ent-8(14),15-Pimaradiene-2ß,19-diol, a diterpene from Aleuritopteris albofusca, inhibits growth and induces protective autophagy in hepatocellular carcinoma cells.

A new pimarane-type diterpene, ent-8(14),15-pimaradiene-2ß,19-diol (JXE-23), was isolated from the fern plant Aleuritopteris albofusca by our previous work; however, the biological activity of this diterpene remains unclear. In the present study, the anti-cancer potential of JXE-23 in various cancer cells was investigated. Among MCF-7 breast cancer cells, A549 lung cancer cells, and HepG2 liver cancer cells, JXE-23 displayed significant cytotoxicity to HepG2 cells with an IC50 value of 17.20 ± 1.73 µM, while showing no obvious toxicity in normal hepatocytes HL7702. JXE-23 inhibited cell growth and colony formation in HepG2 cells. A cell cycle distribution analysis showed that JXE-23 caused G2/M cell cycle arrest. Besides, JXE-23 also suppressed the migration of HepG2 cells. Interestingly, an increase of light chain 3 II (LC3II) and Beclin 1 and a decrease of P62 have occurred in JXE-23-treated cells, as well as the formation of GFP-LC3 dots, indicative of autophagy induction by JXE-23. When combined with autophagy inhibitor 3-methyladenine and chloroquine, the cell viability was significantly reduced, suggesting that JXE-23 triggered protective autophagy in hepatoma cells. Further study showed that JXE-23 inactivated the CIP2A/p-AKT/c-Myc signaling axis in HepG2 cells. Our data provided evidence that JXE-23 inhibited cell growth, arrested cells at the G2/M phase, and induced protective autophagy in HepG2 hepatocellular carcinoma cells. JXE-23 may be a potential lead compound for anti-cancer drug development, and autophagy inhibitor treatment may provide an effective strategy for improving its anti-cancer effect.

Collective effects of rising average temperatures and heat events on oviparous embryos.

Survival of the immobile embryo in response to rising temperature is important to determine a species' vulnerability to climate change. However, the collective effects of 2 key thermal characteristics associated with climate change (i.e., rising average temperature and acute heat events) on embryonic survival remain largely unexplored. We used empirical measurements and niche modeling to investigate how chronic and acute heat stress independently and collectively influence the embryonic survival of lizards across latitudes. We collected and bred lizards from 5 latitudes and incubated their eggs across a range of temperatures to quantify population-specific responses to chronic and acute heat stress. Using an embryonic development model parameterized with measured embryonic heat tolerances, we further identified a collective impact of embryonic chronic and acute heat tolerances on embryonic survival. We also incorporated embryonic chronic and acute heat tolerance in hybrid species distribution models to determine species' range shifts under climate change. Embryos' tolerance of chronic heat (T-chronic) remained consistent across latitudes, whereas their tolerance of acute heat (T-acute) was higher at high latitudes than at low latitudes. Tolerance of acute heat exerted a more pronounced influence than tolerance of chronic heat. In species distribution models, climate change led to the most significant habitat loss for each population and species in its low-latitude distribution. Consequently, habitat for populations across all latitudes will shift toward high latitudes. Our study also highlights the importance of considering embryonic survival under chronic and acute heat stresses to predict species' vulnerability to climate change.

