BACKGROUND: The burgeoning demand for hepatectomy in elderly patients with hepatocellular carcinoma (HCC) necessitates improved perioperative care. Geriatric populations frequently experience functional decline and frailty, predisposing them to adverse postoperative outcomes. The Barthel Index serves as a reliable measure for assessing functional capacity, and this study evaluates its impact on surgical textbook outcomes (TOs) in elderly HCC patients. METHODS: A multicenter retrospective cohort study analyzed elderly patients (≥70 years) following hepatectomy for HCC between 2013 and 2021. Utilizing a Barthel Index cut-off value of 85, patients were divided into two groups: with and without preoperative functional decline and frailty. The primary outcome was the rate of TO, encompassing seven criteria. TO rates were compared between groups, and multivariate logistic regression analyses identified independent risks for achieving TOs. RESULTS: Of 497 elderly patients, 157 (31.6 â%) exhibited preoperative functional decline and frailty (Barthel Index score <85). The overall TO rate was 58.6 â%. Patients with preoperative Barthel Index score <85 had significantly lower TO rates compared to patients with score ≥85 (29.3 â% vs. 72.1 â%, P â< â0.001). Multivariate analysis revealed preoperative Barthel Index score <85 as an independent risk for achieving TO (odds ratio 3.413, 95 â% confidence interval 1.879-6.198, P â< â0.001). Comparable results were observed in the subgroups of patients undergoing open and laparoscopic hepatectomy. CONCLUSION: Preoperative Barthel Index-based assessment of functional decline and frailty significantly predicts TOs following hepatectomy in elderly HCC patients, enabling identification of high-risk patients and informing preoperative management and postoperative care within geriatric oncology.
[This corrects the article DOI: 10.3389/fnins.2023.1321246.].
Chiral multi-resonance thermally activated delayed fluorescence (CP-MR-TADF) materials hold promise for circularly polarized organic light-emitting diode (CP-OLED) and 3D display. Herein, we present two pairs of tetraborated intrinsically axial CP-MR-TADF materials, R/S-BDBF-BOH and R/S-BDBT-BOH, with conjugation-extended bidibenzo[b,d]furan and bidibenzo[b,d]thiophene as chiral sources, which effectively participate in the distribution of frontier molecular orbitals. Due to the heavy-atom effect, sulfur atoms are introduced to accelerate the reverse intersystem crossing process and increase efficiency of molecules. R/S-BDBF-BOH and R/S-BDBT-BOH manifest ultra-pure blue emission peaking at 458/459 nm with full width at half maximum of 27 nm (0.16 eV), photoluminescence quantum yields of 90%/91% and dissymmetry factors (|gPL|) of 6.8 × 10-4/8.5 × 10-4, respectively. Correspondingly, the CP-OLEDs exhibit good performances with external quantum efficiency of 30.1% and |gEL| factors of 1.2 × 10-3.
The current energy crisis is worsening worldwide, and in China, urban expansion and per capita vehicle ownership have created a growing energy imbalance and increased pressure to reduce carbon emissions.The popularization of new energy vehicles (NEVs) can provide a step forward to solving energy shortage problems, environmental pollution, and global warming. In 2022, the average penetration rate, which is ratio of new energy vehicle sales to vehicle sales, is just 19.1 %. This paper analysed the reasons for the differences in the penetration rates of new energy vehicles in China's 269 prefecture-level cities, using a Geo Detector approach, and the results showed that the level of economic development, the average annual temperature difference, the density of charging piles, the charging price and the number of population all had significant effects(qï¼0.12) on the penetration rate. Based on the above studies, a questionnaire was used to investigate the public's acceptance of new energy vehicles in Xinjiang Uygur Autonomous Region, and a PLS-SEM regression analysis was conducted. The results showed that men, young people and people with a certain level of basic education were 5 % more likely to accept new energy vehicles.Unlike previous studies, perceived cost had no significant correlation with the acceptance of new energy vehicles. Perceived risk had a significant negative correlation with the acceptance of new energy vehicles,the path coefficient is -0.1.The acceptance of new energy vehicles was significantly and positively correlated with vehicle quality and service, the public's understanding of new energy vehicles, and subjective norms, their average path coefficients are above 0.1. We argues that the government should maintain a certain level of promotion of new energy vehicles and accelerate the construction of charging piles, based on the aforementioned results.
