A crazy trio in Parkinson's disease: metabolism alteration, α-synuclein aggregation, and oxidative stress.

Parkinson's disease (PD) is an aging-associated neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein within these neurons. Oligomeric α-synuclein exerts neurotoxic effects through mitochondrial dysfunction, glial cell inflammatory response, lysosomal dysfunction and so on. α-synuclein aggregation, often accompanied by oxidative stress, is generally considered to be a key factor in PD pathology. At present, emerging evidences suggest that metabolism alteration is closely associated with α-synuclein aggregation and PD progression, and improvement of key molecules in metabolism might be potentially beneficial in PD treatment. In this review, we highlight the tripartite relationship among metabolic changes, α-synuclein aggregation, and oxidative stress in PD, and offer updated insights into the treatments of PD, aiming to deepen our understanding of PD pathogenesis and explore new therapeutic strategies for the disease.

Differential expression of circular RNAs in human umbilical cord mesenchymal stem cells treated with icariin.

Human umbilical cord mesenchymal stem cells (hUMSCs) belong to a multipotent stem cell population. Transplantation of icariin (ICA)-treated hUMSCs have better tissue repairing function in chronic liver injury. This study was to investigate whether the tissue-repairing effects and migration of hUMSCs after ICA treatment were regulated by circular RNAs (circRNAs). ICA was used to treat hUMSCs in vitro for 1 week and the expression profiles of circRNAs were generated using RNA sequencing. Differentially expressed circRNAs in hUMSCs after ICA intervention were screened. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were carried out to predict the potential function of dysregulated circRNAs. There were 52 differentially expressed circRNAs (32 circRNAs up-regulated and 20 circRNAs down-regulated) with fold change ≥2.0 before and after ICA treatment. ADP-ribosylation factors were associated with the dysregulated circRNAs among Gene Ontology analysis. Kyoto Encyclopedia of Genes and Genomes analysis showed that only endocytosis pathway was associated with up-regulated circRNAs, whereas 4 pathways including homologous recombination, RNA transport, axon guidance, and proteoglycans in cancer were related to down-regulated circRNAs. Fifty-two differentially expressed circRNAs and 238 predicted microRNAs were included in circRNAs-microRNAs network. The mechanism of ICA inducing hUMSCs migration may be through regulating circRNAs expression which affects ADP-ribosylation factors protein signal pathways.

Interplay of CD36, autophagy, and lipid metabolism: insights into cancer progression.

CD36, a scavenger receptor B2 that is dynamically distributed between cell membranes and organelle membranes, plays a crucial role in regulating lipid metabolism. Abnormal CD36 activity has been linked to a range of metabolic disorders, such as obesity, nonalcoholic fatty liver disease, insulin resistance and cardiovascular disease. CD36 undergoes various modifications, including palmitoylation, glycosylation, and ubiquitination, which greatly affect its binding affinity to various ligands, thereby triggering and influencing various biological effects. In the context of tumors, CD36 interacts with autophagy to jointly regulate tumorigenesis, mainly by influencing the tumor microenvironment. The central role of CD36 in cellular lipid homeostasis and recent molecular insights into CD36 in tumor development indicate the applicability of CD36 as a therapeutic target for cancer treatment. Here, we discuss the diverse posttranslational modifications of CD36 and their respective roles in lipid metabolism. Additionally, we delve into recent research findings on CD36 in tumors, outlining ongoing drug development efforts targeting CD36 and potential strategies for future development and highlighting the interplay between CD36 and autophagy in the context of cancer. Our aim is to provide a comprehensive understanding of the function of CD36 in both physiological and pathological processes, facilitating a more in-depth analysis of cancer progression and a better development and application of CD36-targeting drugs for tumor therapy in the near future.

A self-locking mechanism of the frog-legged beetle Sagra femorata.

