnancy also increased the risk of obesity among Chinese preschoolers. We also discovered additive interactive effects between prenatal ETS exposure and no maternal multivitamin, folic acid and iron supplementation in pregnancy on the risk of obesity in preschoolers.ConclusionThe combination of prenatal exposure to ETS with no supplementation of these nutrients might jointly increase the risk of childhood obesity. Public health interventions are needed to reduce prenatal exposure to ETS and to encourage mothers to take appropriate multivitamin, folic acid and iron supplements during pregnancy.

BackgroundWe aim to establish a gestational diabetes mellitus (GDM) mouse model with mice fed with a high-fat diet (HFD) in comparison with pregnant mice with normal blood glucose levels to investigate the role of intestinal microbiota in the development of HFD-induced GDM.MethodsWe divided healthy 6-week-old female C57BL mice into an HFD-induced GDM group and a normal diet group. Their bacterial flora and metabolites in intestinal fecal exosomes were co-analyzed using 16 s multi-region sequencing and compared.FindingsAlpha (α) diversity was lower within the model group compared to the control group. Beta (β) diversity was significantly different between the two groups. The relative abundances of Lactobacillus, Actinomyces, Rothia, and Bacteroidetes were significantly different between the two groups. Fermentation and nitrate consumption were significantly higher in the GDM group. Multiple bacteria were associated with glycerophosphocholine, S-methyl-5′-thioadenosine, quinolinate, galactinol, deoxyadenosine, DL-arginine, and 2-oxoadenic acid.InterpretationImbalances in the production of Lactobacillus, Bacteroidetes, Actinomyces, and Rothia and their related metabolites may lead to metabolic disturbances in GDM. These indicators may be used to assess changes affecting the intestinal microbiota during pregnancy and thus help modulate diet and alter blood glucose.

Abstract Controllable photofluorochromic systems with high contrast and multicolor in both solutions and solid states are ideal candidates for the development of dynamic artificial intelligence. However, it is still challenging to realize multiple photochromism within one single molecule, not to mention good controllability. Herein, we report an aggregation-induced emission luminogen TPE-2MO2NT that undergoes oxidation cleavage upon light irradiation and is accompanied by tunable multicolor emission from orange to blue with time-dependence. The photocleavage mechanism revealed that the self-generation of reactive oxidants driving the catalyst-free oxidative cleavage process. A comprehensive analysis of TPE-2MO2NT and other comparative molecules demonstrates that the TPE-2MO2NT molecular scaffold can be easily modified and extended. Further, the multicolor microenvironmental controllability of TPE-2MO2NT photoreaction within polymer matrices enables the fabrication of dynamic fluorescence images and 4D information codes, providing strategies for advanced controllable information encryption.

Accurate estimation of pasture yield in grasslands is crucial for the sustainable utilization of pasture resources and the optimization of grassland management. This study leveraged the capabilities of machine learning techniques, supported by Google Earth Engine (GEE), to assess pasture yield in the temperate grasslands of northern China. Utilizing Landsat-8 data, band reflectances, vegetation indexes (VIs), and soil water index (SWI) were extracted from 1000 field samples across Xilingol. These data, combined with field-measured pasture yields, were employed to construct models using four machine learning algorithms: elastic net regression (Enet), Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Support Vector Machine (SVM). Among the models, XGBoost demonstrated the best performance for pasture yield estimation, with a coefficient of determination (R2) of 0.94 and a precision of 76.3%. Additionally, models that incorporated multiple VIs demonstrated superior prediction accuracy compared to those using individual VI, and including soil moisture data further enhanced predictive precision. The XGBoost model was subsequently applied to map the spatial patterns of pasture yield in the Xilingol grassland for the years 2014 and 2019. The estimated average annual pasture yield in the Xilingol grassland was 1042.38 and 1013.49 kg/ha in 2014 and 2019, respectively, showing a general decreasing trend from the northeast to the southwest. This study explored the effectiveness of common machine learning algorithms in predicting pasture yield of temperate grasslands utilizing Landsat-8 data and ground sample data and provided the valuable support for long-term historical monitoring of pasture resources. The findings also highlighted the importance of predictor selection in optimizing model performance, except for the reflectance and vegetation indices characterizing vegetation canopy information, the inclusion of soil moisture information could appropriately improve the accuracy of model predictions, especially for grasslands with relatively low vegetation cover.

In the study, the effects of short-chain inulin (OP), natural inulin (OH), and long-chain inulin (OHP) at substitution levels of 3%, 6%, and 9%, as well as freezing of 0, 15, and 30 days, on the farinograph and extensograph characteristics of flour, the rheological properties, water distribution, and microstructure of dough, as well as the quality of the final steamed bread, were investigated. The findings revealed that inulin led to a reduction in the water absorption of the dough while increasing its stable time. Furthermore, inulin delayed the alteration of freezable water within the frozen dough. Notably, the addition of inulin resulted in a more cohesive and evenly arranged network structure within the frozen dough. Steamed bread supplemented with 6% OP, 6% OH, and 3% OHP consistently dislayed a higher specific volume and spread ratio. These findings offer valuable insights into the utilization of inulin in frozen wheat foods.