Efectos colectivos del aumento de las temperaturas promedio y los eventos de calor en embriones ovíparos Resumen La supervivencia de los embriones inmóviles en respuesta al incremento de temperatura es importante para determinar la vulnerabilidad de las especies al cambio climático. Sin embargo, los efectos colectivos de dos características térmicas claves asociadas con el cambio climático (i. e., aumento de temperatura promedio y eventos de calor agudo) sobre la supervivencia embrionaria permanecen en gran parte inexplorados. Utilizamos mediciones empíricas y modelos de nicho para investigar cómo el estrés térmico crónico y agudo influye de forma independiente y colectiva en la supervivencia embrionaria de los lagartos en todas las latitudes. Recolectamos y criamos lagartos de cinco latitudes e incubamos sus huevos en un rango de temperaturas para cuantificar las respuestas específicas de la población al estrés por calor crónico y agudo. Posteriormente, mediante un modelo de desarrollo embrionario parametrizado con mediciones de tolerancia embrionaria al calor, identificamos un impacto colectivo de las tolerancias embrionarias al calor agudo y crónico en la supervivencia embrionaria. También incorporamos la tolerancia embrionaria crónica y aguda al calor en modelos de distribución de especies híbridas para determinar los cambios de distribución de las especies bajo el cambio climático. La tolerancia embrionaria al calor crónico (T­crónico) permaneció constante, mientras que la tolerancia al calor agudo (T­agudo) fue mayor en latitudes altas que en latitudes bajas. La tolerancia al calor agudo ejerció una influencia más pronunciada que la tolerancia al calor crónico. En los modelos de distribución de especies, el cambio climático provocó la pérdida de hábitat más significativa para cada población y especie en su distribución de latitudes bajas. En consecuencia, el hábitat para poblaciones en todas las latitudes se desplazará a latitudes altas. Nuestro estudio también resalta la importancia de considerar la supervivencia embrionaria bajo estrés térmico crónico y agudo para predecir la vulnerabilidad de las especies al cambio climático.

Formation of Anisotropic Conducting Interlayer for High-Resolution Epidermal Electromyography Using Mixed-Conducting Particulate Composite.

Epidermal electrophysiology is a non-invasive method used in research and clinical practices to study the electrical activity of the brain, heart, nerves, and muscles. However, electrode/tissue interlayer materials such as ionically conducting pastes can negatively affect recordings by introducing lateral electrode-to-electrode ionic crosstalk and reducing spatial resolution. To overcome this issue, biocompatible, anisotropic-conducting interlayer composites (ACI) that establish an electrically anisotropic interface with the skin are developed, enabling the application of dense cutaneous sensor arrays. High-density, conformable electrodes are also microfabricated that adhere to the ACI and follow the curvilinear surface of the skin. The results show that ACI significantly enhances the spatial resolution of epidermal electromyography (EMG) recording compared to conductive paste, permitting the acquisition of single muscle action potentials with distinct spatial profiles. The high-density EMG in developing mice, non-human primates, and humans is validated. Overall, high spatial-resolution epidermal electrophysiology enabled by ACI has the potential to advance clinical diagnostics of motor system disorders and enhance data quality for human-computer interface applications.

Giant unruptured sinus of Valsalva aneurysms causing angina pectoris.

BACKGROUND: Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly which can be congenital or acquired. Patients with SVA are commonly asymptomatic when the occupying effect of SVA is insignificant, while ruptured SVA usually causes severe symptoms including heart failure and myocardial ischemia. CASE PRESENTATION: We present an unusual case of a 64-year-old female manifesting with exertional dyspnea as well as angina pectoris for three months. Echocardiography and cardiac computed tomographic angiography confirmed unruptured left-coronary and non-coronary SVAs. The left anterior descending artery and left circumflex artery were stretched and compressed by the SVA which causing myocardial ischemia. The patient finally received aortic root replacement (Bentall procedure) and got symptom relieved. CONCLUSIONS: Giant unruptured SVA originating from left coronary sinus is extremely rare. Our case highlights that giant SVA should be considered in cases with angina pectoris. Echocardiography and coronary computed tomographic angiography are useful and important for diagnosis. Surgery is highly recommended in patients with SVA.

Enhancing the thermopower of single-molecule junctions by edge substitution effects.

