TFEB overexpression through GFAP promoter disrupts neuronal lamination by dysregulating neurogenesis during embryonic development.

INTRODUCTION: Transcription factor EB (TFEB), a key regulator of autophagy and lysosomal biogenesis, has diverse roles in various physiological processes. Enhancing lysosomal function by TFEB activation has recently been implicated in restoring neural stem cells (NSCs) function. Overexpression of TFEB can inhibit the cell cycle of newborn cortical NSCs. It has also been found that TFEB regulates the pluripotency transcriptional network in mouse embryonic stem cells independent of autophagy lysosomal biogenesis. This study aims to explore the effects of TFEB activation on neurogenesis in vivo through transgenic mice. METHODS: We developed a GFAP-driven TFEB overexpression mouse model (TFEB GoE) by crossing the floxed TFEB overexpression mice and hGFAP-cre mice. We performed immunohistochemical and fluorescence staining on brain tissue from newborn mice to assess neurogenesis changes, employing markers such as GFAP, Nestin, Ki67, DCX, Tbr1 and Neun to trace different stages of neural development and cell proliferation. RESULTS: TFEB GoE mice exhibited premature mortality, dying at 10-20 days after birth. Immunohistochemical analysis revealed significant abnormalities, including disrupted hippocampal structure and cortical layering. Compared to control mice, TFEB GoE mice showed a marked increase in radial glial cells (RGCs) in the hippocampus and cortex, with Ki67 staining indicating these cells were predominantly in a quiescent state. This suggests that TFEB overexpression suppresses RGCs proliferation. Additionally, abnormal distributions of migrating neurons and mature neurons were observed, highlighted by DCX, Tbr1 and Neun staining, indicating a disruption in normal neurogenesis. CONCLUSION: This study, using transgenic animals in vivo, revealed that GFAP-driven TFEB overexpression leads to abnormal neural layering in the hippocampus and cortex by dysregulating neurogenesis. Our study is the first to discover the detrimental impact of TFEB overexpression on neurogenesis during embryonic development, which has important reference significance in future TFEB overexpression interventions in NSCs for treatment.

Exploring the role of CBLB in acute myocardial infarction: transcriptomic, microbiomic, and metabolomic analyses.

BACKGROUND: Specific alterations in gut microbiota and metabolites have been linked to AMI, with CBLB potentially playing an essential role. However, the precise interactions remain understudied, creating a significant gap in our understanding. This study aims to address this by exploring these interactions in CBLB-intervened AMI mice using transcriptome sequencing, 16 S rDNA, and non-targeted metabolite analysis. METHODS: To probe the therapeutic potential and mechanistic underpinnings of CBLB overexpression in AMI, we utilized an integrative multi-omics strategy encompassing transcriptomics, metabolomics, and 16s rDNA sequencing. We selected these particular methods as they facilitate a holistic comprehension of the intricate interplay between the host and its microbiota, and the potential effects on the host's metabolic and gene expression profiles. The uniqueness of our investigation stems from utilizing a multi-omics approach to illuminate the role of CBLB in AMI, an approach yet unreported to the best of our knowledge. Our experimental protocol encompassed transfection of CBLB lentivirus-packaged vectors into 293T cells, followed by subsequent intervention in AMI mice. Subsequently, we conducted pathological staining, fecal 16s rDNA sequencing, and serum non-targeted metabolome sequencing. We applied differential expression analysis to discern differentially expressed genes (DEGs), differential metabolites, and differential microbiota. We performed protein-protein interaction analysis to identify core genes, and conducted correlation studies to clarify the relationships amongst these core genes, paramount metabolites, and key microbiota. RESULTS: Following the intervention of CBLB in AMI, we observed a significant decrease in inflammatory cell infiltration and collagen fiber formation in the infarcted region of mice hearts. We identified key changes in microbiota, metabolites, and DEGs that were associated with this intervention. The findings revealed that CBLB has a significant correlation with DEGs, differential metabolites and microbiota, respectively. This suggests it could play a pivotal role in the regulation of AMI. CONCLUSION: This study confirmed the potential of differentially expressed genes, metabolites, and microbiota in AMI regulation post-CBLB intervention. Our findings lay groundwork for future exploration of CBLB's role in AMI, suggesting potential therapeutic applications and novel research directions in AMI treatment strategies.