BACKGROUND: Rising cancer-related mortality underscores the importance of biomarkers for treatment and prognosis, with Chromosome Segregation 1 Like (CSE1L) linked to various cancers yet its roles remain partially understood. This study investigates CSE1L's expression and oncogenic mechanisms in solid tumors. RESEARCH DESIGN AND METHODS: We analyzed multi-omics data from 31 solid tumors, measured CSE1L in 41 head and neck carcinoma patients post-chemotherapy via qRT-PCR, and evaluated the impact of CSE1L knockdown on cell proliferation in A549 and HepG2 cells. RESULTS: In this study, we observed significantly elevated levels of CSE1L RNA in 13 tumor tissues and protein levels in 8 tumor tissues compared to their corresponding adjacent normal tissues. Additionally, our investigation unveiled a correlation between heightened CSE1L expression in tumor tissues and worsened patient prognosis, poor response to immunotherapy, and diminished effectiveness of neoadjuvant chemotherapy. Through an analysis of CSE1L mechanisms, we discovered its potential involvement in promoting tumor cell proliferation, enhancing drug resistance, and influencing immune infiltration, thereby impacting patient prognosis and treatment outcomes. Finally, we delved into the potential mechanisms underlying upregulation of CSE1L in tumor tissues. CONCLUSION: Our findings demonstrate that CSE1L promotes tumor development in various malignancies, highlighting its potential as both a therapeutic target and prognostic indicator.
BACKGROUND: The association between shift/night work and the risk of stroke is not supported by strong evidence. OBJECTIVE: This study aimed to obtain evidence of a potential relationship between shift/night shift work and the risk of stroke. METHODS: We searched PubMed, Embase, the Cochrane Library and Web of science databases for eligible studies from inception to January 19, 2024. We followed the statement in the Preferred Reporting Items for Systematic Evaluations and Meta-Analysis (PRISMA). STATA 14.0 software was used for meta-analysis. RESULTS: A total of five studies involving 700,742 subjects were included in this meta-analysis. We found that shift/night workers had a 1.08 times higher risk of stroke than non-shift/night workers (RR: 1.08; 95 % CI: 1.05-1.10; P < 0.001). CONCLUSION: Shift/night work may be a risk factor for stroke. More objective prospective studies are needed to further support this result.
This study examines spermatogonial numbers in testicular samples from 43 prepubertal patients undergoing haematopoietic stem cell transplantation (HSCT). High-dose chemotherapy and/or radiation during HSCT can impact spermatogenesis requiring fertility preservation. Results show that 49% of patients have decreased and 19% severely depleted spermatogonial pool prior to HSCT. Patients with Fanconi anaemia exhibit significantly reduced spermatogonial numbers. Patients with immunodeficiency or aplastic anaemia generally present within the normal range, while results in patients with myelodysplastic syndrome or myeloproliferative neoplasm vary. The study emphasizes the importance of assessing spermatogonial numbers in patients with severe haematological diseases for informed fertility preservation decisions.