Heteroatom substitution and anchoring groups have an important impact on the thermoelectric properties of single-molecule junctions. Herein, thermoelectric properties of several anthracene derivative based single-molecule junctions are studied by means of first-principles calculations. In particular, we pay great attention to the edge substitution effects and find that edge substitution with nitrogen can induce a transmission peak near the Fermi energy, leading to large transmission coefficients and electrical conductance at the Fermi energy. Additionally, the steep shape of the transmission function gives rise to a high Seebeck coefficient. Therefore, an enhanced power factor can be expected. The robustness of this edge substitution effect has been examined by altering the electrode distance and introducing heteroatoms at different positions. The enhancement of the power factor due to edge substitution makes the studied single-molecule junction a promising candidate for efficient thermoelectric devices.

Centric Sc(HPO3)(H2PO3)(H2O) and Acentric Sc(H2PO3)3: Two Ultraviolet Scandium Phosphite Optical Crystals.

Exploring ultraviolet (UV) nonlinear-optical (NLO) materials is significant for the conversion of a high-frequency laser. Two scandium phosphites, Sc(HPO3)(H2PO3)(H2O) and Sc(H2PO3)3, were successfully synthesized. Centric Sc(HPO3)(H2PO3)(H2O) exhibits a short UV cutoff edge (<200 nm) and a unique double-layer structure of [Sc2(HPO3)2(H2PO3)2(H2O)2]∞. The acentric Sc(H2PO3)3 exhibits a three-dimensional [Sc(H2PO3)3]∞ structure with a large band gap of 4.05 eV, and it demonstrates a moderately phase-matchable second-harmonic-generation response [0.60 × KDP (KH2PO4)] at 1064 nm. The crystal structures, optical properties, and theoretical calculations of the two compounds are discussed. This work will promote the exploration of new NLO phosphite materials.

Inhibition of ACSS2-mediated histone crotonylation alleviates kidney fibrosis via IL-1ß-dependent macrophage activation and tubular cell senescence.

Histone lysine crotonylation (Kcr), as a posttranslational modification, is widespread as acetylation (Kac); however, its roles are largely unknown in kidney fibrosis. In this study, we report that histone Kcr of tubular epithelial cells is abnormally elevated in fibrotic kidneys. By screening these crotonylated/acetylated factors, a crotonyl-CoA-producing enzyme ACSS2 (acyl-CoA synthetase short chain family member 2) is found to remarkably increase histone 3 lysine 9 crotonylation (H3K9cr) level without influencing H3K9ac in kidneys and tubular epithelial cells. The integrated analysis of ChIP-seq and RNA-seq of fibrotic kidneys reveal that the hub proinflammatory cytokine IL-1ß, which is regulated by H3K9cr, play crucial roles in fibrogenesis. Furthermore, genetic and pharmacologic inhibition of ACSS2 both suppress H3K9cr-mediated IL-1ß expression, which thereby alleviate IL-1ß-dependent macrophage activation and tubular cell senescence to delay renal fibrosis. Collectively, our findings uncover that H3K9cr exerts a critical, previously unrecognized role in kidney fibrosis, where ACSS2 represents an attractive drug target to slow fibrotic kidney disease progression.

High-Density, Conformable Conducting Polymer-Based Implantable Neural Probes for the Developing Brain.

Neurologic and neuropsychiatric disorders substantially impact the pediatric population, but there is a lack of dedicated devices for monitoring the developing brain in animal models, leading to gaps in mechanistic understanding of how brain functions emerge and their disruption in disease states. Due to the small size, fragility, and high water content of immature neural tissue, as well as the absence of a hardened skull to mechanically support rigid devices, conventional neural interface devices are poorly suited to acquire brain signals without inducing damage. Here, the authors design conformable, implantable, conducting polymer-based probes (NeuroShanks) for precise targeting in the developing mouse brain without the need for skull-attached, rigid mechanical support structures. These probes enable the acquisition of high spatiotemporal resolution neurophysiologic activity from superficial and deep brain regions across unanesthetized behavioral states without causing tissue disruption or device failure. Once implanted, probes are mechanically stable and permit precise, stable signal monitoring at the level of the local field potential and individual action potentials. These results support the translational potential of such devices for clinically indicated neurophysiologic recording in pediatric patients. Additionally, the role of organic bioelectronics as an enabling technology to address questions in developmental neuroscience is revealed.

