Microstructural and functional substrates underlying dispositional greed and its link with trait but not state impulsivity.

The interplay between personality traits and impulsivity has long been a central theme in psychology and psychiatry. However, the potential association between Greed Personality Traits (GPT) and impulsivity, encompassing both trait and state impulsivity and future time perspective, remains largely unexplored. To address these issues, we employed questionnaires and an inter-temporal choice task to estimate corresponding trait/state impulsivity and collected multi-modal neuroimaging data (resting-state functional imaging: n = 430; diffusion-weighted imaging: n = 426; task-related functional imaging: n = 53) to investigate the underlying microstructural and functional substrates. Behavioral analyses revealed that GPT mediated the association between time perspective (e.g., present fatalism) and trait impulsivity (e.g., motor impulsivity). Functional imaging analyses further identified that brain activation strengths and patterns related to delay length, particularly in the dorsomedial prefrontal cortex, superior parietal lobule, and cerebellum, were associated with GPT. Moreover, individuals with similar levels of greed exhibited analogous spontaneous brain activity patterns, predominantly in the Default Mode Network (DMN), Fronto-Parietal Network (FPN), and Visual Network (VIS). Diffusion imaging analysis observed specific microstructural characteristics in the spinocerebellar/pontocerebellar fasciculus, internal/external capsule, and corona radiata that support the formation of GPT. Furthermore, the corresponding neural activation pattern, spontaneous neural activity pattern, and analogous functional couplings among the aforementioned brain regions mediated the relationships between time perspective and GPT and between GPT and motor impulsivity. These findings provide novel insights into the possible pathway such as time perspective → dispositional greed → impulsivity and uncover their underlying microstructural and functional substrates.

Inner Mitochondrial Membrane Peptidase 2-Like Deletion Aggravates Mitochondrial Apoptosis and Inhibits Autophagy After Hyperglycemia Stroke.

This study investigated the effects of inner mitochondrial membrane peptidase 2-like (Immp2l) deletion on mitochondrial apoptosis and mitochondrial autophagy under hyperglycemic conditions. The middle cerebral artery occlusion (MCAO) model was established in wild-type (WT) mice and Immp2l+/- mice; animals were then exposed to hyperglycemic (induced using 1% streptozotocin) and normoglycemic conditions. Tissues were collected at various time points post-reperfusion. The production of reactive oxygen species (ROS) was assessed by fluorescent measurements, and mitochondrial membrane potential was evaluated using a JC-1 assay kit. Autophagy was analyzed by measuring LC3II/LC3I protein expression and Beclin 1 expression. Mitochondrial ultrastructure was examined through transmission electron microscopy (TEM); neuronal autophagosomes were also assessed. Immp2l mutation in a hyperglycemic environment exacerbated brain injury by increasing ROS production, compromising mitochondrial membrane potential, inducing apoptotic cascades, and impairing mitochondrial autophagy. These findings highlight the critical role of Immp2l in modulating the response to hyperglycemic cerebral ischemia-reperfusion (I/R) injury. Furthermore, the deficiency of Immp2l appears to contribute to increased oxidative stress, mitochondrial dysfunction, and cell death, thereby exacerbating brain injury. These data may provide new insights into therapeutic strategies for reducing the impact of diabetes on stroke outcomes.

The role of polyphenols in modulating mitophagy: Implications for therapeutic interventions.

This review rigorously assesses the burgeoning research into the role of polyphenols in modulating mitophagy, an essential cellular mechanism for the targeted removal of impaired mitochondria. These natural compounds, known for their low toxicity, are underscored for their potential in therapeutic strategies against a diverse array of diseases, such as neurodegenerative, cardiovascular, and musculoskeletal disorders. The analysis penetrates deeply into the molecular mechanisms whereby polyphenols promote mitophagy, particularly by influencing crucial signaling pathways and transcriptional regulators, including the phosphatase and tensin homolog (PTEN) induced putative kinase 1 (PINK1)/parkin and forkhead box O3 (FOXO3a) pathways. Noteworthy discoveries include the neuroprotective properties of resveratrol and curcumin, which affect both autophagic pathways and mitochondrial dynamics, and the pioneering integration of polyphenols with other natural substances to amplify therapeutic effectiveness. Furthermore, the review confronts the issue of polyphenol bioavailability and emphasizes the imperative for clinical trials to corroborate their therapeutic viability. By delivering an exhaustive synthesis of contemporary insights and recent advancements in polyphenol and mitophagy research, this review endeavors to catalyze additional research and foster the creation of innovative therapeutic modalities that exploit the distinctive attributes of polyphenols to manage and prevent disease.