Aberration of social behavior and gut microbiota induced by cross-fostering implicating the gut-brain axis.

The gut microbiota and neurological development of neonatal mice are susceptible to environmental factors that may lead to altered behavior into adulthood. However, the role that changed gut microbiota and neurodevelopment early in life play in this needs to be clarified. In this study, by modeling early-life environmental changes by cross-fostering BALB/c mice, we revealed the effects of the environment during the critical period of postnatal development on adult social behavior and their relationship with the gut microbiota and the nervous system. The neural projections exist between the ascending colon and oxytocin neurons in the paraventricular nuclei (PVN), peripheral oxytocin levels and PVN neuron numbers decreased after cross-fostering, and sex-specific alteration in gut microbiota and its metabolites may be involved in social impairments and immune imbalances brought by cross-fostering via the gut-brain axis. Our findings also suggest that social cognitive impairment may result from a combination of PVN oxytocinergic neurons, gut microbiota, and metabolites.

Oxytocin neurons in the paraventricular nucleus and fear empathy among male mice.

BACKGROUND: Recent studies have identified empathy deficit as a core impairment and diagnostic criterion for people with autism spectrum disorders; however, the improvement of empathy focuses primarily on behavioural interventions without the target regulation. We sought to compare brain regions associated with empathy-like behaviours of fear and pain, and to explore the role of the oxytocin-oxytocin receptor system in fear empathy. METHODS: We used C57BL mice to establish 2 models of fear empathy and pain empathy. We employed immunofluorescence histochemical techniques to observe the expression of c-Fos throughout the entire brain and subsequently quantified the number of c-Fos-positive cells in different brain regions. Furthermore, we employed chemogenetic technology to selectively manipulate these neurons in Oxt-Cre-/+ mice to identify the role of oxytocin in this process. RESULTS: The regions activated by fear empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, paraventricular nucleus (PVN), lateral habenula, and ventral and dorsal hippocampus. The regions activated by pain empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, and lateral habenula. We found that increasing the activity of oxytocin neurons in the PVN region enhanced the response to fear empathy. This enhancement may be mediated through oxytocin receptors. LIMITATIONS: This study included only male animals, which restricts the broader interpretation of the findings. Further investigations on circuit function need to be conducted. CONCLUSION: The brain regions implicated in the regulation of fear and pain empathy exhibit distinctions; the activity of PVN neurons was positively correlated with empathic behaviour in mice. These findings highlight the role of the PVN oxytocin pathway in regulating fear empathy and suggest the importance of oxytocin signalling in mediating empathetic responses.

Upregulation of Angiomotin-like 2 ameliorates experimental pulmonary arterial hypertension by inactivating YAP1 signaling.

ABSTRACT: Angiomotin-like 2 (AMOTL2) is related to numerous physiological and pathological conditions by affecting signal transduction. However, whether AMOTL2 is linked to pulmonary arterial hypertension (PAH) has not been addressed. This work aimed to investigate the potential role of AMOTL2 in PAH. A decrease in AMOTL2 abundance was observed in the lungs of PAH rats. The upregulation of AMOTL2 significantly decreased right ventricle systolic pressure and right ventricular hypertrophy in PAH rats. Overexpression of AMOTL2 also led to a noteworthy decrease in vascular wall thickness, pulmonary artery area, and collagen deposition in rats with PAH. AMOTL2 was downregulated in hypoxia-stimulated pulmonary arterial smooth muscle cells (PASMCs). Moreover, AMOTL2 overexpression impeded hypoxia-evoked proliferation, migration and phenotypic transformation in rat PASMCs. Mechanistic investigation revealed that Yes-associated protein 1 (YAP1) activation in PAH rats or hypoxia-stimulated PASMCs was markedly inhibited by AMOTL2 overexpression, which was associated with increased large tumor suppressor 1/2 (LATS1/2) phosphorylation. The inhibition of LATS1/2 reversed the AMOTL2-mediated inactivation of YAP1. Restoring the activity of YAP1 reversed the inhibitory effect of AMOTL2 on hypoxia-evoked proliferation, migration and phenotypic transformation of PASMCs. Collectively, these results suggest that AMOTL2 can ameliorate PAH in a rat model by interfering with pulmonary arterial remodeling via the inactivation of YAP1 signaling. Our work indicates that AMOTL2 may be a candidate target for novel drug development for the treatment of PAH.

