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Abstract We study the first law for non-stationary perturbations of a stationary black hole whose event horizon is a Killing horizon, that relates the first-order change in the mass and angular momentum to the change in the entropy of an arbitrary horizon cross-section. Recently, Hollands, Wald and Zhang [1] have shown that the dynamical black hole entropy that satisfies this first law, for general relativity, is S dyn = (1 − v∂ v )S BH, where v is the affine parameter of the null horizon generators and S BH is the Bekenstein-Hawking entropy, and for general diffeomorphism covariant theories of gravity S dyn = (1 − v∂ v )S Wall, where S Wall is the Wall entropy. They obtained the first law by applying the Noether charge method to non-stationary perturbations and arbitrary cross-sections. In this formalism, the dynamical black hole entropy is defined as an “improved” Noether charge, which is unambiguous to first order in the perturbation. In the present article we provide a pedagogical derivation of the physical process version of the non-stationary first law for general relativity by integrating the linearised Raychaudhuri equation between two arbitrary horizon cross-sections. Moreover, we generalise the derivation of the first law in [1] to non-minimally coupled matter fields that are smooth on the horizon, using boost weight arguments rather than Killing field arguments, and we relax some of the gauge conditions on the perturbations by allowing for non-zero variations of the horizon Killing field and surface gravity. Finally, for f(Riemann) theories of gravity we show explicitly using Gaussian null coordinates that the improved Noether charge is S dyn = (1 − v∂ v )S Wall, which is a non-trivial check of [1].

Targeted plasticity therapy (TPT) utilizes vagus nerve stimulation (VNS) to promote improvements in function following neurological injury and disease. During TPT, a brief burst of VNS induces neuromodulator release, which when paired with relevant behavioral events can influence functionally relevant neuroplasticity. Functional improvements following TPT are therefore in part mediated by neuromodulator signaling. Unfortunately, comorbidities associated with neurological disease often result in altered cognitive states that can influence neuromodulator signaling, potentially impeding neuroplasticity induced by TPT. Aside from altered cognitive states, cardiorespiratory rhythms also affect neuromodulator signaling, due to the vagus nerve’s role in relaying visceral sensory information from the cardiovascular and respiratory systems. Moreover, precise VNS delivery during specific periods of the cardiorespiratory rhythms may further improve TPT. Ultimately, understanding the impact of patient-specific states on neuromodulator signaling may likely facilitate optimized VNS delivery, paving the way for personalized neuromodulation during TPT. Overall, this review explores challenges and considerations for developing advanced TPT paradigms, focusing on altered cognitive states and cardiorespiratory rhythms. We specifically discuss the possible impact of these cognitive states and autonomic rhythms on neuromodulator signaling and subsequent neuroplasticity. Altered cognitive states (arousal deficits or pain) could affect VNS intensity, while cardiorespiratory rhythms may further inform optimized timing of VNS. We propose that understanding these interactions will lead to the development of personalized state dependent VNS paradigms for TPT.

Extreme urban heat poses significant challenges to the resilience and livability of cities. Urban squares are important open public spaces in cities, serving as main locations for residents' leisure and recreational activities and reflect the identity and cultural background of the cities. Improvement in thermal comfort in urban squares can improve the quality of the urban environment and help mitigate the urban heat island effect. This study developed 18 layout and landscape combination scenarios based on statistical analysis of data from 100 urban squares in regions with hot summers and cold winters. Further, the effectiveness of the proposed design solutions in improving the thermal environment was comprehensively analyzed. The results show that: 1) The block array layout with vegetation, water bodies, and permeable tiles is the most effective scenario, with a PET of 31.84 °C, approaching a comfortable level of heat stress; 2) Among the three layouts, the block array layout optimizes thermal comfort better than the main view entrance layout and main view center layout, and reduces physiological equivalent temperature by 10.51–10.77 °C compared with that of the other two layouts; 3) Scenarios incorporating water bodies provide better optimization effects than those with only trees, even when the total area covered by greenery remains unchanged; and 4) Permeable paving materials with high albedo more effectively improve the thermal comfort. Our results highlight a great potential of comprehensively using multiple landscape strategies to improve outdoor thermal comfort, and provides design basis for enhancing thermal comfort in similar sized urban squares in hot summer and cold winter areas.

Study region: Loess Plateau, China Study focus: The potential soil erosion has commonly been estimated using the revised universal soil loss equation (RUSLE) under bare land conditions. In few studies, biogeochemical models have been employed to simulate natural vegetation dynamics and assess the effects of regional vegetation restoration on soil loss control. In this study, a biogeochemical Biome-BGC (BBGC) model was developed to simulate the potential vegetation dynamics. The soil erosion rate and erosion control indices under both the current land use/cover (A, ERI) and the potential vegetation conditions (A’, ERI’) were estimated using the RUSLE model and an index-based ecosystem service approach, respectively. The effects of vegetation restoration on erosion control services were ultimately evaluated. New hydrologic insights for the region: The BBGC model performed well in simulating the potential vegetation dynamics. The average annual soil retention increased by 84% after vegetation restoration since 1999. The increased erosion control services accounted for 62% of the Loess Plateau. Erosion control services increased to a high degree (ERI-ERI’ >0.4) in the southeast. Our results demonstrated that vegetation restoration effectively improved the erosion control services on the Loess Plateau. The results could provide a guidance in quantifying the regional effects of vegetation restoration on ecohydrological services and protecting the soil conservation function of watershed ecosystems.