Prioritizing Clinically Significant Lung Cancer Somatic Mutations for Targeted Therapy Through Efficient NGS Data Filtering System.

In the realm of lung cancer treatment, where genetic heterogeneity presents formidable challenges, precision oncology demands an exacting approach to identify and hierarchically sort clinically significant somatic mutations. Current Next-Generation Sequencing (NGS) data filtering pipelines, while utilizing various external databases for mutation screening, often fall short in comprehensive integration and flexibility needed to keep pace with the evolving landscape of clinical data. Our study introduces a sophisticated NGS data filtering system, which not only aggregates but effectively synergizes diverse data sources, encompassing genetic variants, gene functions, clinical evidence, and an extensive body of literature. This system is distinguished by a unique algorithm that facilitates a rigorous, multi-tiered filtration process. This allows for the efficient prioritization of 420 genes and 1,193 variants from large datasets, with a particular focus on 80 variants demonstrating high clinical actionability. These variants have been aligned with FDA approvals, NCCN guidelines, and thoroughly reviewed literature, thereby equipping oncologists with a refined arsenal for targeted therapy decisions. The innovation of our system lies in its dynamic integration framework and its algorithm, tailored to emphasize clinical utility and actionability-a nuanced approach often lacking in existing methodologies. Our validation on real-world lung adenocarcinoma NGS datasets has shown not only an enhanced efficiency in identifying genetic targets but also the potential to streamline clinical workflows, thus propelling the advancement of precision oncology. Planned future enhancements include expanding the range of integrated data types and developing a user-friendly interface, aiming to facilitate easier access to data and promote collaborative efforts in tailoring cancer treatments.

Copper-Catalyzed Visible-Light-Induced Allylic Difluoromethylation of Unactivated Alkenes Using Difluoroacetic Acid.

We herein describe a straightforward allylic difluoromethylation reaction of unactivated alkenes. Compared to cross-couplings of prefunctionalized allylic substrates for the construction of allylic CF2H bonds, this reaction employs readily available alkenes as substrates under mild conditions. Difluoroacetic acid is used as an inexpensive and easy-to-handle source of CF2H radical under visible light irradiation with PIDA. The copper catalyst plays an important role of diverting the reaction pathway toward allylic difluoromethylation as opposed to previously found hydrodifluoromethylation.

Electron transfer dynamics and electrocatalytic oxygen evolution activities of the Co3O4 nanoparticles attached to indium tin oxide by self-assembled monolayers.

The Co3O4 nanoparticle-modified indium tin oxide-coated glass slide (ITO) electrodes are successfully prepared using dicarboxylic acid as the self-assembled monolayer through a surface esterification reaction. The ITO-SAM-Co3O4 (SAM = dicarboxylic acid) are active to electrochemically catalyze oxygen evolution reaction (OER) in acid. The most active assembly, with Co loading at 3.31 × 10-8 mol cm-2, exhibits 374 mV onset overpotential and 497 mV overpotential to reach 1 mA cm-2 OER current in 0.1 M HClO4. The electron transfer rate constant (k) is acquired using Laviron's approach, and the results show that k is not affected by the carbon chain lengths of the SAM (up to 18 -CH2 groups) and that an increase in the average diameter of Co3O4 nanoparticles enhances the k. In addition, shorter carbon chains and smaller Co3O4 nanoparticles can increase the turn-over frequency (TOF) of Co sites toward OER. The Co3O4 nanoparticles tethered to the ITO surface show both a higher number of electrochemically active Co sites and a higher TOF of OER than the Co3O4 nanoparticles bound to ITO using Nafion.

Quality of life and related risk factors after breast reconstruction in breast cancer patients.