Clinical performance of 0/1 h cardiac troponin algorithm for diagnosing non-STEMI in an emergency setting.

BACKGROUND: Non-ST-segment elevation myocardial infarction (NSTEMI) is a common form of acute myocardial infarction and rapid and accurate diagnosis is crucial for timely treatment. Current guidelines recommend using high-sensitivity cardiac troponin (hs-cTn) assays to determine circulating cTnI or cTnT levels. While the accuracy of the 0 h/1 h algorithm for diagnosing NSTEMI in different regions and patient populations remains controversial. Additionally, point-of-care testing (POCT) cTn assays have the potential to provide troponin readings to physicians within 15 min, but their accuracy in diagnosing NSTEMI in the emergency department (ED) requires further investigation. METHODS: A single-center prospective observational cohort study was conducted at Shaanxi Provincial People's Hospital to assess the analytical and diagnostic performance of the laboratory-based Roche Modular E170 hs-cTnT using the 0 h/1 h algorithm with Radiometer AQT90-flex POCT cTnT assay in undifferentiated chest pain patients presenting to the ED. Whole-blood samples were collected and hs-cTnT and POCT cTnI were measured simultaneously at baseline and after 1 h. RESULTS: The study results showed that the POCT cTnT assay using the 0 h/1 h algorithm had comparable diagnostic accuracy to the laboratory-based Roche Modular E170 hs-cTnT assay in diagnosing NSTEMI in patients with chest pain. CONCLUSION: The laboratory-based Roche Modular E170 hs-cTnT using the 0 h/1 h algorithm is reliable and accurate method for diagnosing NSTEMI in undifferentiated chest pain patients presenting to the ED. POCT cTnT assay has comparable diagnostic accuracy to the hs-cTnT assay and its rapid turnaround time makes it a valuable tool in expediting the diagnostic workup of chest pain patients.

Simultaneous Sensing of H2S and ATP with a Two-Photon Fluorescent Probe in Alzheimer's Disease: toward Understanding Why H2S Regulates Glutamate-Induced ATP Dysregulation.

Energy deprivation and reduced levels of hydrogen sulfide (H2S) in the brain is closely associated with Alzheimer's disease (AD). However, there is currently no fluorescent probe for precise exploration of both H2S and adenosine triphosphate (ATP) to directly demonstrate their relationship and their dynamic pattern changes. Herein, we developed a two-photon fluorescent probe, named AD-3, to simultaneously image endogenous H2S and ATP from two emission channels of fluorescent signals in live rat brains with AD. The probe achieved excellent selectivity and good detection linearity for H2S in the 0-100 µM concentration range and ATP in the 2-5 mM concentration range, respectively, with a detection limit of 0.19 µM for H2S and 0.01 mM for ATP. Fluorescence imaging in live cells reveals that such probe could successfully apply for simultaneous imaging and accurate quantification of H2S and ATP in neuronal cells. Further using real-time quantitative polymerase chain reaction and Western blots, we confirmed that H2S regulates ATP synthesis by acting on cytochrome C, cytochrome oxidase subunit 3 of complex IV, and protein 6 of complex I in the mitochondrial respiratory chain. Subsequently, we constructed a high-throughput screening platform based on AD-3 probe to rapidly screen the potential anti-AD drugs to control glutamate-stimulated oxidative stress associated with abnormal H2S and ATP levels. Significantly, AD-3 probe was found capable of imaging of H2S and ATP in APP/PS1 mice, and the concentration of H2S and ATP in the AD mouse brain was found to be lower than that in wild-type mice.

TaKLU Plays as a Time Regulator of Leaf Growth via Auxin Signaling.

The growth of leaves is subject to strict time regulation. Several genes influencing leaf growth have been identified, but little is known about how genes regulate the orderly initiation and growth of leaves. Here, we demonstrate that TaKLU/TaCYP78A5 contributes to a time regulation mechanism in leaves from initiation to expansion. TaKLU encodes the cytochrome P450 CYP78A5, and its homolog AtKLU has been described whose deletion is detrimental to organ growth. Our results show that TaKLU overexpression increases leaf size and biomass by altering the time of leaf initiation and expansion. TaKLU-overexpressing plants have larger leaves with more cells. Further dynamic observations indicate that enlarged wheat leaves have experienced a longer expansion time. Different from AtKLU inactivation increases leaf number and initiation rates, TaKLU overexpression only smooths the fluctuations of leaf initiation rates by adjusting the initiation time of local leaves, without affecting the overall leaf number and initiation rates. In addition, complementary analyses suggest TaKLU is functionally conserved with AtKLU in controlling the leaf initiation and size and may involve auxin accumulation. Our results provide a new insight into the time regulation mechanisms of leaf growth in wheat.

