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Background: Hepatocellular carcinoma (HCC) is highly aggressive, with delayed diagnosis, poor prognosis, and a lack of comprehensive and accurate prognostic models to assist clinicians. This study aimed to construct an HCC prognosisrelated gene signature (HPRGS) and explore its clinical application value. Methods: TCGA-LIHC cohort was used for training, and the LIRI-JP cohort and HCC cDNA microarray were used for validation. Machine learning algorithms constructed a prognostic gene label for HCC. Kaplan-Meier (K-M), ROC curve, multiple analyses, algorithms, and online databases were used to analyze differences between high- and low-risk populations. A nomogram was constructed to facilitate clinical application. Results: We identified 119 differential genes based on transcriptome sequencing data from five independent HCC cohorts, and 53 of these genes were associated with overall survival (OS). Using 101 machine learning algorithms, the 10 most prognostic genes were selected. We constructed an HCC HPRGS with four genes (SOCS2, LCAT, ECT2, and TMEM106C). Good predictive performance of the HPRGS was confirmed by ROC, C-index, and K-M curves. Mutation analysis showed significant differences between the low- and high-risk patients. The low-risk group had a higher response to transcatheter arterial chemoembolization (TACE) and immunotherapy. Treatment response of highand low-risk groups to small-molecule drugs was predicted. Linifanib was a potential drug for high-risk populations. Multivariate analysis confirmed that HPRGS were independent prognostic factors in TCGA-LIHC. A nomogram provided a clinical practice reference. Conclusion: We constructed an HPRGS for HCC, which can accurately predict OS and guide the treatment decisions for patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Synchronous occurrence of prostate cancer (PCa) and renal cell carcinoma (RCC) is uncommon. RCC has a higher tendency to metastasize to the adrenal glands, renal hilar, and retroperitoneal lymph nodes compared to PCa. To date, there are no documented cases existing where metastatic tumors in these regions, observed in patients concurrently with PCa and RCC, have originated from the PCa rather than the RCC. Case presentation: In this case report, we described a 67-year-old male presented with dysuria for two months and left lower extremity edema for three days. Percutaneous biopsies revealed synchronous primary RCC and PCa. However, the origin of the metastatic tumors, especially those involving the adrenal glands, renal hilum, and retroperitoneal regions, remained undetermined. Subsequent surgical procedures identified that the metastatic lesions originated from the PCa, while the RCC was localized. Ultimately, the patient with metastatic hormone-sensitive prostate cancer (mHSPC) received combination therapy with rezvilutamide and goserelin, which resulted in a satisfactory treatment response. Conclusion: In patients with concurrent PCa and RCC, metastatic lesions in the adrenal glands, renal hilar, and retroperitoneal lymph nodes may also originate from the PCa. Accurate identification of the primary tumor and proper staging are critical for the appropriate management of patients with multiple primary malignancies with concurrent metastases. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is highly aggressive, with delayed diagnosis, poor prognosis, and a lack of comprehensive and accurate prognostic models to assist clinicians. This study aimed to construct an HCC prognosisrelated gene signature (HPRGS) and explore its clinical application value. Methods: TCGA-LIHC cohort was used for training, and the LIRI-JP cohort and HCC cDNA microarray were used for validation. Machine learning algorithms constructed a prognostic gene label for HCC. Kaplan-Meier (K-M), ROC curve, multiple analyses, algorithms, and online databases were used to analyze differences between high- and low-risk populations. A nomogram was constructed to facilitate clinical application. Results: We identified 119 differential genes based on transcriptome sequencing data from five independent HCC cohorts, and 53 of these genes were associated with overall survival (OS). Using 101 machine learning algorithms, the 10 most prognostic genes were selected. We constructed an HCC HPRGS with four genes (SOCS2, LCAT, ECT2, and TMEM106C). Good predictive performance of the HPRGS was confirmed by ROC, C-index, and K-M curves. Mutation analysis showed significant differences between the low- and high-risk patients. The low-risk group had a higher response to transcatheter arterial chemoembolization (TACE) and immunotherapy. Treatment response of highand low-risk groups to small-molecule drugs was predicted. Linifanib was a potential drug for high-risk populations. Multivariate analysis confirmed that HPRGS were independent prognostic factors in TCGA-LIHC. A nomogram provided a clinical practice reference. Conclusion: We constructed an HPRGS for HCC, which can accurately predict OS and guide the treatment decisions for patients with HCC. [ABSTRACT FROM AUTHOR]

Objective: We conducted this meta-analysis to comprehensively explore the prognostic value of the preoperative plasma fibrinogen in Asian patients diagnosed with urothelial cancer (UC). Methods: After a systematic search of Web of Science, PubMed, and Embase before May 2024, we included 10 studies in our meta-analysis. The hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression free survival (PFS) were estimated using fixed effect model. Results: This meta-analysis included a total of 2875 patients. UC patients with an elevated preoperative plasma fibrinogen had worse OS (pooled HR: 2.13, 95% CI: 1.81-2.51; P<0.001), CSS (pooled HR: 2.22, 95% CI: 1.83-2.70; P<0.001), RFS (pooled HR: 1.90, 95% CI: 1.59-2.27; P<0.001), and PFS (pooled HR: 2.12, 95% CI: 1.36-3.29, P=0.001). No significant heterogeneity or publication bias was found. Additionally, statistically significant pooled HRs were also calculated in subgroup analysis when stratified by cancer type, country, and cut-off value. Conclusions: The presence of elevated preoperative plasma fibrinogen levels is significantly correlated with unfavorable tumor outcomes in UCs. [ABSTRACT FROM AUTHOR]

Whole-genome duplication (WGD; i.e., polyploidy) and chromosomal rearrangement (i.e., genome shuffling) significantly influence genome structure and organization. Many polyploids show extensive genome shuffling relative to their pre-WGD ancestors. No reference genome is currently available for Platanaceae (Proteales), one of the sister groups to the core eudicots. Moreover, Platanus × acerifolia (London planetree; Platanaceae) is a widely used street tree. Given the pivotal phylogenetic position of Platanus and its 2-y flowering transition, understanding its flowering-time regulatory mechanism has significant evolutionary implications; however, the impact of Platanus genome evolution on flowering-time genes remains unknown. Here, we assembled a high-quality, chromosome-level reference genome for P. × acerifolia using a phylogeny-based subgenome phasing method. Comparative genomic analyses revealed that P. × acerifolia (2n = 42) is an ancient hexaploid with three subgenomes resulting from two sequential WGD events; Platanus does not seem to share any WGD with other Proteales or with core eudicots. Each P. × acerifolia subgenome is highly similar in structure and content to the reconstructed pre-WGD ancestral eudicot genome without chromosomal rearrangements. The P. × acerifolia genome exhibits karyotypic stasis and gene sub-/neo-functionalization and lacks subgenome dominance. The copy number of flowering-time genes in P. × acerifolia has undergone an expansion compared to other noncore eudicots, mainly via the WGD events. Sub-/neo-functionalization of duplicated genes provided the genetic basis underlying the unique flowering-time regulation in P. × acerifolia. The P. × acerifolia reference genome will greatly expand understanding of the evolution of genome organization, genetic diversity, and flowering-time regulation in angiosperms. [ABSTRACT FROM AUTHOR]