BACKGROUND: Breast cancer is the most frequently occurring cancer in women globally, using radical mastectomy as the main clinical treatment. This study aims to investigate the quality of life and related factors in patients after breast reconstruction. METHODS: Female patients undergoing breast reconstruction after radical mastectomy between February 20, 2014 and February 20, 2019 in the Department of Tumor or the Department of Thyroid and Breast Surgery in the Affiliated Hospital of North Sichuan Medical College and Nanchong Central Hospital were surveyed. The patients' basic information was collected using a questionnaire prepared by the research team, and the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire was used to assess the patients' quality of life. Multivariate linear regression analysis was performed to explore the factors impacting the change of FACT-B scores one year after surgery. RESULTS: A total of 150 patients were included. 143 of them had complete data, and 7 patients were lost to follow-up. Compared with the preoperative results, the scores of all dimensions of the FACT-B scale and the overall health status of the patients were significantly reduced at 3 months after surgery, which recovered to the preoperative level at 6 months after surgery (P<0.05), and significantly increased at 12 months after surgery (P<0.05). The results showed that age ≥40 years, menopause, postoperative complications, and endocrine therapy were risk factors for decreased quality of life at 12 months after breast reconstruction. Meanwhile, tumor stage 0 or stage I and immediate breast reconstruction were protective factors for quality of life at 12 months after breast reconstruction (P<0.05). CONCLUSIONS: The postoperative quality of life of patients with breast reconstruction is relatively high. Older age, post-menopause, postoperative complications, endocrine therapy, advanced tumor stage, and delayed reconstruction are all risk factors for decreased quality of life of patients. Targeted measures should be taken to improve the postoperative life quality of patients, such as paying more attention to the older or post-menopausal patients, as well as those with postoperative complications, endocrine therapy, high tumor stage, or delayed breast reconstruction.

Impact of knowledge, attitude, and practice (KAP)-based rehabilitation education on the KAP of patients with intervertebral disc herniation.

BACKGROUND: This study aims to quantify the effectiveness of knowledge, attitude, and practice (KAP)-based rehabilitation education on the KAP of patients with intervertebral disc herniation (IDH). METHODS: Seventy IDH patients undergoing conservative treatment in our center from February 2018 to December 2018 were randomly divided into the KAP group and control group by using a table of random numbers. The control group was given traditional health education, while the KAP group was offered with KAP-based rehabilitation education. Both groups were followed up for 3 months after their discharge from the hospital. A self-designed questionnaire form was used to evaluate the KAP quantities of patients. RESULTS: Before health education, the scores of knowledge in the control group and the KAP group were (15.12±3.12) and (15.20±3.28), respectively, showing no significant difference (P>0.05). After the health education, the total score of knowledge, the score of disease knowledge, the score of attitude, and the score of practice were (25.42±3.16), (7.66±0.73), (7.80±0.36), and (7.85±0.68), respectively, in the KAP group, which were significantly higher than those in the control group [(20.31±3.43), (6.83±0.92), (6.41±1.05), and (7.10±1.11), P<0.05]. After health education, the awareness rates of the disease, attitude, and behavior were significantly higher in the KAP group than in the control group (P<0.05). CONCLUSIONS: Rehabilitation education based on the KAP theory can effectively enhance the patients' awareness of the disease, increase their rehabilitation consciousness, and promote them to adopt positive rehabilitation behavior, thus achieving the goal of changing the patients' KAP.

Design, synthesis and biological Evaluation of Dual acetyl cholinesterase and beta-secretase inhibitors in treatment for alzheimer's Disease.

With the recent research advances in molecular biology and technology multiple credible hypotheses about the progress of Alzheimer's disease (AD) have been proposed, among which the amyloid and cholinergic hypotheses are commonly used to develop reliable therapeutic agents. The multitarget-directed ligand (MTDL) approach was taken in this work to develop muilti-functional agents, which can mainly serve as dual beta-secretase (BACE 1) and Acetylcholinesterase (AChE) inhibitors. Series of new compounds were designed, synthesized and evaluated in this work, from which we identified 2-((4-(1,3-dioxoisoindolin-2-yl)benzyl)amino)-2-oxoethyl-2-(4-methoxyphenyl)acetate (1h) as a new dual cholinesterase and beta-secretase inhibitor without toxicity.