Abstract Cepharanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata, is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer is unknown. CEP inhibited the cellular activity of gastric cancer AGS, HGC27 and MFC cell lines in this study. CEP-induced apoptosis reduced Bcl-2 expression and increased cleaved caspase 3, cleaved caspase 9, Bax, and Bad expression. CEP caused a G2 cell cycle arrest and reduced cyclin D1 and cyclin-dependent kinases 2 (CDK2) expression. Meanwhile, it increased oxidative stress, decreased mitochondrial membrane potential, and enhanced reactive oxygen species (ROS) accumulation in gastric cancer cell lines. Mechanistically, CEP inhibited Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor 2 (Nrf2) nuclear translocations, increasing transcription of Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, a combined analysis of targeted energy metabolism and RNA sequencing revealed that CEP could alter the levels of metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic acid, and pyruvic acid, thereby altering energy metabolism in AGS cells. In addition, CEP significantly inhibited tumor growth in MFC BALB/c nude mice in vivo, consistent with the in vitro findings. Overall, CEP can induce oxidative stress by regulating Nrf2/Keap1 and alter energy metabolism, resulting in anti-gastric cancer effects. Our findings suggest a potential application of CEP in gastric cancer treatment.

Pleurotus eryngii mushroom has been proven to have anti-aging bioactivities. However, few studies have focused on edible Pleurotus eryngii mushroom feet peptides (PEMFPeps). In this paper, the effects of delaying the senescence of D-Galactose-induced PC12 cells were evaluated, and the mechanisms were also investigated. PEMFPeps were prepared by alkaline protease enzymolysis of edible Pleurotus eryngii mushroom feet protein (PEMFP), which mainly consisted of a molecular weight of less than 1000 Da peptides, primarily occupying 89.15% of the total. Simulated digestion in vitro of Pleurotus eryngii mushroom feet peptides (SID-PEMFPeps) was obtained in order to further evaluate the bioactivity after digestion. The peptide sequences of PEMFPeps and SID-PEMFPeps were detected by LC-MS/MS subsequently. Five new peptides of PEMFPeps and one new peptide of SID-PEMFPeps were identified. The effects of PEMFP, PEMFPeps, and SID-PEMFPeps on D-Galactose-induced senescence of PC12 cells were evaluated. PEMFP, PEMFPeps, and SID-PEMFPeps could all enhance antioxidant enzyme activities significantly, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT); decrease the intracellular levels of malondialdehyde (MDA) and reactive oxygen species (ROS); and inhibit the senescence-associated β-galactosidase (SA-β-gal) activity, among which SID-PEMFPeps showed the best effects. Western blotting analysis confirmed that SID-PEMFPeps significantly regulated the expressions of key proteins such as TLR4, IKKα, IκBα, p65, ERK, and JNK1/2/3, which indicated that SID-PEMFPeps could delay D-Gal-induced senescence of PC12 cells through TLR4/NF-κB/MAPK signaling pathways. This is the first time to investigate PEMFPeps and SID-PEMFPeps protective effects and mechanisms. Our study could lay a solid foundation for PEMFPeps to be used as nutritional supplementation to reduce aging-related damage. And the application of PEMFPeps could also provide optional solutions in exploring more edible protein resources for human beings.

This study aimed to evaluate the ecohydrological regime and ecological water demand of the Huangshui River Basin under changing environmental conditions, seeking to safeguard its ecosystem. Based on monthly data spanning from 1956 to 2016, the ecohydrological regimes of the Huangshui River and the Datong River were evaluated using methods such as the Pettitt mutation test, the Tennant method, and ecological deficit and surplus analyses. The data were mainly obtained from Xiangtang Station of the Datong River and Minhe Station of the Huangshui River. The results showed the following. (1) The most abrupt increase in measured runoff at Xiangtang Station occurred in 1993, while the point of abrupt change in measured runoff at Minhe Station occurred in 1990. (2) Following an increase in human activities, changes in the ecological surplus at Xiangtang Station were negative in January, April to May, July, and from September to November, while the changes in the ecological deficit were positive from January to April, July to August, and October to December. Changes in the ecological surplus at Minhe Station were negative from March to July and from September to December, while changes in the ecological deficit were positive from January to April and from July to December. (3) The annual average ecological flow of the Datong River, Xiangtang section, was 28.42 m3/s, and the annual average ecological water demand was 896 million m3. The annual average ecological flow of the Minhe section was 19.98 m3/s, and the annual average ecological water demand was 631 million m3. According to a calculation of the degree of ecological water demand and ecological flow satisfaction, prior to the implementation of the Water Diversion Project from the Datong River to Huangshui River, the water volumes in both rivers were generally sufficient to meet the ecological water demand. However, high water consumption during the irrigation period led to an ecological deficit. To address these issues, it is crucial to evaluate the potential impacts of human activities, such as water diversion projects, on river ecological flow. Recommendations include expediting the Water Diversion Project from the Yellow River to Xining to secure sufficient water flow in the Huangshui River and enhancing water conservation efforts in agricultural irrigation.

