Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behaviors in mice.

BACKGROUND: Major depressive disorder (MDD) is a common but severe psychiatric illness characterized by depressive mood and diminished interest. Both nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 1 (NLRP1) inflammasome and autophagy have been reported to implicate in the pathological processes of depression. However, the mechanistic interplay between NLRP1 inflammasome, autophagy, and depression is still poorly known. METHODS: Animal model of depression was established by chronic social defeat stress (CSDS). Depressive-like behaviors were determined by social interaction test (SIT), sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail-suspension test (TST). The protein expression levels of NLRP1 inflammasome complexes, pro-inflammatory cytokines, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K)/PI3K, phosphorylated-AKT (p-AKT)/AKT, phosphorylated-mechanistic target of rapamycin (p-mTOR)/mTOR, brain-derived neurotrophic factor (BDNF), phosphorylated-tyrosine kinase receptor B (p-TrkB)/TrkB, Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl2) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were examined by western blotting. The mRNA expression levels of pro-inflammatory cytokines were tested by quantitative real-time PCR. The interaction between proteins was detected by immunofluorescence and coimmunoprecipitation. Neuronal injury was assessed by Nissl staining. The autophagosomes were visualized by transmission electron microscopy. Nlrp1a knockdown was performed using an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. RESULTS: CSDS exposure caused a bidirectional change in hippocampal autophagy function, which was activated in the initial period but impaired at the later stage. In addition, CSDS exposure increased the expression levels of hippocampal NLRP1 inflammasome complexes, pro-inflammatory cytokines, p-PI3K, p-AKT and p-mTOR in a time-dependent manner. Interestingly, NLRP1 is immunoprecipitated with mTOR but not PI3K/AKT and CSDS exposure facilitated the immunoprecipitation between them. Hippocampal Nlrp1a knockdown inhibited the activity of PI3K/AKT/mTOR signaling, rescued the impaired autophagy and ameliorated depressive-like behavior induced by CSDS. In addition, rapamycin, an autophagy inducer, abolished NLRP1 inflammasome-driven inflammatory reactions, alleviated depressive-like behavior and exerted a neuroprotective effect. CONCLUSIONS: Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behavior in mice and the regulation of autophagy could be a valuable therapeutic strategy for the management of depression.

MXene-Based Pressure Sensor with a Self-Healing Property for Joule Heating and Friction Sliding.

As a kind of flexible electronic device, flexible pressure sensor has attracted wide attention in medical monitoring and human-machine interaction. With the continuous deepening of research, high-sensitivity sensor is developing from single function to multi-function. However, Current multifunctional sensors lack the ability to integrate joule heating, detect sliding friction, and self-healing. Herein, a MXene/polyurethane (PU) flexible pressure sensor with a self-healing property for joule heating and friction sliding is fabricated. The MXene/PU sensitive layer with special spinosum structure is prepared by a simple spraying method. After face-to-face assembly of the sensitive layers, the MXene/PU flexible pressure sensor is obtained and showed excellent sensitivity (150.65 kPa-1), fast response/recovery speed (75.5/63.9 ms), and good stability (10 000 cycles). Based on the self-healing property of PU, the sensor also has the ability to heal after mechanical damage. In addition, the sensor realizes the joule heating function under low voltage, and has the real-time monitoring ability of sliding objects. Combined with low cost and simple manufacturing method, the multi-functional MXene/PU flexible sensor shows a wide range of application potential in human activity monitoring, thermal management, and slip recognition.

Correlation between emotional intelligence and negative emotions of front-line nurses during the COVID-19 epidemic: A cross-sectional study.