A Tetraazapentacene-Pyrene Belt: Toward Synthesis of N-Doped Zigzag Carbon Nanobelts.

Herein, we report a new design of N-doped zigzag carbon nanobelt, which is a structurally defined fragment of N-doped carbon nanotubes, and studies toward synthesis of it. As its synthetic precursor, a tetraepoxy nanobelt consisting of tetraazapentacene and pyrene subunits is successfully synthesized by taking advantage of a "C"-shaped building block. This tetraazapentacene-pyrene nanobelt is identified with single-crystal X-ray crystallography, and its electronic structure is studied with computational and experimental methods.

Crystal Engineering of Biphenylene-Containing Acenes for High-Mobility Organic Semiconductors.

Herein we report the synthesis, crystal structures, and semiconductor properties of new derivatives of bisnaphtho[2',3':3,4]cyclobut[1,2- b:1',2'- i]anthracene (BNCBA). It is found that the π-π stacking of BNCBA in single crystals can be largely modified by alkyl substituting groups of different lengths. In particular, the tetrahexyl derivative exhibits π-π stacking with an unusual zigzag arrangement. The variation of molecular packing also leads to a change in charge transport characteristics as found from the theoretical calculation of mobility on the basis of single-crystal structures. All of these BNCBA derivatives function as p-type semiconductors in solution-processed thin film transistors, and the tetrahexyl derivative exhibits a field effect mobility as high as 2.9 cm2/(V s).

ClinLabGeneticist: a tool for clinical management of genetic variants from whole exome sequencing in clinical genetic laboratories.

Routine clinical application of whole exome sequencing remains challenging due to difficulties in variant interpretation, large dataset management, and workflow integration. We describe a tool named ClinLabGeneticist to implement a workflow in clinical laboratories for management of variant assessment in genetic testing and disease diagnosis. We established an extensive variant annotation data source for the identification of pathogenic variants. A dashboard was deployed to aid a multi-step, hierarchical review process leading to final clinical decisions on genetic variant assessment. In addition, a central database was built to archive all of the genetic testing data, notes, and comments throughout the review process, variant validation data by Sanger sequencing as well as the final clinical reports for future reference. The entire workflow including data entry, distribution of work assignments, variant evaluation and review, selection of variants for validation, report generation, and communications between various personnel is integrated into a single data management platform. Three case studies are presented to illustrate the utility of ClinLabGeneticist. ClinLabGeneticist is freely available to academia at http://rongchenlab.org/software/clinlabgeneticist .

Butyrylcholinesterase K variant and Alzheimer's disease risk: a meta-analysis.

BACKGROUND: Although many studies have estimated the association between the butyrylcholinesterase (BCHE) K variant and Alzheimer's disease (AD) risk, the results are still controversial. We thus conducted this meta-analysis. MATERIAL/METHODS: We searched NCBI, Medline, Web of Science, and Embase databases to find all eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. RESULTS: We found a significant association between BCHE K variant and AD risk (OR=1.20; 95% CI 1.03-1.39; P=0.02). In the stratified analysis by ethnicity, we observed a significant association between BCHE K variant and AD risk in Asians (OR=1.32; 95% CI 1.02-1.72; P=0.04). However, no significant association between BCHE K variant and AD risk in Caucasians was found (OR=1.14; 95% CI 0.95-1.37; P=0.16). When stratified by the age of AD onset, we found that late-onset AD (LOAD) was significantly associated with BCHE K variant (OR=1.44; 95% CI 1.05-1.97; P=0.02). No significant association between BCHE K variant and early-onset AD (EOAD) risk was observed (OR=1.16; 95% CI 0.89-1.51; P=0.27). Compared with non-APOE ε4 and non-BCHE K carriers, no significant association between BCHE K variant and AD risk was found (OR=1.11; 95% CI 0.91-1.35; P=0.30). However, APOE ε4 carriers showed increased AD risk in both non-BCHE K carriers (OR=2.81; 95% CI 1.75-4.51; P=0.0001) and BCHE K carriers (OR=3.31; 95% CI 1.82-6.02; P=0.0001). CONCLUSIONS: The results of this meta-analysis indicate that BCHE K variant might be associated with AD risk.