Investment strategy for blockchain technology in a shipping supply chain.

In the post-COVID-19 pandemic era, how to promote blockchain technology to improve the efficiency of port customs clearance and logistics transparency has become a hot research question in the shipping industry. In this paper, we investigate the value of blockchain-based vertical cooperation led by a port or a shipping company in a one-to-two shipping service competition model. A status quo scenario and two different investment scenarios led by different stakeholders are constructed, and equilibrium solutions of the Stackelberg game in three scenarios are proposed. Meanwhile, consumer surplus and social welfare under different cooperation frameworks are discussed. We find that i) investment in blockchain technology can significantly increase the profits of shipping supply chain participants. ii) From the point of view of profit, when the investment efficiency of the port and the shipping company satisfies a certain relationship, there is a balanced strategy for both parties to invest in blockchain technology. iii) The more intense the competition for the services of shipping companies, the lower the level of blockchain technology to improve the logistics capabilities of the shipping supply chain participants. iv) The port's investment in blockchain technology brings more consumer surplus and social welfare. The abovementioned findings can provide managerial insights for ports and shipping companies and present decision support for the government to formulate blockchain technology promotion policies.

Lin28a protects against diabetic cardiomyopathy through Mst1 inhibition.

Lin28a has been found to enhance glucose uptake and insulin sensitivity. Lin28a alleviates cardiac dysfunction under various pathological conditions. However, the effects and underlying mechanisms of Lin28a on diabetic cardiomyopathy (DCM) are not well-understood. The aim of this study was to determine whether Lin28a protects against DCM and the potential mechanisms. Two to three days old mouse neonatal primary cardiomyocytes were randomized for treatment with adenoviruses harboring Lin28a and mammalian sterile 20-like kinase 1 (Mst1) short hairpin RNA, 48 hr before culturing in normal or high glucose medium. Cardiomyocyte apoptosis, autophagy, mitochondrial morphology, adenosine triphosphate content, and cytokine levels in the high glucose or normal conditions were observed between all groups. Either Lin28a overexpression or Mst1 knockdown alleviated mitochondrial ultrastructure impairment, decreased cytokine levels, inhibited apoptosis, and enhanced autophagy in primary neonatal mouse cardiomyocytes treated with high glucose. Importantly, the protective effects of Lin28a and Mst1 disappeared after treatment with 3-methyladenine, an autophagy inhibitor. Interestingly, in Mst1 knockdown cardiomyocytes, Lin28a overexpression failed to further enhance autophagy and alleviate high glucose-induced cardiomyocyte injury, which implies the protective roles of Lin28a counteracting high glucose-induced cardiomyocyte injury are dependent on Mst1 inhibition. Furthermore, co-immunoprecipitation and immunofluorescence double staining suggested that there were no direct interactions between Mst1 and Lin28a. Lin28a increased the expression of Akt, which inhibited the activation of Mst1-mediated apoptotic pathways.

Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson's Disease: Synaptic Pathology and Neuronal Aging.

The motor and nonmotor symptoms of PD involve several brain regions. However, whether α-syn pathology originating from the SNc can directly lead to the pathological changes in distant cerebral regions and induce PD-related symptoms remains unclear. Here, AAV9-synapsin-mCherry-human SNCA (A53T) was injected into the unilateral SNc of mice. Motor function and olfactory sensitivity were evaluated. Our results showed that AAV9-synapsin-mCherry-human SNCA was continuously expressed in SNc. The animals showed mild motor and olfactory dysfunction at 7 months after viral injection. The pathology in SNc was characterized by the loss of dopaminergic neurons accompanied by ER stress. In the striatum, hα-syn expression was high, CaMKß-2 and NR2B expression decreased, and active synapses reduced. In the olfactory bulb, hα-syn expression was high, and aging cells in the mitral layer increased. The results suggested that hα-syn was transported in the striatum and OB along the nerve fibers that originated from the SNc and induced pathological changes in the distant cerebral regions, which contributed to the motor and nonmotor symptoms of PD.

