Establishment and validation of a predictive model for peripherally inserted central catheter-related thrombosis in patients with liver cancer.

BACKGROUND: Peripherally inserted central catheters (PICCs) are commonly used in hospitalized patients with liver cancer for the administration of chemotherapy, nutrition, and other medications. However, PICC-related thrombosis is a serious complication that can lead to morbidity and mortality in this patient population. Several risk factors have been identified for the development of PICC-related thrombosis, including cancer type, stage, comorbidities, and catheter characteristics. Understanding these risk factors and developing a predictive model can help healthcare providers identify high-risk patients and implement preventive measures to reduce the incidence of thrombosis. AIM: To analyze the influencing factors of PICC-related thrombosis in hospitalized patients with liver cancer, construct a predictive model, and validate it. METHODS: Clinical data of hospitalized patients with liver cancer admitted from January 2020 to December 2023 were collected. Thirty-five cases of PICC-related thrombosis in hospitalized patients with liver cancer were collected, and 220 patients who underwent PICC placement during the same period but did not develop PICC-related thrombosis were randomly selected as controls. A total of 255 samples were collected and used as the training set, and 77 cases were collected as the validation set in a 7:3 ratio. General patient information, case data, catheterization data, coagulation indicators, and Autar Thrombosis Risk Assessment Scale scores were analyzed. Univariate and multivariate unconditional logistic regression analyses were performed on relevant factors, and the value of combined indicators in predicting PICC-related thrombosis in hospitalized patients with liver cancer was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Univariate analysis showed statistically significant differences (P < 0.05) in age, sex, Karnofsky performance status score (KPS), bedridden time, activities of daily living impairment, parenteral nutrition, catheter duration, distant metastasis, and bone marrow suppression between the thrombosis group and the non-thrombosis group. Other aspects had no statistically significant differences (P > 0.05). Multivariate regression analysis showed that age ≥ 60 years, KPS score ≤ 50 points, parenteral nutrition, stage III to IV, distant metastasis, bone marrow suppression, and activities of daily living impairment were independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer (P < 0.05). Catheter duration of 1-6 months and catheter duration > 6 months were protective factors for PICC-related thrombosis (P < 0.05). The predictive model for PICC-related thrombosis was obtained as follows: P predictive probability = [exp (Logit P)]/[1 + exp (Logit P)], where Logit P = age × 1.907 + KPS score × 2.045 + parenteral nutrition × 9.467 + catheter duration × 0.506 + tumor-node-metastasis (TNM) staging × 2.844 + distant metastasis × 2.065 + bone marrow suppression × 2.082 + activities of daily living impairment × 13.926. ROC curve analysis showed an area under the curve (AUC) of 0.827 (95%CI: 0.724-0.929, P < 0.001), with a corresponding optimal cut-off value of 0.612, sensitivity of 0.755, and specificity of 0.857. Calibration curve analysis showed good consistency between the predicted occurrence of PICC-related thrombosis and actual occurrence (P > 0.05). ROC analysis showed AUCs of 0.888 and 0.729 for the training and validation sets, respectively. CONCLUSION: Age, KPS score, parenteral nutrition, TNM staging, distant metastasis, bone marrow suppression, and activities of daily living impairment are independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer, while catheter duration is a protective factor for the disease. The predictive model has an AUC of 0.827, indicating high predictive accuracy and clinical value.

Accumulated ß-catenin is associated with human atrial fibrosis and atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with increased risk of stroke and mortality. It has been reported that the process of atrial fibrosis was regulated by ß-catenin in rats with AF. However, pathophysiological mechanisms of this process in human with AF remain unclear. This study aims to investigate the possible mechanisms of ß-catenin in participating in the atrial fibrosis using human right atrial appendage (hRAA) tissues . METHODS: We compared the difference of ß-catenin expression in hRAA tissues between the patients with AF and sinus rhythm (SR). The possible function of ß-catenin in the development of AF was also explored in mice and primary cells. RESULTS: Firstly, the space between the membrane of the gap junctions of cardiomyocytes was wider in the AF group. Secondly, the expression of the gap junction function related proteins, Connexin40 and Connexin43, was decreased, while the expression of ß-catenin and its binding partner E-cadherin was increased in hRAA and cardiomyocytes of the AF group. Thirdly, ß-catenin colocalized with E-cadherin on the plasma membrane of cardiomyocytes in the SR group, while they were dissociated and accumulated intracellularly in the AF group. Furthermore, the expression of glycogen synthase kinase 3ß (GSK-3ß) and Adenomatous Polyposis Coli (APC), which participated in the degradation of ß-catenin, was decreased in hRAA tissues and cardiomyocytes of the AF group. Finally, the development of atrial fibrosis and AF were proved to be prevented after inhibiting ß-catenin expression in the AF model mice. CONCLUSIONS: Based on human atrial pathological and molecular analyses, our findings provided evidence that ß-catenin was associated with atrial fibrosis and AF progression.