IntroductionColeoptera is the most species-rich order of animals with the widest distribution area; however, little is known about its global suitability distribution, and a substantial number of species are experiencing silent extinction. Most of Earth’s biocommunities are concentrated in biodiversity hotspots, and these hotspots receive the largest investment of conservation funds. The survival of beetles is closely related to the richness of biodiversity, so habitat loss in hotspots results in a high extinction risk for beetles.MethodsWe used the MaxEnt model to simulate the spatial suitable distribution in six time periods (1970-1980, 1980-1990, 1990-2000, 2000-2010, 2010-2020, and 1970-2020). Furthermore, we determined the priority suitable regions in hotspots after coupling the current biodiversity zones and evaluated the congruence between the suitable habitat of beetles and hotspots.ResultsThe results revealed that less than 30% of suitable regions were located in hotspots, and approximately 49.08% of the suitable habitat remained constant in all six periods, and can be regarded as climatically stable refugia. The Mediterranean Basin had the largest suitable area in each period and was always ranked first; other regions, such as Indo-Burma, Irano-Anatolian, and Mesoamerica, also had large areas of suitable habitat. Nine excellent, ten stable, and seventeen lower hotspots were identified based on their dynamic changes in 36 hotspots.DiscussionBased on these results, corresponding planning and management measures should be implemented in different biodiversity hotspots according to the changes in geographic distribution. In this paper, we propose practical advice for different regions to improve isolated and fragmented habitats, which will support the conservation of Coleoptera taxa and the restoration of biodiversity.

Thermal desalination evaporation of high-salt wastewater has been widely used in industry because of the proposed concept of ‘zero liquid discharge’. However, due to the high content of Ca2+ and Mg2+ in high-salt wastewater, the heat exchanger, as the main treatment equipment, suffers from serious scaling problems. This review presents descaling and scale inhibition technologies of high-salt wastewater. The advantages and disadvantages of various technologies are summarized and analyzed to provide theoretical support for the research of descaling and anti-scaling of heat exchangers with high-salt wastewater. In future industrial development, the synergistic application of electromagnetic water treatment technology and scale inhibitors can significantly improve the anti-scaling effect, which can reach over 95% stably. Furthermore, the addition of a physical field can also expand the application range of scale inhibitors. HIGHLIGHTS Mechanisms and limitations of the descaling technology of heat exchangers are explained.; The mechanism of chemical anti-scaling technology is introduced.; The anti-scaling technology in use for high-salt wastewater desalination is reviewed.; The synergistic effects of scale inhibitors and physical fields are put forward.; Future development of anti-scaling technology should notice post-treatment of scales.;

ResNet-based correlation models excel in age recognition algorithms, but specific age recognition research is currently limited and often plagued by substantial errors. We introduce an enhanced portrait age recognition algorithm based on ResNet, using CORAL (consistent rank logits) rank consistent ordered regression instead of traditional classification to predict precise ages. We further improve this approach by incorporating DCN (deformable convolution), resulting in the DCN-R model. DCN dynamically adjusts convolution kernels for diverse faces, improving accuracy and robustness. We tested DCN-R34 and DCN-R50 against the SOTA model, achieving better results with the same complexity. This reduces the computational load while maintaining or enhancing performance.

Abstract Objective To investigate the clinical outcomes and recurrence patterns of high‐intermediate‐risk (HIR)‐ and high‐risk (HR) early‐stage endometrial cancer (EC) treated with postoperative intracavitary brachytherapy alone. Methods We included 152 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I‐II endometrial cancer with HIR and HR factors who received vaginal brachytherapy alone after surgery in our center between April 2008 and December 2017. The irradiation area was the top and upper halves of the vagina. The reference point was defined as 0.5 cm below the vaginal mucosa. The radiation dose was 25–30 Gy 5–6 times. The Kaplan–Meier method was used to calculate the survival rate; differences were assessed using the log‐rank test, and univariate and multivariate prognostic analyses were performed using the Cox regression model. Result The median follow‐up was 49.2 months (range 3–132 months). The 5‐year overall survival (OS), disease‐free survival (DFS), locoregional failure‐free survival time (LRFS), and distant metastasis‐free survival (DMFS) rates were 93.2%, 83.4%, 87.9%, and 86.6%, respectively. Treatment failure occurred in 18 patients, locoregional recurrence in 11, and distant metastasis in 14 (four with locoregional recurrence). Distant metastasis is the main recurrence pattern in patients at HIR and HR. Univariate and multivariate analyses revealed that age was an independent prognostic factor for OS, DFS, DMFS, and LRFS. Conclusion The main recurrence pattern after adjuvant vaginal brachytherapy alone was distant metastasis in patients with HIR and HR early‐stage EC. Age at onset was an independent prognostic factor for survival. Vaginal brachytherapy alone is an acceptable treatment option for patients with HIR and HR early‐stage endometrial cancer.

