Janus-graphene: a two-dimensional half-auxetic carbon allotropes with non-chemical Janus configuration

The asymmetric properties of Janus two-dimensional materials commonly depend on chemical effects, such as different atoms, elements, material types, etc. Herein, based on carbon gene recombination strategy, we identify an intrinsic non-chemical Janus configuration in a novel purely sp$^2$ hybridized carbon monolayer, named as Janus-graphene. With the carbon gene of tetragonal, hexagonal, and octagonal rings, the spontaneous unilateral growth of carbon atoms drives the non-chemical Janus configuration in Janus-graphene, which is totally different from the chemical effect in common Janus materials such as MoSSe. A structure-independent half-auxetic behavior is mapped in Janus-graphene that the structure maintains expansion whether stretched or compressed, which lies in the key role of $p_z$ orbital. The unprecedented half-auxeticity in Janus-graphene extends intrinsic auxeticity into pure sp$^2$ hybrid carbon configurations. With the unique half-auxeticity emerged in the non-chemical Janus configuration, Janus-graphene enriches the functional carbon family as a promising candidate for micro/nanoelectronic device applications

Superfolded configuration induced low thermal conductivity in two-dimensional carbon allotropes revealed via machine learning force constant potential

Understanding the fundamental link between structure and functionalization is crucial for the design and optimization of functional materials, since different structural configurations could trigger materials to demonstrate diverse physical, chemical, and electronic properties. However, the correlation between crystal structure and thermal conductivity (\k{appa}) remains enigmatic. In this study, taking two-dimensional (2D) carbon allotropes as study cases, we utilize phonon Boltzmann transport equation (BTE) along with machine learning force constant potential to thoroughly explore the complex folding structure of pure sp2 hybridized carbon materials from the perspective of crystal structure, mode-level phonon resolved thermal transport, and atomic interactions, with the goal of identifying the underlying relationship between 2D geometry and \k{appa}. We propose two potential structure evolution mechanisms for targeted thermal transport properties: in-plane and out-of-plane folding evolutions, which are generally applicable to 2D carbon allotropes. It is revealed that the folded structure produces strong symmetry breaking, and simultaneously produces exceptionally strongly suppressed phonon group velocities, strong phonon-phonon scattering, and weak phonon hydrodynamics, which ultimately lead to low \k{appa}. The insight into the folded effect of atomic structures on thermal transport deepens our understanding of the relationship between structure and functionalization, which offers straightforward guidance for designing novel nanomaterials with targeted \k{appa}, as well as propel developments in materials science and engineering

The Role of Autophagy in Parkinson's Disease: Rotenone-Based Modeling

Background: Autophagy-mediated self-digestion of cytoplasmic inclusions may be protective against neurodegenerative diseases such as Parkinson’s disease (PD). However, excessive autophagic activation evokes autophagic programmed cell death. Methods: In this study, we aimed at exploring the role of autophagy in the pathogenesis of rotenone-induced cellular and animal models for PD. Results: Reactive oxygen species over-generation, mitochondrial membrane potential reduction or apoptosis rate elevation occurred in a dose-dependent fashion in rotenone-treated human neuroblastoma cell line SH-SY5Y. The time- and dose-dependent increases in autophagic marker microtubule-associated protein1 light chain 3 (LC3) expression and decreases in autophagic adaptor protein P62 were observed in this cellular model. LC3-positive autophagic vacuoles were colocalized with alpha-synuclein-overexpressed aggregations. Moreover, the number of autophagic vacuoles was increased in rotenone-based PD models in vitro and in vivo. Conclusions: These data, along with our previous finding showing rotenone-induced toxicity was prevented by the autophagy enhancers and was aggravated by the autophagy inhibitors in SH-SY5Y, suggest that autophagy contributes to the pathogenesis of PD, attenuates the rotenone toxicity and possibly represents a new subcellular target for treating PD

Glucocerebrosidase L444P Mutation Confers Genetic Risk for Parkinson’s Disease in Central China

Background: Mutations of the glucocerebrosidase (GBA) gene have reportedly been associated with Parkinson disease (PD) in various ethnic populations such as Singaporean, Japanese, Formosan, Canadian, American, Portuguese, Greek, Brazilian, British, Italian, Ashkenazi Jewish, southern and southwestern Chinese. The purpose of this study is to determine in central China whether or not the reported GBA mutations remain associated with PD. Methods: In this project, we conducted a controlled study in a cohort of 208 central Chinese PD patients and 298 controls for three known GBA mutations (L444P, N370S and R120W). Results: Our data reveals a significantly higher frequency of L444P mutation in GBA gene of PD cases (3.4%) compared with the controls (0.3%) (P = 0.007, OR = 10.34, 95% CI = 1.26 - 84.71). Specifically, the frequency of L444P mutation was higher in the late onset PD (LOPD) cases compared with that in control subjects. The N370S and R120W mutations were detected in neither the PD group nor the control subjects. Conclusions: Our observations demonstrated that the GBA L444P mutation confers genetic risk for PD, especially LOPD, among the population in the central China area

A systematic bibliometric analysis on the clinical practice of CGM in diabetes mellitus from 2012 to 2022