The functional connectome changes with aging. We systematically evaluated aging related alterations in the functional connectome using a whole-brain connectome network analysis in 39,675 participants in UK Biobank project. We used adaptive dense network discovery tools to identify networks directly associated with aging from resting-state fMRI data. We replicated our findings in 499 participants from the Lifespan Human Connectome Project in Aging study. The results consistently revealed two motor-related subnetworks (both permutation test p-values <0.001) that showed a decline in resting-state functional connectivity (rsFC) with increasing age. The first network primarily comprises sensorimotor and dorsal/ventral attention regions from precentral gyrus, postcentral gyrus, superior temporal gyrus, and insular gyrus, while the second network is exclusively composed of basal ganglia regions, namely the caudate, putamen, and globus pallidus. Path analysis indicates that white matter fractional anisotropy mediates 19.6% (p<0.001, 95% CI [7.6% 36.0%]) and 11.5% (p<0.001, 95% CI [6.3% 17.0%]) of the age-related decrease in both networks, respectively. The total volume of white matter hyperintensity mediates 32.1% (p<0.001, 95% CI [16.8% 53.0%]) of the aging-related effect on rsFC in the first subnetwork.
PURPOSE: In this study, we identified and diagnosed a novel inherited condition called Dyschromatosis, Ichthyosis, Deafness, and Atopic Disease (DIDA) syndrome. We present a series of studies to clarify the pathogenic variants and specific mechanism. METHODS: Exome sequencing and Sanger sequencing was conducted in affected and unaffected family members. A variety of human and cell studies were performed to explore the pathogenic process of keratosis. RESULTS: Our finding indicated that DIDA syndrome was caused by compound heterozygous variants in the oxysterol-binding protein-related protein 2 (OSBPL2) gene. Furthermore, our findings revealed a direct interaction between OSBPL2 and Phosphoinositide phospholipase C-beta-3 (PLCB3), a key player in hyperkeratosis. OSBPL2 effectively inhibits the ubiquitylation of PLCB3, thereby stabilizing PLCB3. Conversely, OSBPL2 variants lead to enhanced ubiquitination and subsequent degradation of PLCB3, leading to epidermal hyperkeratosis, characterized by aberrant proliferation and delayed terminal differentiation of keratinocytes. CONCLUSIONS: Our study not only unveiled the association between OSBPL2 variants and the newly identified DIDA syndrome but also shed light on the underlying mechanism.
Deafness , Ichthyosis , Pedigree , Phospholipase C beta , Humans , Deafness/genetics , Deafness/pathology , Phospholipase C beta/genetics , Phospholipase C beta/metabolism , Female , Male , Ichthyosis/genetics , Ichthyosis/pathology , Ichthyosis/metabolism , Heterozygote , Ubiquitination , Keratinocytes/metabolism , Keratinocytes/pathology , Exome Sequencing , Adult , Syndrome , HEK293 Cells , Receptors, Steroid
The homogeneous Fenton process involves both coagulation and oxidation, but it requires added acidity, so it is rarely used to control membrane fouling. This work found that the pH of neutral simulated wastewater sharply declined to 4.1 after pre-treatment with 0.1 mM Fenton reagent (Fe2+:H2O2=1:1) without added acidity. This occurred mainly because the trace homogeneous Fenton reagent induced in situ acid production by organic matter in the wastewater, which supplied the acidic conditions required for the Fenton reaction and ensured that the reaction could proceed continuously. Then, oxidation during the pre-Fenton process enhanced the electrostatic repulsion forces and effectively weakened the hydrogen bonds of organic matter at the membrane surface by altering the net charge and hydroxyl content of organic matter, while coagulation caused the foulants to gather and form large aggregates. These changes diminished the deposition of foulants onto the membrane surface and resulted in a looser fouling layer, which eventually caused the membrane fouling rate to decline from 83 % to 24 % and the flux recovery rate to increase from 44 % to 98 % during 2 h of filtration. This membrane fouling mitigation ability is much superior to that of pre-H2O2, pre-Fe2+ or pre-Fe3+ processes with equivalent doses.