To date, five species of reddish-brown Neotriplax have been described, but their highly similar body color and other phenotypic traits make accurate taxonomy challenging. To clarify species-level taxonomy and validate potential new species, the cytochrome oxidase subunit I (COI) was used for phylogenetic analysis and the geometric morphometrics of elytron, pronotum, and hind wing were employed to distinguish all reddish-brown Neotriplax species. Phylogenetic results using maximum likelihood and Bayesian analyses of COI sequences aligned well with the current taxonomy of the Neotriplax species group. Significant K2P divergences, with no overlap between intra- and interspecific genetic distances, were obtained in Neotriplax species. The automatic barcode gap discovery (ABGD), assemble species by automatic partitioning (ASAP), and generalized mixed Yule coalescent (GMYC) approaches concurred, dividing the similar species into eight molecular operational taxonomic units (MOTUs). Geometric morphometric analysis using pronotum, elytron, hind wing shape and wing vein patterns also validated the classification of all eight species. By integrating these analytical approaches with morphological evidence, we successfully delineated the reddish-brown species of Neotriplax into eight species with three new species: N. qinghaiensis sp. nov., N. maoershanensis sp. nov., and N. guangxiensis sp. nov. Furthermore, we documented the first record of N. lewisii in China. This study underscores the utility of an integrative taxonomy approach in species delimitation within Neotriplax and serves as a reference for the taxonomic revision of other morphologically challenging beetles through integrative taxonomy.

Van der Waals heterostructures with incommensurate contact interfaces show excellent tribological performance, which provides solutions for the development of new solid lubricants. In this paper, a facile electrostatic layer-by-layer self-assembly (LBL) technique was proposed to prepare multi-layer van der Waals heterostructures tungsten disulfide/hexagonal boron nitride (vdWH WS2/h-BN). The h-BN and WS2 were modified with poly (diallyldimethylammonium chloride) (PDDA) and sodium dodecyl benzene sulfonate (SDBS) to obtain the positively charged PDDA@h-BN and the negatively charged SDBS@WS2, respectively. When the mass ratio of PDDA to h-BN and SDBS to WS2 were both 1:1 and the pH was 3, the zeta potential of PDDA@h-BN and SDBS@WS2 were 60.0 mV and −50.1 mV, respectively. Under the electrostatic interaction, the PDDA@h-BN and SDBS@WS2 attracted each other and stacked alternately along the (002) crystal plane forming the multi-layer (four-layer) vdWH WS2/h-BN. The addition of the multi-layer vdWH WS2/h-BN (1.0 wt%) to the base oil resulted in a significant reduction of 33.8% in the friction coefficient (0.104) and 16.8% in the wear rate (4.43 × 10−5 mm3/(N·m)). The excellent tribological property of the multi-layer vdWH WS2/h-BN arose from the lattice mismatch (26.0%), a 15-fold higher interlayer slip possibility, and the formation of transfer film at the contact interface. This study provided an easily accessible method for the multi-layer vdWH with excellent tribological properties.

BackgroundGliomas, the most prevalent primary malignant tumors of the central nervous system in adults, exhibit slow growth in lower-grade gliomas (LGG). However, the majority of LGG cases progress to high-grade gliomas, posing challenges for prognostication. The tumor microenvironment (TME), characterized by telomere-related genes and immune cell infiltration, strongly influences glioma growth and therapeutic response. Therefore, our objective was to develop a Telomere-TME (TM-TME) classifier that integrates telomere-related genes and immune cell landscape to assess prognosis and therapeutic response in glioma.MethodsThis study encompassed LGG patients from the TCGA and CCGA databases. TM score and TME score were derived from the expression signatures of telomere-related genes and the presence of immune cells in LGG, respectively. The TM-TME classifier was established by combining TM and TME scores to effectively predict prognosis. Subsequently, we conducted Kaplan-Meier survival estimation, univariate Cox regression analysis, and receiver operating characteristic curves to validate the prognostic prediction capacity of the TM-TME classifier across multiple cohorts. Gene Ontology (GO) analysis, biological processes, and proteomaps were performed to annotate the functional aspects of each subgroup and visualize the cellular signaling pathways.ResultsThe TM_low+TME_high subgroup exhibited superior prognosis and therapeutic response compared to other subgroups (P

Enrichment of erythrocytes is a necessary step in the diagnosis of blood diseases. Due to the high deformability and viscosity of erythrocytes, they cannot be regarded as stable point-like solids, so the influence of their deformability on fluid dynamics must be considered. Therefore, by using the special effect of an I-shaped pillar (I-pillar) on erythrocytes, erythrocytes with different deformability can be made to produce different provisional distances in the chip, so as to achieve the separation of the two kinds of erythrocytes. In this study, a microfluidic chip was designed to conduct a control test between erythrocytes stored for a long time and fresh erythrocytes. At a specific flow rate, the different deformable erythrocytes in the chip move in different paths. Then, the influence of erythrocyte deformability on its movement trajectory was analyzed by two-dimensional finite element flow simulation. DLD sorting technology provides a new method for the sorting and enrichment of diseased erythrocytes.