The transformation of ecosystem structure leads to changes in ecosystem services (ESs) and their relationship. However, most research in this area has focused on particular scales and timeframes, often overlooking the significance of spatial and temporal variations. Therefore, we used the equivalent value method to evaluate seven typical ESs in the Yangtze River Delta (YRD) between 2000 and 2020: food production (FP), water supply (WS), climate regulation (CR), environmental purification (EP), soil conservation (SC), biodiversity maintenance (BM), and aesthetic landscape (AL). We further employed the Spearman correlation coefficient and bivariate Moran’s I to evaluate the relationship of ESs and their spatial heterogeneity at grid, township, county and city scales. Our results show that (1) All ESs except AL exhibited a fluctuating upward trend from 2000 to 2020, resulting in a total increase in ecosystem service (ES) value of RMB 650.63 billion. (2) Approximately 70% of the ES pairs demonstrated a synergistic relationship, with the exception of FP and other ESs, which mainly showed a trade-off. (3) With the scale increased from grid to city level, the degree of trade-off between FP and other ESs strengthened at different levels, while the synergy degree of among other ESs gradually decreased. (4) The relationship between ESs demonstrated strong spatial heterogeneity, with FP and other ESs exhibiting trade-offs primarily in the northern and southern YRD, while other ES pairs exhibited mostly synergy in these regions. This study provides scientific information for governments to optimize land use distribution and improve ESs.

Canavan disease (CD, OMIM# 271900) is an autosomal recessive neurodegenerative disorder caused by homozygous or compound heterozygous mutations in ASPA gene, which result in catalytic deficiency of the aspartoacylase enzyme and the accumulation of N-acetylaspartic acid (NAA). Clinical presentation varies according to the age of disease onset. Here, we generated a human induced pluripotent stem cell line (hiPSCs) SDQLCHi064-A from a 5-month old boy with CD carrying two novel frame shift mutations c.556_559dupGTTC (p.L187Rfs*5) and c.919delA (p.S307Vfs*24) of the ASPA gene, in order for us to better understanding the disease.

Epilepsy affects ∼ 65 million people worldwide. Status epilepticus can lead to life-threatening if untreated. In this study, peripheral blood mononuclear cells were isolated from a young patient patient bearing a Nitrogen Perntease Regulator Like 2 Protein (NPRL2) mutation and suffering from Epilepsy verified by clinical and genetic diagnosis. Induced pluripotent stem cells (iPSCs) were established by a non-integrative method, using plasmids carrying OCT4, SOX2, KLF4, BCL-XL and C-MYC. The established iPSCs presented typical pluripotent cells morphology, normal karyotype, and potential to differentiate into three germ layers. Our approach offers a useful model to explore pathogenesis and therapy of Epilepsy.

The symptoms and signs of infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are milder in children than in adults. However, in April 2020, British pediatricians first reported that coronavirus disease 2019 (COVID-19) may present as multisystem inflammatory syndrome in children and adolescents (MIS-C), similar to that observed in Kawasaki disease. MIS-C can be associated with multiple systemic injuries and even death in children. In addition to digestive system involvement, cardiac injury is prominent. This article reviews the pathogenesis, clinical manifestations, and treatment of cardiac injury caused by MIS-C, which may help clinicians in early diagnosis and timely commencement of treatment.

Gestational diabetes mellitus is a prevalent metabolic disease that can impact the normal course of pregnancy and delivery, leading to adverse outcomes for both mother and child. Its pathogenesis is complex and involves various factors, such as insulin resistance and β-cell dysfunction. Metabolic reprogramming, which involves mitochondrial oxidative phosphorylation and glycolysis, is crucial for maintaining human metabolic balance and is involved in the pathogenesis and progression of gestational diabetes mellitus. However, research on the link and metabolic pathways between metabolic reprogramming and gestational diabetes mellitus is limited. Therefore, we reviewed the relationship between metabolic reprogramming and gestational diabetes mellitus to provide new therapeutic strategies for maternal health during pregnancy and reduce the risk of developing gestational diabetes mellitus.

Non-specific phospholipase C (NPC) is a plant-specific phospholipid-hydrolyzing enzyme. Here, the authors define the molecular basis of how Arabidopsis NPC works, and provide new mechanistic insights into the members of phospholipase family.

Soil organic carbon stock (SOCS) changes caused by land use changes are still unclear, and understanding this response is essential for many environmental policies and land management practices. In this study, we investigated the temporal–spatial and vertical distribution characteristics of the SOCS in the Western Sichuan Plateau (WSP) using the sparrow search algorithm–random forest regression (SSA-RFR) models with excellent model applicability and accuracy. The temporal–spatial variations in the SOCS were modeled using 1080 soil samples and a set of nine environmental covariates. We analyzed the effect of land use changes on the SOCS in the WSP. The total SOCS increased by 18.03 Tg C from 1990 to 2020. The results of this study confirmed a significant increase in the SOCS in the study area since 2010. There was a 27.88 Tg C increase in the SOCS in 2020 compared to the total SOCS in 2010. We found that the spatial distribution of the SOCS increased from southeast to northwest, and the vertical distribution of the SOCS in the study area decreased with increasing soil depth. Forests and grasslands are the main sources of SOCS the total SOCS in the forest and grassland accounted for 37.53 and 59.39% of the total soil organic carbon (SOC) pool in 2020, respectively. The expansion of the wetlands, forest, and grassland areas could increase the SOCS in the study area. A timely and accurate understanding of the dynamics of SOC is crucial for developing effective land management strategies to enhance carbon sequestration and mitigate land degradation.