AIMS AND OBJECTIVES: The purpose of this study was to understand the emotional intelligence level (EI) and negative emotional status of the front-line nurses in the epidemic situation and to further explore the relationship between them. BACKGROUND: During the COVID-19 epidemic, under the influence of multiple factors, nurses were vulnerable to negative emotions. While previous studies have explored, the role of emotional intelligence in negative emotions, the relationship between the two has not been sufficiently discussed in the context of COVID-19. DESIGN: The study carried out a cross-sectional survey. The STROBE was selected as the checklist in this study. METHODS: 202 nurses from Wuhan makeshift hospital participated in the questionnaire survey. Data collection tools included a general data questionnaire designed by the researchers, Chinese version of EI scale (WLEIS-C) and Chinese version of Depression Anxiety Stress Scale (DASS-21). Descriptive statistics, single factor analysis and correlation analysis were used to analyse the data. RESULTS: The emotional intelligence of the front-line nurses was in the upper middle range. Among the negative emotions, anxiety was the most prominent symptom. CONCLUSIONS: Managers should pay attention to the negative emotional problems of front-line nurses, improve their EI level and promote mental health and the progress of epidemic prevention. RELEVANCE TO CLINICAL PRACTICE: Improving the level of emotional intelligence can reduce the frequency and intensity of negative emotions. In clinical work, emotional intelligence can be used as a skill to carry out relevant training, which is conducive to playing a positive role in future emergencies.

Animal carcass- and wood-derived biochars improved nutrient bioavailability, enzyme activity, and plant growth in metal-phthalic acid ester co-contaminated soils: A trial for reclamation and improvement of degraded soils.

Reclamation of degraded soils such as those with low organic carbon content and soils co-contaminated with toxic elements and phthalic acid esters (PAEs) is of great concern. Little is known about the efficiency of plant- and animal-derived biochars for improving plant growth and physicochemical and biological properties of co-contaminated soils, particularly under low content of organic matter. Hence, a pot trial was carried out by growing pak choi (Brassica chinensis L.) to assess the influence of different doses (0, 0.5, 1, 2, and 4%) of animal (pig carcass) and wood (Platanus orientalis) derived biochars on soil properties, nutrient availabilities, plant growth, and soil enzyme activities in two soils containing low (LOC) and high (HOC) organic carbon contents and co-contaminated with di-(2-ethylhexyl) phthalic acid (DEHP) and cadmium (Cd). Biochar applications improved pH, salinity, carbon content, and cation exchange capacity of both soils. Addition of biochars significantly increased the bioavailability and uptake of phosphorus and potassium in the plants in both soils with greater effects from pig biochar than wood biochar. Biochar additions also significantly enhanced urease, sucrase, and catalase activities, but suppressed acid phosphatase activity in both soils. The impact of pig biochar was stronger on urease and acid phosphatase, while the wood biochar was more effective with sucrase and catalase activities. The biomass yield of pak choi was significantly increased after biochar addition to both soils, especially in 2% pig biochar treatment in the LOC soil. The positive response of soil enzymes activities and plant growth for biochar addition to the Cd and DEHP co-contaminated soils indicate that both biochars, particularly the pig biochar can mitigate the risk of these pollutants and prove to be eco-friendly and low-cost amendments for reclaiming these degraded soils.

[Analysis and Prospect of Classifcation Management of Medical Device for Rehabilitation].

Based on analyzing the classification catalog of medical device for rehabilitation, combined with the example, this paper discusses the principle of judgment of the classification of medical device for rehabilitation, and the naming and technical standards related to classification, puts forward the suggestions of classification management, attributes definition, and the naming, in order to provide support for promoting the reform of medical device classification management, and improving the level of scientific supervision.

Theoretical studies on the effect of a bithiophene bridge with different substituent groups (R = H, CH3, OCH3 and CN) in donor-π-acceptor copolymers for organic solar cell applications.

