Unravelling the pseudocapacitive origin of graphene oxide-based aerogels by comparative insights.

We reveal the intrinsic pseudocapacitive center of graphene-oxide-based aerogels by investigating different modified graphene skeletons from various approaches. A high proportion of carbonyl groups in carbon networks is shown to optimize the construction of rational pseudocapacitive sites by triggering reversible proton-induced surface reactions, leading to satisfactory electrochemical performance.

Investigating the WNT/TCF pathway and the value of DCE-MRI in predicting and evaluating the efficacy of neoadjuvant radiotherapy and chemotherapy for locally advanced rectal cancer.

The purpose of this research was to Detach the DCE-MRI value in predicting and evaluating the efficacy of neoadjuvant radiotherapy and chemotherapy in middle and low locally advanced rectal cancer (READ). For this purpose, 40 patients with READ were examined by DCE-MRI and DWI before CRT treatment and 4 weeks after CRT treatment, and examined by Avanto1.5T magnetic resonance imaging scanner. According to the comparison of the postoperative pathological T stage and pre-nCRT T stage, the patients with decreased stage were defined as the T-descending group, and those with unchanged or elevated staging were defined as the T-undescending group. The ROC curve was used to evaluate the value of ADC value and Ktrans value to predict the early curative effect of neoadjuvant radiation therapy and chemotherapy for READ. Results showed that The ADC values of the two groups after nCRT were higher than those before nCRT (P<0.05). Compared with the pre-nCRT T-decline group and T-non-decline group, the Ktrans value of the pre-T-decline group was higher than that of the T-non-decline group (P<0.05), and the Ktrans value of both groups after the nCRT was higher than that before nCRT (P<0.05). The difference and the rate of ADC in the T-depression group were higher than in the T-undescending group (P<0.05). Taking the change rate of the ADC value 0.17 as the optimal threshold, the sensitivity and specificity of predicting the T-descending stage of patients with READ after neoadjuvant radiotherapy and chemotherapy were 72.69% and 75.84%, respectively (95%CI:0.608-0.954); taking the pre-nCRTKtrans value 1.18/min as the optimal threshold, the sensitivity and specificity to predict the T-descending stage of READ patients after neoadjuvant radiation therapy and chemotherapy was 78.65% and 80.47%, respectively (95%CI:0.637-0.971). There was no significant difference between the change rate of ADC value and the Ktrans value before nCRT in predicting the early efficacy of neoadjuvant radiotherapy and chemotherapy for READ. In conclusion, ADC value and Ktrans value can reflect the tissue structure changes of READ after neoadjuvant chemotherapy. It can be seen that the change rate of ADC value and pre-nCRTKtrans value can predict the early efficacy of neoadjuvant radiotherapy and chemotherapy for READ. The results showed that Axin2 and ß-catenin factors along with other factors such as APC and CKI proteins are effective at the molecular level along with other factors in the WNT/TCF signaling pathway. These agents start their activity in the cytoplasm and exert their final effect on the genes in the nucleus.

Microglia modulate general anesthesia through P2Y12 receptor.

General anesthesia (GA) is an unconscious state produced by anesthetic drugs, which act on neurons to cause overall suppression of neuronal activity in the brain. Recent studies have revealed that GA also substantially enhances the dynamics of microglia, the primary brain immune cells, with increased process motility and territory surveillance. However, whether microglia are actively involved in GA modulation remains unknown. Here, we report a previously unrecognized role for microglia engaging in multiple GA processes. We found that microglial ablation reduced the sensitivity of mice to anesthetics and substantially shortened duration of loss of righting reflex (LORR) or unconsciousness induced by multiple anesthetics, thereby promoting earlier emergence from GA. Microglial repopulation restored the regular anesthetic recovery, and chemogenetic activation of microglia prolonged the duration of LORR. In addition, anesthesia-accompanying analgesia and hypothermia were also attenuated after microglial depletion. Single-cell RNA sequencing analyses showed that anesthesia prominently affected the transcriptional levels of chemotaxis and migration-related genes in microglia. By pharmacologically targeting different microglial motility pathways, we found that blocking P2Y12 receptor (P2Y12R) reduced the duration of LORR of mice. Moreover, genetic ablation of P2Y12R in microglia also promoted quicker recovery in mice from anesthesia, verifying the importance of microglial P2Y12R in anesthetic regulation. Our work presents the first evidence that microglia actively participate in multiple processes of GA through P2Y12R-mediated signaling and expands the non-immune roles of microglia in the brain.