Abstract Background A brain arteriovenous malformation (BAVM) is a tangle of abnormal blood vessels connecting the arteries and veins in the brain and is associated with a higher risk for intracerebral hemorrhage (ICH). RNA sequencing technology has been recently used to investigate the mechanism of diseases owing to its ability to identify the gene changes on a transcriptome-wide level. This study aims to gain insights into the potential mechanism involved in BAVM rupture. Methods Sixty-five BAVM nidus samples were collected, among which 28 were ruptured and 37 were un-ruptured. Then, next-generation RNA sequencing was performed on all of them to obtain differential expressed genes (DEGs) between the two groups. In addition, bioinformatics analysis was performed to evaluate the involved biological processes and pathways by GO and KEGG analysis. Finally, we performed a univariate Cox regression analysis to obtain the early rupture-prone DEGs. Results A total of 951 genes were differentially expressed between the ruptured and un-ruptured BAVM groups, of which 740 genes were upregulated and 211 genes were downregulated in ruptured BAVMs. Then, bioinformatics analysis showed the biological processes and pathways related to the inflammatory processes and extracellular matrix organization were significantly enriched. Meanwhile, some downregulated genes are involved in cell adhesion and genes participating in response to muscle activity and the terms of nervous system development. Finally, one hundred twenty-five genes, many were involved in inflammation, were correlated with the early rupture of BAVMs. Conclusions The upregulated genes in the ruptured BAVM group were involved in inflammatory processes and extracellular matrix organization. Some of the downregulated genes participated in cell adhesion and myofibril assembly, indicating the role of enhanced inflammation and reduced inflammation vessel strength in BAVMs rupture.

Abstract Eye tracking is a widely used technique. To enhance eye gaze estimation in different contexts, many eye tracking datasets have been proposed. However, these datasets depend on calibrations in data capture and its applications. We seek to construct a dataset that enables the design of a calibration-free eye tracking device irrespective of users and scenes. To reach this goal, we present ARGaze, a dataset with 1,321,968 pairs of eye gaze images at 32 × 32 pixel resolution and 50 corresponding videos of world views based on a replicable augmented reality headset. The dataset was captured from 25 participants who completed eye gaze tasks for 30 min in both real-world and augmented reality scenes. To validate the dataset, we compared it against state-of-the-art eye gaze datasets in terms of effectiveness and accuracy and report that the ARGaze dataset achieved record low gaze estimation error by 3.70 degrees on average and 1.56 degrees on specific participants without calibrations to the two scenes. Implications for generalising the use of the dataset are discussed.

Next-generation humidity sensor, as one of the smart devices in artificial skin or flexible electronics, will need to be self-powered, flexible, fast and accurately detecting in the microenvironment. Although various flexible humidity sensors have already been demonstrated, most of them rely on large external power sources to operate, and still suffer from slow response, poor selectivity in environmental stimuli, and expensive and complicated procedures. Here, we realize a self-powered humidity sensor with ultrafast response and recovery time of less than 0.3 s by flexible GO film. Importantly, of all state-of-the-art humidity sensors, this is the fastest response for humidity sensor. Moreover, the sensor has a high sensitivity within a wide range of RH from 33% to 98%, and an excellent selective response to humidity under multiple environmental stimuli, due to its moist-induced generator. Theoretical computations reveal that protons generated spontaneously from oxygen-containing groups and water molecules, have a fast diffusion behavior as Grotthuss hopping. In particular, we build four real-time measurement systems capable of respiration monitoring of human, smart leaf surface humidity sensor, and energy harvesting. Our work provides a simple way to fabricate next-generation self-powered sensor using GO film with outstanding humidity sensor performance.

Augmented reality museums allow visitors to jointly view and interact with exhibits. However, real-time exhibit browsing does not accommodate latecomers to museums and offers limited support to temporally separated visitors. To stimulate asynchronous exhibit browsing, we developed a distance-driven user interface that divided the augmented reality exhibit-egocentric space into four distance ranges, each having a set of social networking features and different privileges for exhibit viewing and interaction. The user interface enables asynchronous exhibit browsing for visitors participating at different times. We conducted empirical studies to evaluate how the user interface affected visitors’ collaborative exhibit browsing in terms of perceived usability and learning gains. The results show that the perceived usability of the user interface is consistently high across all distance ranges. The user interface stimulates collaborative exhibit browsing with significant improvements in learning efficiency and learning attention durations, although learning satisfaction showed no difference across the participants. Implications for how the distance-driven user interface can be generalized for other interactive applications are discussed.