Background: Hyaluronan-mediated motility receptor (HMMR) is overexpressed in multiple carcinomas and influences the development and treatment of several cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear. Methods: The "limma" and "GSVA" packages in R were used to perform differential expression analysis and to assess the activity of signalling pathways, respectively. InferCNV was used to infer copy number variation (CNV) for each hepatocyte and "CellChat" was used to analyse intercellular communication networks. Recursive partitioning analysis (RPA) was used to re-stage HCC patients. The IC50 values of various drugs were evaluated using the "pRRophetic" package. In addition, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm HMMR expression in an HCC tissue microarray. Flow cytometry (FCM) and cloning, Edu and wound healing assays were used to explore the capacity of HMMR to regulate HCC tumour. Results: Multiple cohort studies and qRT-PCR demonstrated that HMMR was overexpressed in HCC tissue compared with normal tissue. In addition, HMMR had excellent diagnostic performance. HMMR knockdown inhibited the proliferation and migration of HCC cells in vitro. Moreover, high HMMR expression was associated with "G2M checkpoint" and "E2F targets" in bulk RNA and scRNA-seq, and FCM confirmed that HMMR could regulate the cell cycle. In addition, HMMR was involved in the regulation of the tumour immune microenvironment via immune cell infiltration and intercellular interactions. Furthermore, HMMR was positively associated with genomic heterogeneity with patients with high HMMR expression potentially benefitting more from immunotherapy. Moreover, HMMR was associated with poor prognosis in patients with HCC and the re-staging by recursive partitioning analysis (RPA) gave a good prognosis prediction value and could guide chemotherapy and targeted therapy. Conclusion: The results of the present study show that HMMR could play a role in the diagnosis, prognosis, and treatments of patients with HCC based on bulk RNA-seq and scRAN-seq analyses and is a promising molecular marker for HCC. [ABSTRACT FROM AUTHOR]

Introduction: Diet-induced obesity has been shown to decrease the abundance of Turicibacter, a genus known to play a role in the serotonin signaling system, which is associated with colorectal tumorigenesis, making the presence of Turicibacter potentially influential in the protection of intestinal tumorigenesis. Recently, Antrodia camphorata (AC), a medicinal fungus native to Taiwan, has emerged as a promising candidate for complementary and alternative cancer therapy. Small molecules and polysaccharides derived from AC have been reported to possess health-promoting effects, including anti-cancer properties. Methods: Bacterial culture followed with cell culture were used in this study to determine the role of Turicibacter in colorectal tumorigenesis and to explore the anti-cancer mechanism of AC with Turicibacter fermentation. Results: Turicibacter fermentation and the addition of AC polysaccharide led to a significant increase in the production of nutrients and metabolites, including α-ketoglutaric acid and lactic acid (p < 0.05). Treatment of Turicibacter fermented AC polysaccharide was more effective in inhibiting serotonin signaling-related genes, including Tph1, Htr1d, Htr2a, Htr2b, and Htr2c (p < 0.05), and Wnt-signaling related protein and downstream gene expressions, such as phospho-GSK-3β, active β-catenin, c-Myc, Ccnd1, and Axin2 (p < 0.05). Additionally, it triggered the highest generation of reactive oxygen species (ROS), which activated PI3K/Akt and MAPK/Erk signaling and resulted in cleaved caspase-3 expression. In comparison, the treatment of AC polysaccharide without Turicibacter fermentation displayed a lesser effect. Discussion: Our findings suggest that AC polysaccharide effectively suppresses the tumorigenic serotonin and Wnt-signaling pathways, and promotes ROS-mediated apoptosis in Caco-2 cells. These processes are further enhanced by Turicibacter fermentation. [ABSTRACT FROM AUTHOR]

Objective: Parkinson’s disease (PD) and dystonia are two closely related movement disorders with overlaps in clinical phenotype. Variants in several dystonia-related genes were demonstrated to be associated with PD; however, genetic evidence for the involvement of dystonia-related genes in PD has not been fully studied. Here, we comprehensively investigated the association between rare variants in dystonia-related genes and PD in a large Chinese cohort. Methods: We comprehensively analyzed the rare variants of 47 known dystoniarelated genes by mining the whole-exome sequencing (WES) and whole-genome sequencing (WGS) data from 3,959 PD patients and 2,931 healthy controls. We initially identified potentially pathogenic variants of dystonia-related genes in patients with PD based on dierent inheritance models. Sequence kernel association tests were conducted in the next step to detect the association between the burden of rare variants and the risk for PD. Results: We found that five patients with PD carried potentially pathogenic biallelic variants in recessive dystonia-related genes including COL6A3 and TH. Additionally, we identified 180 deleterious variants in dominant dystonia-related genes based on computational pathogenicity predictions and four of which were considered as potentially pathogenic variants (p.W591X and p.G820S in ANO3, p.R678H in ADCY5, and p.R458Q in SLC2A1). A gene-based burden analysis revealed the increased burden of variant subgroups of TH, SQSTM1, THAP1, and ADCY5 in sporadic early-onset PD, whereas COL6A3 was associated with sporadic late-onset PD. However, none of them reached statistical significance after the Bonferroni correction. Conclusion: Our findings indicated that rare variants in several dystonia-related genes are suggestively associated with PD, and taken together, the role of COL6A3 and TH genes in PD is highlighted [ABSTRACT FROM AUTHOR]

Background. The homeodomain-leucine zipper I (HD-Zip I) transcription factor is a plant-specific protein that plays an essential role in the abiotic stress response of plants. Research on the HD-Zip I family in Salvia miltiorrhiza is still lacking. Methods and Results. In this study, a total of 25 SmHD-Zip I proteins were identified. Their characterizations, phylogenetic relationships, conserved motifs, gene structures, and cis-elements were analyzed comprehensively using bioinformatics methods. Expression profiling revealed that SmHD-Zip I genes exhibited distinctive tissue-specific patterns and divergent responses to ABA, PEG, and NaCl stresses. SmHD-Zip12 responded the most strongly to ABA, PEG, and NaCl, so it was used for transgenic experiments. The overexpression of SmHD-Zip12 significantly increased the content of cryptotanshinone, dihydrotanshinone I, tanshinone I, and tanshinone IIA by 2.89-fold, 1.85-fold, 2.14-fold, and 8.91-fold compared to the wild type, respectively. Moreover, in the tanshinone biosynthetic pathways, the overexpression of SmHD-Zip12 up-regulated the expression levels of SmAACT, SmDXS, SmIDS, SmGGPPS, SmCPSl, SmCPS2, SmCYP76AH1, SmCYP76AH3, and SmCYP76AK1 compared with the wild type. Conclusions. This study provides information the possible functions of the HD-Zip I family and lays a theoretical foundation for clarifying the functional mechanism of the SmHD-Zip12 gene in regulating the synthesis of tanshinone in S. miltiorrhiza. [ABSTRACT FROM AUTHOR]