CeO2 is an outstanding support commonly used for the CuO-based CO oxidation catalysts due to its excellent redox property and oxygen storage–release property. However, the inherently small specific surface area of CeO2 support restricts the further enhancement of its catalytic performance. In this work, the novel mesoporous CeO2 nanosphere with a large specific surface area (~190.4 m2/g) was facilely synthesized by the improved hydrothermal method. The large specific surface area of mesoporous CeO2 nanosphere could be successfully maintained even at high temperatures up to 500 °C, exhibiting excellent thermal stability. Then, a series of CuO-based CO oxidation catalysts were prepared with the mesoporous CeO2 nanosphere as the support. The large surface area of the mesoporous CeO2 nanosphere support could greatly promote the dispersion of CuO active sites. The effects of the CuO loading amount, the calcination temperature, mesostructure, and redox property on the performances of CO oxidation were systematically investigated. It was found that high Cu+ concentration and lattice oxygen content in mesoporous CuO/CeO2 nanosphere catalysts greatly contributed to enhancing the performances of CO oxidation. Therefore, the present mesoporous CeO2 nanosphere with its large specific surface area was considered a promising support for advanced CO oxidation and even other industrial catalysts.

Abstract Background Artificial intelligence (AI) algorithms are capable of automatically detecting contouring boundaries in medical images. However, the algorithms impact on clinical practice of cervical cancer are unclear. We aimed to develop an AI-assisted system for automatic contouring of the clinical target volume (CTV) and organs-at-risk (OARs) in cervical cancer radiotherapy and conduct clinical-based observations. Methods We first retrospectively collected data of 203 patients with cervical cancer from West China Hospital. The proposed method named as SegNet was developed and trained with different data groups. Quantitative metrics and clinical-based grading were used to evaluate differences between several groups of automatic contours. Then, 20 additional cases were conducted to compare the workload and quality of AI-assisted contours with manual delineation from scratch. Results For automatic CTVs, the dice similarity coefficient (DSC) values of the SegNet trained with incorporating multi-group data achieved 0.85 ± 0.02, which was statistically better than the DSC values of SegNet independently trained with the SegNet(A) (0.82 ± 0.04), SegNet(B) (0.82 ± 0.03) or SegNet(C) (0.81 ± 0.04). Moreover, the DSC values of the SegNet and UNet, respectively, 0.85 and 0.82 for the CTV (P

Abstract Background Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it’s role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. Methods In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. Results As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p

Abstract Periplakin (PPL) is a main member in plakin family, which plays important role in cellular adhesion complexes supporting and cytoskeletal integrity supplying. PPL was reported to be a potential biomarker candidate for several types of cancers. However, the biological functions and underlying mechanisms of PPL in ovarian cancer (OV) remain unclear. In the present study, we used GEPIA 2, Human Protein Atlas, Oncomine, LinkedOmics, Kaplan–Meier Plotter, STRING, CytoHubba plug-in and TIMER to determine the associations among PPL expression, prognosis, and immune cell infiltration in OV. RT-qPCR and IHC analysis were conducted to validated the role of PPL in an independent OV cohort. Compared with the normal ovary tissues, the levels of PPL mRNA and protein expression were both obviously higher in OV tumors from multiple datasets (P

Dual photo- and metal-catalysis is generally not well-understood when the metal catalyst is a gold complex. Here the authors show that a variation of a known metallaphotoredox annulation is possible without an added photocatalyst, proceeding putatively through a gold–intermediate photosensitization by the aggregate of a potassium amide reactant, and yielding indole derivatives.

Abstract Background Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of life-threatening systemic autoimmune diseases. The aim of this study was to determine the relationship between the AAV hub gene and immune cell infiltration, and its value for clinical disease treatment. Methods We downloaded the microarray information of 37 AAV patients and 27 controls from Gene Expression Omnibus (GEO). Genes were classified into totally different modules exploitation weighted gene co-expression network analysis (WGCNA). AAV diagnostic indicators were screened and then assessed immune cell infiltration by the least absolute shrinkage and selection operator (LASSO) and CIBERSORT. Finally, Connectivity Map analysis was applied to predict possible AAV glomerulus injury improvement therapies. Results WGCNA was developed and differentially expressed genes were classified into 6 modules, the black module was most tightly correlated to AAV. Among them, TIMP1 and FCER1G were most closely related to clinical features. Resting mast cells and monocytes emerged as having the foremost distinguished variations in AAV. C3AR1 and FCER1G were involved in AAV development by immune regulation. Connectivity Map analysis indicated the most significant compound was fisetin. Conclusions The present study is that the initial to spot immune cell infiltration with microarray data of glomeruli in AAV, which provides novel proof and clues for additional analysis of the molecular mechanisms.