Factors Influencing Stent Restenosis After Percutaneous Coronary Intervention in Patients with Coronary Heart Disease: A Clinical Trial Based on 1-Year Follow-Up.

BACKGROUND This study observed the incidence of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) and discusses the risk factors of ISR based on clinical data, coronary angiography, and stent features, to provide a theoretical basis for the prevention and treatment of ISR. MATERIAL AND METHODS We selected 1132 cases who received stent implantation at the Shaanxi People's Hospital from June 2014 to June 2016 and were followed up by coronary angiography within 1 year. Based on coronary angiography, the cases were divided into ISR and non-ISR groups. ISR was defined as a reduction in lumen diameter by over 50% after PCI. The ISR group consisted of 93 cases and the non-ISR group consisted of 1039 cases. Medical history, biochemical indicators, features of coronary artery lesions, and stent status were analyzed retrospectively. Risk factors of ISR were identified by univariate and multivariate logistic regression analyses. RESULTS Among 1132 cases, 93 cases had ISR, with the overall incidence of 8.21%. Univariate and multivariate logistic regression analyses indicated that postoperative hypersensitive C-reactive protein (hs-CRP) levels (OR=2.309, 1.579-3.375 mg/L), postoperative homocysteine (HCY) levels (OR=2.202, 1.268-3.826 µmol/L), history of diabetes (OR=1.955,1.272-3.003), coronary bifurcation lesions (OR=3.785, 2.246-6.377), and stent length (OR=1.269, 1.179-1.365 mm) were independent risk factors of ISR after PCI (P<0.05). CONCLUSIONS Elevated hs-CRP and HCY levels after PCI, history of diabetes, coronary bifurcation lesions, and greater stent length were associated with a higher risk of ISR. Patients with a higher risk of ISR should receive routine follow-up and intense medication management after PCI to control the risk factors and to reduce ISR.

Interaction of basolateral amygdala, ventral hippocampus and medial prefrontal cortex regulates the consolidation and extinction of social fear.

BACKGROUND: Following a social defeat, the balanced establishment and extinction of aversive information is a beneficial strategy for individual survival. Abnormal establishment or extinction is implicated in the development of mental disorders. This study investigated the time course of the establishment and extinction of aversive information from acute social defeat and the temporal responsiveness of the basolateral amygdala (BLA), ventral hippocampus (vHIP) and medial prefrontal cortex (mPFC) in this process. METHODS: Mouse models of acute social defeat were established by using the resident-intruder paradigm. To evaluate the engram of social defeat, the intruder mice were placed into the novel context at designated time to test the social behavior. Furthermore, responses of BLA, vHIP and mPFC were investigated by analyzing the expression of immediate early genes, such as zif268, arc, and c-fos. RESULTS: The results showed after an aggressive attack, aversive memory was maintained for approximately 7 days before gradually diminishing. The establishment and maintenance of aversive stimulation were consistently accompanied by BLA activity. By contrast, vHIP and mPFC response was inhibited from this process. Additionally, injecting muscimol (Mus), a GABA receptor agonist, into the BLA alleviated the freezing behavior and social fear and avoidance. Simultaneously, Mus treatment decreased the zif268 and arc expression in BLA, but it increased their expression in vHIP. CONCLUSION: Our data support and extend earlier findings that implicate BLA, vHIP and mPFC in social defeat. The time courses of the establishment and extinction of social defeat are particularly consistent with the contrasting BLA and vHIP responses involved in this process.

Low-Cost Aqueous Electrolyte with MBA Additives for Uniform and Stable Zinc Deposition.

Aqueous zinc ion batteries (AZIBs) are attracting increasing research interest due to their intrinsic safety, low cost, and scalability. However, the issues including hydrogen evolution, interface corrosion, and zinc dendrites at anodes have seriously limited the development of aqueous zinc ion batteries. Here, N,N-methylenebis(acrylamide) (MBA) additives with -CONH- groups are introduced to form hydrogen bonds with water and suppress H2O activity, inhibiting the occurrence of hydrogen evolution and corrosion reactions at the interface. In situ optical microscopy demonstrates that the MBA additive promotes the uniform deposition of Zn2+ and then suppresses the dendrite growth on the zinc anode. Therefore, Zn//Ti asymmetric batteries demonstrate a high plating/stripping efficiency of 99.5%, while Zn//Zn symmetric batteries display an excellent cycle stability for more than 1000 h. The Zn//MnO2 full cells exhibit remarkable cycling stability for 700 cycles in aqueous electrolytes with MBA additives. The additive engineering via MBA achieved the dendrite-free Zn anodes and stable full batteries, which is favorable for advanced AZIBs in practical applications.