Insect legs play a crucial role in various modes of locomotion, including walking, jumping, swimming, and other forms of movement. The flexibility of their leg joints is critical in enabling various modes of locomotion. The frog-legged leaf beetle Sagra femorata possesses remarkably enlarged hind legs, which are considered to be a critical adaptation that enables the species to withstand external pressures. When confronted with external threats, S. femorata initiates a stress response by rapidly rotating its hind legs backward and upward to a specific angle, thereby potentially intimidating potential assailants. Based on video analysis, we identified 4 distinct phases of the hind leg rotation process in S. femorata, which were determined by the range of rotation angles (0°-168.77°). Utilizing micro-computed tomography (micro-CT) technology, we performed a 3-dimensional (3D) reconstruction and conducted relative positioning and volumetric analysis of the metacoxa and metatrochanter of S. femorata. Our analysis revealed that the metacoxa-trochanter joint is a "screw-nut" structure connected by 4 muscles, which regulate the rotation of the legs. Further testing using a 3D-printed model of the metacoxa-trochanter joint demonstrated its possession of a self-locking mechanism capable of securing the legs in specific positions to prevent excessive rotation and dislocation. It can be envisioned that this self-locking mechanism holds potential for application in bio-inspired robotics.

Assaying Effector Cell-to-Cell Mobility in Plant Tissues Identifies Hypermobility and Indirect Manipulation of Plasmodesmata.

In plants, plasmodesmata establish cytoplasmic continuity between cells to allow for communication and resource exchange across the cell wall. While plant pathogens use plasmodesmata as a pathway for both molecular and physical invasion, the benefits of molecular invasion (cell-to-cell movement of pathogen effectors) are poorly understood. To establish a methodology for identification and characterization of the cell-to-cell mobility of effectors, we performed a quantitative live imaging-based screen of candidate effectors of the fungal pathogen Colletotrichum higginsianum. We predicted C. higginsianum effectors by their expression profiles, the presence of a secretion signal, and their predicted and in planta localization when fused to green fluorescent protein. We assayed for cell-to-cell mobility of nucleocytosolic effectors and identified 14 that are cell-to-cell mobile. We identified that three of these effectors are "hypermobile," showing cell-to-cell mobility greater than expected for a protein of that size. To explore the mechanism of hypermobility, we chose two hypermobile effectors and measured their impact on plasmodesmata function and found that even though they show no direct association with plasmodesmata, each increases the transport capacity of plasmodesmata. Thus, our methods for quantitative analysis of cell-to-cell mobility of candidate microbe-derived effectors, or any suite of host proteins, can identify cell-to-cell hypermobility and offer greater understanding of how proteins affect plasmodesmal function and intercellular connectivity. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Cumulative remnant cholesterol as a causal risk factor for ischemic heart disease: A prospective cohort study.

BACKGROUND: While previous studies have established a significant correlation between baseline remnant cholesterol (RC) and ischemic heart disease (IHD), the enduring impact of RC on incident IHD remains to be elucidated. This study aimed to investigate the association between cumulative remnant cholesterol(cumRC) and IHD susceptibility. METHODS: Participating from the Kailuan Study (2006-2010) were enrolled, excluding those with prior myocardial infarction, coronary artery revascularization and cancer across three consecutive examinations. The cumRC derived by multiplying the average RC with the interval between the two consecutive assessments. Participants were segmented into quartiles based on cumRC levels: Q1 (cumRC < 2.69 mmol/l); Q2 (2.69 ≤ cumRC < 4.04 mmol/l); Q3(4.04 ≤ cumRC < 5.65 mmol/l) and Q4 (cumRC ≥ 5.65 mmol/l). The correlation between cumRC and IHD risk was ascertained by using multivariable Cox proportional hazard models. RESULT: The analysis encompassed 42,639 participants. Over an average tracking period of 9.97 years, 1,205 instances of IHD were identified. IHD susceptibility augmented with rising cumRC quartiles. After adjusting for potential confounders, the hazard ratios for IHD events were 1.06 (0.88-1.29) for Q2, 1.30 (1.08-1.56) for Q3 and 1.69 (1.42-2.01) for Q4, relative to Q1. Elevated cumRC was significantly associated with a heightened IHD risk, a trend consistent in both subgroup and sensitivity analyses. CONCLUSION: Elevated cumRC significantly correlates with a higher risk of IHD, suggesting that consistent monitoring and regulation of RC might be instrumental in IHD prevention.