ObjectiveTo examine the clinical effectiveness and tolerability of perampanel (PER) as initial monotherapy in pediatric patients with newly diagnosed focal epilepsy.MethodsA retrospective analysis was conducted on 62 children with newly diagnosed focal epilepsy who were treated with PER at the Epilepsy Center of Jinan Children's Hospital from July 2021 to July 2022. The treatment status, prognosis, and adverse reactions were followed up for a minimum of 6 months after the initiation of PER monotherapy. The effectiveness of the patients was estimated by the PER effective rate at 3-, 6-, and 12-month follow-up evaluations and adverse reactions were also recorded. The effective rates of PER in different etiologies and epilepsy syndromes were also statistically analyzed.ResultsThe effective rates of PER treatment at the different time points of evaluation were 88.7% (3 months), 79.1% (6 months), and 80.4% (12 months). With PER treatment, seizure freedom varied over time, with 61.3%, 71.0%, and 71.7% of patients at the 3-, 6-, and 12-month follow-ups, respectively. Among the etiologies of epilepsy, the effective rates of genetic etiology, structural etiology, and unknown etiology were generally above 50% at the 3-, 6-, and 12-month follow-ups. Among the epilepsy syndromes, the categories with higher treatment efficacy were self-limiting epilepsy with centrotemporal spikes (SeLECTs), self-limited epilepsy with autonomic seizures (SeLEAS), and childhood occipital visual epilepsy (COVE), with an effective rate of above 80%. Adverse events were documented in 22 patients (35.5%), but they were mild and tolerable. The most common adverse events comprised irritability, drowsiness, dizziness, and increased appetite.ConclusionPER has favorable effectiveness and tolerability as initial monotherapy for children with newly diagnosed focal epilepsy, which could be a potential option for long-term medication in the treatment of focal epilepsy in children. The current study provided potential evidence for PER as initial monotherapy in children with focal epilepsy in clinical practice.

ObjectivesProthrombin time (PT) and PT-INR are independent predictors of mortality in patients with cancer. The PT and PT-INR of cancer patients are independent predictive variables of mortality. However, whether the PT or PT-INR is related to in-hospital mortality in severely ill patients with tumors remains unknown.DesignThis was a case–control study based on a multicenter public database.SettingsThis study is a secondary analysis of data extracted from 2014 to 2015 from the Electronic Intensive Care Unit Collaborative Research Database.ParticipantsThe data relevant to seriously ill patients with tumors were obtained from 208 hospitals spread throughout the USA. This research included a total of 200,859 participants. After the samples were screened for patients with combination malignancies and prolonged PT-INR or PT, the remaining 1745 and 1764 participants, respectively, were included in the final data analysis.Primary and secondary outcome measuresThe key evaluation methodology was the PT count and PT-INR, and the main outcome was the in-hospital mortality rate.ResultsAfter controlling for confounding variables, we found a curvilinear connection between PT-INR and in-hospital mortality (p

Although numerous studies have investigated that atmospheric fine particulate matter (PM2.5) can be toxic to environmental organisms, the research on the reproductive toxicity of PM2.5 is limited, and the key toxic components and underlying mechanisms remain unknown. In this work, PM2.5 samples of four seasons in Nanjing from March 1, 2021, to February 28, 2022 were collected and the chemical components were analyzed. Caenorhabditis elegans (C. elegans) was employed to conduct the toxicological testing. The reproductive toxicity of PM2.5 to C. elegans in different seasons was evaluated by multiple reproductive endpoints. Exposure to high concentrations of PM2.5 significantly decreased the brood size and the number of fertilized eggs in utero. PM2.5 exposure also increased the number of germ cell corpses and caused abnormal expression of apoptosis-related genes (ced-9, ced-4, and ced-3), which confirmed that PM2.5 induced germline apoptosis. In addition, PM2.5 exposure significantly increased the production of reactive oxygen species (ROS) in C. elegans and the fluorescence intensity of HUS-1 protein in of transgenic strain WS1433. Meanwhile, the expression of genes related to DNA damage (cep-1, clk-2, egl-1, and hus-1) and oxidative stress (mev-1, isp-1, and gas-1) also significantly altered in C. elegans, suggesting induction of DNA damage and oxidative stress. According to Pearson correlation analyses, DNA damage and oxidative stress were significantly correlated with multiple reproductive endpoints in C. elegans. Thus, it was speculated that PM2.5 caused reproductive dysfunction and germ cell apoptosis in C. elegans may be by inducing ROS and DNA damage. In addition, heavy metals in PM2.5 were significantly correlated with multiple endpoints at physiological and biochemical, suggesting that the heavy metals might be an important contributor to the reproductive toxicity induced by PM2.5.

