Magnetic excitations in strained infinite-layer nickelate PrNiO2 films.

Strongly correlated materials respond sensitively to external perturbations such as strain, pressure, and doping. In the recently discovered superconducting infinite-layer nickelates, the superconducting transition temperature can be enhanced via only ~ 1% compressive strain-tuning with the root of such enhancement still being elusive. Using resonant inelastic x-ray scattering (RIXS), we investigate the magnetic excitations in infinite-layer PrNiO2 thin films grown on two different substrates, namely SrTiO3 (STO) and (LaAlO3)0.3(Sr2TaAlO6)0.7 (LSAT) enforcing different strain on the nickelates films. The magnon bandwidth of PrNiO2 shows only marginal response to strain-tuning, in sharp contrast to the enhancement of the superconducting transition temperature Tc in the doped superconducting samples. These results suggest the bandwidth of spin excitations of the parent compounds is similar under strain while Tc in the doped ones is not, and thus provide important empirics for the understanding of superconductivity in infinite-layer nickelates.

Dendrobine Ameliorates Glucocorticoid-Induced Osteoporosis by Promoting Osteogenesis through JNK/p38 MAPK Pathway Activation and GR Nuclear Translocation Inhibition.

Glucocorticoid-induced osteoporosis (GIOP) is the common reason for secondary osteoporosis. Dendrobine (DEN) is the major biologically active component of Dendrobium officinale with anti-inflammatory and antiaging properties. Whether DEN could alleviate osteogenic inhibition in GIOP rats is still unknown. The influence on osteogenic function caused by DEN on dexamethasone-treated bone marrow mesenchymal stem cells and rats was observed. The in vitro results showed that DEN reversed the inhibition of osteogenic differentiation by dexamethasone. Moreover, DEN supplementation attenuated dexamethasone-induced bone loss in vivo. DEN activated JNK and p38 MAPK pathways and restrained GR nuclear translocation, which could be prevented by the JNK (SP600125) or p38 (SB203580) pathway inhibitor. This study verified that DEN alleviated dexamethasone-induced nuclear translocation of GR, and inhibition of osteogenesis via JNK and p38 pathways, laying the foundation for DEN as a therapeutic agent for GIOP.

Elucidating the transport of water and ions in the nanochannel of covalent organic frameworks by molecular dynamics.

Inspired by biological channels, achieving precise separation of ion/water and ion/ion requires finely tuned pore sizes at molecular dimensions and deliberate exposure of charged groups. Covalent organic frameworks (COFs), a class of porous crystalline materials, offer well-defined nanoscale pores and diverse structures, making them excellent candidates for nanofluidic channels that facilitate ion and water transport. In this study, we perform molecular simulations to investigate the structure and kinetics of water and ions confined within the typical COFs with varied exposure of charged groups. The COFs exhibit vertically arrayed nanochannels, enabling diffusion coefficients of water molecules within COFs to remain within the same order of magnitude as in the bulk. The motion of water molecules manifests in two distinct modes, creating a mobile hydration layer around acid groups. The ion diffusion within COFs displays a notable disparity between monovalent (M+) and divalent (M2+) cations. As a result, the selectivity of M+/M2+ can exceed 100, while differentiation among M+ is less pronounced. In addition, our simulations indicate a high rejection (R > 98%) in COFs, indicating their potential as ideal materials for desalination. The chemical flexibility of COFs indicates that would hold significant promise as candidates for advanced artificial ion channels and separation membranes.

The neurological effects of acute physical exhaustion on inhibitory function.

OBJECTIVE: We aimed to investigate the neural mechanisms underlying the inhibitory function performance of maritime Search and Rescue (SAR) personnel in states of physical exhaustion. BACKGROUND: SAR missions pose serious challenges to the cognitive function of SAR personnel, especially in extreme environments and physical exhaustion. It is important to understand SAR personnel's cognitive performance and neural activity under exhaustion to improve the efficiency of task execution and ensure work safety. METHOD: Twenty-six maritime SAR personnel were recruited to simulate boat operations until they reached a self-imposed state of exhaustion. The exhaustion state was monitored by maximum heart rate and subjective fatigue scale. Two event-related potentials, N200 and P300, were measured during a Go-Nogo task before and after a session of acute exhaustive tasks. RESULTS: After exhaustion, a marked reduction in accuracy, a notable increase in N200 amplitude, and a substantial decline in P300 amplitude under the Nogo condition were observed compared to the baseline phase. Pre- and post-exhaustion comparisons using standardized low-resolution brain electromagnetic tomography revealed reduced activations in the right middle temporal gyrus's N200 component after exhaustion in SAR personnel during the Nogo condition. CONCLUSION: The results suggest that acute physical exhaustion significantly impacts the inhibition ability of SAR personnel, prolonging the conflict monitoring phase and weakening the response inhibition phase. These findings provide valuable insights into how physical exhaustion affects cognitive functions critical to the safety and effectiveness of SAR operations, and can inform strategies to improve training and equipment to enhance performance under extreme conditions.