 Mazusjiangshiense (Mazaceae), a new species from China: evidence from morphological and molecular analyses.

Utilising both morphological and molecular analyses, this study unveils Mazusjiangshiensesp. nov., a novel addition to the Mazaceae family, discovered in Shaowu County, Fujian Province, China. The comprehensive description and illustrations provided here are a result of a meticulous exploration of its morphological features. While bearing a resemblance to M.gracilis, this new-found species is distinguished by three distinct characteristics: its stems are delicately soft, its leaves possess a membranous quality and the ovary is notably villous at the apex. Integration of molecular evidence, derived from the nuclear ribosomal DNA (nrITS) and three plastid DNA sequences (rps16, rbcL and trnL-trnF), unequivocally supports the classification of M.jiangshiense as a distinct species. Notably, the molecular analysis positions it as a sister species to M.spicatus, underscoring the phylogenetic relationships within the genus Mazus. Our research not only introduces M.jiangshiense as a novel taxonomic entity, but also provides a nuanced understanding of its morphological differences and molecular affinities, enriching our comprehension of the diversity and evolutionary relationships of Mazaceae.

Multimodal Connectivity-based Individual Parcellation and Analysis for Humans and Rhesus Monkeys.

Individual brains vary greatly in morphology, connectivity and organization. Individualized brain parcellation is capable of precisely localizing subject-specific functional regions. However, most individualization approaches examined single modality of data and have not generalized to nonhuman primates. The present study proposed a novel multimodal connectivity-based individual parcellation (MCIP) method, which optimizes within-region homogeneity, spatial continuity and similarity to a reference atlas with the fusion of personal functional and anatomical connectivity. Comprehensive evaluation demonstrated that MCIP outperformed state-of-the-art multimodal individualization methods in terms of functional and anatomical homogeneity, predictability of cognitive measures, heritability, reproducibility and generalizability across species. Comparative investigation showed a higher topographic variability in humans than that in macaques. Therefore, MCIP provides improved accurate and reliable mapping of brain functional regions over existing methods at an individual level across species, and could facilitate comparative and translational neuroscience research.

Stabilizing the Bulk-phase and Solid Electrolyte Interphase of Silicon Microparticle Anode by Constructing Gradient-Hierarchically Ordered Conductive Networks.

The poor bulk-phase and interphase stability, attributable to adverse internal stress, impede the cycling performance of silicon microparticles (µSi) anodes and its commercial application for high-energy-density lithium-ion batteries. In this work, we propose a groundbreaking gradient-hierarchically ordered conductive (GHOC) network structure, ingeniously engineered to enhance the stability of both bulk-phase and the solid electrolyte interphase (SEI) configurations of µSi. Within the GHOC network architecture, two-dimensional transition metal carbides (Ti3C2Tx) acts as a conductive "brick", establishing a highly conductive inner layer on µSi, while the porous outer layer, composed of one-dimensional Tempo-oxidized cellulose nanofibers (TCNF) and polyacrylic acid (PAA) macromolecule, functions akin to structural "rebar" and "concrete", effectively preserves the tightly interconnected conductive framework though multiple bonding mechanisms, including covalent and hydrogen bonds. Additionally, Ti3C2Tx enhances the development of a LiF-enriched SEI. Consequently, the µSi-MTCNF-PAA anode presents a high discharge capacity of 1413.7 mAh g-1 even after 500 cycles at 1.0 C. Moreover, a full cell, integrating LiNi0.8Mn0.1Co0.1O2 with µSi-MTCNF-PAA, exhibits a capacity retention rate of 92.0% following 50 cycles. This GHOC network structure could offer an efficacious pathway for stabilizing both the bulk-phase and interphase structure of anode materials with high volumetric strain. This article is protected by copyright. All rights reserved.