Learning implementation of a guideline based decision support system to improve hypertension treatment in primary care in China: pragmatic cluster randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of a clinical decision support system (CDSS) in improving the use of guideline accordant antihypertensive treatment in primary care settings in China. DESIGN: Pragmatic, open label, cluster randomised trial. SETTING: 94 primary care practices in four urban regions of China between August 2019 and July 2022: Luoyang (central China), Jining (east China), and Shenzhen (south China, including two regions). PARTICIPANTS: 94 practices were randomised (46 to CDSS, 48 to usual care). 12 137 participants with hypertension who used up to two classes of antihypertensives and had a systolic blood pressure <180 mm Hg and diastolic blood pressure <110 mm Hg were included. INTERVENTIONS: Primary care practices were randomised to use an electronic health record based CDSS, which recommended a specific guideline accordant regimen for initiation, titration, or switching of antihypertensive (the intervention), or to use the same electronic health record without CDSS and provide treatment as usual (control). MAIN OUTCOME MEASURES: The primary outcome was the proportion of hypertension related visits during which an appropriate (guideline accordant) treatment was provided. Secondary outcomes were the average reduction in systolic blood pressure and proportion of participants with controlled blood pressure (<140/90 mm Hg) at the last scheduled follow-up. Safety outcomes were patient reported antihypertensive treatment related events, including syncope, injurious fall, symptomatic hypotension or systolic blood pressure <90 mm Hg, and bradycardia. RESULTS: 5755 participants with 23 113 visits in the intervention group and 6382 participants with 27 868 visits in the control group were included. Mean age was 61 (standard deviation 13) years and 42.5% were women. During a median 11.6 months of follow-up, the proportion of visits at which appropriate treatment was given was higher in the intervention group than in the control group (77.8% (17 975/23 113) v 62.2% (17 328/27 868); absolute difference 15.2 percentage points (95% confidence interval (CI) 10.7 to 19.8); P<0.001; odds ratio 2.17 (95% CI 1.75 to 2.69); P<0.001). Compared with participants in the control group, those in the intervention group had a 1.6 mm Hg (95% CI -2.7 to -0.5) greater reduction in systolic blood pressure (-1.5 mm Hg v 0.3 mm Hg; P=0.006) and a 4.4 percentage point (95% CI -0.7 to 9.5) improvement in blood pressure control rate (69.0% (3415/4952) v 64.6% (3778/5845); P=0.07). Patient reported antihypertensive treatment related adverse effects were rare in both groups. CONCLUSIONS: Use of a CDSS in primary care in China improved the provision of guideline accordant antihypertensive treatment and led to a modest reduction in blood pressure. The CDSS offers a promising approach to delivering better care for hypertension, both safely and efficiently. TRIAL REGISTRATION: ClinicalTrials.gov NCT03636334.

Sensitive detection of H2S based on Ce doped ZnCo2O4 hollow microspheres at low working temperature.

In order to develop a highly efficient H2S gas sensor at low working temperature, in this work, a kind of novel Ce-doped ZnCo2O4 hollow microspheres (Ce/ZnCo2O4 HMSs) were successfully synthesized using a template-free one-pot method, showing a sensitive response toward H2S. The microstructure and morphology of the material were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The gas-sensing performance of the composite was investigated, showing that the ZnCo2O4 doped with 6 mol% Ce had the highest response to 20 ppm H2S at a low operating temperature of 160 °C with a response value of 67.42, which was about 2 times higher than that of original ZnCo2O4. The prepared Ce/ZnCo2O4 HMS sensor in response to H2S exhibited a linear range of 0.1-200 ppm with a low detection limit of 0.1 ppm under the conditions of ambient humidity of 45% and ambient temperature of 20 °C. Meanwhile, it also possessed good selectivity, repeatability and reproducibility. The response value of the sensor decreased by 5.32% after 7 months of continuous monitoring of H2S in an atmospheric environment of a pig farm, indicating that the sensor had a long-term stability and continuous service life with important application prospects.