Abstract Background Cerebral arteriovenous malformation (AVM) is a serious life-threatening congenital cerebrovascular disease. Specific anatomical features, such as nidus size, location, and venous drainage, have been validated to affect treatment outcomes. Until recently, molecular biomarkers and corresponding molecular mechanism related to anatomical features and treatment outcomes remain unknown. Methods RNA N6-methyladenosine (m6A) Methyltransferase METTL3 was identified as a differentially expressed gene in groups with different lesion sizes by analyzing the transcriptome sequencing (RNA-seq) data. Tube formation and wound healing assays were performed to investigate the effect of METTL3 on angiogenesis. In addition, Methylated RNA Immunoprecipitation Sequencing technology (MeRIP-seq) was performed to screen downstream targets of METTL3 in endothelial cells and to fully clarify the specific underlying molecular mechanisms affecting the phenotype of cerebral AVM. Results In the current study, we found that the expression level of METTL3 was reduced in the larger pathological tissues of cerebral AVMs. Moreover, knockdown of METTL3 significantly affected angiogenesis of the human endothelial cells. Mechanistically, down-regulation of METTL3 reduced the level of heterodimeric Notch E3 ubiquitin ligase formed by DTX1 and DTX3L, thereby continuously activating the Notch signaling pathway. Ultimately, the up-regulated downstream genes of Notch signaling pathway dramatically affected the angiogenesis of endothelial cells. In addition, we demonstrated that blocking Notch pathway with DAPT could restore the phenotype of METTL3 deficient endothelial cells. Conclusions Our findings revealed the mechanism by which m6A modification regulated the angiogenesis and might provide potential biomarkers to predict the outcome of treatment, as well as provide suitable pharmacological targets for preventing the formation and progression of cerebral AVM.

As a technique to help achieve high performance in parallel and distributed heterogeneous computing systems, task scheduling has attracted considerable interest. In this paper, we propose an effective Cuckoo Search algorithm based on Gaussian random walk and Adaptive discovery probability which combined with a cost-to-time ratio Modification strategy (GACSM), to address task scheduling on heterogeneous multiprocessor systems using Dynamic Voltage and Frequency Scaling (DVFS). First, to overcome the shortcomings of poor performance in exploitation of the cuckoo search algorithm, we use chaos variables to initialize populations to maintain the population diversity, a Gaussian random walk strategy to balance the exploration and exploitation capabilities of the algorithm, and an adaptive discovery probability strategy to improve population diversity. Then, we apply the improved Cuckoo Search (CS) algorithm to assign tasks to resources, and a widely used downward rank heuristic strategy to find the corresponding scheduling sequence. Finally, we apply a cost-to-time ratio improvement strategy to further improve the performance of the improved CS algorithm. Extensive experiments are conducted to evaluate the effectiveness and efficiency of our method. The results validate our approach and show its superiority in comparison with the state-of-the-art methods.

Progressive loss of pancreatic β-cell functional mass and anti-diabetic drug responsivity are classic findings in diabetes, frequently attributed to compensatory insulin hypersecretion and β-cell exhaustion. However, loss of β-cell mass and identity still occurs in mouse models of human KATP-gain-of-function induced Neonatal Diabetes Mellitus (NDM), in the absence of insulin secretion. Here we studied the temporal progression and mechanisms underlying glucotoxicity-induced loss of functional β-cell mass in NDM mice, and the effects of sodium-glucose transporter 2 inhibitors (SGLT2i) therapy. Upon tamoxifen induction of transgene expression, NDM mice rapidly developed severe diabetes followed by an unexpected loss of insulin content, decreased proinsulin processing and increased proinsulin at 2-weeks of diabetes. These early events were accompanied by a marked increase in β-cell oxidative and ER stress, without changes in islet cell identity. Strikingly, treatment with the SGLT2 inhibitor dapagliflozin restored insulin content, decreased proinsulin:insulin ratio and reduced oxidative and ER stress. However, despite reduction of blood glucose, dapagliflozin therapy was ineffective in restoring β-cell function in NDM mice when it was initiated at >40 days of diabetes, when loss of β-cell mass and identity had already occurred. Our data from mouse models demonstrate that: i) hyperglycemia per se, and not insulin hypersecretion, drives β-cell failure in diabetes, ii) recovery of β-cell function by SGLT2 inhibitors is potentially through reduction of oxidative and ER stress, iii) SGLT2 inhibitors revert/prevent β-cell failure when used in early stages of diabetes, but not when loss of β-cell mass/identity already occurred, iv) common execution pathways may underlie loss and recovery of β-cell function in different forms of diabetes. These results may have important clinical implications for optimal therapeutic interventions in individuals with diabetes, particularly for those with long-standing diabetes.