An effective way to enhance the efficiency of bulk heterojunction (BHJ) solar cells is to insert suitable bridges (π) between donor units (D) and acceptor units (A) in D-π-A copolymers. This work is devoted to uncovering how the characteristics of a HT (the substituent groups via head- to-tail (HT) connection) bithiophene bridge with different substituent groups (R = H, CH3, OCH3 and CN) affect the ground state structure, electronic, optical and charge transport properties of D-π-A copolymers for improving the photovoltaic performance. Based on the D-π-A copolymer PPBzT(2)-CEHß (P1) with a HT bridge of 3,4'-diethylhexyl-2,2'-bithiophene (π1), we designed six new copolymers (P2-P6') by introducing six kinds of HT bridges. From the calculated results, the introduction of different substituent groups into the bithiophene-bridge can markedly affect the HOMO and LUMO levels, band gaps, light-absorbing efficiency and hole transport ability of the copolymers. In particular, the copolymer P6 combining the cyano and methoxyl groups into the bridge has remarkable electronic and optical properties and hole transport ability among all the copolymers P1-P6', and it can be a candidate for donor materials of organic solar cells. We hope that the present results could provide a theoretical guidance for designing efficient donors in organic solar cells.

Autophagy inhibitors promoted aristolochic acid I induced renal tubular epithelial cell apoptosis via mitochondrial pathway but alleviated nonapoptotic cell death in mouse acute aritolochic acid nephropathy model.

Aristolochic acid I (AAI) can induce renal tubular epithelial cells (RTECs) autophagy, which thereby extenuates apoptosis in vitro. In this study, we aimed to determine whether the in vitro data also apply to the AAI-induced pathologic condition in vivo. BALB/c mice were treated with AAI, autophagy inhibitors [3-methyladenine (3MA) or chloroquine diphosphate salt (CQ)], and AAI plus the inhibitors for consecutive 5 days, respectively. Mice were euthanized on day 3 and 5. AAI induced RTECs autophagy was confirmed by electron microscopy and western blot. The results showed induction of apoptotic RTECs and up-regulation of mitochondrial and endoplasmic reticulum stress-related proteins in AAI-treated mice at both of the two time points. There were more apoptotic RTECs in AAI + inhibitor groups, which might be due to increased mitochondrial stress-related proteins (cytochrome C and apoptotic protease activating factor 1, APAF-1). On day 5, severe tubulointerstitial injuries induced by AAI led to a significant decline in kidney function. There were numerous autolysosomes in dying RTECs of the AAI group. Autophagy inhibitors increased AAI-induced RTECs mitochondrial apoptosis by increasing mitochondrial stress-related proteins, but they partially mitigated the AAI-induced severe renal tubulointerstitial injury. These results confirmed that AAI could induce autophagy in RTECs, which prevented apoptosis via mitochondrial pathway in vivo. However, continuous stimulation with AAI induced excess autophagy, which ultimately resulted in AAI-induced cell death. It suggested that apoptosis wasn't the main culprit in acute aristolochic acid nephropathy mice model.

Ultrasonic-assisted production of antioxidative polysaccharides from Crassostrea hongkongensis.

The beneficial effects of oyster extract against various disorders and diseases induced by oxidative stress have aroused great interest. In this article, ultrasonic-assisted enzymolysis was employed to produce polysaccharides of Crassostrea hongkongensis (CHP) and their antioxidant activity was investigated. A single-factor experiment and then a four-factor, three-level Box-Behnken design were first used to optimize ultrasonic extraction for polysaccharides. On the basis of ridge analysis, the optimum conditions are obtained as ultrasonic treatment time of 24 min, power of 876 W, temperature of 49°C, and material-solvent ratio of 1:6 (w/v). It is found that ultrasound pretreatment before protease hydrolysis was a great help to improve CHP yield and purity, especially more favorable with flavorzyme, neutrase, alcalase, and pepsin. Furthermore, the polysaccharide fraction, which was obtained by ultrasonic pretreatment and then alcalase hydrolysis at the conditions of 3000 U/g, 55°C, pH 8.0, for 4 hr, exhibited an obvious scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical (98.48 ± 0.55% and 99.20 ± 0.12%, respectively) and a lenoleic acid peroxidation inhibition effect (85.48 ± 0.65%) at a concentration of 5.0 mg/mL. These results reveal the potential application of CHP in functional food and nutraceuticals.