A biologically inspired computational model of human ventral temporal cortex.

Our minds represent miscellaneous objects in the physical world metaphorically in an abstract and complex high-dimensional object space, which is implemented in a two-dimensional surface of the ventral temporal cortex (VTC) with topologically organized object selectivity. Here we investigated principles guiding the topographical organization of object selectivities in the VTC by constructing a hybrid Self-Organizing Map (SOM) model that harnesses a biologically inspired algorithm of wiring cost minimization and adheres to the constraints of the lateral wiring span of human VTC neurons. In a series of in silico experiments with functional brain neuroimaging and neurophysiological single-unit data from humans and non-human primates, the VTC-SOM predicted the topographical structure of fine-scale category-selective regions (face-, tool-, body-, and place-selective regions) and the boundary in large-scale abstract functional maps (animate vs. inanimate, real-word small-size vs. big-size, central vs. peripheral), with no significant loss in functionality (e.g., categorical selectivity and view-invariant representations). In addition, when the same principle was applied to V1 orientation preferences, a pinwheel-like topology emerged, suggesting the model's broad applicability. In summary, our study illustrates that the simple principle of wiring cost minimization, coupled with the appropriate biological constraint of lateral wiring span, is able to implement the high-dimensional object space in a two-dimensional cortical surface.

Impact of Tumor Size and Differentiation Grade on Survival After Lobectomy and Segmentectomy for Patients with Early-Stage Lung Adenocarcinoma.

BACKGROUND: The purpose of this study was to investigate the effect of tumor size and differentiation grade on long term survival in patients with early-stage lung adenocarcinoma (LUAD) after lobectomy and segmentectomy. PATIENTS AND METHODS: Patients with stage T1-2N0M0 LUAD who underwent lobectomy and segmentectomy were identified from the Surveillance, Epidemiology, and End Results database. Patients were stratified as grade I (well differentiated), grade II (moderately differentiated), and grade III/IV (poorly differentiated/undifferentiated) carcinomas. The effect of tumor size on overall survival (OS) and lung cancer-specific survival (LCSS) was evaluated using the multivariate Cox regression model, including the interaction between tumor size, type of surgery, and tumor differentiation grade. The inverse probability of treatment weighting method was used to adjust for bias between the groups. RESULTS: A total of 19,857 patients were identified, including 18,759 (94.4%) who underwent lobectomy and 1098 (5.5%) who underwent segmentectomy. A three-way interaction among tumor size, differentiation grade, and type of surgery was observed in the overall cohort. After stratifying by differentiation grade, plots of interaction revealed that lobectomy was associated with improved survival compared with segmentectomy when the tumor size exceeded 23 mm for grade I LUAD and 14 mm for grade II LUAD. No interaction was observed between the studied factors in grade III/IV carcinomas. CONCLUSIONS: This study interpreted the interaction between tumor size and type of surgery on long-term survival in patients with early stage LUAD and established a tumor size threshold beyond which lobectomy provided survival benefits compared with segmentectomy.

Congener-welded crystalline carbon nitride membrane for robust and highly selective Li/Mg separation.

Extracting lithium from salt-lake brines critically relies on the separation of Li+ and Mg2+, which could combat the lithium shortage. However, designing robust sieving membrane with high Li+/Mg2+ selectivity in the long-time operation has remained highly challenging. Here, we demonstrate a bioinspired congener-welded crystalline carbon nitride membrane that can accomplish efficient and stable monovalent ion sieving over divalent Mg ion. The crystalline carbon nitrides have uniform and narrow pore size to reject the large hydrated Mg2+ and rich ligating sites to facilitate an almost barrierless Li+ transport as suggested by ab initio simulations. These crystals were then welded by vapor-deposited congeners, i.e., amorphous polymer carbon nitride, which have similar composition and chemistry with the crystals, forming intimate and compatible crystal/polymer interface. As a result, our membrane can sieve out highly dilute Li+ (0.002 M) from concentrated Mg2+ (1.0 M) with a high selectivity of 1708, and can be continuously operated for 10 days.

Psychometrics validation of the Chinese version of social support for exercise scale among adolescents in China.