The Morphological Transformation of the Thorax during the Eclosion of Drosophila melanogaster (Diptera: Drosophilidae).

The model organism Drosophila melanogaster, as a species of Holometabola, undergoes a series of transformations during metamorphosis. To deeply understand its development, it is crucial to study its anatomy during the key developmental stages. We describe the anatomical systems of the thorax, including the endoskeleton, musculature, nervous ganglion, and digestive system, from the late pupal stage to the adult stage, based on micro-CT and 3D visualizations. The development of the endoskeleton causes original and insertional changes in muscles. Several muscles change their shape during development in a non-uniform manner with respect to both absolute and relative size; some become longer and broader, while others shorten and become narrower. Muscular shape may vary during development. The number of muscular bundles also increases or decreases. Growing muscles are probably anchored by the tissues in the stroma. Some muscles and tendons are absent in the adult stage, possibly due to the hardened sclerites. Nearly all flight muscles are present by the third day of the pupal stage, which may be due to the presence of more myofibers with enough mitochondria to support flight power. There are sexual differences in the same developmental period. In contrast to the endodermal digestive system, the functions of most thoracic muscles change in the development from the larva to the adult in order to support more complex locomotion under the control of a more structured ventral nerve cord based on the serial homology proposed herein.

Reciprocal Interactions of Abiotic and Biotic Dechlorination of Chloroethenes in Soil.

Chloroethenes (CEs) as common organic pollutants in soil could be attenuated via abiotic and biotic dechlorination. Nonetheless, information on the key catalyzing matter and their reciprocal interactions remains scarce. In this study, FeS was identified as a major catalyzing matter in soil for the abiotic dechlorination of CEs, and acetylene could be employed as an indicator of the FeS-mediated abiotic CE-dechlorination. Organohalide-respiring bacteria (OHRB)-mediated dechlorination enhanced abiotic CEs-to-acetylene potential by providing dichloroethenes (DCEs) and trichloroethene (TCE) since chlorination extent determined CEs-to-acetylene potential with an order of trans-DCE > cis-DCE > TCE > tetrachloroethene/PCE. In contrast, FeS was shown to inhibit OHRB-mediated dechlorination, inhibition of which could be alleviated by the addition of soil humic substances. Moreover, sulfate-reducing bacteria and fermenting microorganisms affected FeS-mediated abiotic dechlorination by re-generation of FeS and providing short chain fatty acids, respectively. A new scenario was proposed to elucidate major abiotic and biotic processes and their reciprocal interactions in determining the fate of CEs in soil. Our results may guide the sustainable management of CE-contaminated sites by providing insights into interactions of the abiotic and biotic dechlorination in soil.

The morphology and spectral characteristics of the compound eye of Agasicleshygrophila (Selman & Vogt, 1971) (Coleoptera, Chrysomelidae, Galerucinae, Alticini).

The first exploratory study was conducted on the compound eye morphology and spectral characteristics of Agasicleshygrophila (Selman & Vogt, 1971) to clarify its eye structure and its spectral sensitivity. Scanning electron microscopy, paraffin sectioning, and transmission electron microscopy revealed that A.hygrophila has apposition compound eyes with both eucones and open rhabdom. The micro-computed tomography (CT) results after 3D reconstruction demonstrated the precise position of the compound eyes in the insect's head and suggested that the visual range was mainly concentrated in the front and on both sides of the head. The electroretinogram (ERG) experiment showed that red, yellow, green, blue, and ultraviolet light could stimulate the compound eyes of A.hygrophila to produce electrical signals. The behavioural experiment results showed that both males and females had the strongest phototaxis to yellow light and positive phototaxis to red, green, and blue light but negative phototaxis to UV light. This study of the compound eyes of A.hygrophila will be helpful for decoding its visual mechanism in future studies.

Prevalence and Risk Factors Underlying Occupational Stress and Depression Among Clinical Nurses in Secondary and Tertiary Hospitals of China During COVID-19 Setting.