[High-temperature adaptation mechanisms and biotechnological potentials of thermophilic cyanobacteria].

Thermophilic cyanobacteria are prokaryotic organisms that possess exceptional heat-resistant characteristics. This group serves as an excellent model for investigating the heat tolerance of higher photosynthetic organisms, including higher plants, some protists (such as algae and euglena), and bacteria. Analyzing the mechanisms of high-temperature adaptation in thermophilic cyanobacteria can enhance our understanding of how photosynthetic organisms and microorganisms tolerate high temperatures at the molecular level. Additionally, these thermotolerant cyanobacteria have the potential to contribute to breeding heat-tolerant plants and developing microbial cell factories. This review summarizes current research on thermophilic cyanobacteria, focusing on their ecology, morphology, omics studies, and mechanisms of high-temperature tolerance. It offers insight into the potential biotechnological applications of thermophilic cyanobacteria and highlights future research opportunities. Specifically, attention is given to the photosynthetic physiology and metabolism of cyanobacteria, and the molecular basis of heat-tolerance mechanisms in thermophilic cyanobacteria is explored.

Transformational Modulation of Fluorescence to Room Temperature Phosphorescence in Metal-Organic Frameworks with Flexible C-S-C Bonds.

Photoluminescent metal-organic frameworks (MOFs) have been a subject of considerable interest for many years. However, the regulation of excited states of MOFs at the single crystal level remains restricted due to a lack of control methods. The singlet-triplet emissive property can be significantly influenced by crystal conformational distortions. This review introduces an intelligent responsive MOF material, denoted as LIFM-SHL-3a, characterized by flexible C-S-C bonds. LIFM-SHL-3a integrates elastic structural dynamics with fluorescence and room temperature phosphorescence (RTP) modulation under heating conditions. The deformable carbon-sulfur bond essentially propels the distortion of molecular conformation and alters the stacking mode, as illustrated by single-crystal-to-single-crystal transformation detection. The deformation of flexible C-S-C bonds leads to different noncovalent interactions in the crystal system, thereby achieving modulation of the fluorescence (F) and RTP bands. In the final state structure, the ratio of fluorescence is 66.7%, and the ratio of RTP is 32.6%. This stands as a successful demonstration of modulating F/RTP within the dynamic MOF, unlocking potential applications in optical sensing and beyond. Especially, a PL thermometer with a relative sensitivity of 0.096-0.104%·K-1 in the range of 300-380 K and a H2S probe with a remarkably low LOD of 125.80 nM can be obtained using this responsive MOF material of LIFM-SHL-3a.

Thermal control over phosphorescence or thermally activated delayed fluorescence in a metal-organic framework.

By integrating a tailor-made donor-acceptor (D-A) ligand in a metal-organic framework (MOF), a material with unprecedented features emerges. The ligand combines a pair of cyano groups as acceptors with four sulfanylphenyls as donors, which expose each a carboxylic acid as coordination sites. Upon treatment with zinc nitrate in a solvothermal synthesis, the MOF is obtained. The new material combines temperature-assisted reverse intersystem crossing (RISC) and intersystem crossing (ISC). As these two mechanisms are active in different temperature windows, thermal switching between their characteristic emission wavelengths is observed for this material. The two mechanisms can be activated by both, one-photon absorption (OPA) and two-photon absorption (TPA) resulting in a large excitement window ranging from ultraviolet (UV) over visible light (VL) to near infrared (NIR). Furthermore, the emission features of the material are pH sensitive, such that its application potential is demonstrated in a first ammonia sensor.

Artemether regulates liver glycogen and lipid utilization through mitochondrial pyruvate oxidation in db/db mice.