Introduction: Low back pain (LBP) is a prevalent and complex condition that poses significant medical, social, and economic burdens worldwide. The accurate and timely assessment and diagnosis of LBP, particularly non-specific LBP (NSLBP), are crucial to developing effective interventions and treatments for LBP patients. In this study, we aimed to investigate the potential of combining B-mode ultrasound image features with shear wave elastography (SWE) features to improve the classification of NSLBP patients. Methods: We recruited 52 subjects with NSLBP from the University of Hong Kong-Shenzhen Hospital and collected B-mode ultrasound images and SWE data from multiple sites. The Visual Analogue Scale (VAS) was used as the ground truth to classify NSLBP patients. We extracted and selected features from the data and employed a support vector machine (SVM) model to classify NSLBP patients. The performance of the SVM model was evaluated using five-fold cross-validation and the accuracy, precision, and sensitivity were calculated. Results: We obtained an optimal feature set of 48 features, among which the SWE elasticity feature had the most significant contribution to the classification task. The SVM model achieved an accuracy, precision, and sensitivity of 0.85, 0.89, and 0.86, respectively, which were higher than the previously reported values of MRI. Discussion: In this study, we aimed to investigate the potential of combining B-mode ultrasound image features with shear wave elastography (SWE) features to improve the classification of non-specific low back pain (NSLBP) patients. Our results showed that combining B-mode ultrasound image featureswith SWE features and employing an SVM model can improve the automatic classification of NSLBP patients. Our findings also suggest that the SWE elasticity feature is a crucial factor in classifying NSLBP patients, and the proposed method can identify the important site and position of the muscle in the NSLBP classification task. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence, evolution, clinical characteristics, correlates and predictors of fatigue as well as to investigate the influence of comorbid fatigue on the longitudinal changes in motor and non-motor symptoms over a 2-year longitudinal follow-up period in a large cohort of patients with Parkinson’s disease (PD). Materials and methods: A total of 2,100 PD patients were enrolled from the Parkinson’s Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC), and their motor and non-motor symptoms were assessed biennially using comprehensive scales, including the 16-item Parkinson Fatigue Scale (PFS-16). Each PD patient was categorized as PD with or without fatigue on the basis of a cut-off mean PFS-16 score of 3.3. Results: The prevalence of fatigue in our cohort was 36.8%. Compared to PD patients without fatigue, PD patients with fatigue were more likely to be older, have a longer disease duration, and higher baseline levodopa equivalent daily dose (all p < 0.05). Moreover, PD patients with fatigue showed more severe motor and non-motor phenotypes than those without fatigue. Overall, high total Unified Parkinson’s Disease Rating Scale (UPDRS) score (odds ratio [OR] = 1.016, 95% confidence interval [CI]: 1.009–1.024), Non-Motor Symptoms Scale score (OR = 1.022, 95% CI: 1.015–1.029), postural instability and gait difficulty (PIGD) subtype (OR = 1.586, 95% CI: 1.211–2.079), presence of excessive daytime sleepiness (EDS; OR = 1.343, 95% CI: 1.083–1.666), and wearing-off (OR = 1.282, 95% CI: 1.023–1.607) were significantly associated with fatigue in PD patients (all p < 0.05). High total UPDRS score at baseline (OR = 1.014, 95% CI: 1.002–1.027, p = 0.028) increased the risk of developing fatigue during follow-up. Although significant, the odds ratios were low and confidence intervals were narrow. Analysis of disease progression showed significant group differences in motor and non-motor symptoms. In comparison with the never-fatigue group, the persistent-fatigue group showed significantly greater progression in motor, autonomic dysfunction, sleep, depression and cognitive symptoms (all p < 0.05). Conclusion: Increased disease severity, presence of the PIGD subtype, EDS, and wearing-off were associated with fatigue in PD patients. Significant subgrouplevel differences were observed in the progression of motor and non-motor symptoms across different fatigue subgroups of PD patients. [ABSTRACT FROM AUTHOR]

Seven universities in China currently offer undergraduate programs in chemical processing engineering of forest products (CPEFP), which play a crucial role in training professionals to meet the evolving demands of the forest-based chemical industry. However, these programs in Chinese universities face several challenges that require attention in order to better serve the development of the forest chemical industry. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is a progressivemovement disorder caused by a loss of dopaminergic neurons. Previous studies have highlighted the importance of mitochondria dynamics in the pathogenesis of PD. Dynamin-1-like (DNM1L) is a gene that encodes dynamin-related protein 1 (DRP1), a GTPase essential for proper mitochondria fission. In the present study, we evaluated the relationship between DNM1L variants and PD in the Chinese population. Methods: A total of 3,879 patients with PD and 2,931 healthy controls were recruited and burden genetic analysis combined with high-throughput sequencing was applied. Results: We identified 23 rare variants in the coding region of DNM1L, while no difference in variant burden was shown between the cases and controls. We also identified 201 common variants in the coding and flanking regions and found two significant SNPs, namely, rs10844308 and rs143794289 [odds ratio (OR) = 1.220 and 0.718, p = 0.025 and 0.036, respectively]. We also performed a meta-analysis to correlate the two SNPs with PD risk. However, none of the common variants was significant using logistic regression. Conclusion: Despite the critical role of DRP1, our study did not support the relationship between DNM1L variants and PD risk in the Chinese population. [ABSTRACT FROM AUTHOR]