Due to the great successes of Graph Neural Networks (GNN) in numerous fields, growing research interests have been devoted to applying GNN to molecular learning tasks. The molecule structure can be naturally represented as graphs where atoms and bonds refer to nodes and edges respectively. However, the atoms are not haphazardly stacked together but combined into various spatial geometries. Meanwhile, since chemical reactions mainly occur in substructures such as functional groups, the substructure plays a decisive role in the molecule's properties. Therefore, directly applying GNN to molecular representation learning could ignore the molecular spatial structure and the substructure properties which in turn degrades the performance of downstream tasks. In this paper, we propose Knowledge-Driven Self-Supervised Model for Molecular Representation Learning (KSMRL) to address above problems. The KSMRL consists of two major pathways: (1) the Spatial Information (SI) based pathway which preserves the spatial information of molecular structure, (2) the Subgraph Constraint (SC) based pathway which retains the properties of substructures into the molecular representation. In this manner, both the atomic level and substructure level information can be included in modeling. According to the experimental results on multiple datasets, the proposed KSMRL can generate discriminative molecular representations. In molecular generation tasks, KSMRL combined with Autoregressive Flow (AF) models or Discrete Flow (DF) models outperforms the state-of-the-art baselines over all datasets. In addition, we demonstrate the effectiveness of KSMRL with property optimization experiments. To indicate the ability of predicting specified potential Drug-Target Interactions (DTIs), a case study for discriminating the interactions between molecule generated by KSMRL and targets is also given.
Relying on the strong optical absorption of hemoglobin to pulsed laser energy, photoacoustic microscopy provides morphological and functional information on microvasculature label-freely. Here, we propose speckle variance photoacoustic microscopy (SV-PAM), which harnesses intrinsic imaging contrast from temporal-varied photoacoustic signals of moving red blood cells in blood vessels, for recovering three-dimension hemodynamic images down to capillary-level resolution within the microcirculatory tissue beds in vivo. Calculating the speckle variance of consecutive photoacoustic B-scan frames acquired at the same lateral position enables accurate identification of blood perfusion and occlusion, which provides interpretations of dynamic blood flow in the microvasculature, in addition to the microvascular anatomic structures. We demonstrate high-resolution hemodynamic imaging of vascular occlusion and reperfusion in the microvasculature of mice ears in vivo. The results suggest that our SV-PAM is potentially invaluable for biomedical hemodynamic investigations, for example, imaging ischemic stroke and hemorrhagic stroke.
Microscopy , Photoacoustic Techniques , Photoacoustic Techniques/methods , Animals , Mice , Microscopy/methods , Hemodynamics/physiology , Ear/blood supply , Ear/diagnostic imaging , Microvessels/diagnostic imaging , Erythrocytes , Microcirculation
A facile and efficient radical tandem vinylogous aldol and intramolecular [2 + 2] cycloaddition reaction for direct synthesis of cyclobutane-containing benzocyclobutenes (BCBs) under extremely mild conditions without using any photocatalysts is reported. This approach exhibited definite compatibility with functional groups and afforded new BCBs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost, and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.
Myocardial ischemia/reperfusion injury (MI/RI) is identified as a severe vascular emergency, and the treatment strategy of MI/RI still needs further improvement. The present study aimed to investigate the potential effects of mild therapeutic hypothermia (MTH) on MI/RI and underlying mechanisms. In ischemia/reperfusion (I/R) rats, MTH treatment significantly improved myocardial injury, attenuated myocardial infarction, and inhibited the mitochondrial apoptosis pathway. The results of proteomics identified SLC25A10 as the main target of MTH treatment. Consistently, SLC25A10 expressions in I/R rat myocardium and hypoxia and reoxygenation (H/R) cardiomyocytes were significantly suppressed, which was effectively reversed by MTH treatment. In H/R cardiomyocytes, MTH treatment significantly improved cell injury, mitochondrial dysfunction, and inhibited the mitochondrial apoptosis pathway, which were partially reversed by SLC25A10 deletion. These findings suggested that MTH treatment could protect against MI/RI by modulating SLC25A10 expression to suppress mitochondrial apoptosis pathway, providing new theoretical basis for clinical application of MTH treatment for MI/RI.