Dual roles of hexokinase 2 in shaping microglial function by gating glycolytic flux and mitochondrial activity.

Microglia continuously survey the brain parenchyma and actively shift status following stimulation. These processes demand a unique bioenergetic programme; however, little is known about the metabolic determinants in microglia. By mining large datasets and generating transgenic tools, here we show that hexokinase 2 (HK2), the most active isozyme associated with mitochondrial membrane, is selectively expressed in microglia in the brain. Genetic ablation of HK2 reduced microglial glycolytic flux and energy production, suppressed microglial repopulation, and attenuated microglial surveillance and damage-triggered migration in male mice. HK2 elevation is prominent in immune-challenged or disease-associated microglia. In ischaemic stroke models, however, HK2 deletion promoted neuroinflammation and potentiated cerebral damages. The enhanced inflammatory responses after HK2 ablation in microglia are associated with aberrant mitochondrial function and reactive oxygen species accumulation. Our study demonstrates that HK2 gates both glycolytic flux and mitochondrial activity to shape microglial functions, changes of which contribute to metabolic abnormalities and maladaptive inflammation in brain diseases.

Poly(ethylene oxide)-Based Composite Electrolyte with Lithium-Doped High-Entropy Oxide Ceramic Enabled Robust Solid-State Lithium-Metal Batteries.

Solid polymer electrolytes using poly(ethylene oxide) (PEO) as matrix are mostly applied due to the superior Li+ transfer ability of oxyethyl chain. However, the high crystallinity, low oxidation potential window, and insufficient mechanical strength hinder PEO deployment in solid-state batteries. Here, a novel composite solid electrolyte combined PEO with a lithium-doped high-entropy oxide (Li0.25 HEO) ceramic powder is presented, which exhibits excellent properties for solid-state lithium metal battery applications. On one hand, the rich oxygen vacancies of Li0.25 HEO surface are favorable to capturing anionic groups (e. g. TFSI- ), reinforcing the Li+ dissociation. On the other hand, Li0.25 HEO with abundant Lewis acid sites markedly promotes the PEO oxidation potential window. Additionally, the incorporation of Li0.25 HEO ceramic powder can effectively inhibit the PEO crystallization and enhance the mechanic strength of the composite electrolyte as well. The assembled solid-state lithium metal battery based on the composite solid electrolyte exhibits high rate capacity and durable cycle performance, showing potential development and application prospects.

Screening of cell-virus, cell-cell, gene-gene crosstalk among animal kingdom at single cell resolution.

BACKGROUND: The exact animal origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains obscure and understanding its host range is vital for preventing interspecies transmission. METHODS: Herein, we applied single-cell sequencing to multiple tissues of 20 species (30 data sets) and integrated them with public resources (45 data sets covering 26 species) to expand the virus receptor distribution investigation. While the binding affinity between virus and receptor is essential for viral infectivity, understanding the receptor distribution could predict the permissive organs and tissues when infection occurs. RESULTS: Based on the transcriptomic data, the expression profiles of receptor or associated entry factors for viruses capable of causing respiratory, blood, and brain diseases were described in detail. Conserved cellular connectomes and regulomes were also identified, revealing fundamental cell-cell and gene-gene cross-talks from reptiles to humans. CONCLUSIONS: Overall, our study provides a resource of the single-cell atlas of the animal kingdom which could help to identify the potential host range and tissue tropism of viruses and reveal the host-virus co-evolution.

Single cell atlas for 11 non-model mammals, reptiles and birds.

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.

A high-resolution cell atlas of the domestic pig lung and an online platform for exploring lung single-cell data.