OBJECTIVES: Diabetes is an important global health problem. The occurrence and development of type 2 diabetes (T2D) involves multiple organs, among which the liver is an important organ. Artemether is a methyl ether derivative of artemisinin and has displayed significant antidiabetic effects. However, its regulation of glucose metabolism is not clearly elucidated. This study explored the effect of artemether on liver mitochondrial pyruvate metabolism. METHODS: T2D db/db mice were used and grouped into db/db and db/db+Art groups. Lean wild type mice served as control. After artemether intervention for 12 weeks, the respiratory exchange ratio (RER), redox state, relevant serum lipid content, liver glycogen and lipid content, liver insulin and insulin-like growth factor 1 (IGF-1) signal transduction, mitochondrial pyruvate oxidation pathway, fatty acid and glycogen metabolic pathways were evaluated. RESULTS: This experiment demonstrated that artemether raised RER and enhanced liver mitochondrial pyruvate metabolism in db/db mice. Artemether also reduced serum and urinary lipid peroxidation products and regulated the redox status in liver. The accumulation of liver glycogen in diabetic mice was attenuated, the proportion of lipid content in serum and liver was changed by artemether. The signal pathway associated with liver glycogen metabolism was also regulated by artemether. In addition, artemether increased serum insulin and regulated insulin/IGF-1 signal pathway in liver. CONCLUSIONS: The present study confirmed that artemether can regulate liver glycogen and lipid utilization in T2D mice, its biological mechanisms were associated with mitochondrial pyruvate oxidation in the liver.

Brain age prediction and deviations from normative trajectories in the neonatal connectome.

Structural and functional connectomes undergo rapid changes during the third trimester and the first month of postnatal life. Despite progress, our understanding of the developmental trajectories of the connectome in the perinatal period remains incomplete. Brain age prediction uses machine learning to estimate the brain's maturity relative to normative data. The difference between the individual's predicted and chronological age-or brain age gap (BAG)-represents the deviation from these normative trajectories. Here, we assess brain age prediction and BAGs using structural and functional connectomes for infants in the first month of life. We used resting-state fMRI and DTI data from 611 infants (174 preterm; 437 term) from the Developing Human Connectome Project (dHCP) and connectome-based predictive modeling to predict postmenstrual age (PMA). Structural and functional connectomes accurately predicted PMA for term and preterm infants. Predicted ages from each modality were correlated. At the network level, nearly all canonical brain networks-even putatively later developing ones-generated accurate PMA prediction. Additionally, BAGs were associated with perinatal exposures and toddler behavioral outcomes. Overall, our results underscore the importance of normative modeling and deviations from these models during the perinatal period.

Structural insight into the functional regulation of Elongation factor Tu by reactive oxygen species in Synechococcus elongatus PCC 7942.

In cyanobacteria, Elongation factor Tu (EF-Tu) plays a crucial role in the repair of photosystem II (PSII), which is highly susceptible to oxidative stress induced by light exposure and regulated by reactive oxygen species (ROS). However, the specific molecular mechanism governing the functional regulation of EF-Tu by ROS remains unclear. Previous research has shown that a mutated EF-Tu, where C82 is substituted with a Ser residue, can alleviate photoinhibition, highlighting the important role of C82 in EF-Tu photosensitivity. In this study, we elucidated how ROS deactivate EF-Tu by examining the crystal structures of EF-Tu in both wild-type and mutated form (C82S) individually at resolutions of 1.7 Šand 2.0 Šin Synechococcus elongatus PCC 7942 complexed with GDP. Specifically, the GDP-bound form of EF-Tu adopts an open conformation with C82 located internally, making it resistant to oxidation. Coordinated conformational changes in switches I and II create a tunnel that positions C82 for ROS interaction, revealing the vulnerability of the closed conformation of EF-Tu to oxidation. An analysis of these two structures reveals that the precise spatial arrangement of C82 plays a crucial role in modulating EF-Tu's response to ROS, serving as a regulatory element that governs photosynthetic biosynthesis.

Power and reproducibility in the external validation of brain-phenotype predictions.