Context: The swim bladder of the croceine croaker is believed to have a therapeutic effect on various diseases. However, there is no research about its effect on mammalian spermatogenesis. Objective: We investigated the swim bladder peptides (SBPs) effect on busulfan-induced oligoasthenospermia in mice. Materials and methods: We first extracted SBP from protein hydrolysate of the croceine croaker swim bladder, and then five groups of ICR male mice were randomly assigned: control, controlþSBP 60 mg/kg, busulfan, busulfanþSBP 30mg/kg and busulfanþSBP 60 mg/kg. Mice received bilateral intratesticular injections of busulfan to establish oligoasthenospermia model. After treatment with SBP for 4 weeks, testis and epididymis were collected from all mice for further analysis. Results: After treatment with SBP 30-60 mg/kg for 4 weeks, epididymal sperm concentration and motility increased by 3.9-9.6- and 1.9-2.4-fold than those of oligoasthenospermia mice induced by busulfan. Meanwhile, histology showed that spermatogenic cells decreased, leading to increased lumen diameters and vacuolization in the busulfan group. These features were reversed by SBP treatment. RNA-sequencing analysis revealed that, compared with the busulfan group, Lin28b and Igf2bp1 expression related to germ cell proliferation, increased with a >1.5-fold change after SBP treatment. Additionally, PGK2 and Cfap69 mRNAs associated with sperm motility, also increased with a >1.5-fold change. Furthermore, these findings were validated by quantitative real-time PCR and Western blotting. Discussion and conclusions: This is the first reported evidence for the therapeutic effect of SBP on oligoasthenospermia. SBP may be a promising drug for oligoasthenospermia in humans. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence suggests that early-onset Parkinson's disease (EOPD) is heterogeneous in its clinical presentation and progression. Defining subtypes of EOPD is needed to better understand underlying mechanisms, predict disease course, and eventually design more efficient personalized management strategies. Objective: To identify clinical subtypes of EOPD, assess the clinical characteristics of each EOPD subtype, and compare the progression between EOPD subtypes. Materials and methods: A total of 1,217 patients were enrolled from a large EOPD cohort of the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) between January 2017 and September 2021. A comprehensive spectrum of motor and nonmotor features were assessed at baseline. Cluster analysis was performed using data on demographics, motor symptoms and signs, and other nonmotor manifestations. In 454 out of total patients were reassessed after a mean follow-up time of 1.5 years to compare progression between different subtypes. Results: Three subtypes were defined: mild motor and non-motor dysfunction/slow progression, intermediate and severe motor and non-motor dysfunction/malignant. Compared to patients with mild subtype, patients with the severe subtype were more likely to have rapid eye movement sleep behavior disorder, wearing-off, and dyskinesia, after adjusting for age and disease duration at baseline, and showed a more rapid progression in Unified Parkinson's Disease Rating Scale (UPDRS) total score (P = 0.002), UPDRS part II (P = 0.014), and III (P = 0.001) scores, Hoehn and Yahr stage (P = 0.001), and Parkinson's disease questionnaire-39 item version score (P = 0.012) at prospective follow-up. Conclusion: We identified three different clinical subtypes (mild, intermediate, and severe) using cluster analysis in a large EOPD cohort for the first time, which is important for tailoring therapy to individuals with EOPD. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effect of regional white matter hyperintensities (WMHs) on Essential tremor (ET) subtypes and to explore the association between WMHs load and the severity of motor and non-motor symptoms in patients with ET. Methods: A cohort of 176 patients with ET (including 86 patients with pure ET and 90 patients with ET plus) and 91 normal controls (NC) was consecutively recruited. Demographic, clinical, and imaging characteristics were compared between individuals with pure ET, ET plus, and NC. The cross-sectional association among regional WMHs and the severity of tremor and non-motor symptoms were assessed within each group. Results: Compared with the pure ET subgroup, the ET plus subgroup demonstrated higher TETRAS scores, NMSS scores, and lower MMSE scores (all P < 0.05). Periventricular and lobar WMHs’ loads of pure ET subgroup intermediated between NC subjects and ET plus subgroup. WMHs in the frontal horn independently increased the odds of ET (OR = 1.784, P < 0.001). The age (P = 0.021), WMHs in the frontal lobe (P = 0.014), and WMHs in the occipital lobe (P = 0.020) showed a significant impact on TETRAS part II scores in the ET plus subgroup. However, only the disease duration was positively associated with TETRAS part II scores in patients with pure ET (P = 0.028). In terms of non-motor symptoms, NMSS scores of total patients with ET were associated with disease duration (P = 0.029), TETRAS part I scores (P = 0.017), and WMH scores in the frontal lobe (P = 0.033). MMSE scores were associated with age (P = 0.027), body mass index (P = 0.006), education level (P < 0.001), and WMHs in the body of the lateral ventricle (P = 0.005). Conclusion: Our results indicated that the WMHs in the frontal horn could lead to an increased risk of developing ET. WMHs may be used to differentiate pure ET and ET plus. Furthermore, WMHs in the frontal and occipital lobes strong predictors of worse tremor severity in the ET plus subgroup. Regional WMHs are associated with cognitive impairment in patients with ET. [ABSTRACT FROM AUTHOR]

Purpose: Cuprotosis is a newly discovered form of non-apoptotic regulated cell death and is characterized by copper-dependent and associated with mitochondrial respiration. However, the prognostic significance and function of cuprotosis-related genes (CRGs) in hepatocellular carcinoma (HCC) are unknown. This study aims to develop cuprotosis-mediated patterns-related gene (CMPRG) prediction models for the prognosis of patients with HCC, exploring the functional underlying the CRGs on the influence of tumor microenvironment (TME) features. Experimental design: This study obtained transcriptome profiling and the corresponding clinical information from the TCGA and GEO databases. Besides, the Cox regression model with LASSO was implemented to build a multi-gene signature, which was then validated in an internal validation set and two external validation sets through Kaplan-Meier, DCA, and ROC analyses. Results: According to the LASSO analysis, we screened out a cuprotosismediated pattern 5-gene combination (including PBK; MMP1; GNAZ; GPC1 and AKR1D1). A nomogram was constructed for the presentation of the final model. The ROC curve assessed the model’s predictive ability, which resulted in an area under the curve (AUC) values ranging from 0.604 to 0.787 underwent internal and two external validation sets. Meanwhile, the risk score divided the patients into two groups of high and low risk, and the survival rate of high-risk patients was significantly lower than that of low-risk patients (P<0.01). The risk score could be an independent prognostic factor in the multifactorial Cox regression analysis (P<0.01). Functional analysis revealed that immune status, mutational loads, and drug sensitivity differed between the two risk groups. Conclusions: In summary, we identified three cuprotosis-mediated patterns in HCC. And CMPRGs are a promising candidate biomarker for HCC early detection, owing to their strong performance in predicting HCC prognosis and therapy. Quantifying cuprotosis-mediated patterns in individual samples may help improve the understanding of multiomic characteristics and guide the development of targeted therapy for HCC. [ABSTRACT FROM AUTHOR]