Spatiotemporal alterations in the brain oscillations of Arctic explorers.

BACKGROUND: The limited understanding of the physiology and psychology of polar expedition explorers has prompted concern over the potential cognitive impairments caused by exposure to extreme environmental conditions. Prior research has demonstrated that such stressors can negatively impact cognitive function, sleep quality, and behavioral outcomes. Nevertheless, the impact of the polar environment on neuronal activity remains largely unknown. METHODS: In this study, we aimed to investigate spatiotemporal alterations in brain oscillations of 13 individuals (age range: 22-48 years) who participated in an Arctic expedition. We utilized electroencephalography (EEG) to record cortical activity before and during the Arctic journey, and employed standardized low resolution brain electromagnetic tomography to localize changes in alpha, beta, theta, and gamma activity. RESULTS: Our results reveal a significant increase in the power of theta oscillations in specific regions of the Arctic, which differed significantly from pre-expedition measurements. Furthermore, microstate analysis demonstrated a significant reduction in the duration of microstates (MS) D and alterations in the local synchrony of the frontoparietal network. CONCLUSION: Overall, these findings provide novel insights into the neural mechanisms underlying adaptation to extreme environments. These findings have implications for understanding the cognitive consequences of polar exploration and may inform strategies to mitigate potential neurological risks associated with such endeavors. Further research is warranted to elucidate the long-term effects of Arctic exposure on brain function.

FGL1: a novel biomarker and target for non-small cell lung cancer, promoting tumor progression and metastasis through KDM4A/STAT3 transcription mechanism.

Non-small cell lung cancer (NSCLC) is characterized by a high incidence rate and poor prognosis worldwide. A deeper insight into the pathogenesis of NSCLC and identification of novel therapeutic targets are essential to improve the prognosis of NSCLC. In this study, we revealed that fibrinogen-like protein 1 (FGL1) promotes proliferation, migration, and invasion of NSCLC cells. Mechanistically, we found that Stat3 acts as a transcription factor and can be recruited to the FGL1 promoter, enhancing FGL1 promoter activity. Lysine-specific demethylase 4A (KDM4A) interacts with Stat3 and facilitates the removal of methyl groups from H3K9me3, thereby enhancing Stat3-mediated transcription of FGL1. Furthermore, we observed that Stat3 and KDM4A promote NSCLC cell proliferation, migration, and invasion partly by upregulating FGL1 expression. Additionally, the expression of FGL1 was significantly higher in cancer tissues (n = 90) than in adjacent non-cancerous tissues (n = 90). Furthermore, patients with high FGL1 expression had a shorter overall survival (OS) compared to those with low FGL1 expression. We measured the expression levels of FGL1 on circulating tumor cells (CTCs) in 65 patients and found that patients with a dynamic decrease in FGL1 expression on CTCs exhibited a better therapeutic response. These findings suggest that the dynamic changes in FGL1 expression can serve as a potential biomarker for predicting treatment efficacy in NSCLC. Overall, this study revealed the significant role and regulatory mechanisms of FGL1 in the development of NSCLC, suggesting its potential as a therapeutic target for patients with NSCLC. Future studies should provide more personalized and effective treatment options for patients with NSCLC to improve clinical outcomes.

A 3-year follow-up analysis of renal function in elderly patients with type 2 diabetes mellitus and an estimated glomerular filtration rate <90 mL/min/1.73m2: A retrospective cohort study.