Brain-phenotype predictive models seek to identify reproducible and generalizable brain-phenotype associations. External validation, or the evaluation of a model in external datasets, is the gold standard in evaluating the generalizability of models in neuroimaging. Unlike typical studies, external validation involves two sample sizes: the training and the external sample sizes. Thus, traditional power calculations may not be appropriate. Here we ran over 900 million resampling-based simulations in functional and structural connectivity data to investigate the relationship between training sample size, external sample size, phenotype effect size, theoretical power and simulated power. Our analysis included a wide range of datasets: the Healthy Brain Network, the Adolescent Brain Cognitive Development Study, the Human Connectome Project (Development and Young Adult), the Philadelphia Neurodevelopmental Cohort, the Queensland Twin Adolescent Brain Project, and the Chinese Human Connectome Project; and phenotypes: age, body mass index, matrix reasoning, working memory, attention problems, anxiety/depression symptoms and relational processing. High effect size predictions achieved adequate power with training and external sample sizes of a few hundred individuals, whereas low and medium effect size predictions required hundreds to thousands of training and external samples. In addition, most previous external validation studies used sample sizes prone to low power, and theoretical power curves should be adjusted for the training sample size. Furthermore, model performance in internal validation often informed subsequent external validation performance (Pearson's r difference <0.2), particularly for well-harmonized datasets. These results could help decide how to power future external validation studies.

Lisinopril protects against the adriamycin nephropathy and reverses the renalase reduction: potential role of renalase in adriamycin nephropathy.

AIMS: To investigate the potential role of renalase in adriamycin nephropathy and the effect of lisinopril on the regulation of renalase. METHODS: Adriamycin nephropathy was induced in male Wistar rats (n=12) by a single injection of adriamycin at 2 mg/kg body weight. Rats were then randomly assigned to a model group or a treatment group, to which were administered distilled water or the angiotensin converting enzyme inhibitor lisinopril, respectively, for 12 weeks. Six normal rats served as controls. At the end of study, physiological parameters and systolic blood pressure were measured. Glomerulosclerosis and tubulointerstitial injury were assessed by histopathology Renalase protein expression in kidney was quantified by immunohistochemistry and immunoblotting. The serum concentration and urinary excretion of renalase were determined by enzyme-linked immunosorbent assay. RESULTS: In model group rats, proteinuria and systolic blood pressure were elevated. Increased serum renalase concentration was observed; however, renalase protein expression in the kidney was significantly decreased. Compared with the model group, decreased proteinuria, lower systolic blood pressure, and fewer morphologic lesions were detected in the treatment group. Although levels of serum renalase were similar, accumulation of renalase in urine and kidney tissue increased notably in the treatment group compared with the model group. CONCLUSIONS: This study suggests that renalase may be involved in the process of adriamycin-induced renal injuries. Lisinopril may attenuate adriamycin-induced kidney injury by controlling blood pressure, which may be partially attributed to the renalase expression and secretion.

[Identification of adulterated milk based on two-dimensional correlation near-infrared spectra parameterization and BP neural network].

Discriminant models of adulterated milk and pure milk were established using BP neural network combined with two-dimensional (2D) correlation near-infrared spectra parameterization. Forty pure milk samples, 40 adulterated milk samples with urea (1-20 g x L(-1)) and 40 adulterated milk samples with melamine (0.01-3 g x L(-1)) were prepared respectively. Based on the characteristics of 2D correlation near-infrared spectra of pure milk and adulterated milk, 5 apparent statistic parameters were calculated based on the parameterization theory. Using 5 characteristic parameters, discriminant models of urea adulterated milk, melamine adulterated milk and two types of adulterated milk were built by BP neural network The prediction rate of unknown samples were 95%, 100% and 96.7%, respectively. The results show that this method can extract effectively feature information of adulterant, reduce the input dimensions of BP neural network, and better realize qualitative analysis of adulterant in milk.