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. Currently, there are no effective drugs for the treatment of DN. Although several studies have reported the therapeutic potential of mesenchymal stem cells, the underlying mechanisms remain largely unknown. Here, we report that both human umbilical cord MSCs (UC-MSCs) and UC-MSC-derived exosomes (UC-MSC-exo) attenuate kidney damage, and inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis in streptozotocin-induced DN rats. Strikingly, the Hedgehog receptor, smoothened (SMO), was significantly upregulated in the kidney tissues of DN patients and rats, and positively correlated with EMT and renal fibrosis. UC-MSC and UC-MSC-exo treatment resulted in decrease of SMO expression. In vitro co-culture experiments revealed that UC-MSC-exo reduced EMT of tubular epithelial cells through inhibiting Hedgehog/SMO pathway. Collectively, UC-MSCs inhibit EMT and renal fibrosis by delivering exosomes and targeting Hedgehog/SMO signaling, suggesting that UC-MSCs and their exosomes are novel anti-fibrotic therapeutics for treating DN.
Diabetes Mellitus , Diabetic Nephropathies , Exosomes , Mesenchymal Stem Cells , Humans , Rats , Animals , Diabetic Nephropathies/metabolism , Exosomes/metabolism , Smoothened Receptor , Hedgehog Proteins/metabolism , Fibrosis , Mesenchymal Stem Cells/metabolism , Umbilical Cord/metabolism , Diabetes Mellitus/metabolism
Due to the widespread abuse of antibiotics, drug resistance in Enterococcus has been increasing. However, the speed of antibiotic discovery cannot keep pace with the acquisition of bacterial resistance. Thus, drug repurposing is a proposed strategy to solve the crises. Lusutrombopag (LP) has been approved as a thrombopoietin receptor agonist by the Food and Drug Administration. This study demonstrated that LP exhibited significant antimicrobial activities against vancomycin-resistant Enterococcus in vitro with rare resistance occurrence. Further, LP combined with tobramycin exhibited synergistic antimicrobial effects in vitro and in vivo against Enterococcus. No in vitro or in vivo detectable toxicity was observed when using LP. Mechanism studies indicated that the disrupted proton motive force may account for LP's antimicrobial activity. In summary, these results demonstrate that LP has the previously undocumented potential to serve as an antibacterial agent against refractory infections caused by Enterococcus.
Aminoglycosides , Cinnamates , Thiazoles , Vancomycin-Resistant Enterococci , United States , Aminoglycosides/pharmacology , Vancomycin/pharmacology , Pharmaceutical Preparations , Drug Repositioning , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
BACKGROUND AND PURPOSE: Because of the absence of effective therapies for metabolic dysfunction-associated steatohepatitis (MASH), there is a rising interest in fibroblast growth factor 21 (FGF21) analogues due to their potential anti-fibrotic activities in MASH treatment. PsTag-FGF21, a long-acting FGF21 analogue, has demonstrated promising therapeutic effects in several MASH mouse models. However, its efficacy and mechanism against MASH-related fibrosis remain less well defined, compared with the specific mechanisms through which FGF21 improves glucose and lipid metabolism. EXPERIMENTAL APPROACH: The effectiveness of PsTag-FGF21 was evaluated in two MASH-fibrosis models. Co-culture systems involving macrophages and hepatic stellate cells (HSCs) were employed for further assessment. Hepatic macrophages were selectively depleted by administering liposome-encapsulated clodronate via tail vein injections. RNA sequencing and cytokine profiling were conducted to identify key factors involved in macrophage-HSC crosstalk. KEY RESULTS: We first demonstrated the significant attenuation of hepatic fibrosis by PsTag-FGF21 in two MASH-fibrosis models. Furthermore, we highlighted the crucial role of macrophage phenotypic switch in PsTag-FGF21-induced HSC deactivation. FGF21 was demonstrated to regulate macrophages in a PsTag-FGF21-like manner. NR4A1, a nuclear factor which is notably down-regulated in human livers with MASH, was identified as a mediator responsible for PsTag-FGF21-induced phenotypic switch. Transcriptional control over insulin-like growth factor 1, a crucial factor in macrophage-HSC crosstalk, was exerted by the intrinsically disordered region domain of NR4A1. CONCLUSION AND IMPLICATIONS: Our results have elucidated the previously unclear mechanisms through which PsTag-FGF21 treats MASH-related fibrosis and identified NR4A1 as a potential therapeutic target for fibrosis.