Type 2 diabetes mellitus (T2DM) is a risk factor for patients with impaired renal function. The onset of T2DM-induced diabetic kidney disease (DKD) is frequently sub-clinical, potentially culminating in end-stage renal disease. In the current study the factors influencing DKD in elderly patients diagnosed with T2DM were determined. A retrospective cohort study was conducted involving patients ≥60 years of age with T2DM from June 2019 to December 2022. The Cockcroft-Gault formula was used to estimate the glomerular filtration rate. The clinical information and biochemical indicators of patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 were collected. Patients were grouped based on a 3-year eGFR decline < 15% and ≥ 15%. The differences between the two groups were compared and the factors influencing the 3-year eGFR decline ≥ 15% were analyzed. A total of 242 patients were included, including 154 in the group with a 3-year eGFR decline < 15% and 88 in the group with a three-year eGFR decline ≥ 15%. Univariate logistic regression analysis showed that smoking cigarettes, and triglycerides (TG) and high-density lipoprotein levels were related to a 3-year eGFR decline ≥ 15% (P = .039, P < .001, and P = .011, respectively). Multivariate logistic regression analysis showed that the TG level was independently related to a 3-year eGFR decline ≥ 15% (P = .004; OR = 2.316). There was a significant linear relationship between the eGFR decline and TG level (P = .002). Patients with a TG concentration > 1.7 mmol/L had a more apparent decrease in the eGFR (P < .05). For elderly patients with T2DM and an eGFR < 90 mL/min/1.73m2, the TG level may be an important risk factor for deteriorating renal function that warrants actively intervention.

Do multisource data matter for NGP prediction? Evidence from the G-LSTM model.

Precisely predicting natural gas prices (NGPs) is important because it can provide the necessary decision-making basis for energy scheduling, planning and control. However, NGPs are affected by many factors and exhibit the characteristics of nonlinearity and randomness, which makes accurate predictions challenging. Therefore, in this paper, the information gain of multisource data and the global optimization ability of the gray wolf algorithm are used to build a multifactor-driven NGP hybrid forecasting model to improve the prediction performance. First, the emotional tendency and readability of news text are extracted and calculated by using VADER and textstat tools, respectively. Then the network search index is filtered and integrated by using the correlation coefficient method and the CRITIC method to form alternative variables of multisource data (news and search index). Second, the gray wolf optimization algorithm is used to find and determine the best key parameter group in long short-term memory model. Finally, the spot price of natural gas in Henry Hub from March 1, 2012 to February 28, 2022 is selected as the prediction object, and multi-scenario numerical experiments are carried out to verify the effectiveness of the proposed model. The ablation experiment results show that the information gain brought by multisource data can effectively improve the prediction effect of NGPs. Furthermore, the proposed model has the best prediction performance in different scenarios and can be regarded as a promising prediction tool.

Antinociceptive role of the thalamic dopamine D3 receptor in descending modulation of intramuscular formalin-induced muscle nociception in a rat model of Parkinson's disease.

Pain in Parkinson's disease (PD) has been validated as one of the major non-motor dysfunctions affecting the quality of life and subsequent rehabilitation. In the present study, we investigated the role of the dopamine D3 receptor in the thalamic mediodorsal (MD) and ventromedial (VM) nuclei mediated descending control of nociception and intramuscular (i.m.) 2.5% formalin-induced persistent muscle nociception. Paw withdrawal reflexes were measured in naive rats and rats subjected to PD induced by unilateral microinjection of 6 µg 6-OHDA into the rat striatum. Formalin-induced muscle nociception in phase 1, inter-phase, and phase 2 was significantly greater in PD rats compared to naive and vehicle-treated rats (P < 0.001). PD rats exhibited bilaterally mechanical hyperalgesia and heat hypoalgesia in formalin-induced muscle nociception. Microinjection of SK609, a dopamine D3 receptor agonist, at various doses (2.5-7.5 nmol/0.5 µl) into the thalamic VM nucleus dose-dependently prolonged heat-evoked paw withdrawal latencies in both naive and PD rats. Administration of SK609 to either the MD or VM nuclei had no effect on noxious mechanically evoked paw withdrawal reflexes. Pre-treatment of the thalamic MD nucleus with SK609 significantly attenuated formalin-induced nociception, and reversed mechanical hyperalgesia, but not heat hypoalgesia. Pre-treatment of the thalamic VM nucleus with SK609 inhibited formalin-induced nociception in the late phase of phase 2 (30-75 min) and heat hypoalgesia, but not mechanical hyperalgesia (P < 0.05). It is suggested that the dopamine D3 receptors in the thalamus play an antinociceptive role in the descending modulation of nociception. Activation of D3 receptors within the thalamic MD and VM nuclei attenuates descending facilitation and enhances descending inhibition in rats during PD.