Replenishment of mitochondrial Na+ and H+ by ionophores potentiates cutaneous wound healing in diabetes.

Diabetic foot ulcer (DFU) is a highly morbid complication in patients with diabetes mellitus, necessitating the development of innovative pharmaceuticals to address unmet medical needs. Sodium ion (Na+) is a well-established mediator for membrane potential and osmotic equilibrium. Recently, Na+ transporters have been identified as a functional regulator of regeneration. However, the role of Na+ in the intricate healing process of mammalian wounds remains elusive. Here, we found that the skin wounds in hyponatremic mice display a hard-to-heal phenotype. Na+ ionophores that were employed to increase intracellular Na+ content could facilitate keratinocyte proliferation and migration, and promote angiogenesis, exhibiting diverse biological activities. Among of them, monensin A emerges as a promising agent for accelerating the healing dynamics of skin wounds in diabetes. Mechanistically, the elevated mitochondrial Na+ decelerates inner mitochondrial membrane fluidity, instigating the production of reactive oxygen species (ROS), which is identified as a critical effector on the monensin A-induced improvement of wound healing. Concurrently, Na+ ionophores replenish H+ to the mitochondrial matrix, causing an enhancement of mitochondrial energy metabolism to support productive wound healing programs. Our study unfolds a new role of Na+, which is a pivotal determinant in wound healing. Furthermore, it directs a roadmap for developing Na+ ionophores as innovative pharmaceuticals for treating chronic dermal wounds in diabetic patients.

Basic magnesium sulfate@TiO2 composite for efficient adsorption and photocatalytic degradation of 4-dodecylmorpholine in brine.

More than 70% of the potash fertilizer globally is produced by the froth flotation process, in which 4-dodecylmorpholine (DMP) serves as a reverse flotation agent. As the potash fertilizer production rapidly rises, the increased DMP levels in discharged brine pose a threat to the production of high-value chemicals. In this paper, composite particles of basic magnesium sulfate@TiO2 (BMS@TiO2) were prepared using a simple and mild loading method. These particles were utilized for the adsorption and photocatalytic degradation of DMP in brine. Compared with normal powdered materials, the granular BMS@TiO2 in this study can be easily separated from liquid, and the degradation intermediates will not enter the brine without causing secondary pollution. BMS@TiO2 consists of 5·1·7 phase (5Mg(OH)2·MgSO4·7H2O) whisker clusters embedding 2.3% TiO2. The adsorption equilibrium of DMP on BMS@TiO2 particles was achieved through hydrogen bonding and pore interception with the adsorption capacity of approximately 5 mg g-1 after 6 h. The photodegradation efficiency of DMP adsorbed on BMS@TiO2 reached about 92% within 16 h, which is compared with that of pure TiO2 nanoparticles. Additionally, excellent stability and recyclability of BMS@TiO2 were also observed in five cycle tests of adsorption and photocatalytic degradation of DMP, and the possible photocatalytic degradation pathways and mechanism of DMP are proposed following molecular electrostatic potential analysis. This work provides a sustainable and environmentally friendly approach for eliminating organic micropollutants from water environments.

Prospect of value and application of transcutaneous electrical acupoint stimulation to control blood pressure in proactive healthcare perspective. / 主动健康视域下经皮穴位电刺激调控血压的价值与应用展望.

Hypertension is a global problem threatening human health and life. Although there are many antihypertensive drugs, the low compliance of medication affects its efficacy, and the effect in regulating hypertension has become increasingly prominent. Focusing on the new trend of proactive healthcare management, in the present paper, we made a summary about the status and existing problems of transcutaneous electrical acupoint stimulation (TEAS) in the regulation of blood pressure, and put forward some suggestions, such as selecting acupoints based on classical acupuncture theory to highlight the advantages of TEAS to control blood pressure as a whole, optimizing and screening the parameters of TEAS in the regulation of blood pressure, expanding the research observation indexes etc. We also made a prospect about its future application, hoping to provide new ideas for the proactive regulation, whole-process regulation and integrated regulation of blood pressure.