The genetically engineered pig is regarded as an optimal source of organ transplantation for humans and an excellent model for human disease research, given its comparable physiology to human beings. A myriad of single-cell RNA sequencing (scRNA-seq) data on humans has been reported, but such data on pigs are scarce. Here, we apply scRNA-seq technology to study the cellular heterogeneity of 3-month-old pig lungs, generating the single-cell atlas of 13,580 cells covering 16 major cell types. Based on these data, we systematically characterize the similarities and differences in the cellular cross-talk and expression patterns of respiratory virus receptors in each cell type of pig lungs compared with human lungs. Furthermore, we analyze pig lung xenotransplantation barriers and reported the cell-type expression patterns of 10 genes associated with pig-to-human immunobiological incompatibility and coagulation dysregulation. We also investigate the conserved transcription factors (TFs) and their candidate target genes and constructed five conserved TF regulatory networks in the main cell types shared by pig and human lungs. Finally, we present a comprehensive and openly accessible online platform, ScdbLung. Our scRNA-seq atlas of the domestic pig lung and ScdbLung database can guide pig lung research and clinical applicability.

Single-cell brain atlas of Parkinson's disease mouse model.

Parkinson's disease (PD) is a neurodegenerative disease, leading to the impairment of movement execution. PD pathogenesis has been largely investigated, either limited to bulk transcriptomic levels or at certain cell types, which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types. Here, we report the application of single-nucleus RNA-seq on midbrain, striatum, and cerebellum of the α-syn-A53T mouse, a well-established PD mouse model, and matched controls, generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells. Additionally, we comprehensively depicte the dysfunctions in PD pathology, covering the elevation of NF-κB activity, the alteration of ion channel components, the perturbation of protein homeostasis network, and the dysregulation of glutamatergic signaling. Notably, we identify a variety of cell types closely associated with PD risk genes. Taken together, our study provides valuable resources to systematically dissect the molecular mechanism of PD pathogenesis at the single-cell resolution, which facilitates the development of novel approaches for diagnosis and therapies against PD.

Single-cell atlas of domestic pig cerebral cortex and hypothalamus.

The brain of the domestic pig (Sus scrofa domesticus) has drawn considerable attention due to its high similarities to that of humans. However, the cellular compositions of the pig brain (PB) remain elusive. Here we investigated the single-nucleus transcriptomic profiles of five regions of the PB (frontal lobe, parietal lobe, temporal lobe, occipital lobe, and hypothalamus) and identified 21 cell subpopulations. The cross-species comparison of mouse and pig hypothalamus revealed the shared and specific gene expression patterns at the single-cell resolution. Furthermore, we identified cell types and molecular pathways closely associated with neurological disorders, bridging the gap between gene mutations and pathogenesis. We reported, to our knowledge, the first single-cell atlas of domestic pig cerebral cortex and hypothalamus combined with a comprehensive analysis across species, providing extensive resources for future research regarding neural science, evolutionary developmental biology, and regenerative medicine.

Genome re-sequencing reveals the evolutionary history of peach fruit edibility.

Peach (Prunus persica) is an economically important fruit crop and a well-characterized model for studying Prunus species. Here we explore the evolutionary history of peach using a large-scale SNP data set generated from 58 high-coverage genomes of cultivated peach and closely related relatives, including 44 newly re-sequenced accessions and 14 accessions from a previous study. Our analyses suggest that peach originated about 2.47 Mya in southwest China in glacial refugia generated by the uplift of the Tibetan plateau. Our exploration of genomic selection signatures and demographic history supports the hypothesis that frugivore-mediated selection occurred several million years before the eventual human-mediated domestication of peach. We also identify a large set of SNPs and/or CNVs, and candidate genes associated with fruit texture, taste, size, and skin color, with implications for genomic-selection breeding in peach. Collectively, this study provides valuable information for understanding the evolution and domestication of perennial fruit tree crops.

Nα-Acetyltransferases 10 and 15 are Required for the Correct Initiation of Endosperm Cellularization in Arabidopsis.

The endosperm and embryo originate from the fertilized central cell and egg cell through a programmed series of cell division and differentiation events. Characterization of more vital genes involved in endosperm and embryo development can help us to understand the regulatory mechanism in more depth. In this study, we found that loss of NAA10 and NAA15, the catalytic and auxiliary subunits of Arabidopsis thaliana N-terminal acetyltransferase A (AtNatA), respectively, led to severely delayed and incomplete endosperm cellularization, accompanied by disordered cell division in the early embryo. Studies on the marker genes/lines of the endosperm (AGL62-GFP, pDD19::GFP, pDD22::NLS-GFP and N9185) and embryo (STM, FIL, SCR and WOX5) in naa10/naa15 mutants showed that expression patterns of these markers were significantly affected, which were tightly associated with the defective feature of endosperm cellularization and embryo cell differentiation. Subsequently, embryonic complementation rescued the abortive embryos, but failed to initiate endosperm cellularization properly, further confirming the essential role of AtNatA in both endosperm and embryo development. Moreover, repression of AGL62 in naa10 and naa15 restored the endosperm cellularization, suggesting that NAA10/NAA15 functions in initiation of endosperm cellularization by inhibiting the expression of AGL62 in Arabidopsis. Therefore, NAA10 and NAA15 could be considered as crucial factors involved in promoting endosperm cellularization in Arabidopsis.