Engineering Cyanobacterial Cell Factories for Photosynthetic Production of Fructose.

Fructose is an important monosaccharide product widely applied in the food, medicine, and chemical industries. Currently, fructose is mainly manufactured with plant biomass-sourced polysaccharides through multiple steps of digestion, conversion, separation, and purification. The development of cyanobacterial metabolic engineering provides an attractive alternative route for the one-step direct production of fructose utilizing carbon dioxide and solar energy. In this work, we developed a paradigm for engineering cyanobacterial chassis cells into efficient cell factories for the photosynthetic production of fructose. In a representative cyanobacterial strain, Synechococcus elongatus PCC 7942, knockout of fructokinase effectively activated the synthesis and secretion of fructose in hypersaline conditions, independent of any heterologous transporters. The native sucrose synthesis pathway was identified as playing a primary role in fructose synthesis. Through combinatory optimizations on the levels of metabolism, physiology, and cultivation, the fructose yield of the Synechococcus cell factories was stepwise improved to 3.9 g/L. Such a paradigm was also adopted to engineer another Synechococcus strain, the marine species Synechococcus sp. PCC 7002, and facilitated an even higher fructose yield of over 6 g/L. Finally, the fructose synthesized and secreted by the cyanobacterial photosynthetic cell factories was successfully extracted and prepared from the culture broth in the form of products with 86% purity through multistep separation-purification operations. This work demonstrated a paradigm for systematically engineering cyanobacteria for photosynthetic production of desired metabolites, and it also confirmed the feasibility and potential of cyanobacterial photosynthetic biomanufacturing as a simple and efficient route for fructose production.

Artemether ameliorates adriamycin induced cardiac atrophy in mice.

Adriamycin is a widely used and effective antitumor drug; however, its application is limited by various side effects, including irreversible cardiotoxicity. The central role of cardiac atrophy in Adriamycin­induced cardiotoxicity has been revealed; however, the underlying mechanism of this process remains unclear. Artemether is a well­known Chinese herbal medicine, and its pharmacological action is related to the regulation of mitochondrial function and redox status. The present study determined the effects of artemether on Adriamycin­induced cardiotoxicity and investigated the underlying mechanisms. After mouse model establishment and artemether intervention, experimental methods including pathological staining, immunohistochemistry, immunofluorescence, immunoblotting, ELISA and reverse transcription­quantitative PCR were used to evaluate the therapeutic effect. The results demonstrated that artemether prevented Adriamycin­induced cardiac atrophy and recovered the intercombination of connexin 43 and N­cadherin at the intercalated discs. Artemether also regulated the autophagy pathway and restored the unbalanced ratio of Bax and Bcl­2 in myocardial cells. In addition, the increased serum H2O2 levels after Adriamycin exposure were significantly decreased by artemether, and the mitochondrial alterations and redox imbalance in myocardial cells were also improved to varying degrees. In summary, the findings of the present study provide reliable evidence that artemether could ameliorate cardiac atrophy induced by Adriamycin. This therapeutic approach may be translated to the clinic for preventing drug­induced heart diseases.

Network controllability of structural connectomes in the neonatal brain.

White matter connectivity supports diverse cognitive demands by efficiently constraining dynamic brain activity. This efficiency can be inferred from network controllability, which represents the ease with which the brain moves between distinct mental states based on white matter connectivity. However, it remains unclear how brain networks support diverse functions at birth, a time of rapid changes in connectivity. Here, we investigate the development of network controllability during the perinatal period and the effect of preterm birth in 521 neonates. We provide evidence that elements of controllability are exhibited in the infant's brain as early as the third trimester and develop rapidly across the perinatal period. Preterm birth disrupts the development of brain networks and altered the energy required to drive state transitions at different levels. In addition, controllability at birth is associated with cognitive ability at 18 months. Our results suggest network controllability develops rapidly during the perinatal period to support cognitive demands but could be altered by environmental impacts like preterm birth.