Pathway and network approaches for identification of cancer signature markers from omics data.

The advancement of high throughput omic technologies during the past few years has made it possible to perform many complex assays in a much shorter time than the traditional approaches. The rapid accumulation and wide availability of omic data generated by these technologies offer great opportunities to unravel disease mechanisms, but also presents significant challenges to extract knowledge from such massive data and to evaluate the findings. To address these challenges, a number of pathway and network based approaches have been introduced. This review article evaluates these methods and discusses their application in cancer biomarker discovery using hepatocellular carcinoma (HCC) as an example.

Silver(I)-catalyzed ring-contractive rearrangement: a new entry to 5-alkylidene-2-cyclopentenones.

A novel silver(I)-catalyzed ring-contractive rearrangement of 5-substituted 6-diazo-2-cyclohexenones has been developed, providing a new and efficient access to 5-alkylidene-2-cyclopentenones. The AgOTf-catalyzed reaction proceeds through metal-carbenoid formation followed by endocyclic allyl [1,2] migration with excellent stereoselectivity and broad substrate scope.

Differential impact of tumor-infiltrating immune cells on basal and luminal cells: implications for tumor invasion and metastasis.

BACKGROUND/AIM: Regarding the impact of tumor-infiltrating immune cells on tumor cells, many contradictory reports have been published. We have hypothesized that these controversies result from differences in tissue types and tumor stages, in which immune cells are variably distributed and differentially associated with epithelial cells. Our current study compared the pattern and frequency of physical association of tumor-infiltrating immune cells with different parenchymal cells of human breast and prostate tumors harboring normal, hyperplastic, in situ, and invasive components. MATERIALS AND METHODS: The cytological, biological, and molecular alterations were assessed with double immunohistochemistry, double fluorescent labeling, apoptosis assay, and gene expression profiling. RESULTS: Our study detected several previously undescribed features: (i) over 95% of infiltrating immune cells were seen within normal, hyperplastic, or in situ cancer structures with focally-disrupted capsules, and fewer than 5% were found within invasive cancer; (ii) over 95% of normal, hyperplastic, and in situ cancerous epithelial cells were physically shielded from immune cells by the surrounding myoepithelial or basal cell layer; (iii) about 90% of myoepithelial or basal cells physically associated with immune cells and such residual cells within focally disrupted layers exhibited distinct degeneration, including apoptosis, necrosis, and reduced expression of tumor suppressor p63; (iv) epithelial cells overlying focally disrupted tumor capsules surrounded by immune cells had substantially higher proliferation than their adjacent counterparts, and some of the proliferating cells were arranged as tongue-like projections invading the stroma; and (v) microdissected cells overlying focally disrupted tumor capsules had more than 5-fold higher expression of stem cell lineage markers KIT and NCOR2. CONCLUSION: Tumor-infiltrating immune cells are primarily associated with degenerated myoepithelial or basal cells causing focal disruptions of the capsule, which selectively favor proliferation, invasion, and dissemination of the overlying tumor stem cells.

Identification of gene signatures used to recognize biological characteristics of gastric cancer upon gene expression data.

High-throughput gene expression microarrays can be examined by machine-learning algorithms to identify gene signatures that recognize the biological characteristics of specific human diseases, including cancer, with high sensitivity and specificity. A previous study compared 20 gastric cancer (GC) samples against 20 normal tissue (NT) samples and identified 1,519 differentially expressed genes (DEGs). In this study, Classification Information Index (CII), Information Gain Index (IGI), and RELIEF algorithms are used to mine the previously reported gene expression profiling data. In all, 29 of these genes are identified by all three algorithms and are treated as GC candidate biomarkers. Three biomarkers, COL1A2, ATP4B, and HADHSC, are selected and further examined using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) staining in two independent sets of GC and normal adjacent tissue (NAT) samples. Our study shows that COL1A2 and HADHSC are the two best biomarkers from the microarray data, distinguishing all GC from the NT, whereas ATP4B is diagnostically significant in lab tests because of its wider range of fold-changes in expression. Herein, a data-mining model applicable for small sample sizes is presented and discussed. Our result suggested that this mining model may be useful in small sample-size studies to identify putative biomarkers and potential biological features of GC.