Anlotinib is a new multitarget tyrosine kinase inhibitor for tumor angiogenesis, and its monotherapy exhibits a decent clinical efficacy. However, the process of combining Anlotinib and immune checkpoint therapy to achieve optimal antitumor effects while limiting side effects remains unclear. In this study, we found that effective low-dose Anlotinib was sufficient to inhibit tumor growth while reducing side effects compared with high doses. Effective low-dose Anlotinib treatments induced durable tumor vascular normalization and improved anti-PD-1 therapy in both short- and long-term treatment regimens. Mechanistically, the combination therapy increased the proportions of intratumoral CD4+ T, CD8+ T, and NK cells. Anlotinib-associated antitumor effects were independent of interferon γ, however, the combination therapy required CD8+ T cells to suppress tumor growth. Together, these results suggest that the combination of effective low-dose Anlotinib and PD-1 blockade induces durable antitumor effects with fewer side effects. Our findings indicate that antiangiogenic treatments combined with immune checkpoint therapy at an effective low-dose, rather than a tolerable high dose, would be more efficacious and safer. [ABSTRACT FROM AUTHOR]

Belowground interactions mediated by root exudates are critical for the productivity and efficiency of intercropping systems. Herein, we investigated the process of microbial community assembly in maize, peanuts, and shared rhizosphere soil as well as their regulatory mechanisms on root exudates under different planting patterns by combining metabolomic and metagenomic analyses. The results showed that the yield of intercropped maize increased significantly by 21.05% (2020) and 52.81% (2021), while the yield of intercropped peanut significantly decreased by 39.51% (2020) and 32.58% (2021). The nitrogen accumulation was significantly higher in the roots of the intercropped maize than in those of sole maize at 120 days after sowing, it increased by 129.16% (2020) and 151.93% (2021), respectively. The stems and leaves of intercropped peanut significantly decreased by 5.13 and 22.23% (2020) and 14.45 and 24.54% (2021), respectively. The root interaction had a significant effect on the content of ammonium nitrogen (NH4 +-N) as well as the activities of urease (UE), nitrate reductase (NR), protease (Pro), and dehydrogenase (DHO) in the rhizosphere soil. A combined network analysis showed that the content of NH4 +-N as well as the enzyme activities of UE, NR and Pro increased in the rhizosphere soil, resulting in cyanidin 3-sambubioside 5-glucoside and cyanidin 3-O-(6-Op-coumaroyl) glucoside-5-O-glucoside; shisonin were significantly up-regulated in the shared soil of intercropped maize and peanut, reshaped the bacterial community composition, and increased the relative abundance of Bradyrhizobium. These results indicate that interspecific root interactions improved the soil microenvironment, regulated the absorption and utilization of nitrogen nutrients, and provided a theoretical basis for high yield and sustainable development in the intercropping of maize and peanut. [ABSTRACT FROM AUTHOR]

Objective: Although risk factors for excessive daytime sleepiness (EDS) have been reported, there are still few cohort-based predictive models for EDS in Parkinson’s disease (PD). This 1-year longitudinal study aimed to develop a predictive model of EDS in patients with PD using a nomogram and machine learning (ML). Materials and methods: A total of 995 patients with PD without EDS were included, and clinical data during the baseline period were recorded, which included basic information as well as motor and non-motor symptoms. One year later, the presence of EDS in this population was re-evaluated. First, the baseline characteristics of patients with PD with or without EDS were analyzed. Furthermore, a Cox proportional risk regression model and XGBoost ML were used to construct a prediction model of EDS in PD. Results: At the 1-year follow-up, EDS occurred in 260 of 995 patients with PD (26.13%). Baseline features analysis showed that EDS correlated significantly with age, age of onset (AOO), hypertension, freezing of gait (FOG). In the Cox proportional risk regression model, we included high body mass index (BMI), late AOO, low motor score on the 39-item Parkinson’s Disease Questionnaire (PDQ-39), low orientation score on the Mini-Mental State Examination (MMSE), and absence of FOG. Kaplan–Meier survival curves showed that the survival prognosis of patients with PD in the high-risk group was significantly worse than that in the low-risk group. XGBoost demonstrated that BMI, AOO, PDQ-39 motor score, MMSE orientation score, and FOG contributed to the model to different degrees, in decreasing order of importance, and the overall accuracy of the model was 71.86% after testing. Conclusion: In this study, we showed that risk factors for EDS in patients with PD include high BMI, late AOO, a low motor score of PDQ-39, low orientation score of MMSE, and lack of FOG, and their importance decreased in turn. Our model can predict EDS in PD with relative effectivity and accuracy. [ABSTRACT FROM AUTHOR]

Objectives: Parkinson’s disease (PD) is a neurodegenerative disorder with the manifestation of motor symptoms and non-motor symptoms. Previous studies have indicated the role of several transmembrane (TMEM) protein family genes in PD pathogenesis. Materials and Methods: In order to better investigate the genetic role of PDrelated TMEM protein family genes in PD, including TMEM230, TMEM59, TMEM108, TMEM163, TMEM175, and TMEM229B, 1,917 sporadic early onset PD (sEOPD) or familial PD (FPD) patients and 1,652 healthy controls were analyzed by whole-exome sequencing (WES) while 1,962 sporadic late-onset PD (sLOPD) and 1,279 healthy controls were analyzed by whole-genome sequencing (WGS). Rare and common variants for each gene were included in the analysis. Results: One hundred rare damaging or loss of function variants of six genes were found at the threshold of MAF < 0.1%. Three rare Dmis variants of TMEM230 were specifically identified in PD. Rare missense variants of TMEM59 were statistically significantly associated with PD in the WES cohort, indicating the role of TMEM59 in FPD and sEOPD. Rare missense variants of TMEM108 were suggestively associated with PD in the WGS cohort, indicating the potential role of TMEM108 in sLOPD. The rare variant of the other three genes and common variants of six genes were not significantly associated with PD. Conclusion: We performed a large case-control study to systematically investigate the role of several PD-related TMEM protein family genes in PD. We identified three PDspecific variants in TMEM230, the significant association of TMEM59 with FPD, and sEOPD and the suggestive association of TMEM108 with sLOPD. [ABSTRACT FROM AUTHOR]

[Objectives] To investigate the effect of healthcare failure mode and effect analysis (HFMEA) on reducing error risk of neonatal parenteral nutrition solution dispensing. [Methods] A research team was established to identify the failure mode (FM) in each link of the formulation process of neonatal parenteral nutrition solution by HFMEA, quantify the severity (S), occurrence (O) and detection (D) of FM, and evaluate FM by risk priority number (RPN). For FM with the values of RPN > 16, failure cause analysis was conducted, and corresponding improvement measures were formulated. The weight coefficient and random consistency ratio (CR) of deployment process were calculated in Matlab R2018a by compiling the Analytic Hierarchy Process (AHP) program. Six months after the implementation of improvement measures, the implementation effect was evaluated by comparing the changes of the values of RPN which was evaluated comprehensively and the rate of dispensing errors before and after the implementation of HFMEA. [Results] In the preparation process of neonatal parenteral nutrition solution, a total of 13 FMs with medium and above risk were found, the weight coefficient of medical order review, dosing and mixing was 0.270 3, the weight coefficient of drug dispensing check and review was 0.143 2, the weight coefficient of print label was 0.101 5, the weight coefficient of distribution was 0.071 6, and CR =0.049 1 <0.1. After six months of intervention, the total RPN value decreased by 64.81% from 127.8 to 45. 0. The deployment error rates were significantly lower after the implementation, and the difference was statistically significant (P < 0.05). [Conclusions] HFMEA can effectively reduce the error risk in preparation of neonatal parenteral nutrition solution, improve the quality of dispensing and promote the safety of neonatal medication. [ABSTRACT FROM AUTHOR]