A two-layer structure prediction framework for microscopy cell detection.

The task of microscopy cell detection is of great biological and clinical importance. However, existing algorithms for microscopy cell detection usually ignore the large variations of cells and only focus on the shape feature/descriptor design. Here we propose a new two-layer model for cell centre detection by a two-layer structure prediction framework, which is respectively built on classification for the cell centres implicitly using rich appearances and contextual information and explicit structural information for the cells. Experimental results demonstrate the efficiency and effectiveness of the proposed method over competing state-of-the-art methods, providing a viable alternative for microscopy cell detection.

Anesthesia information management system-based near real-time decision support to manage intraoperative hypotension and hypertension.

BACKGROUND: Intraoperative hypotension and hypertension are associated with adverse clinical outcomes and morbidity. Clinical decision support mediated through an anesthesia information management system (AIMS) has been shown to improve quality of care. We hypothesized that an AIMS-based clinical decision support system could be used to improve management of intraoperative hypotension and hypertension. METHODS: A near real-time AIMS-based decision support module, Smart Anesthesia Manager (SAM), was used to detect selected scenarios contributing to hypotension and hypertension. Specifically, hypotension (systolic blood pressure <80 mm Hg) with a concurrent high concentration (>1.25 minimum alveolar concentration [MAC]) of inhaled drug and hypertension (systolic blood pressure >160 mm Hg) with concurrent phenylephrine infusion were detected, and anesthesia providers were notified via "pop-up" computer screen messages. AIMS data were retrospectively analyzed to evaluate the effect of SAM notification messages on hypotensive and hypertensive episodes. RESULTS: For anesthetic cases 12 months before (N = 16913) and after (N = 17132) institution of SAM messages, the median duration of hypotensive episodes with concurrent high MAC decreased with notifications (Mann Whitney rank sum test, P = 0.031). However, the reduction in the median duration of hypertensive episodes with concurrent phenylephrine infusion was not significant (P = 0.47). The frequency of prolonged episodes that lasted >6 minutes (sampling period of SAM), represented in terms of the number of cases with episodes per 100 surgical cases (or percentage occurrence), declined with notifications for both hypotension with >1.25 MAC inhaled drug episodes (δ = -0.26% [confidence interval, -0.38% to -0.11%], P < 0.001) and hypertension with phenylephrine infusion episodes (δ = -0.92% [confidence interval, -1.79% to -0.04%], P = 0.035). For hypotensive events, the anesthesia providers reduced the inhaled drug concentrations to <1.25 MAC 81% of the time with notifications compared with 59% without notifications (P = 0.003). For hypertensive episodes, although the anesthesia providers' reduction or discontinuation of the phenylephrine infusion increased from 22% to 37% (P = 0.030) with notification messages, the overall response was less consistent than the response to hypotensive episodes. CONCLUSIONS: With automatic acquisition of arterial blood pressure and inhaled drug concentration variables in an AIMS, near real-time notification was effective in reducing the duration and frequency of hypotension with concurrent >1.25 MAC inhaled drug episodes. However, since phenylephrine infusion is manually documented in an AIMS, the impact of notification messages was less pronounced in reducing episodes of hypertension with concurrent phenylephrine infusion. Automated data capture and a higher frequency of data acquisition in an AIMS can improve the effectiveness of an intraoperative clinical decision support system.

Near real-time notification of gaps in cuff blood pressure recordings for improved patient monitoring.