Insights into the cycling stability of manganese-based zinc-ion batteries: from energy storage mechanisms to capacity fluctuation and optimization strategies.

Manganese-based materials are considered as one of the most promising cathodes in zinc-ion batteries (ZIBs) for large-scale energy storage applications owing to their cost-effectiveness, natural availability, low toxicity, multivalent states, high operation voltage, and satisfactory capacity. However, their intricate energy storage mechanisms coupled with unsatisfactory cycling stability hinder their commercial applications. Previous reviews have primarily focused on optimization strategies for achieving high capacity and fast reaction kinetics, while overlooking capacity fluctuation and lacking a systematic discussion on strategies to enhance the cycling stability of these materials. Thus, in this review, the energy storage mechanisms of manganese-based ZIBs with different structures are systematically elucidated and summarized. Next, the capacity fluctuation in manganese-based ZIBs, including capacity activation, degradation, and dynamic evolution in the whole cycle calendar are comprehensively analyzed. Finally, the constructive optimization strategies based on the reaction chemistry of one-electron and two-electron transfers for achieving durable cycling performance in manganese-based ZIBs are proposed.

A ratiometric fluorescent probe revealing the abnormality of acetylated tau by visualizing polarity in Alzheimer's disease.

Abnormal neuronal polarity leads to early deficits in Alzheimer's disease (AD) by affecting the function of axons. Precise and rapid evaluation of polarity changes is very important for the early prevention and diagnosis of AD. However, due to the limitations of existing detection methods, the mechanism related to how neuronal polarity changes in AD is unclear. Herein, we reported a ratiometric fluorescent probe characterized by neutral molecule to disclose the polarity changes in nerve cells and the brain of APP/PS1 mice. Cy7-K showed a sensitive and selective ratiometric fluorescence response to polarity. Remarkably, unlike conventional intramolecular charge transfer fluorescent probes, the fluorescence quantum yield of Cy7-K in highly polar solvents is higher than that in low polar solvents due to the transition of neutral quinones to aromatic zwitterions. Using the ratiometric fluorescence imaging, we found that beta-amyloid protein (Aß) inhibits the expression of histone deacetylase 6, thereby increasing the amount of acetylated Tau protein (AC-Tau) and ultimately enhancing cell polarity. There was a high correlation between polarity and AC-Tau. Furthermore, Cy7-K penetrated the blood-brain barrier to image the polarity of different brain regions and confirmed that APP/PS1 mice had higher polarity than Wild-type mice. The probe Cy7-K will be a promising tool for assessing the progression of AD development by monitoring polarity.

The functional and anatomical characterization of three spinal output pathways of the anterolateral tract.

The nature of spinal output pathways that convey nociceptive information to the brain has been the subject of controversy. Here, we provide anatomical, molecular, and functional characterizations of two distinct anterolateral pathways: one, ascending in the lateral spinal cord, triggers nociceptive behaviors, and the other one, ascending in the ventral spinal cord, when inhibited, leads to sensorimotor deficits. Moreover, the lateral pathway consists of at least two subtypes. The first is a contralateral pathway that extends to the periaqueductal gray (PAG) and thalamus; the second is a bilateral pathway that projects to the bilateral parabrachial nucleus (PBN). Finally, we present evidence showing that activation of the contralateral pathway is sufficient for defensive behaviors such as running and freezing, whereas the bilateral pathway is sufficient for attending behaviors such as licking and guarding. This work offers insight into the complex organizational logic of the anterolateral system in the mouse.

Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN) for cross-modal individual analysis of the whole brain.