Aim: This study was designed to develop an effective measurement tool for occupational stress among medical staff and to identify the underlying risk factors among clinical nurses in China under depression during and after COVID-19. Methods: In the first stage, an occupational stress scale was developed for medical staff based on qualitative and quantitative methods. The dimensions of the scale were based on childhood stress and seven other parameters of working stress. In the second stage, a provincial survey was conducted among clinical nurses in Hainan. The structure of Medical Staff Occupational Stress Scale was tested in secondary and tertiary hospitals. The socio-demographic information, occupational stress (measured using the developed scale), and current depression symptoms (assessed with the nine-item Patient Health Questionnaire) were evaluated. The risk factors for occupational stress-induced depression were tested using multivariate logistic regression. Results: The Medical Staff Occupational Stress Scale consisted of 42 items under eight dimensions with strong reliability and validity. Almost 80% of the clinical nurses reported obvious symptoms of depression. Based on multivariate logistical regression analysis, the significant risk factors for depression in nurses at secondary hospitals and tertiary hospitals were childhood stress, teaching stress, relationship with patient stress, and administration stress. Conclusion: The Medical Staff Occupational Stress Scale utilized in nursing population is based on strong psychometric features. Childhood stress contributes to occupational stress in nurses. The selection of nurses for clinical work may require evaluation of past history for childhood stress to prevent occupational depression. Teaching stress, relationship with patient stress and administration stress play significant roles in the prevention of depression among clinical nurses.

Detection of Hindwing Landmarks Using Transfer Learning and High-Resolution Networks.

Hindwing venation is one of the most important morphological features for the functional and evolutionary analysis of beetles, as it is one of the key features used for the analysis of beetle flight performance and the design of beetle-like flapping wing micro aerial vehicles. However, manual landmark annotation for hindwing morphological analysis is a time-consuming process hindering the development of wing morphology research. In this paper, we present a novel approach for the detection of landmarks on the hindwings of leaf beetles (Coleoptera, Chrysomelidae) using a limited number of samples. The proposed method entails the transfer of a pre-existing model, trained on a large natural image dataset, to the specific domain of leaf beetle hindwings. This is achieved by using a deep high-resolution network as the backbone. The low-stage network parameters are frozen, while the high-stage parameters are re-trained to construct a leaf beetle hindwing landmark detection model. A leaf beetle hindwing landmark dataset was constructed, and the network was trained on varying numbers of randomly selected hindwing samples. The results demonstrate that the average detection normalized mean error for specific landmarks of leaf beetle hindwings (100 samples) remains below 0.02 and only reached 0.045 when using a mere three samples for training. Comparative analyses reveal that the proposed approach out-performs a prevalently used method (i.e., a deep residual network). This study showcases the practicability of employing natural images-specifically, those in ImageNet-for the purpose of pre-training leaf beetle hindwing landmark detection models in particular, providing a promising approach for insect wing venation digitization.

A bioinspired silica nanocomposite for enhanced multidrug-resistant bacteria treatment and wash-free imaging.

Bacterial infections have posed significant threats to public health due to the emergence of antibiotic resistance. In this work, a novel antibacterial composite nanomaterial based on spiky mesoporous silica spheres loaded with poly(ionic liquid)s and aggregation-induced emission luminogens (AIEgens) was designed for efficient multidrug-resistant (MDR) bacteria treatment and imaging. The nanocomposite exhibited excellent and long-term antibacterial activity towards both Gram-negative and Gram-positive bacteria. Meanwhile, fluorescent AIEgens facilitate real-time bacterial imaging. Our study provides a multifunctional platform and a promising alternative to antibiotics for combating pathogenic MDR bacteria.

Xylan glucuronic acid side chains fix suberin-like aliphatic compounds to wood cell walls.