HDAC1 Promotes Mitochondrial Pathway Apoptosis and Inhibits the Endoplasmic Reticulum Stress Response in High Glucose-Treated Schwann Cells via Decreased U4 Spliceosomal RNA.

Dysfunction of Schwann cells, including cell apoptosis, autophagy inhibition, dedifferentiation, and pyroptosis, is a pivotal pathogenic factor in induced diabetic peripheral neuropathy (DPN). Histone deacetylases (HDACs) are an important family of proteins that epigenetically regulate gene transcription by affecting chromatin dynamics. Here, we explored the effect of HDAC1 on high glucose-cultured Schwann cells. HDAC1 expression was increased in diabetic mice and high glucose-cultured RSC96 cells, accompanied by cell apoptosis. High glucose also increased the mitochondrial pathway apoptosis-related Bax/Bcl-2 and cleaved caspase-9/caspase-9 ratios and decreased endoplasmic reticulum response-related GRP78, CHOP, and ATF4 expression in RSC96 cells (P < 0.05). Furthermore, overexpression of HDAC1 increased the ratios of Bax/Bcl-2, cleaved caspase-9/caspase-9, and cleaved caspase-3 and reduced the levels of GRP78, CHOP, and ATF4 in RSC96 cells (P < 0.05). In contrast, knockdown of HDAC1 inhibited high glucose-promoted mitochondrial pathway apoptosis and suppressed the endoplasmic reticulum response. Moreover, RNA sequencing revealed that U4 spliceosomal RNA was significantly reduced in HDAC1-overexpressing RSC96 cells. Silencing of U4 spliceosomal RNA led to an increase in Bax/Bcl-2 and cleaved caspase-9 and a decrease in CHOP and ATF4. Conversely, overexpression of U4 spliceosomal RNA blocked HDAC1-promoted mitochondrial pathway apoptosis and inhibited the endoplasmic reticulum response. In addition, alternative splicing analysis of HDAC1-overexpressing RSC96 cells showed that significantly differential intron retention (IR) of Rpl21, Cdc34, and Mtmr11 might be dominant downstream targets that mediate U4 deficiency-induced Schwann cell dysfunction. Taken together, these findings indicate that HDAC1 promotes mitochondrial pathway-mediated apoptosis and inhibits the endoplasmic reticulum stress response in high glucose-cultured Schwann cells by decreasing the U4 spliceosomal RNA/IR of Rpl21, Cdc34, and Mtmr11.

Discovery and Manipulation of van der Waals Polarons in Sb2O3 Ultrathin Molecular Crystal.

Manipulating single electrons at the atomic scale is vital for mastering complex surface processes governed by the transfer of individual electrons. Polarons, composed of electrons stabilized by electron-phonon coupling, offer a pivotal medium for such manipulation. Here, using scanning tunneling microscopy and spectroscopy (STM/STS) and density functional theory (DFT) calculations, we report the identification and manipulation of a new type of polaron, dubbed van der Waals (vdW) polaron, within mono- to trilayer ultrathin films composed of Sb2O3 molecules that are bonded via vdW attractions. The Sb2O3 films were grown on a graphene-covered SiC(0001) substrate via molecular beam epitaxy. Unlike prior molecular polarons, STM imaging observed polarons at the interstitial sites of the molecular film, presenting unique electronic states and localized band bending. DFT calculations revealed the lowest conduction band as an intermolecular bonding state, capable of ensnaring an extra electron through locally diminished intermolecular distances, thereby forming an intermolecular vdW polaron. We also demonstrated the ability to generate, move, and erase such vdW polarons using an STM tip. Our work uncovers a new type of polaron stabilized by coupling with intermolecular vibrations where vdW interactions dominate, paving the way for designing atomic-scale electron transfer processes and enabling precise tailoring of electron-related properties and functionalities.

Multiplexed representation of others in the hippocampal CA1 subfield of female mice.