Helotid beetles are commonly found in places where sap flows from tree trunks and in crevices in bark. The Helotidae family is a rare and primitive group of Cucujoidea. To date, no complete mitochondrial (mt) genome has been sequenced for this family. To better understand the characteristics of the mt genome and the evolution of Cucujoidea, we sequenced and annotated the complete mt genomes of Helota thoracica (Ritsema, 1895) and Helota yehi Lee, 2017 using next-generation sequencing. These are the first record of Helotidae mt genomes. The RNA secondary structures of both species were also predicted in this study. The mt genomes of H. thoracica and H. yehi are circular, with total lengths of 16,112 bp and 16,401 bp, respectively. After comparing the mt genomes of H. thoracica and H. yehi, we observed the gene arrangement, codon usage patterns, base content, and RNA secondary structures of both species to be similar, which has also been noted in other Coleoptera insects. The nucleotide sequence of the coding regions and the control region has small differences. The phylogenetic analysis indicated that Helotidae and Protocucujidae are sister groups and revealed the relationship between seven families; however, the validity of the two series (Erotylid series and Nitidulid series) as larger groups in the superfamily was not supported. The mt phylogenomic relationships have strong statistical support. Therefore, the division of Cucujoidea into series should be re-examined. Our results will provide a better understanding of the mt genome and phylogeny of Helotidae and Cucujoidea and will provide valuable molecular markers for further genetic studies.

Transmissible gastroenteritis virus (TGEV) is a coronavirus (CoV) that is a major pathogenity of viral enteritis and diarrhea in suckling piglets, causing high morbidity and mortality. In this study, a TGEV strain HQ2016 was isolated from northeast China and characterized its genome sequence and pathogenicity. The phylogenetic analysis indicated that the TGEV HQ2016 strain was more similar to the TGEV Purdue cluster than to the Miller cluster. Both recombination and phylogenetic analysis based on each structural and non-structural gene revealed no recombination event in the HQ2016 strain. Experimental infection study using colostrum-deprived newborn piglets successfully showed that the HQ2016 can cause clinical symptoms including anorexia and yellow-to-whitish watery diarrhea, which are characteristics of TGE, in the inoculated piglets 48 h post-inoculation. These results provide valuable information about the evolution of the porcine CoVs.

Cantu syndrome (CS) is caused by gain-of-function (GOF) mutations in pore-forming (Kir6.1, KCNJ8) and accessory (SUR2, ABCC9) ATP-sensitive potassium (KATP) channel subunits, the most common mutations being SUR2[R1154Q] and SUR2[R1154W], carried by approximately 30% of patients. We used CRISPR/Cas9 genome engineering to introduce the equivalent of the human SUR2[R1154Q] mutation into the mouse ABCC9 gene. Along with minimal CS disease features, R1154Q cardiomyocytes and vascular smooth muscle showed much lower KATP current density and pinacidil activation than WT cells. Almost complete loss of SUR2-dependent protein and KATP in homozygous R1154Q ventricles revealed underlying diazoxide-sensitive SUR1-dependent KATP channel activity. Surprisingly, sequencing of SUR2 cDNA revealed 2 distinct transcripts, one encoding full-length SUR2 protein; and the other with an in-frame deletion of 93 bases (corresponding to 31 amino acids encoded by exon 28) that was present in approximately 40% and approximately 90% of transcripts from hetero- and homozygous R1154Q tissues, respectively. Recombinant expression of SUR2A protein lacking exon 28 resulted in nonfunctional channels. CS tissue from SUR2[R1154Q] mice and human induced pluripotent stem cell–derived (hiPSC-derived) cardiomyocytes showed only full-length SUR2 transcripts, although further studies will be required in order to fully test whether SUR2[R1154Q] or other CS mutations might result in aberrant splicing and variable expressivity of disease features in human CS.

The immune microenvironment is important for the development, progression, and prognosis of anaplastic glioma (AG). This complex milieu has not been fully elucidated, and a high-dimensional analysis is urgently required. Utilizing mass cytometry (CyTOF), we performed an analysis of immune cells from 5 patients with anaplastic astrocytoma, IDH-mutant (AAmut) and 10 patients with anaplastic oligodendroglioma, IDH-mutant and 1p/19q codeletion (AOD) and their paired peripheral blood mononuclear cells (PBMCs). Based on a panel of 33 biomarkers, we demonstrated the tumor-driven immune changes in the AG immune microenvironment. Our study confirmed that mononuclear phagocytes and T cells are the most abundant immunocytes in the AG immune microenvironment. Glioma-associated microglia/macrophages in both AAmut and AOD samples showed highly immunosuppressive characteristics. Compared to those in the PBMCs, the ratios of immune checkpoint-positive exhausted CD4+ T cells and CD8+ T cells were higher at the AG tumor sites. The AAmut immune milieu exhibits more immunosuppressive characteristics than that in AOD.