Wood is the most important repository of assimilated carbon in the biosphere, in the form of large polymers (cellulose, hemicelluloses including glucuronoxylan, and lignin) that interactively form a composite, together with soluble extractives including phenolic and aliphatic compounds. Molecular interactions among these compounds are not fully understood. We have targeted the expression of a fungal α-glucuronidase to the wood cell wall of aspen (Populus tremula L. × tremuloides Michx.) and Arabidopsis (Arabidopsis thaliana (L.) Heynh), to decrease contents of the 4-O-methyl glucuronopyranose acid (mGlcA) substituent of xylan, to elucidate mGlcA's functions. The enzyme affected the content of aliphatic insoluble cell wall components having composition similar to suberin, which required mGlcA for binding to cell walls. Such suberin-like compounds have been previously identified in decayed wood, but here, we show their presence in healthy wood of both hardwood and softwood species. By contrast, γ-ester bonds between mGlcA and lignin were insensitive to cell wall-localized α-glucuronidase, supporting the intracellular formation of these bonds. These findings challenge the current view of the wood cell wall composition and reveal a novel function of mGlcA substituent of xylan in fastening of suberin-like compounds to cell wall. They also suggest an intracellular initiation of lignin-carbohydrate complex assembly.

Association Between Arterial Stiffness and New-Onset Heart Failure: The Kailuan Study.

BACKGROUND: Arterial stiffness (AS) was associated with heart failure (HF) in previous studies based on specific populations with small samples and the effects of age and blood pressure on AS were not taken into account. Whether AS was independently associated with new-onset HF in community dwellers has not been fully investigated to date. METHODS: Individuals who participated in health evaluations and underwent synchronized brachial-ankle pulse wave velocity (baPWV) screening in 2010 to 2019 were included. They were free of HF and atrial fibrillation at baseline. The participants were allocated to 3 groups according to their baPWV values. Normal AS was defined as baPWV <1400 cm/s, borderline AS was defined as 1400≤baPWV<1800 cm/s, and elevated AS was defined as baPWV ≥1800 cm/s. Cox proportional hazard regression was used to calculate hazard ratios with 95% CIs of new-onset HF across different AS groups. RESULTS: A total of 40 064 participants were enrolled with a mean age of 48.81±12.67 years. During a mean 5.53 years of follow-up, 411 participants developed HF. Compared with the normal AS group, the hazard ratio (95% CI) for incident HF was 1.97 (1.36-2.86) for the borderline AS group and 2.24 (1.49-3.38) for the elevated AS group in the multivariable-adjusted model. For each 1 SD (359 cm/s) increase in baPWV, the hazard ratio (95% CI) for new-onset HF was 1.10 (1.02-1.20). CONCLUSIONS: AS was positively associated with a higher risk of new-onset HF independently of traditional risk factors, with a dose-responsive effect.

The right microbe-associated molecular patterns for effective recognition by plants.

Plants are constantly exposed to diverse microbes and thus develop a sophisticated perceive system to distinguish non-self from self and identify non-self as friends or foes. Plants can detect microbes in apoplast via recognition of microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs) on the cell surface to activate appropriate signaling in response to microbes. MAMPs are highly conserved but essential molecules of microbes and often buried in microbes' complex structure. Mature MAMPs are released from microbes by invasion-induced hydrolytic enzymes in apoplast and accumulate in proximity of plasma membrane-localized PRRs to be perceived as ligands to activate downstream signaling. In response, microbes developed strategies to counteract these processing. Here, we review how the form, the concentration, and the size of mature MAMPs affect the PRR-mediated immune signaling. In particular, we describe some potential applications and explore potential open questions in the fields.

Down-regulation of EVA1A by miR-103a-3p promotes hepatocellular carcinoma cells proliferation and migration.