BackgroundScreen time during early life has increased dramatically among Chinese children. Excessive screen time has raised growing concerns about the neuropsychological development of children. The effects of screen exposure on early life and the boundary between screen time and hyperactive behaviors are well worth investigating. We examined associations between screen time and hyperactive behaviors in children under the age of 3 years using data from the Longhua Children Cohort Study (LCCS).MethodsA cross-sectional study was conducted among 42,841 3-year-old children from Longhua District, Shenzhen. Information on socio-demographic characteristics, children’s annual screen time since birth, and hyperactive behaviors (measured by the Conners Parental Symptom Questionnaire) was collected through self-administered structured questionnaires completed by the primary caregiver. A series of logistic regression models assessed the association between screen time and hyperactive behaviors.ResultsThe average daily screen time of children under the age of 3 years was 55.83 ± 58.54 min, and screen time increased with age. Binomial logistic regression analysis found that the earlier the screen exposure, the greater the risk of hyperactive behaviors. Using binary logistic regression model, after controlling for confounding factors, the study found that more screen time was more associated with hyperactive behaviors. For children aged 0–3 years with daily screen time exceeding 90, 120, 150, and 180 min, the risk values for hyperactive behaviors were 1.98 [95% confidence interval (CI): 1.05, 3.78), 2.71 (95%CI:1.38, 5.30), 3.17 (95% CI: 1.50, 6.65), and 4.62 (95% CI: 2.45, 8.71)], respectively.ConclusionEarly screen exposure may be associated with hyperactive behaviors in children under the age of 3 years. More than 90 min of screen time per day in children under 3 years was associated with hyperactive behaviors. The findings support the importance of screen time interventions for children under 3 years.

BackgroundClinical T4 stage (cT4) esophageal tumors are difficult to be surgically resected, and definitive radiotherapy (RT) or chemoradiotherapy (dCRT) remains the main treatment. The study aims to analyze the association between the status of lymph node (LN) metastasis and survival outcomes in the cT4 stage esophageal squamous cell carcinoma (ESCC) patients that underwent treatment with dCRT or RT.MethodsThis retrospective study analyzed the clinical data of 555 ESCC patients treated with dCRT or RT at the Shandong Cancer Hospital and the Liaocheng People’s Hospital from 2010 to 2017. Kaplan–Meier and Cox regression analyses was performed to determine the relationship between LN metastasis and survival outcomes of cT4 and non-cT4 ESCC patients. The chi-square test was used to evaluate the differences in the local and distal recurrence patterns in the ESCC patients belonging to various clinical T stages.ResultsThe 3-year survival rates for patients with non-cT4 ESCC and cT4 ESCC were 47.9% and 30.8%, respectively. The overall survival (OS) and progression-free survival (PFS) rates were strongly associated with the status of LN metastasis in the entire cohort (all P < 0.001) and the non-cT4 group (all P < 0.001) but not in the cT4 group. The local recurrence rates were 60.7% for the cT4 ESCC patients and 45.1% for the non-cT4 ESCC patients (P < 0.001). Multivariate analysis showed that clinical N stage (P = 0.002), LN size (P = 0.007), and abdominal LN involvement (P = 0.011) were independent predictors of favorable OS in the non-cT4 group. However, clinical N stage (P = 0.824), LN size (P = 0.383), and abdominal LN involvement (P = 0.337) did not show any significant correlation with OS in the cT4 ESCC patients.ConclusionsOur data demonstrated that the status of LN metastasis did not correlate with OS in the cT4 ESCC patients that received dCRT or RT. Furthermore, the prevalence of local recurrence was higher in the cT4 ESCC patients.

In the context of low-carbon globalization, green development has become the common pursuit of all countries and the theme of China’s development in the new era. Fine particulate matter (PM2.5) is one of the main challenges affecting air quality, and how to accurately predict PM2.5 plays a pivotal role in environmental governance. However, traditional data-driven approaches and deep learning methods for prediction rarely consider spatiotemporal features. Furthermore, different regions always have various implicit or hidden states, which have rarely been considered in the off-the-shelf model. To solve these problems, this study proposed a novel Spatial-Temporal Matrix Factorization Generative Adversarial Network (ST MFGAN) to capture spatiotemporal correlations and overcome the regional diversity problem at the same time. Specifically, Generative Adversarial Network (GAN) composed of graph Convolutional Network (GCN) and Long-Short-Term Memory (LSTM) network is used to generate a large amount of reliable spatiotemporal data, and matrix factorization network is used to decompose the vector output by GAN into multiple sub-networks. PM2.5 are finally combined and jointly predicted by the fusion layer. Extensive experiments show the superiority of the newly designed method.