Identification of functional modules by integration of multiple data sources using a Bayesian network classifier.

BACKGROUND: Prediction of functional modules is indispensable for detecting protein deregulation in human complex diseases such as cancer. Bayesian network is one of the most commonly used models to integrate heterogeneous data from multiple sources such as protein domain, interactome, functional annotation, genome-wide gene expression, and the literature. METHODS AND RESULTS: In this article, we present a Bayesian network classifier that is customized to (1) increase the ability to integrate diverse information from different sources, (2) effectively predict protein-protein interactions, (3) infer aberrant networks with scale-free and small-world properties, and (4) group molecules into functional modules or pathways based on the primary function and biological features. Application of this model in discovering protein biomarkers of hepatocellular carcinoma leads to the identification of functional modules that provide insights into the mechanism of the development and progression of hepatocellular carcinoma. These functional modules include cell cycle deregulation, increased angiogenesis (eg, vascular endothelial growth factor, blood vessel morphogenesis), oxidative metabolic alterations, and aberrant activation of signaling pathways involved in cellular proliferation, survival, and differentiation. CONCLUSIONS: The discoveries and conclusions derived from our customized Bayesian network classifier are consistent with previously published results. The proposed approach for determining Bayesian network structure facilitates the integration of heterogeneous data from multiple sources to elucidate the mechanisms of complex diseases.

Isolation of stem cells using spheroids from fresh surgical specimen: an analytic mini-review.

It is a commonly held belief that adult stem cells represent the "seeds" for normal cellular replenishment and also for carcinogenesis. The identification and characterization of stem cells for clinical therapeutic applications, however, is extremely challenging for a number of reasons. Recently, our group and others have attempted to isolate stem cells using spheroids from fresh surgical specimens and utilize them for in vitro and in vivo studies. This mini-review summarizes the major technical steps of these methods along with the primary findings. Besides, it critically analyzes the advantages and limitations of the concept and technical approaches. Finally, this mini-review presents our thoughts on the potential future directions of stem cell isolation and cancer stem cell-related research and clinical applications.

Destructive impact of T-lymphocytes, NK and Mast cells on basal cell layers: implications for tumor invasion.

BACKGROUND: Our previous studies have suggested that the primary impact of immune cell infiltration into the normal or pre-invasive tissue component is associated with the physical destruction of epithelial capsules, which may promote tumor progression and invasion. Our current study attempted to further verify our previous observations and determine the primary type(s) of infiltrating immune cells and the possible mechanism associated with physical destructions of the epithelial capsules. METHODS: In total, the study was conducted with 250 primary breast and prostate tumors, the primary immune cell of cytotoxic T-lymphocytes (CTL), Natural killer cells (NK) and Mast cells were analyzed by immunohistochemistry, fluorescent labeling and apoptosis assay. qRT-PCR was used for gene expression analysis. Our current study assessed the physical disruption of these immune cells and potential impact on the epithelial capsule of human breast and prostate tumors. RESULTS: Our study yield several clinically-relevant findings that have not been studied before. (1) A vast majority of these infiltrating immune cells are distributed in the normal-appearing or pre-invasive tissue components rather than in invasive cancer tissues. (2) These cells often form rings or semilunar structures that either surround focally-disrupted basal cell layers or physically attach to the basal cells. (3) Basal cells physically associated with these immune cells generally displayed distinct signs of degeneration, including substantially elevated apoptosis, necrosis, and reduced tumor suppressor p63 expression. In contrast, luminal cells overlying focally disrupted basal cell layers had a substantially increased proliferation rate and elevated expression of stem cell markers compared to their adjacent morphologically similar counterparts that overlie a non-disrupted capsule. CONCLUSION: Our findings suggest that at the early stage of tumor invasion, CTL, NK and Mast cells are the main types of tumor infiltrating immune cells involved in focal degenerative products in the tumor capsules. The primary impact of these infiltrating immune cells is that they are associated with focal disruptions of the tumor capsule, which selectively favor tumor stem cells proliferation and invasion.