Deep learning of pretreatment multiphase CT images for predicting response to lenvatinib and immune checkpoint inhibitors in unresectable hepatocellular carcinoma.

Objectives: Combination therapy of lenvatinib and immune checkpoint inhibitors (CLICI) has emerged as a promising approach for managing unresectable hepatocellular carcinoma (HCC). However, the response to such treatment is observed in only a subset of patients, underscoring the pressing need for reliable methods to identify potential responders. Materials & methods: This was a retrospective analysis involving 120 patients with unresectable HCC. They were divided into training (n = 72) and validation (n = 48) cohorts. We developed an interpretable deep learning model using multiphase computed tomography (CT) images to predict whether patients will respond or not to CLICI treatment, based on the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). We evaluated the models' performance and analyzed the impact of each CT phase. Critical regions influencing predictions were identified and visualized through heatmaps. Results: The multiphase model outperformed the best biphase and uniphase models, achieving an area under the curve (AUC) of 0.802 (95% CI = 0.780-0.824). The portal phase images were found to significantly enhance the model's predictive accuracy. Heatmaps identified six critical features influencing treatment response, offering valuable insights to clinicians. Additionally, we have made this model accessible via a web server at http://uhccnet.com/ for ease of use. Conclusions: The integration of multiphase CT images with deep learning-generated heatmaps for predicting treatment response provides a robust and practical tool for guiding CLICI therapy in patients with unresectable HCC.

Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma.

Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a "spatially competing distribution" (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.

CircRNA CDR1as affects functional repair after spinal cord injury and regulates fibrosis through the SMAD pathway.

Spinal cord injury (SCI) is a complex problem in modern medicine. Fibroblast activation and fibroscarring after SCI impede nerve recovery. Non-coding RNA plays an important role in the progression of many diseases, but the study of its role in the progression of spinal fibrosis is still emerging. Here, we investigated the function of circular RNAs, specifically antisense to the cerebellar degeneration-related protein 1 (CDR1as), in spinal fibrosis and characterized its molecular mechanism and pathophysiology. The presence of CDR1as in the spinal cord was verified by sequencing and RNA expression assays. The effects of inhibition of CDR1as on scar formation, inflammation and nerve regeneration after spinal cord injury were investigated in vivo and in vitro. Further, gene expression of miR-7a-5p and protein expression of transforming Growth Factor Beta Receptor II (TGF-ßR2) were measured to evaluate their predicted interactions with CDR1as. The regulatory effects and activation pathways were subsequently verified by miR-7a-5p inhibitor and siCDR1as. These results indicate that CDR1as/miR-7a-5p/TGF-ßR2 interactions may exert scars and nerves functions and suggest potential therapeutic targets for treating spinal fibrotic diseases.

Retracing the evolution of Pneumocystis species, with a focus on the human pathogen Pneumocystis jirovecii.

SUMMARYEvery human being is presumed to be infected by the fungus Pneumocystis jirovecii at least once in his or her lifetime. This fungus belongs to a large group of species that appear to exclusively infect mammals, with P. jirovecii being the only one known to cause disease in humans. The mystery of P. jirovecii origin and speciation is just beginning to unravel. Here, we provide a review of the major steps of P. jirovecii evolution. The Pneumocystis genus likely originated from soil or plant-associated organisms during the period of Cretaceous ~165 million years ago and successfully shifted to mammals. The transition coincided with a substantial loss of genes, many of which are related to the synthesis of nutrients that can be scavenged from hosts or cell wall components that could be targeted by the mammalian immune system. Following the transition, the Pneumocystis genus cospeciated with mammals. Each species specialized at infecting its own host. Host specialization is presumably built at least partially upon surface glycoproteins, whose protogene was acquired prior to the genus formation. P. jirovecii appeared at ~65 million years ago, overlapping with the emergence of the first primates. P. jirovecii and its sister species P. macacae, which infects macaques nowadays, may have had overlapping host ranges in the distant past. Clues from molecular clocks suggest that P. jirovecii did not cospeciate with humans. Molecular evidence suggests that Pneumocystis speciation involved chromosomal rearrangements and the mounting of genetic barriers that inhibit gene flow among species.