Background and aims: The role of statins in unruptured intracranial aneurysm (UIA) growth and rupture remains ambiguous. This study sought to determine whether atorvastatin is associated with aneurysm growth and rupture in patients harboring UIA

Cantú syndrome (CS), caused by gain-of-function (GOF) mutations in pore-forming (Kir6.1, KCNJ8) and accessory (SUR2, ABCC9) ATP-sensitive potassium (KATP) channel subunit genes, is frequently accompanied by gastrointestinal (GI) dysmotility, and we describe 1 CS patient who required an implanted intestinal irrigation system for successful stooling. We used gene-modified mice to assess the underlying KATP channel subunits in gut smooth muscle and to model the consequences of altered KATP channels in CS gut. We show that Kir6.1/SUR2 subunits underlie smooth muscle KATP channels throughout the small intestine and colon. Knockin mice, carrying human KCNJ8 and ABCC9 CS mutations in the endogenous loci, exhibited reduced intrinsic contractility throughout the intestine, resulting in death when weaned onto solid food in the most severely affected animals. Death was avoided by weaning onto a liquid gel diet, implicating intestinal insufficiency and bowel impaction as the underlying cause, and GI transit was normalized by treatment with the KATP inhibitor glibenclamide. We thus define the molecular basis of intestinal KATP channel activity, the mechanism by which overactivity results in GI insufficiency, and a viable approach to therapy.

The refined characterization of groundwater pollution is an important prerequisite for efficient and effective remediation. A high-resolution survey of a contaminated site in a chemical pesticide factory was carried out using non-invasive geophysical sensing technology. Modern electrical resistivity tomography (ERT) technology can rapidly identify and characterize the groundwater pollution plumes of organochlorine pesticides, which was demonstrated in this study by the significantly abnormal resistivity sensing in stratums and aquifers under the raw material tanks, production, and loading areas. The results were found to be highly consistent with the ERT sensing results achieved via incorporating borehole sampling and hydrochemical analysis. With high abnormal resistivity, the range of contamination within the profile was characterized on the meter level. We also unexpectedly found new pollution and explained its source. This study confirmed that the modern refined ERT method has a high feasibility and accuracy in characterizing the spatial distribution of organochlorine pesticide plumes in groundwater.

The Glioblastoma (GBM) immune microenvironment plays a critical role in tumor development, progression, and prognosis. A comprehensive understanding of the intricate milieu and its interactions remains unclear, and single-cell analysis is crucially needed. Leveraging mass cytometry (CyTOF), we analyzed immunocytes from 13 initial and three recurrent GBM samples and their matched peripheral blood mononuclear cells (pPBMCs). Using a panel of 30 markers, we provide a high-dimensional view of the complex GBM immune microenvironment. Hematoxylin and eosin staining and polychromatic immunofluorescence were used for verification of the key findings. In the initial and recurrent GBMs, glioma-associated microglia/macrophages (GAMs) constituted 59.05 and 27.87% of the immunocytes, respectively; programmed cell death-ligand 1 (PD-L1), T cell immunoglobulin domain and mucin domain-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), interleukin-10 (IL-10) and transforming growth factor-β (TGFβ) demonstrated different expression levels in the GAMs among the patients. GAMs could be subdivided into different subgroups with different phenotypes. Both the exhausted T cell and regulatory T (Treg) cell percentages were significantly higher in tumors than in pPBMCs. The natural killer (NK) cells that infiltrated into the tumor lesions expressed higher levels of CXC chemokine receptor 3 (CXCR3), as these cells expressed lower levels of interferon-γ (IFNγ). The immune microenvironment in the initial and recurrent GBMs displayed similar suppressive changes. Our study confirmed that GAMs, as the dominant infiltrating immunocytes, present great inter- and intra-tumoral heterogeneity and that GAMs, increased exhausted T cells, infiltrating Tregs, and nonfunctional NK cells contribute to local immune suppressive characteristics. Recurrent GBMs share similar immune signatures with the initial GBMs except the proportion of GAMs decreases.

The tumor immune microenvironment (TIME) plays a pivotal role in tumor development, progression, and prognosis. However, the characteristics of the TIME in diffuse astrocytoma (DA) are still unclear. Leveraging mass cytometry with a panel of 33 markers, we analyzed the infiltrating immune cells from 10 DA and 4 oligodendroglioma (OG) tissues and provided a single cell-resolution landscape of the intricate immune microenvironment. Our study profiled the composition of the TIME in DA and confirmed the presence of immune cells, such as glioma-associated microglia/macrophages (GAMs), CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), and natural killer cells. Increased percentages of PD-1+ CD8+ T cells, TIM-3+ CD4+ T cell subpopulations, Tregs and pro-tumor phenotype GAMs substantially contribute to the local immunosuppressive microenvironment in DA. DAs and OGs share similar compositions in terms of immune cells, while GAMs in DA exhibit more inhibitory characteristics than those in OG.