Wireless data collection requires a sequence of resource provisioning decisions due to the limited battery capacity of wireless sensors. The corresponding online resource provisioning problem is challenging. Recently, many prediction methods have been proposed that can be used to benefit the performance of various systems through their incorporation. Therefore, in this article, we focus on online resource provisioning problems with short-term predictions motivated by the wireless data collection problem. Specifically, we design separate online algorithms for systems in which the state evolves in either a stationary manner or an arbitrarily determined manner and prove their performance bounds where their bounds improve as the amount of available predictions increases. Additionally, we design a meta-algorithm that can choose which online algorithm to implement at each point in time, depending on the recent behavior of the system environment. The practical performances of the proposed algorithms are corroborated in trace-driven numerical simulations of data collection of shared bikes. Additionally, we show that the performance of our meta-algorithm in various system environments can be better than that of the single best algorithm chosen in hindsight. [ABSTRACT FROM AUTHOR]

Objectives] To explore the compatibility rules of neonatal parenteral nutrition $ PN) prescriptions based on asociation rules and hierarchical cluster analysis, thereby providing a reference for standardizing neonatal parenteral nutrition supportive therapy. "Methods] The data about neonatal PN formulations prepared by the Pharmacy Intravenous Admixture Services $ PIVAS) of the Affiliated Hospital of Chengde Medical University from July 2015 to June 2021 were collected. The general information of the prescriptions and the frequency of drug use were analyzed with Excel 2019; the boxplot of drug dosing was drawn using GraphPad 8. 0 software; and SPSS Modeler 18.0 and SPSS Statistics 26.0 were used to perform association rules and hierarchical cluster analysis. " Results] A total of 11 488 PN prescriptions were coHected from 1 421 newborns, involving 18 kinds of drugs, which were divided into 11 types of nutrients. Association rules analysis yielded 84 nutrient substance combinations. The combination of fat emulsion-water-soluble vitamins-fat-soluble vitamins--glucose-amino acids had the highest confidence $99. 95 T ). The hierarchical cluster analysis divided nutrients into 5 types. " Conclusions] The prescriptions of PN for newborns were composed of five types of nutrients: amino acids, fat emulsion, glucose, water-soluble vitamins, and fat-soluble vitamins. According to the lack of electrolytes and trace elements, appropriate drugs can be chosen to meet nutritional demands. This study provides reference basis for reasonable selection of drugs for neonatal PN prescriptions and further standardization of PN supportive therapy in newborns. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of Hashimoto’s thyroiditis (HT) on the extent of ablation zone in ultrasound (US)-guided radiofrequency ablation (RFA) for early stages of papillary thyroid microcarcinoma (PTMC). Method: We selected 772 patients with 797 PTMCs who underwent with RFA from August 2017 to August 2020. They were subdivided into two groups as follows: (i) 216 patients (224 PTMCs) with HT in the ‘HT þ PTMC’ group and (ii) 556 patients (573 PTMCs) with healthy thyroid in the ‘PTMC’ group. We assessed the extent (maximum diameter and volume) of the ablation zone by contrast-enhanced ultrasound (CEUS) immediately, one day, and 1 week following RFA. Results: The ablation zone of the ‘HT þ PTMC’ group was smaller than that of the ‘PTMC’ group at 1 week of RFA (maximum diameter: 14.6 ± 3.1 mm vs. 15.2 ± 3.2 mm and volume: 0.932 ± 0.498 mL vs. 1.028 ± 0.540 mL, respectively, p < .05). However, there were no differences before, immediately, and one day post-RFA (p > .05). Life-threatening complications did not develop in any of the patients. Conclusion: RFA-treated PTMCs were smaller in size in patients with HT than in those with a healthy thyroid at 1 week of RFA. However, the exact mechanism underlying this phenomenon and its clinical significance warrant further investigation. [ABSTRACT FROM AUTHOR]

Purpose Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required. Materials and Methods In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance. Results The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-tomesenchymal transition in SCLC cells. Conclusion Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management. [ABSTRACT FROM AUTHOR]

The research of modern pharmacology displays that main material basis of Danggui Shaoyao Powder exerting efficacy includes ligustilide, paeoniflorin, poria acid, ferulic acid, ligustrazine and so on, and its efficacy is mainly realized by regulating neural receptor-ligand interaction, cytokine release, and TNF-α inflammatory pathway. Systematic study of metabonomics, serum pharmacochemistry and network pharmacology of Danggui Shaoyao Powder sufficiently clarifies its potential pharmacodynamic mechanism, and it could provide scientific theoretical basis for its clinical application. In this paper, by systemically analyzing material basis of Danggui Shaoyao Powder, and exploring its complex pharmacological mechanism and clinical application in vivo, it could comprehensively understand the clinical value of Danggui Shaoyao Powder, so as to provide beneficial reference for further development of the material basis, quality control and classical prescription of Danggui Shaoyao Powder. [ABSTRACT FROM AUTHOR]

[Objectives] To explore the correlation of processing technology, physical parameters and chemical components during plain stir-baking of Trichosanthis Radix. [Methods] Based on mixture uniform experiment design, the Trichosanthis Radix was prepared by plain stir-bake method. Delphi method was used to evaluate and select the highest-scoring processed product for measuring physical parameters. UV spectrophotometry was used to determine the contents of starch and polysaccharide. The correlation and linear regression model of processing technology, physical parameters and chemical components were established with the aid of SPSS 26.0 [Results] After processing by plain stir-bake method, the relative density and chromaticity showed a decreasing trend in the processed products of Trichosanthis Radix, the oxidation value, hydroscopic rate and swelling decreased firstly and then increased, and pH increased firstly and then decreased. The content of total starch decreased, the content of polysaccharide increased, and there was a negative correlation between them. There was a significant positive correlation between temperature and oxidation value, swelling and hydroscopic rate, hydroscopic rate and polysaccharide, and there was a significant negative correlation between relative density and hydroscopic rate or polysaccharide, total starch and hydroscopic rate or swelling. The linear relation model between processing technology and physical parameters and chemical components was r~2>0.9. [Conclusions] After processing by plain stir-bake method, the physical parameters of Trichosanthis Radix changed, and there may be mutual conversion between total starch and polysaccharides. To a certain extent, physical parameters can be used to evaluate the quality of processed products of Trichosanthis Radix. This study is expected to provide a reference for research on quality evaluation of processed products of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