Blood pressure monitoring during anesthesia is an American Society of Anesthesiology standard. However, the anesthesia provider sometimes fails to engage the patient monitor to make periodic (generally every 3-5 min) measurements of Non-Invasive Blood Pressure (NIBP), which can lead to extended periods (>5 min) when blood pressure is not monitored. We describe a system to automatically detect such gaps in NIBP measurement and notify clinicians in real-time to initiate measurement. We applied a decision support system called the Smart Anesthesia Messenger (SAM) to notify the anesthesia provider if NIBP measurements have not been made in the last 7 min. Notification messages were generated only if direct arterial blood pressure was not being monitored. NIBP gaps were analyzed for 9 months before and after SAM notification was initiated (12,000 cases for each period). SAM notification was able to reduce the occurrence of extended NIBP gaps >15 min from 15.7 ± 4.5 to 6.7 ± 2.0 instances per 1,000 cases (p < 0.001). In addition, for extended gaps (>15 min) the mean gap duration declined from 23.1 ± 2.0 to 18.6 ± 1.1 min after SAM notification was initiated (p < 0.001). However, for 7-15 min gaps, SAM notification was not effective in reducing the occurrence. The maximum gap encountered before SAM was 64 min, while it was 27 min with SAM notification. Real-time notification using SAM is an effective way to reduce both the number of instances and the duration of inadvertent, extended (>15 min) gaps in blood pressure measurements in the operating room. However, the frequency of gaps <15 min could not be reduced using the current configuration of SAM.

Improving documentation of a beta-blocker quality measure through an anesthesia information management system and real-time notification of documentation errors.

BACKGROUND: Continuation of perioperative beta-blockers for surgical patients who are receiving beta-blockers prior to arrival for surgery is an important quality measure (SCIP-Card-2). For this measure to be considered successful, name, date, and time of the perioperative beta-blocker must be documented. Alternately, if the beta-blocker is not given, the medical reason for not administering must be documented. METHODS: Before the study was conducted, the institution lacked a highly reliable process to document the date and time of self-administration of beta-blockers prior to hospital admission. Because of this, compliance with the beta-blocker quality measure was poor (-65%). To improve this measure, the anesthesia care team was made responsible for documenting perioperative beta-blockade. Clear documentation guidelines were outlined, and an electronic Anesthesia Information Management System (AIMS) was configured to facilitate complete documentation of the beta-blocker quality measure. In addition, real-time electronic alerts were generated using Smart Anesthesia Messenger (SAM), an internally developed decision-support system, to notify users concerning incomplete beta-blocker documentation. RESULTS: Weekly compliance for perioperative beta-blocker documentation before the study was 65.8 +/- 16.6%, which served as the baseline value. When the anesthesia care team started documenting perioperative beta-blocker in AIMS, compliance was 60.5 +/- 8.6% (p = .677 as compared with baseline). Electronic alerts with SAM improved documentation compliance to 94.6 +/- 3.5% (p < .001 as compared with baseline). CONCLUSIONS: To achieve high compliance for the beta-blocker measure, it is essential to (1) clearly assign a medical team to perform beta-blocker documentation and (2) enhance features in the electronic medical systems to alert the user concerning incomplete documentation.

Feedback mechanisms including real-time electronic alerts to achieve near 100% timely prophylactic antibiotic administration in surgical cases.

BACKGROUND: Administration of prophylactic antibiotics during surgery is generally performed by the anesthesia providers. Timely antibiotic administration within the optimal time window before incision is critical for prevention of surgical site infections. However, this often becomes a difficult task for the anesthesia team during the busy part of a case when the patient is being anesthetized. METHODS: Starting with the implementation of an anesthesia information management system (AIMS), we designed and implemented several feedback mechanisms to improve compliance of proper antibiotic delivery and documentation. This included generating e-mail feedback of missed documentation, distributing monthly summary reports, and generating real-time electronic alerts with a decision support system. RESULTS: In 20,974 surgical cases for the period, June 2008 to January 2010, the interventions of AIMS install, e-mail feedback, summary reports, and real-time alerts changed antibiotic compliance by -1.5%, 2.3%, 4.9%, and 9.3%, respectively, when compared with the baseline value of 90.0% ± 2.9% when paper anesthesia records were used. Highest antibiotic compliance was achieved when using real-time alerts. With real-time alerts, monthly compliance was >99% for every month between June 2009 and January 2010. CONCLUSIONS: Installation of AIMS itself did not improve antibiotic compliance over that achieved with paper anesthesia records. However, real-time guidance and reminders through electronic messages generated by a computerized decision support system (Smart Anesthesia Messenger, or SAM) significantly improved compliance. With such a system a consistent compliance of >99% was achieved.