Background The blood flow rate of brain arteriovenous malformations (bAVMs) is an important clinical characteristic closely associated with the hemorrhage risk and radiosurgery obliteration rate of bAVMs. However, the underlying molecular properties remain unclear. To identify potential key molecules, signaling pathways, and vascular cell types involved, we compared gene expression profiles between bAVMs with high flow rates and low flow rates (LFR) and validated the functions of selected key molecules in vitro. Methods and Results We performed RNA‐sequencing analysis on 51 samples, including 14 high flow rate bAVMs and 37 LFR bAVMs. Functional pathway analysis was performed to identify potential signals influencing the flow rate phenotype of bAVMs. Candidate genes were investigated in bAVM specimens by immunohistochemical staining. Migration, tube formation, and proliferation assays were used to test the effects of candidate genes on the phenotypic properties of cultured human umbilical vein endothelial cells and human brain vascular smooth muscle cells. We identified 250 upregulated and 118 downregulated genes in LFR bAVMs compared with high flow rate bAVMs. Wnt signaling was activated in the LFR group via upregulation of FZD10 and MYOC. Immunohistochemical staining showed that vascular endothelial and smooth muscle cells of LFR bAVMs exhibited increased FZD10 and MYOC expression. Experimentally elevating these genes promoted human umbilical vein endothelial cells and migration and tube formation by activating canonical Wnt signaling in vitro. Conclusions Our results suggest that canonical Wnt signaling mediated by FZD10 and MYOC is activated in vascular endothelial and smooth muscle cells in LFR bAVMs.

While numerous studies have explored using various sensing techniques to measure attention states, moment-to-moment attention fluctuation measurement is unavailable. To bridge this gap, we applied a novel paradigm in psychology, the gradual-onset continuous performance task (gradCPT), to collect the ground truth of attention states. GradCPT allows for the precise labeling of attention fluctuation on an 800 ms time scale. We then developed a new technique for measuring continuous attention fluctuation, based on a machine learning approach that uses the spectral properties of EEG signals as the main features. We demonstrated that, even using a consumer grade EEG device, the detection accuracy of moment-to-moment attention fluctuations was 73.49%. Next, we empirically validated our technique in a video learning scenario and found that our technique match with the classification obtained through thought probes, with an average F1 score of 0.77. Our results suggest the effectiveness of using gradCPT as a ground truth labeling method and the feasibility of using consumer-grade EEG devices for continuous attention fluctuation detection.

ATP-sensitive potassium channels (KATP channels) are critical nutrient sensors in many mammalian tissues. In the pancreas, KATP channels are essential for coupling glucose metabolism to insulin secretion. While orthologous genes for many components of metabolism–secretion coupling in mammals are present in lower vertebrates, their expression, functionality and ultimate impact on body glucose homeostasis are unclear. In this paper, we demonstrate that zebrafish islet β-cells express functional KATP channels of similar subunit composition, structure and metabolic sensitivity to their mammalian counterparts. We further show that pharmacological activation of native zebrafish KATP using diazoxide, a specific KATP channel opener, is sufficient to disturb glucose tolerance in adult zebrafish. That β-cell KATP channel expression and function are conserved between zebrafish and mammals illustrates the evolutionary conservation of islet metabolic sensing from fish to humans, and lends relevance to the use of zebrafish to model islet glucose sensing and diseases of membrane excitability such as neonatal diabetes.

Targeted plasticity therapy (TPT) utilizes vagus nerve stimulation (VNS) to promote improvements in function following neurological injury and disease. During TPT, a brief burst of VNS induces neuromodulator release, which when paired with relevant behavioral events can influence functionally relevant neuroplasticity. Functional improvements following TPT are therefore in part mediated by neuromodulator signaling. Unfortunately, comorbidities associated with neurological disease often result in altered cognitive states that can influence neuromodulator signaling, potentially impeding neuroplasticity induced by TPT. Aside from altered cognitive states, cardiorespiratory rhythms also affect neuromodulator signaling, due to the vagus nerve’s role in relaying visceral sensory information from the cardiovascular and respiratory systems. Moreover, precise VNS delivery during specific periods of the cardiorespiratory rhythms may further improve TPT. Ultimately, understanding the impact of patient-specific states on neuromodulator signaling may likely facilitate optimized VNS delivery, paving the way for personalized neuromodulation during TPT. Overall, this review explores challenges and considerations for developing advanced TPT paradigms, focusing on altered cognitive states and cardiorespiratory rhythms. We specifically discuss the possible impact of these cognitive states and autonomic rhythms on neuromodulator signaling and subsequent neuroplasticity. Altered cognitive states (arousal deficits or pain) could affect VNS intensity, while cardiorespiratory rhythmsmay further inform optimized timing of VNS. We propose that understanding these interactions will lead to the development of personalized state dependent VNS paradigms for TPT. [ABSTRACT FROM AUTHOR]