The immunosuppressive and hypoxic tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we showed that elevated levels of Delta-like 1 (DLL1) in the breast and lung TME induced long-term tumor vascular normalization to alleviate tumor hypoxia and promoted the accumulation of interferon? (IFN-γ)-expressing CD8+ T cells and the polarization of M1-like macrophages. Moreover, increased DLL1 levels in the TME sensitized anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) treatment in its resistant tumors, resulting in tumor regression and prolonged survival. Mechanically, in vivo depletion of CD8+ T cells or host IFN-γ deficiency reversed tumor growth inhibition and abrogated DLL1-induced tumor vascular normalization without affecting DLL1-mediated macrophage polarization. Together, these results demonstrate that elevated DLL1 levels in the TME promote durable tumor vascular normalization in a CD8+ T cell- and IFN-γ-dependent manner and potentiate anti-CTLA4 therapy. Our findings unveil DLL1 as a potential target to persistently normalize the TME to facilitate cancer immunotherapy. [ABSTRACT FROM AUTHOR]

The antimicrobial activity and the underlying action mechanisms of dihydrotanshinone I against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamases Staphylococcus aureus were investigated with Kleihauer-Betke (K-B) test. The antibacterial mechanisms of dihydrotanshinone I were investigated by monitoring the changes in electric conductivity, concentration of AKP, protein content, and patterns of protein electrophoretic bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The antibacterial rings showed that antimicrobial activity of dihydrotanshinone I at 18 mM was stronger to Staphylococcus aureus than to methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamases Staphylococcus aureus. The minimum inhibitory concentration (MIC) and IC50 values showed that dihydrotanshinone I had the strongest inhibitory activity against S. aureus (MIC = 280 µM, IC50 = 874 ± 0.01 µM, respectively). Dihydrotanshinone I could increase the electric conductivity, concentration of alkaline phosphatase (AKP) and protein content. The patterns of protein bands in SDS-PAGE were changed obviously. Dihydrotanshinone I also significantly inhibited S. aureus, methicillin-resistant S. aureus, and extended-spectrum beta-lactamases S. aureus, indicating that dihydrotanshinone I can damage the structures of cell wall and cell membrane to increase permeability of cell membrane and release of cell components. Dihydrotanshinone I could influence the synthesis of bacterial protein, destroy the protein, or reject the anabolism or expression of the protein, and finally lead to the loss of normal physiological function of bacteria. [ABSTRACT FROM AUTHOR]

A pervaporation separation active layer by emulsion polymerization was prepared by using acrylate monomer and nano silica sol solution. Porous polyacrylonitrile substrate was used to construct composite pervaporation membranes. We used CPL/water mixture system (caprolactam (CPL)) to analyze the pervaporation separation performance of composite membranes, and studied the morphology and properties of the membranes by scanning electron microscopy, Fourier transform infrared, thermogravimetric analysis, X-ray diffraction, and contact angle. Given the formation of composite structures, the thermal stability of the nano silica/polyacrylate composite membrane is enhanced. A pervaporation transport equation was introduced to the permeation flux of normalized emulsion polymerization composite membranes. This equation relates to water permeability, CPL permeability, and membrane selectivity to assess pervaporation performance and potential mechanisms. The results show that the maximum total permeate flux of the CPL/water system reaches 1,138 g/(m²h) with a separation factor of 353, which was remarkable compared with previous research. Membrane materials obtained by emulsion polymerization can be introduced to the field of pervaporation, providing a novel way to obtain excellent pervaporation membrane materials. [ABSTRACT FROM AUTHOR]

Eucinetus parvus sp. nov. is described from late Cretaceous Burmese amber, representing the second record of Eucinetidae from the Burmese amber and the first species of the family with simple, not piercing, mouthparts. A comparison between Mesocinetidae and Eucinetidae is provided. [ABSTRACT FROM AUTHOR]

Multicarpellate fruits are larger and produce more seeds than mono- or bicarpellate fruits, enhancing the reproductive capacity of the plant. To identify the phenotypic and molecular differences among florets of different carpel types, we studied carpel formation and fusion in the grapevine (Vitis vinifera) cultivar ‘Xiangfei’, which produces a high proportion of multicarpellate fruit. We also determined the function of VvSUPERMAN-like (VvSUP-like) and explored its relationship with VvWUS (VvWUSCHEL) and VvAG1 (VvAGAMOUS), which is related to the formation of carpel primordia. We showed that carpel formation and fusion were largely consistent between bicarpellate and tricarpellate ovaries, which both involve congenital fusion; rather, the differences between these ovary types arose from variation in carpel primordia number and location. Transgenic tomato (Solanum lycopersicum) plants expressing VvSUPlike produced significantly fewer carpels and other floral organs than the wild type. Moreover, transcriptome sequencing results indicate that VvSUP-like was more highly expressed in bicarpellate than in tricarpellate ‘Xiangfei’ florets. Luciferase reporter assays indicated that VvSUP-like inhibits the expression of VvAG1 and VvWUS by directly binding to their promoters, and VvWUS promotes VvAG1 expression by directly binding to its promoter. VvSUP-like inhibits the feedback signaling between VvWUS and VvAG1. Together, these results suggest that VvSUP-like negatively regulates the number of carpels that develop by inhibiting VvAG1 and VvWUS expression. [ABSTRACT FROM AUTHOR]

Background. During the outbreak of coronavirus disease 2019 (COVID-19), people are under the dual pressure of interpersonal isolation and concerns about infection. An evaluation of people's psychological status and risk factors is needed to conduct target interventions. Methods. This was a nationwide, multicenter, cross-sectional study using quota and snowball sampling methods during the COVID-19 epidemic in China. Participants' characteristics and experiences were obtained by an online questionnaire and telephone review. Psychological distress and sleep problems were measured by the Generalized Anxiety Disorder-7, the Patient Health Questionnaire-9, and the Insomnia Severity Index. Results. A total of 23,500 participants were recruited, and 19,372 valid questionnaires were received from 11 centers. Overall, 11.0-13.3% of the participants had anxiety, depression, or insomnia symptoms, and 1.9-2.7% had severe symptoms. The prevalence of psychological and sleep problems has increased. Working as frontline medical staff (Odds Ratio OR= 3.406), living in Hubei Province (OR= 2.237), close contacts with COVID-19 (OR= 1.808), and age 35-49 years (OR= 1.310) were risk factors for anxiety symptoms; no outside activity for 2 weeks (OR= 2.167) and age 35-49 years (OR= 1.198) were risk factors for depression symptoms; and living in Hubei Province (OR= 2.376), no outside activity for 2 weeks (OR= 1.927), and age 35-49 years (OR= 1.262) were risk factors for insomnia symptoms. Only 1.9% of participants received counseling during the epidemic. Conclusions. Psychological and sleep problems increased during interpersonal isolation due to COVID-19. Current psychological interventions are far from sufficient. [ABSTRACT FROM AUTHOR]