BACKGROUND: EVA1A (Eva-1 homolog A), a novel protein involved in autophagy and apoptosis, functions as a tumor suppressor in some human primary cancers, including hepatocellular carcinoma (HCC). While it is consistently downregulated in several cancers, its involvement in hepatocarcinogenesis is still largely unknown. METHODS: We first detected the expression of EVA1A in HCC tissues and cell lines using RT‒qPCR, immunohistochemistry and western blotting and detected the expression of miR-103a-3p by RT‒qPCR. Then, bioinformatics prediction, dual-luciferase reporter gene assays and western blotting were used to screen and identify the upstream microRNA of EVA1A. After manipulating the expression of miR-103a-3p or EVA1A, wound healing, invasion, proliferation, colony formation, apoptosis, autophagy, mitosis and mitochondrial function assays, including mitochondrial membrane potential, ROS and ATP production assays, were performed to investigate the functions of miR-103a-3p targeting EVA1A in HCC cells. Apoptosis-related proteins were assessed by RT‒qPCR (TP53) or western blotting (TP53, BAX, Bcl-2 and caspase-3). Autophagy level was evaluated by observing LC3 puncta and examining the protein levels of p62, Beclin1 and LC3-II/I. RESULTS: We found that EVA1A expression was decreased while miR-103a-3p expression was increased in HCC tissues and cell lines and that their expression was inversely correlated in HCC patients. The expression of miR-103a-3p was associated with HCC tumor stage and poor prognosis. miR-103a-3p could target EVA1A through direct binding to its 3'-UTR and suppress its expression. Overexpression of miR-103a-3p significantly downregulated the expression of EVA1A, TP53 and BAX, upregulated the JAK2/STAT3 pathway and promoted HCC cell migration, invasion and proliferation, while repression of miR-103a-3p dramatically upregulated the expression of EVA1A, TP53, BAX and cleaved-caspase-3, inhibited HCC cell migration, invasion and proliferation, and caused mitochondrial dysfunction and apoptosis. Overexpression of EVA1A significantly attenuated the cancer-promoting effects of miR-103a-3p in HCC cells, while knockdown of EVA1A alleviated the mitochondrial dysfunction and apoptosis caused by miR-103a-3p inhibition. Overexpression of EVA1A did not induce significant changes in autophagy levels, nor did it affect G2/M transition or mitosis. CONCLUSION: These findings indicate that the downregulation of the tumor suppressor EVA1A by miR-103a-3p potentially acts as a key mediator in HCC progression, mainly by inhibiting apoptosis and promoting metastasis. The miR-103a/EVA1A/TP53 axis provides a new potential diagnostic and therapeutic target for HCC treatment.

The Degradation of TMEM166 by Autophagy Promotes AMPK Activation to Protect SH-SY5Y Cells Exposed to MPP.

Neuronal oxidative stress caused by mitochondrial dysfunction plays a crucial role in the development of Parkinson's disease (PD). Growing evidence shows that autophagy confers neuroprotection in oxidative-stress-associated PD. This work aims to investigate the involvement of TMEM166, an endoplasmic-reticulum-localized autophagy-regulating protein, in the process of PD-associated oxidative stress through the classic cellular PD model of neuroblastoma SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP+). Reactive oxygen species (ROS) production and mitochondrial membrane potential were checked to assess the oxidative stress induced by MPP+ and the cellular ATP generated was determined to evaluate mitochondrial function. The effect on autophagy induction was evaluated by analyzing p62 and LC3-II/I expression and by observing the LC3 puncta and the colocalization of LC3 with LAMP1/ LAMP2. The colocalization of mitochondria with LC3, the colocalization of Tom20 with LAMP1 and Tom20 expression were analyzed to evaluate mitophagy. We found that TMEM166 is up-regulated in transcript levels, but up-regulated first and then down-regulated by autophagic degradation in protein levels upon MPP+-treatment. Overexpression of TMEM166 induces mitochondria fragmentation and dysfunction and exacerbates MPP+-induced oxidative stress and cell viability reduction. Overexpression of TMEM166 is sufficient to induce autophagy and mitophagy and promotes autophagy and mitophagy under MPP+ treatment, while knockdown of TMEM166 inhibits basal autophagic degradation. In addition, overexpressed TMEM166 suppresses AMPK activation, while TMEM166 knockdown enhances AMPK activation. Pharmacological activation of AMPK alleviates the exacerbation of oxidative stress induced by TMEM166 overexpression and increases cell viability, while pharmacological inhibition mitophagy aggravates the oxidative stress induced by MPP+ treatment combined with TMEM166 overexpression. Finally, we find that overexpressed TMEM166 partially localizes to mitochondria and, simultaneously, the active AMPK in mitochondria is decreased. Collectively, these findings suggest that TMEM166 can translocate from ER to mitochondria and inhibit AMPK activation and, in response to mitochondrial oxidative stress, neuronal cells choose to up-regulate TMEM166 to promote autophagy/mitophagy; then, the enhancing autophagy/mitophagy degrades the TMEM166 to activate AMPK, by the two means to maintain cell survival. The continuous synthesis and degradation of TMEM166 in autophagy/mitochondria flux suggest that TMEM166 may act as an autophagy/mitochondria adaptor.