Mushroom bioactive peptides (MBPs) are bioactive peptides extracted directly or indirectly from edible mushrooms. MBPs are known to have antioxidant, anti-aging, antibacterial, anti-inflammatory and anti-hypertensive properties, and facilitate memory and cognitive improvement, antitumour and anti-diabetes activities, and cholesterol reduction. MBPs exert antioxidant and anti-inflammatory effects by regulating the MAPK, Keap1-Nrf2-ARE, NF-κB and TNF pathways. In addition, MBPs exert antibacterial, anti-tumour and anti-inflammatory effects by stimulating the proliferation of macrophages. The bioactivities of MBPs are closely related to their molecular weights, charge, amino acid compositions and amino acid sequences. Compared with animal-derived peptides, MBPs are ideal raw materials for healthy and functional products with the advantages of their abundance of resources, safety, low price, and easy-to-achieve large-scale production of valuable nutrients for health maintenance and disease prevention. In this review, the preparation, bioactivities, mechanisms and structure–activity relationships of MBPs were described. The main challenges and prospects of their application in functional products were also discussed. This review aimed to provide a comprehensive perspective of MBPs.

Abstract Background The objective of the present micro-computed tomography (micro-CT) study was to assess the presence of voids in band-shaped isthmuses obturated using three different filling techniques. Methods Twenty-four artificial molar teeth with a band-shaped isthmus were allocated to three groups (n = 8) for obturation, according to the filling technique: single-cone (SC), continuous wave of condensation (CWC) or lateral condensation (LC). Obturation was performed with gutta-percha (GP) cones and iRoot SP (Innovative Bioceramix, Vancouver, Canada). Post-filling micro-CT scanning was performed. The percentage of filling materials and void volumes were calculated in the isthmus areas and data were analyzed using one-way ANOVA and Tukey tests. Results The mean percentage of void volumes and corresponding filling percentages in the isthmus areas after obturation in the SC groups was 22.98 % ± 1.19 %, 77.02 % ± 1.19 %; in the CWC groups 10.46 % ± 2.28 %, 89.54 % ± 2.28 %; and in the LC groups was 13.14 % ± 1.85 %, 86.86 % ± 1.85 %, respectively. Conclusions In band-shaped isthmus area, the obturation quality of CWC was superior to SC and LC techniques.

Abstract Synergistic chemo-photodynamic therapy has garnered attention in the field of cancer treatment. Here, a pH cascade-responsive micellar nanoplatform with nucleus-targeted ability, for effective synergistic chemo-photodynamic cancer treatment, was fabricated. In this micellar nanoplatform, 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (Por), a photodynamic therapy (PDT) agent was utilized for carrying the novel anticancer drug GNA002 to construct a hydrophobic core, and cyclic RGD peptide (cRGD)-modified polyethylene glycol (PEG) (cRGD-PEG) connected the cell-penetrating peptide hexaarginine (R6) through a pH-responsive hydrazone bond (cRGD-PEG-N = CH-R6) to serve as a hydrophilic shell for increasing blood circulation time. After passively accumulating in tumor sites, the self-assembled GNA002-loaded nanoparticles were actively internalized into cancer cells via the cRGD ligands. Once phagocytosed by lysosomes, the acidity-triggered detachment of the cRGD-PEG shell led to the formation of R6-coated secondary nanoparticles and subsequent R6-mediated nucleus-targeted drug delivery. Combined with GNA002-induced nucleus-specific chemotherapy, reactive oxygen species produced by Por under 532-nm laser irradiation achieved a potent synergistic chemo-photodynamic cancer treatment. Moreover, our in vitro and in vivo anticancer investigations revealed high cancer-suppression efficacy of this ideal multifunctional nanoplatform, indicating that it could be a promising candidate for synergistic anticancer therapy.

The Yellow River Basin is of great significance to China’s economic and social development and ecological security. The Yellow River Basin is not only an important ecological barrier but also an important economic zone. In this article, natural hydrological conditions were taken as a reference, a habitat simulation model of the key sections of the Yellow River was constructed based on the MIKE 21 model, and an ecological water requirement assessment method for river ecological integrity combined with habitat simulation and features of the hydrological reference group was established, which took account of the survival and reproduction of indicator species. The suitable flow rates for the spawning period (i.e., April to June) of Silurus lanzhouensis in Lanzhou (LZ) and Cyprinus carpio in Longmen (LM) were 350–720 and 260–400 m3/s, respectively. Therefore, high pulse flow with a low flow peak should be guaranteed in mid- to late April. The peak flow should be at least approximately 1,000 m3/s to ensure that fish receive spawning signals, with a high pulse flow process occurring 1–2 times in May to June. The annual ecological water requirement of the Lanzhou and Longmen section was 9.1 × 109–11 × 109 and 4.7 × 109–11.3 × 109 m3. The model quantitatively simulated the changes in ecological water requirement of indicator fishes in key sections of the Yellow River, and an effective and realistic tool for ecological water requirement accounting of the Yellow River was provided.

Abstract Background Sun’s procedure is currently recognized as the standard procedure for acute type A aortic dissection (AAAD). But the operation istoo difficult for beginners. We hope to reduce the difficulty and complications of this operation. Methods The aortic arch was immediately cross-clamped after the stented graft was inserted into the distal aorta. Thereafter, the lower-body perfusion was restored. Then, anastomosis was performed between the proximal stent graft and the distal 4-branched Dacron graft. The other arteries were anastomosed to the arched branch of the 4-branched graft. Results The cardiopulmonary bypass (CPB) time was (207 ± 52) min, and the aortic cross-clamp time was (114 ± 39) min. The circulatory arrest time was (38 ± 16) sec. One patient (4%) died. The incidence of complications was stroke (4%), renal dysfunction requiring dialysis (4%), prolonged intubation(12%). Conclusions The time of circulatory arrest in this operation is less than 1 min, which can avoid the complications caused by DHCA and decrease risk of bleeding and complexity by shifting anastomosis more proximally. The effect of our operation is similar to and even better than that of Sun’s procedure. It does not even require relatively advanced skill, much experience and excellent psychological quality, especially suitable for beginners.