The mature larva and pupa of the Australian silvanid species, Macrohyliota militaris (Erichson) are described from laboratory reared material. This is the first description of immature stages of Silvanidae from Australia. The larva of M. militaris conforms to the general body shape and apparent morphological features of known Brontini and is very similar to the Asian M. sculptus Yoshida & Hirowatari. Larval and pupal features of M. militaris are compared with other known larvae and pupae of Brontini described in the literature. [ABSTRACT FROM AUTHOR]

Background: Oral breathing can cause morphological changes in the oral and maxillofacial regions. Aims: To investigate whether oral breathing affected structural changes in bone tissues. Study Design: Animal experimentation. Methods: A total of 48 8-day-old male Sprague--Dawley rats were divided into two groups: a breathing group and a sham (control) group. All Sprague--Dawley rats were killed at 7 weeks after unilateral nostril obstruction modeling. Then, structural changes in bone tissues were detected by micro-computed tomography, and the expression levels of receptor activator of nuclear factor-κB, osteoprotegerin, and receptor activator of nuclear factor-κB ligand in the signal pathway of bone metabolism within the local alveolar bone and serum of rats were detected by reverse transcription-quantitative polymerase chain reaction and Western blotting. Results: The results showed that receptor activator of nuclear factor-κB ligand and receptor activator of nuclear factor-κB levels in bone tissues and serum in the oral breathing group were higher than those in the control group [Maxillary alveolar bone: receptor activator of nuclear factor-κB ligand (pRNA=0.009, pprotein=0.008), receptor activator of nuclear factor-κB (pRNA=0.008, pprotein=0.009); Mandibular alveolar bone: receptor activator of nuclear factor-κB ligand (pRNA=0.047, pprotein=0.042), receptor activator of nuclear factor-κB (pRNA=0.041, pprotein=0.007); Serum: receptor activator of nuclear factor-κB ligand (pRNA<0.001, pprotein<0.001), receptor activator of nuclear factor-κB (pRNA<0.001, pprotein<0.001)], along with decreased osteoprotegerin expression (Maxillary alveolar bone: pRNA=0.038, pprotein=0.048; Mandibular alveolar bone: pRNA<0.001, pprotein<0.001; Serum: pRNA=0.009, pprotein=0.006) and elevated receptor activator of nuclear factor- κB ligand/osteoprotegerin. Micro-computed tomography analysis indicated a significant difference in the level of bone volume fraction, as well as trabecular thickness in maxillary alveolar bone between the experimental and control groups (p=0.049, p=0.047). Meanwhile, trabecular thickness, and cortical thickness levels in mandibular alveolar bone also differed significantly between the experimental and control groups (p=0.043, p=0.024). Conclusion: Structural changes of the respiratory system affect the alveolar bone structure and unilateral nasal obstruction may lead to a change in regional specific bone density. [ABSTRACT FROM AUTHOR]

Long non-coding RNA (lncRNA) plays a key regulatory role in the pathogenesis of colorectal cancer (CRC). In the present study, the specific regulatory role of lncRNA ezrin antisense RNA 1 (EZR-AS1) on CRC was investigated. The expression of lncRNA EZR-AS1 was significantly up-regulated in CRC cell lines (HCT8, HCT116, HT29, and SW620 cells), which was significantly different from that of normal human fetal colonic mucosa cells (FHC cells) (P<0.01). HCT116 and HT29 cells were then transfected with EZR-AS1 shRNA (sh-EZR-AS1) to silence lncRNA EZR-AS1 (P<0.01). When compared with the Control, after transfection of SH-EZR-AS1, E-cadherin was up-regulated, Vimentin was down-regulated, the apoptosis rate was increased, the cell viability, wound healing rate, and the number of invasive cells were decreased in HCT116 and HT29 cells (P<0.05). Silencing of lncRNA EZR-AS also significantly reduced the tumor volume and weight in mice injected with sh-EZR-AS1-transfected HCT116 and HT29 cells (P<0.05). The regulatory relationship between lncRNA EZR-AS1 and transforming growth factor β (TGF-β) signaling was further identified in CRC cells. Silencing of lncRNA EZR-AS1 significantly down-regulated TGF-β, Smad2, and a-SMA expression in HCT116 and HT29 cells at the protein level (P<0.05). The intervention of SB431542 (a TGF-β receptor blocker) and silencing of Smad2 both significantly down-regulated lncRNA EZR-AS1 expression in HCT116 and HT29 cells (P<0.01). In conclusion, silencing of lncRNA EZR-AS1 inhibited the proliferation, invasion, migration, and epithelial-mesenchymal transition, and promoted the apoptosis of CRC cells through blocking TGF-β signaling. [ABSTRACT FROM AUTHOR]

Obesity is associated with enhanced colonic inflammation, which is a major risk factor for colorectal cancer. Considering the obesity epidemic in Western countries, it is important to identify novel therapeutic targets for obesity-induced colonic inflammation, to develop targeted strategies for prevention. Eicosanoids are endogenous lipid signaling molecules involved in regulating inflammation and immune responses. Using an LC-MS/MS-based lipidomics approach, we find that obesity-induced colonic inflammation is associated with increased expression of soluble epoxide hydrolase (sEH) and its eicosanoid metabolites, termed fatty acid diols, in colon tissue. Furthermore, we find that pharmacological inhibition or genetic ablation of sEH reduces colonic concentrations of fatty acid diols, attenuates obesity-induced colonic inflammation, and decreases obesity-induced activation ofWnt signaling in mice. Together, these results support that sEH could be a novel therapeutic target for obesity-induced colonic inflammation and associated diseases. [ABSTRACT FROM AUTHOR]

An efficient and transition-metal-free protocol for the synthesis of (Z)-N-arylnitrones from the direct coupling of N-nosylhydrazones with nitrosoarenes under mild conditions is described. The protocol is compatible with a wide range of functional groups placed on both the reagents and provided the corresponding nitrones in good to excellent yields by simple recrystallization process. The use of these 1,3-dipoles for the synthesis of substituted indoles is elaborated for 2,3-diphenyl- 1H-indole. [ABSTRACT FROM AUTHOR]