Hippocampal place cells represent the position of a rodent within an environment. In addition, recent experiments show that the CA1 subfield of a passive observer also represents the position of a conspecific performing a spatial task. However, whether this representation is allocentric, egocentric or mixed is less clear. In this study we investigated the representation of others during free behavior and in a task where female mice learned to follow a conspecific for a reward. We found that most cells represent the position of others relative to self-position (social-vector cells) rather than to the environment, with a prevalence of purely egocentric coding modulated by context and mouse identity. Learning of a pursuit task improved the tuning of social-vector cells, but their number remained invariant. Collectively, our results suggest that the hippocampus flexibly codes the position of others in multiple coordinate systems, albeit favoring the self as a reference point.

Cerium oxide /Co-Co Prussian blue analogue composite catalyst for enhanced peroxymonosulfate activation for effective removal of tetracycline hydrochloride from water.

In this paper, a novel CeO2/Co3[Co(CN)6]2 (CeO2/PBACo-Co) composite was prepared with co-precipitation and utilized to activate peroxymonosulfate (PMS) to eliminate tetracycline hydrochloride (TCH). Catalyst screening showed that the composite with a CeO2:PBACo-Co mass ratio of 1:5 (namely, 0.2-CeO2/PBACo-Co) had the best performance. The degradation efficiency of TCH in 0.2-CeO2/PBACo-Co/Oxone system was investigated. The experimental results illustrated that 98% of 50 mg/L TCH and 48.5% of TOC were degraded by 50 mg/L 0.2-CeO2/PBACo-Co and 400 mg/L Oxone within 120 min at 25 °C and initial pH 5.3. Recycling studies showed that the elimination rate of TCH can still achieve 85.8% after five cycles, suggesting that 0.2-CeO2/PBACo-Co composite processes good reusability. Trapping experiments and EPR tests revealed that the reaction system produced multiple active species (1O2, O2•-, SO4•-, and •OH). We proposed the catalytic mechanism of 0.2-CeO2/PBACo-Co for PMS activation, which mainly involves the promoted Co3+/Co2+ cycle by Ce3+ donated electrons. These results indicate that CeO2/PBACo-Co composite is an effective catalyst for wastewater remediation.

Identification of molecular subtypes based on chromatin regulator-related genes and experimental verification of the role of ASCL1 in conferring chemotherapy resistance to breast cancer.

Objective: The aim of this study was to identify the molecular subtypes of breast cancer based on chromatin regulator-related genes. Methods: The RNA sequencing data of The Cancer Genome Atlas-Breast Cancer cohort were obtained from the official website, while the single-cell data were downloaded from the Gene Expression Omnibus database (GSE176078). Validation was performed using the Molecular Taxonomy of Breast Cancer International Consortium dataset. Furthermore, the immune characteristics, tumor stemness, heterogeneity, and clinical characteristics of these molecular subtypes were analyzed. The correlation between chromatin regulators and chemotherapy resistance was examined in vitro using the quantitative real-time polymerase chain reaction (qRT-PCR) and Cell Counting Kit-8 (CCK8) assays. Results: This study identified three stable molecular subtypes with different prognostic and pathological features. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction analyses revealed that the differentially expressed genes were associated with disease processes, such as mitotic nuclear division, chromosome segregation, condensed chromosome, and specific chromosome region. The T stage and subtypes were correlated with the clinical features. Tumor heterogeneity (mutant-allele tumor heterogeneity, tumor mutational burden, purity, and homologous recombination deficiency) and tumor stemness (RNA expression-based stemness score, epigenetically regulated RNA expression-based stemness score, DNA methylation-based stemness score, and epigenetically regulated DNA methylation-based stemness score) significantly varied between the three subtypes. Furthermore, Western blotting, qRT-PCR, and CCK8 assays demonstrated that the expression of ASCL1 was positively correlated with chemotherapy resistance in breast cancer. Conclusion: This study identified the subtypes of breast cancer based on chromatin regulators and analyzed their clinical features, gene mutation status, immunophenotype, and drug sensitivity. The results of this study provide effective strategies for assessing clinical prognosis and developing personalized treatment strategies.

Gold-Catalyzed Reactions of Enynals with Alkenes for Synthesis Binaphthyl Derivatives.

A PPh3Au[B(C6F5)4]-catalyzed reaction of enynals and alkenes for the construction of binaphthyl derivatives was described. This transformation was achieved through o-Quinodimethane (o-QDM) intermediate's extended conjugated addition process. The reaction has the advantages of wide substrate scopes, mild reaction conditions, high efficiency, and good scalability.