Abstract Objective Aortic arch replacement in acute type A aortic dissection patients remains the most challenging cardiovascular operation. Herein, we described our modified Y-graft technique using the Femoral Artery Bypass (FAB) and the One Minute Systemic Circulatory Arrest (OSCA) technique, and assessed the short-term outcomes of the patients. Methods Between February 2015 and November 2017, 51 patients with acute type A aortic dissection underwent aortic arch replacement. Among them, 23 patients underwent FAB while 28 patients underwent both FAB and OSCA. The intraoperative data and postoperative follow-up data were recorded. The follow-up data of patients with traditional Y-graft technique were collected from previously reported studies. Results In the FAB group, two patients died due to pulmonary infection (30-day survival rate, 91.3%), and two patients were paralyzed from the waist down. Hemodialysis was performed for five patients (21.7%) before hospital discharge. Fifteen patients (65.2%) received respiratory support for more than 2-days and eight patients (34.8%) for more than 5-days. These follow-up results were comparable or better than the patients with traditional Y-graft technique. Furthermore, compared to the FAB group, the morbidity due to neurological dysfunction and acute renal failure was significantly reduced in the FAB+OSCA group. Moreover, the respiratory support, length of postoperative stay and ICU stay were shortened. Conclusions This study clarified the feasibility of FAB and OSCA technique in modifying Y-graft technique. The acute type A aortic dissection patients showed less surgical complications and favorable short-term outcomes after this surgery.

Ovarian cancer (OC) is the main cause of deaths worldwide in female reproductive system malignancies. Growing studies have indicated that eRNAs could regulate cellular activities in various tumors. Yet the potential roles of eRNAs in OC progression have not been elucidated. Thus, comprehensive assays were needed to screen the critical eRNAs and to explore their possible function in OC. We used Kaplan–Meier methods to identify survival-associated eRNAs in OC based on TCGA datasets. The levels of ZFHX4-AS1 were examined using TCGA datasets. Further exploration was carried out based on the following assays: clinical and survival assays, GO terms, and KEGG assays. TIMER was applied to delve into the relationships between ZFHX4-AS1 and tumor immune infiltration. In this research, we observed 71 survival-related eRNAs in OC patients. ZFHX4-AS1 was highly expressed in OC specimens and predicted a poor prognosis of OC patients. In addition, high ZFHX4-AS1 expression was positively related to the advanced stages of OC specimens. Multivariate assays revealed that ZFHX4-AS1 was an independent prognostic factor for overall survival of OC patients. KEGG analysis indicated that ZFHX4-AS1 may play a regulatory effect on TGF-beta signaling, PI3K-Akt signaling, and proteoglycans in cancer. The pan-cancer validation indicated that ZFHX4-AS1 was related to survival in eight tumors, namely, UCEC, STAD, SARC, OV, ACC, KICH, KIRC, and BLCA. The expression of ZFHX4-AS1 was correlated with the levels of B cells, T cell CD8+, neutrophil, macrophage, and myeloid dendritic cells. Simultaneously, ZFHX4-AS1 may be a prognostic biomarker and a distinctly immunotherapy-related eRNA in OC.

Background/Aims: Hodgkin Lymphoma (HL) has become one of the most treatable cancers, with more than 80% patients in the advanced stage being cured through improvement of therapeutic regimens. Nevertheless, some treatments were accompanied with toxicities.Methods: In the current study, a network meta-analysis (NMA) was conducted to compare the efficacies and toxicities of different chemotherapy regimens for advanced Hodgkin lymphoma (HL). We reviewed PubMed and EMBASE databases from inception to May 2018, and identified randomized controlled trials (RCTs) in which advanced HL patients received chemotherapy. Fourteen eligible RCTs published between 1992 and 2017 were enrolled in this NMA. These studies included a total of 5,964 HL patients, and assessed at least one of seven different chemotherapy regimens. Direct and indirect evidence was combined to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs), and to establish a surface under the cumulative ranking (SUCRA) curve.Results: A cluster analysis was performed to evaluate efficacies and toxicities of different regimens. The COPP + ABVD (cyclophosphamide + vincristine + procarbazine + prednisone + doxorubicin + bleomycin + vinblastine + dacarbazine) regimen had the highest SUCRA partial response and overall remission rate values, while the ABVD regimen resulted in the lowest incidences of anemia, thrombocytopenia, neutropenia, and leucopenia.Conclusion: Cluster analysis revealed that COPP + ABVD had the best efficacy against advanced HL among the seven regimens, and ABVD had the lowest toxicity.