Physical activity (PA) is widely recognized as crucial for human health, yet the low level of PA in adolescents continues to raise major concerns. This study aims to validate the Chinese version of the Social Support Scale for Exercise (SE) and establish its reliability among Chinese adolescents. A cross-sectional study was conducted on two primary and two secondary schools in central China. Students were recruited using a random cluster sampling method, and written informed consent was provided after they were briefed on the purpose of the study. The standard forward-backward translation was applied to translate the English version of the SE into Chinese. The Social Support Scale used in this study consists of two factors: family support and friend support. Data were analyzed using Mplus 8 for the CFA, composite reliability (CR), average variance extracted (AVE), and intra-class correlation coefficients (ICC) were calculated. A total of 1422 students (boys = 838, girls = 604) with a mean age of 11 years (SD = 1.6) participated in the study. The measurement model of the translated social support scale fit the data well: CFI = .935; TLI = .929; SRMR = .038; RMSEA = .053, with a 90% confidence interval of (.051, .056; RMSEA p < .001). The composite reliability values of .935 for family support and .948 for friend support were acceptable. The intra-class correlation coefficients (ICC) based on test-retest were .928 for family support, and .904 for friend support. Hence, the Chinese version of the SE was valid and reliable, its implementation will provide researchers with a valuable tool to comprehensively assess Chinese adolescents' exercise-related social support and help develop targeted and effective interventions to improve their physical activity levels.

Discovery of a Novel and Potent LCK Inhibitor for Leukemia Treatment via Deep Learning and Molecular Docking.

The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger's suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50 of 0.43 nM. Further in vitro bioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivo antileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.

Orienting role of the putative human posterior infero-temporal area in visual attention.

The dorsal attention network (DAN) is a network of brain regions essential for attentional orienting, which includes the lateral intraparietal area (LIP) and frontal eye field (FEF). Recently, the putative human dorsal posterior infero-temporal area (phPITd) has been identified as a new node of the DAN. However, its functional relationship with other areas of the DAN and its specific role in visual attention remained unclear. In this study, we analyzed a large publicly available neuroimaging dataset to investigate the intrinsic functional connectivities (FCs) of the phPITd with other brain areas. The results showed that the intrinsic FCs of the phPITd with the areas of the visual network and the DAN were significantly stronger than those with the ventral attention network (VAN) areas and areas of other networks. We further conducted individual difference analyses with a sample size of 295 participants and a series of attentional tasks to investigate which attentional components each phPITd-based DAN edge predicts. Our findings revealed that the intrinsic FC of the left phPITd with the LIPv could predict individual ability in attentional orienting, but not in alerting, executive control, and distractor suppression. Our results not only provide direct evidence of the phPITd's functional relationship with the LIPv, but also offer a comprehensive understanding of its specific role in visual attention.

Directly Converting Bulk Wood into Branch Micro-Nano Fibers to Synergistically Enhance the Strength and Toughness via Interface Engineering.

Hierarchical biobased micro/nanomaterials offer great potential as the next-generation building blocks for robust films or macroscopic fibers with high strength, while their capability in suppressing crack propagation when subject to damage is hindered by their limited length. Herein, we employed an approach to directly convert bulk wood into fibers with a high aspect ratio and nanosized branching structures. Particularly, the length of microfibers surpassed 1 mm with that of the nanosized branches reaching up to 300 µm. The presence of both interwoven micro- and nanofibers endowed the product with substantially improved tensile strength (393.99 MPa) and toughness (19.07 MJ m-3). The unique mechanical properties arose from mutual filling and the hierarchical deformation facilitated by branched nanofibers, which collectively contributed to effective energy dissipation. Hence, the nanotransformation strategy opens the door toward a facial, scalable method for building high-strength film or macroscopic fibers available in various advanced applications.

Design, synthesis, in vitro and in vivo evaluation and molecular docking study of novel pleuromutilin derivatives as antibacterial agents.

14 novel pleuromutilin derivatives were designed and synthesized as inhibitors against Staphylococcus aureus (S. aureus). The modification was focused on the C22 position of pleuromutilin. We conducted the characterization, in vitro and in vivo biological assessment of the compounds. Compound 18 exhibited the best antibacterial effect against MRSA (MIC = 0.015 µg/mL, MBC = 0.125 µg/mL). Compound 18 was further studied by time-kill kinetic and post-antibiotic effect (PAE) approaches. Besides, most compounds exhibited low cytotoxicity to RAW 264.7 cells. Compound 18 displayed decent bactericidal activity in vivo (-0.51 log10 CFU/mL). Molecular docking study indicated that compound 18 could be located stably at the ribosome (ΔGb = -7.30 kcal/mol). The results revealed that compound 18 might be further developed into a novel antibiotic.