Macaque Brainnetome Atlas: A multifaceted brain map with parcellation, connection, and histology.

The rhesus macaque (Macaca mulatta) is a crucial experimental animal that shares many genetic, brain organizational, and behavioral characteristics with humans. A macaque brain atlas is fundamental to biomedical and evolutionary research. However, even though connectivity is vital for understanding brain functions, a connectivity-based whole-brain atlas of the macaque has not previously been made. In this study, we created a new whole-brain map, the Macaque Brainnetome Atlas (MacBNA), based on the anatomical connectivity profiles provided by high angular and spatial resolution ex vivo diffusion MRI data. The new atlas consists of 248 cortical and 56 subcortical regions as well as their structural and functional connections. The parcellation and the diffusion-based tractography were evaluated with invasive neuronal-tracing and Nissl-stained images. As a demonstrative application, the structural connectivity divergence between macaque and human brains was mapped using the Brainnetome atlases of those two species to uncover the genetic underpinnings of the evolutionary changes in brain structure. The resulting resource includes: (1) the thoroughly delineated Macaque Brainnetome Atlas (MacBNA), (2) regional connectivity profiles, (3) the postmortem high-resolution macaque diffusion and T2-weighted MRI dataset (Brainnetome-8), and (4) multi-contrast MRI, neuronal-tracing, and histological images collected from a single macaque. MacBNA can serve as a common reference frame for mapping multifaceted features across modalities and spatial scales and for integrative investigation and characterization of brain organization and function. Therefore, it will enrich the collaborative resource platform for nonhuman primates and facilitate translational and comparative neuroscience research.

Prognostic value of neutrophil-to-lymphocyte ratio dynamics in patients with septic acute kidney injury: a cohort study.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a prognostic marker for various diseases, but whether NLR dynamics (ΔNLR) is related to mortality and disease severity in patients with septic acute kidney injury (AKI) has not been determined. METHODS: Between August 2013 and August 2021, septic AKI patients at our center were retrospectively enrolled. ΔNLR was defined as the difference between the NLR at septic AKI diagnosis and at hospital admission. The relationship between the ΔNLR and mortality was evaluated by Kaplan-Meier curves, Cox proportional hazards, and cubic spline analyses. The prediction values were compared by area under the receiver-operating characteristic curve (AUROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses. RESULTS: Of the 413 participants, the mean age was 63 ± 17 years, and 134 were female (32.4%). According to the median value, patients in the high-ΔNLR group had significantly greater 90-d mortality (74.4% vs. 46.6%, p < 0.001). After adjustment for potential confounders, high ΔNLR remained an independent predictor of 90-d mortality (HR = 2.80; 95% CI = 1.74-4.49, p < 0.001). Furthermore, ΔNLR had the highest AUROC for 90-d mortality (0.685) among the various biomarkers and exhibited an improved NRI (0.314) and IDI (0.027) when incorporated with PCT and CRP. For secondary outcomes, patients with high ΔNLR had increased risk of 30-d mortality (p = 0.004), need for renal replacement therapy (p = 0.011), and developing stage-3 AKI (p = 0.040) according to the adjusted models. CONCLUSIONS: High ΔNLR is independently associated with increased risk of patient mortality and adverse outcomes. ΔNLR might be utilized to facilitate risk stratification and optimize septic AKI management.