Cross-modal analysis of the same whole brain is an ideal strategy to uncover brain function and dysfunction. However, it remains challenging due to the slow speed and destructiveness of traditional whole-brain optical imaging techniques. Here we develop a new platform, termed Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN), for non-destructive, high-speed, 3D imaging of ex vivo rodent, ferret, and non-human primate brains. Using an optimally designed image acquisition scheme and an accompanying machine-learning algorithm, PATTERN extracts signals of genetically-encoded probes from photobleaching-based temporal modulation and enables reliable visualization of neural projection in the whole central nervous system with 3D isotropic resolution. Without structural and biological perturbation to the sample, PATTERN can be combined with other whole-brain imaging modalities to acquire the whole-brain image with both high resolution and morphological fidelity. Furthermore, cross-modal transcriptome analysis of an individual brain is achieved by PATTERN imaging. Together, PATTERN provides a compatible and versatile strategy for brain-wide cross-modal analysis at the individual level.

miR-200a-3p overexpression alleviates diabetic cardiomyopathy injury in mice by regulating autophagy through the FOXO3/Mst1/Sirt3/AMPK axis.

Objective: Hyperglycemia and insulin resistance or deficiency are characteristic features of diabetes. Diabetes is accompanied by cardiomyocyte hypertrophy, fibrosis and ventricular remodeling, and eventually heart failure. In this study, we established a diabetic cardiomyopathy (DCM) mouse model to explore the role and mechanism of miR-200a-3p in DCM. Methods: We used db/db mice to simulate the animal model of DCM and the expression of miR-200a-3p was then examined by RT-qPCR. Tail vein injection of mice was done with rAAV-miR-200a-3p for 8 weeks, and cardiac function was assessed by cardiac ultrasound. The levels of myocardial tissue injury, fibrosis, inflammation, apoptosis and autophagy in mice were detected by histological staining, TUNEL and other molecular biological experiments. Results: miR-200a-3p expression levels were significantly decreased in the myocardium of DCM mice. Diabetic mice developed cardiac dysfunction and presented pathological changes such as myocardial injury, myocardial interstitial fibrosis, cardiomyocyte apoptosis, autophagy, and inflammation. Overexpression of miR-200a-3p expression significantly ameliorated diabetes induced-cardiac dysfunction and myocardial injury, myocardial interstitial fibrosis, cardiomyocyte apoptosis, and inflammation, and enhanced autophagy. Mechanistically, miR-200a-3p interacted with FOXO3 to promote Mst1 expression and reduce Sirt3 and p-AMPK expression. Conclusion: In type 2 diabetes, increased miR-200a-3p expression enhanced autophagy and participated in the pathogenic process of cardiomyopathy throug7 Mst1/Sirt3/AMPK axis regulation by its target gene FOXO3. This conclusion provides clues for the search of new gene targeted therapeutic approaches for diabetic cardiomyopathy.

Heterogeneous Ni-Co phosphide/phosphate with a specific hollow sea-urchin-like structure for high-performance hybrid supercapacitor and alkaline zinc-metal battery applications.

Constructing well-defined nanostructures consisting of the multiple components with distinctive features are a promising but challenging strategy to develop advanced electroactive materials for energy storage applications. Herein, heterogeneous Ni-Co phosphide/phosphate with a specific hollow sea-urchin-like structure has been synthesized as advanced electroactive materials for both hybrid supercapacitor (HSC) and alkaline zinc-metal battery (AZB) applications. The heterogeneous Ni-Co phosphide/phosphate combines the merits of improved electrolyte interfacial property from the specific hollow sea-urchin-like structure, high electron-conductivity of phosphide, and better ion adsorption and solid diffusion property of phosphate. As a result, the Ni-Co phosphide/phosphate achieves a high capacity to 180.7 mA h g-1 at 1 A g-1, excellent rate capability of 51% capacity retention when the specific current increases by 50 times, and stable cycling stability of 85% capacity retention when cycled for 1000 cycles. Ex situ test was conducted to investigate the formation mechanism for the hollow and sea-urchin-like structure, which can be ascribed to the anion exchange reaction between pre-formed hydroxide and CO32- ions. When used to assemble HSCs with reduced graphene oxide (RGO), the HSCs exhibit a high specific energy of 49.4 W h kg-1, an ultrahigh specific power to 11.7 kW kg-1, and an eminent cycling stability over 10,000 cycles. Meanwhile, Ni2Co-P/POx-based AZB also achieves both high-energy and high-power performance with the specific energy of 308.0 W h kg-1 at 828.4 W kg-1 and 117.4 W h kg-1 at 30.8 kW kg-1. These results above suggest that heterogeneous Ni-Co phosphide/phosphate has great potential to be used as a candidate for both HSC and AZB applications.