Pathological pain: Non-motor manifestations in Parkinson disease and its treatment.

In addition to motor symptoms, non-motor manifestations of Parkinson's disease (PD), i.e. pain, depression, sleep disturbance, and autonomic disorders, have received increasing attention. As one of the non-motor symptoms, pain has a high prevalence and is considered an early pre-motor symptom in the development of PD. In relation to pathological pain and its management in PD, particularly in the early stages, it is hypothesized that the loss of dopaminergic neurons causes a functional deficit in supraspinal structures, leading to an imbalance in endogenous descending modulation. Deficits in dopaminergic-dependent pathways also affect non-dopaminergic neurotransmitter systems that contribute to the pathological processing of nociceptive input, the integration, and modulation of pain in PD. This review examines the onset and progression of pain in PD, with a particular focus on alterations in the central modulation of nociception. The discussion highlights the importance of abnormal endogenous descending facilitation and inhibition in PD pain, which may provide potential clues to a better understanding of the nature of pathological pain and its effective clinical management.

[Neurotrophin-associated mechanisms of delayed-onset muscle soreness: research progress and perspective].

Delayed-onset muscle soreness (DOMS) is a common phenomenon that occurs following a sudden increase in exercise intensity or unfamiliar exercise, significantly affecting athletic performance and efficacy in athletes and fitness individuals. DOMS is characterized by allodynia and hyperalgesia, and their mechanisms remain unclear. Recent studies have reported that neurotrophic factors, such as nerve growth factor (NGF) and glial cell derived neurotrophic factor (GDNF), are involved in the development and maintenance of DOMS. This article provides a review of the research progress on the signaling pathways related to the involvement of NGF and GDNF in DOMS, hoping to provide novel insights into the mechanisms underlying allodynia and hyperalgesia in DOMS, as well as potential targeted treatment.

DNA double-strand break-capturing nuclear envelope tubules drive DNA repair.

Current models suggest that DNA double-strand breaks (DSBs) can move to the nuclear periphery for repair. It is unclear to what extent human DSBs display such repositioning. Here we show that the human nuclear envelope localizes to DSBs in a manner depending on DNA damage response (DDR) kinases and cytoplasmic microtubules acetylated by α-tubulin acetyltransferase-1 (ATAT1). These factors collaborate with the linker of nucleoskeleton and cytoskeleton complex (LINC), nuclear pore complex (NPC) protein NUP153, nuclear lamina and kinesins KIF5B and KIF13B to generate DSB-capturing nuclear envelope tubules (dsbNETs). dsbNETs are partly supported by nuclear actin filaments and the circadian factor PER1 and reversed by kinesin KIFC3. Although dsbNETs promote repair and survival, they are also co-opted during poly(ADP-ribose) polymerase (PARP) inhibition to restrain BRCA1-deficient breast cancer cells and are hyper-induced in cells expressing the aging-linked lamin A mutant progerin. In summary, our results advance understanding of nuclear structure-function relationships, uncover a nuclear-cytoplasmic DDR and identify dsbNETs as critical factors in genome organization and stability.

Pathway Activation Analysis for Pan-Cancer Personalized Characterization Based on Riemannian Manifold.

The pathogenesis of carcinoma is believed to come from the combined effect of polygenic variation, and the initiation and progression of malignant tumors are closely related to the dysregulation of biological pathways. Quantifying the alteration in pathway activation and identifying coordinated patterns of pathway dysfunction are the imperative part of understanding the malignancy process and distinguishing different tumor stages or clinical outcomes of individual patients. In this study, we have conducted in silico pathway activation analysis using Riemannian manifold (RiePath) toward pan-cancer personalized characterization, which is the first attempt to apply the Riemannian manifold theory to measure the extent of pathway dysregulation in individual patient on the tangent space of the Riemannian manifold. RiePath effectively integrates pathway and gene expression information, not only generating a relatively low-dimensional and biologically relevant representation, but also identifying a robust panel of biologically meaningful pathway signatures as biomarkers. The pan-cancer analysis across 16 cancer types reveals the capability of RiePath to evaluate pathway activation accurately and identify clinical outcome-related pathways. We believe that RiePath has the potential to provide new prospects in understanding the molecular mechanisms of complex diseases and may find broader applications in predicting biomarkers for other intricate diseases.