BackgroundContinuous glucose monitoring (CGM) has revolutionized diabetes management, but a comprehensive analysis of its clinical implementation is lacking. This study aims to explore CGM in diabetes practice over the past decade using bibliometric analysis. It will identify trends, research focal points, and provide a framework for future investigations.Materials and methodsThe Web of Science Core Collection (WOSCC) was utilized to acquire literature pertaining to the employment of continuous glucose monitoring (CGM) in diabetes that was published between the years 2012 and 2022, and to conduct a comprehensive analysis of the associated citation data. To achieve bibliometric visualization and analysis of the collated data, the bibliography package in the Rstudio(v.4.2.2), Citespace 6.2.R4, and VOS viewer were employed.ResultsA total of 3024 eligible publications were extracted from 91 countries, with the United States being the leading country in terms of the number of issued articles. Furthermore, the annual publication rate has shown a gradual increase during the past decade. Among the various journals in this field, DIABETES TECHNOLOGY & THERAPEUTICS was identified as the most highly cited one. Keyword clustering analysis of the extracted publications indicates that the research hotspots in the past decade have primarily focused on “continuous glucose monitoring”, “glycemic variability”, “type 1 diabetes”, “hypoglycemia”, and “glycemic control”. Moreover, the analysis of keyword emergence reveals that “Time In Range” and “Young Adult” represent the current research frontiers for the years 2012-2022.ConclusionThe concept of Time in Range (TIR) has garnered considerable attention as a significant area of inquiry and an emerging research trend in the clinical practice of Continuous Glucose Monitoring (CGM) for Diabetes Mellitus. Moreover, recent investigations have demonstrated a growing focus on young adults with type 1 diabetes as the research population of interest. In the foreseeable future, research endeavors will persist in the pursuit of improving glycemic management among young adults through the utilization of continuous glucose monitoring (CGM) technology, while also delving into the examination of the Time in Range metric via supplementary clinical investigations

E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice

Gene therapy is an attractive approach for hepatocellular carcinoma (HCC) patients. Nevertheless, efficient transgene delivery remains a challenge. In this study, we explored a new targeted system based on human umbilical cord-derived mesenchymal stem cells (HUMSCs), which were engineered to deliver adenovirus to tumor sites, and to replicate and assemble into new adenovirus against HCC. Our results showed that HUMSCs infected by Ad-hTERTp-IL24 followed by LentiR.E1A infection could specifically migrate to HepG2 tumor cells and support adenoviral replication in vitro and in vivo 36 h after LentiR.E1A infection. Ad-hTERTp-IL24 specifically inhibited HepG2 cells growth, and this inhibitory effect was enhanced by low doses of 5-fluorouracil (5-Fu), because the expression levels of coxsackie adenovirus receptor (CAR) and integrin ανβ3 on tumor cells were significantly increased, causing higher viral uptake. Compared with the no treatment groups, Ad-hTERTp-IL24 and LentiR.E1A co-loaded HUMSCs exhibited significant anti-tumor activity in vivo, particularly in combination with low doses of 5-Fu. In summary, this study provides a promising targeted gene therapeutic strategy dependent on the tumor tropism of HUMSCs, to improve the outcome of virotherapy for tumor patients especially those with metastatic diseases

A study of factors influencing long-term glycemic variability in patients with type 2 diabetes: a structural equation modeling approach

AimThe present study aims to utilize structural equation modeling (SEM) to investigate the factors impacting long-term glycemic variability among patients afflicted with type 2 diabetes.MethodThe present investigation is a retrospective cohort study that involved the collection of data on patients with type 2 diabetes mellitus who received care at a hospital located in Chengdu, Sichuan Province, over a period spanning from January 1, 2013, to October 30, 2022. Inclusion criteria required patients to have had at least three laboratory test results available. Pertinent patient-related information encompassing general demographic characteristics and biochemical indicators was gathered. Variability in the dataset was defined by standard deviation (SD) and coefficient of variation (CV), with glycosylated hemoglobin variation also considering variability score (HVS). Linear regression analysis was employed to establish the structural equation models for statistically significant influences on long-term glycemic variability. Structural equation modeling was employed to analyze effects and pathways.ResultsDiabetes outpatient special disease management, uric acid variability, mean triglyceride levels, mean total cholesterol levels, total cholesterol variability, LDL variability, baseline glycated hemoglobin, and recent glycated hemoglobin were identified as significant factors influencing long-term glycemic variability. The overall fit of the structural equation model was found to be satisfactory and it was able to capture the relationship between outpatient special disease management, biochemical indicators, and glycated hemoglobin variability. According to the total effect statistics, baseline glycated hemoglobin and total cholesterol levels exhibited the strongest impact on glycated hemoglobin variability.ConclusionThe factors that have a significant impact on the variation of glycosylated hemoglobin include glycosylated hemoglobin itself, lipids, uric acid, and outpatient special disease management for diabetes. The identification and management of these associated factors can potentially mitigate long-term glycemic variability, thereby delaying the onset of complications and enhancing patients’ quality of life

Tceal7 Regulates Skeletal Muscle Development through Its Interaction with Cdk1

We have previously reported Tceal7 as a muscle-specific gene that represses myoblast proliferation and promotes myogenic differentiation. The regulatory mechanism of Tceal7 gene expression has been well clarified recently. However, the underlying mechanism of Tceal7 function in skeletal muscle development remains to be elucidated. In the present study, we have generated an MCK 6.5 kb-HA-Tceal7 transgenic model. The transgenic mice are born normally, while they have displayed defects in the growth of body weight and skeletal muscle myofiber during postnatal development. Although four RxL motifs have been identified in the Tceal7 protein sequence, we have not detected any direct protein-protein interaction between Tceal7 and Cyclin A2, Cyclin B1, Cylin D1, or Cyclin E1. Further analysis has revealed the interaction between Tceal7 and Cdk1 instead of Cdk2, Cdk4, or Cdk6. Transgenic overexpression of Tceal7 reduces phosphorylation of 4E-BP1 Ser65, p70S6K1 Thr389, and Cdk substrates in skeletal muscle. In summary, these studies have revealed a novel mechanism of Tceal7 in skeletal muscle development