Combined analysis of whole-exome sequencing and RNA sequencing in type 2 diabetes mellitus patients with thirst and fatigue.

BACKGROUND: The principal objective of this study was to gain a better understanding of the mechanisms of type 2 diabetes mellitus (T2DM) patients with fatigue (D-T2DM) through exome and transcriptome sequencing. METHODS: After whole-exome sequencing on peripheral blood of 6 D-T2DM patients, the consensus mutations were screen out and analyzed by a series of bioinformatics analyses. Then, we combined whole-exome sequencing and transcriptome sequencing results to find the important genes that changed at both the DNA and RNA levels. RESULTS: The results showed that a total of 265,393 mutation sites were found in D-T2DM patients compared with normal individuals, 235 of which were consensus mutations shared with D-T2DM patients. These genes significantly enriched in HIF-1 signaling pathway and sphingolipid signaling pathway. At the RNA level, a total of 375 genes were identified to be differentially expressed. After the DNA-RNA joint analysis, eight genes were screened that changed at both DNA and RNA levels. Among these genes, FUS and LMNA were related to carbohydrate metabolism, energy metabolism, and mitochondrial function. Subsequently, we predicted the herbs, including Qin Pi and Hei Zhi Ma, that might play a therapeutic role in D-T2DM through the SymMap database. CONCLUSION: These findings have significant implications for understanding the mechanisms of D-T2DM and provide potential targets for D-T2DM diagnosis and treatment.

Effect of Entresto on Clinical Symptoms, Ventricular Remodeling, Rehabilitation, and Hospitalization Rate in Patients with Both Acute Myocardial Infarction and Acute Heart Failure.

Objective: To determine the influence of Entresto on clinical symptoms, ventricular remodeling (VR), and economic stress of patients with both acute myocardial infarction (AMI) and acute heart failure (AHF). Methods: Totally 120 patients with AMI complicated with AHF admitted to our hospital between January 2017 and August 2019 were enrolled and randomly assigned to an observation group (obs group) and a control group (con group) (each n = 60). The obs group was treated with Entresto, while the other with angiotensin-converting enzyme inhibitors (ACEI). After treatment, the efficacy on both groups was evaluated, and their cardiac function-associated indexes (left ventricular end-systolic diameter (LVESd), left ventricular end-diastolic dimension (LVEDd), left ventricular ejection fraction (LVEF), VR-associated indexes (interventricular septal thickness (IVST), and left ventricular mass index (LVMI)) were determined and compared before treatment and after 1 month of treatment. Additionally, their NT-pro-BNP, CRP, and TNF-α were tested and compared before and after treatment, and they were also compared in hospitalization time, treatment expense, readmission rate within one year after discharge, and adverse events. Results: After treatment, the obs group showed notably higher efficacy than the con group (P < 0.05). Before treatment, the two groups were not greatly different in LVESd, LVEDd, LVEF, IVST, LVMI, NT-pro BNP, CRP, and TNF-α (all P > 0.05), while after treatment, these indexes of both groups were improved, but the improvement in the obs group was more notable (P < 0.05). Additionally, the hospitalization time, treatment expense, readmission rate one year after discharge, and incidence of adverse events in the obs group were notably lower (all P < 0.05). Conclusion: For patients with both AMI and AHF, Entresto can contribute to strong amelioration of their clinical symptoms and prognosis and ventricular reverse-remodeling, with a high safety, so it is worthy of clinical promotion.