The effects of the predictability of acclimatory temperature on the growth and thermal tolerance of juvenile Spinibarbus sinensis.

Heated effluent injection, cold hypolimnetic water inputs from dams, and extreme weather events can lead to unpredictable temperature fluctuations in natural waters, impacting fish performance and fitness. We hypothesized that fish exposed to such unpredictable fluctuations would exhibit weaker growth and enhanced thermal tolerance compared to predictable conditions. Qingbo (Spinibarbus sinensis) was selected as the experimental subject in this study. The qingbo were divided into a constant temperature group (C, 22 ± 0.5 °C), a predictable temperature fluctuation group (PF, 22 ± 4 °C, first warming, then cooling within a day) and an unpredictable temperature fluctuation group (UF, 22 ± 4 °C, the order of warming or cooling is random). After 40 days of temperature acclimation, the growth, metabolic rate, spontaneous activity, thermal tolerance, plasma cortisol concentration and liver hsp70 level of the fish were measured. Unexpectedly, neither the PF nor the UF group showed decreased growth compared to the C group. This could be attributed to the fact that temperature variation did not lead to a substantial increase in basic energy expenditure. Furthermore, feeding rates increased due to temperature fluctuations, although the difference was not significant. Both the PF and UF groups exhibited increased upper thermal tolerance, but only the UF group exhibited improved lower thermal tolerance and higher liver hsp70 levels compared to the C group. The qingbo that experienced unpredictable temperature fluctuations had the best thermal tolerance among the 3 groups, which might have occurred because they had the highest level of hsp70 expression. This may safeguard fish against the potential lethal consequences of extreme temperatures in the future. These findings suggested that qingbo exhibited excellent adaptability to both predictable and unpredictable temperature fluctuations, which may be associated with frequent temperature fluctuations in its natural habitat.

Novel Providencia xianensis sp. nov.: A multidrug-resistant species identified in clinical infections.

Providencia genus is known to harbor certain opportunistic pathogens capable of causing human infections. Here, we report two strains of multidrug-resistant bacteria initially identified as Providencia rettgeri by mass spectrometry, but genome analysis revealed their ANI (79.84-84.20%) and dDDH (21.1-25.6%) values to fall below the accepted species threshold for known Providencia species. We therefore propose that these isolates be recognized as a novel species, Providencia xianensis sp. nov. Alarmingly, both strains, isolated from locations far apart, exhibited resistance to last-resort antibiotics, indicating their possible wide distribution, underscoring the urgency for immediate attention and enhanced surveillance for this emerging multidrug-resistant pathogen.

Exosomes regulate doxorubicin resistance in breast cancer via miR-34a-5p/NOTCH1.

Breast cancer (BRCA) is the most common cancer among women. Adriamycin (ADR), also known as doxorubicin (Dox), is a commonly used chemotherapeutic agent for BRCA patients, however, the susceptibility of tumor cells to develop resistance to Dox has severely limited its clinical use. One new promising therapeutic target for breast cancer patients is exosomes. The objective of this study was to investigate the role of exosomes in regulating Dox resistance in BRCA. In this study, the exosomes from both types of cells were extracted by differential centrifugation. The effect of exosomes on drug resistance was assessed by laser confocal microscopy, MTT assay, and qRT-PCR. The miRNA was transfected into cells using Lipofectamine 2000, which was then evaluated for downstream genes and changes in drug resistance. Exosomes from MCF-7 cells (MCF-7/exo) and MCF-7/ADR cells (ADR/exo) were effectively extracted in this study. The ADR/exo was able to endocytose MCF-7 cells and make them considerably more resistant to Dox. Moreover, we observed a significant difference in miR-34a-5p expression in MCF-7/ADR and ADR/exo compared to MCF-7 and MCF-7/exo. Among the miR-34a-5p target genes, NOTCH1 displayed a clear change with a negative correlation. In addition, when miR-34a-5p expression was elevated in MCF-7/ADR cells, the expression of miR-34a-5p in ADR/exo was also enhanced alongside NOTCH1, implying that exosomes may carry miRNA into and out of cells and perform their function. In conclusion, exosomes can influence Dox resistance in breast cancer cells by regulating miR-34a-5p/NOTCH1. These findings provide novel insights for research into the causes of tumor resistance and the enhancement of chemotherapy efficacy in breast cancer.

Identifying potential drug targets for idiopathic pulmonary fibrosis: a mendelian randomization study based on the druggable genes.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic interstitial lung disease characterized by progressive dyspnea and decreased lung function, yet its exact etiology remains unclear. It is of great significance to discover new drug targets for IPF. METHODS: We obtained the cis-expression quantitative trait locus (cis-eQTL) of druggable genes from eQTLGen Consortium as exposure and the genome wide association study (GWAS) of IPF from the International IPF Genetics Consortium as outcomes to simulate the effects of drugs on IPF by employing mendelian randomization analysis. Then colocalization analysis was performed to calculate the probability of both cis-eQTL of druggable genes and IPF sharing a causal variant. For further validation, we conducted protein quantitative trait locus (pQTL) analysis to reaffirm our findings. RESULTS: The expression of 45 druggable genes was significantly associated with IPF susceptibility at FDR < 0.05. The expression of 23 and 15 druggable genes was significantly associated with decreased forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLco) in IPF patients, respectively. IPF susceptibility and two significant genes (IL-7 and ABCB2) were likely to share a causal variant. The results of the pQTL analysis demonstrated that high levels of IL-7 in plasma are associated with a reduced risk of IPF (OR = 0.67, 95%CI: 0.47-0.97). CONCLUSION: IL-7 stands out as the most promising potential drug target to mitigate the risk of IPF. Our study not only sheds light on potential drug targets but also provides a direction for future drug development in IPF.

Reviving Bistable Perception in Patients With Depression by Decreasing the Overestimation of Prior Precision.

Slower perceptual alternations, a notable perceptual effect observed in psychiatric disorders, can be alleviated by antidepressant therapies that affect serotonin levels in the brain. While these phenomena have been well documented, the underlying neurocognitive mechanisms remain to be elucidated. Our study bridges this gap by employing a computational cognitive approach within a Bayesian predictive coding framework to explore these mechanisms in depression. We fitted a prediction error (PE) model to behavioral data from a binocular rivalry task, uncovering that significantly higher initial prior precision and lower PE led to a slower switch rate in patients with depression. Furthermore, serotonin-targeting antidepressant treatments significantly decreased the prior precision and increased PE, both of which were predictive of improvements in the perceptual alternation rate of depression patients. These findings indicated that the substantially slower perception switch rate in patients with depression was caused by the greater reliance on top-down priors and that serotonin treatment's efficacy was in its recalibration of these priors and enhancement of PE. Our study not only elucidates the cognitive underpinnings of depression, but also suggests computational modeling as a potent tool for integrating cognitive science with clinical psychology, advancing our understanding and treatment of cognitive impairments in depression.

Effects of Huangqi Gancao Decoction on intestinal immunity and microbiota in immunocompromised mice models.

Background: The classical medicinal formula Huangqi Gancao Decoction (HQGCD), originating from the medical book" Yi Lin Gai Cuo". Up to now, the studies focusing on the immunoenhancement effects of HQGCD are few, and the actionpathway is not yet clear. Method: In this study, SPF male KM mice were utilized as a model for immunosuppression. Comprehensive observations were made regarding the general behavior and condition of the mice, in addition to monitoring fluctuations in body weight and food intake. The blood routine index was measured, and morphological changes in the ileum and colon tissues were examined. The level of secretory immunoglobulin A (sIgA), superoxide dismutase (SOD), and malondialdehyde (MDA) in ileum and colon tissues were quantified. Additionally, the bone marrow total DNA index was assessed. Flow cytometry analyzed the proportions of CD3⁺, CD4⁺, CD8⁺, and CD4+CD8+ double-positive (DP) T lymphocytes in small intestinal intraepithelial lymphocytes (IELs). Lastly, the composition and diversity of the cecal microbiota were evaluated using 16S rDNA sequencing technology. Results: After HQGCD intervention, there were no significant changes in the mice's feed intake and body weight. However, the tissue structures of the ileum and colon showed recovery. In the blood routine index, there was an increase in the total white blood cell count, lymphocyte count, red blood cell count, hematocrit, and hemoglobin content. Additionally, the bone marrow total DNA index was elevated. Level of SOD and sIgA in ileum and colon tissues increased, while the level of MDA decreased. The proportions of CD3⁺ and CD4⁺ T lymphocytes within IELs increased, along with an increase in DP T lymphocytes in IELs (DP IELs), whereas the proportion of CD8⁺ T lymphocytes decreased. The cecal microbiota underwent changes, with an increase in the variety and number of beneficial microbiota. Conclusion: HQGCD could restore the intestinal immune function of immunocompromised mice, and had a certain positive effect on cecal microbiota.