Neurons in the hippocampus exhibit spontaneous spiking activity during rest that appears to recapitulate previously experienced events. While this replay activity is frequently linked to memory consolidation and learning, the underlying mechanisms are not well understood. Recent large-scale neural recordings in mice have demonstrated that resting-state spontaneous activity is expressed as quasi-periodic cascades of spiking activity that pervade the forebrain, with each cascade engaging a high proportion of recorded neurons. Hippocampal ripples are known to be coordinated with cortical dynamics; however, less is known about the occurrence of replay activity relative to other brain-wide spontaneous events. Here we analyzed responses across the mouse brain to multiple viewings of natural movies, as well as subsequent patterns of neural activity during rest. We found that hippocampal neurons showed time-selectivity, with individual neurons responding consistently during particular moments of the movie. During rest, the population of time-selective hippocampal neurons showed both forward and time-reversed replay activity that matched the sequence observed in the movie. Importantly, these replay events were strongly time-locked to brain-wide spiking cascades, with forward and time-reversed replay activity associated with distinct cascade types. Thus, intrinsic hippocampal replay activity is temporally structured according to large-scale spontaneous physiology affecting areas throughout the forebrain. These findings shed light on the coordination between hippocampal and cortical circuits thought to be critical for memory consolidation.
OBJECTIVES: Artificial intelligence (AI) systems have the potential to revolutionize clinical practices, including improving diagnostic accuracy and surgical decision-making, while also reducing costs and manpower. However, it is important to recognize that these systems may perpetuate social inequities or demonstrate biases, such as those based on race or gender. Such biases can occur before, during, or after the development of AI models, making it critical to understand and address potential biases to enable the accurate and reliable application of AI models in clinical settings. To mitigate bias concerns during model development, we surveyed recent publications on different debiasing methods in the fields of biomedical natural language processing (NLP) or computer vision (CV). Then we discussed the methods, such as data perturbation and adversarial learning, that have been applied in the biomedical domain to address bias. METHODS: We performed our literature search on PubMed, ACM digital library, and IEEE Xplore of relevant articles published between January 2018 and December 2023 using multiple combinations of keywords. We then filtered the result of 10,041 articles automatically with loose constraints, and manually inspected the abstracts of the remaining 890 articles to identify the 55 articles included in this review. Additional articles in the references are also included in this review. We discuss each method and compare its strengths and weaknesses. Finally, we review other potential methods from the general domain that could be applied to biomedicine to address bias and improve fairness. RESULTS: The bias of AIs in biomedicine can originate from multiple sources such as insufficient data, sampling bias and the use of health-irrelevant features or race-adjusted algorithms. Existing debiasing methods that focus on algorithms can be categorized into distributional or algorithmic. Distributional methods include data augmentation, data perturbation, data reweighting methods, and federated learning. Algorithmic approaches include unsupervised representation learning, adversarial learning, disentangled representation learning, loss-based methods and causality-based methods.
Artificial Intelligence , Bias , Natural Language Processing , Humans , Surveys and Questionnaires , Machine Learning , Algorithms
The presence of interface defects between the perovskite layer and the underlying substrate has a significant impact on the power conversion efficiency (PCE) and stability of perovskite solar cells (PSCs). S n O 2 thin films are employed in PSCs as electron transport layers to achieve high PCE. However, the significant lattice mismatch between S n O 2 and the perovskite material leads to a large number of uncoordinated defects at the interface between perovskite and substrate, resulting in recombination losses at the interface. In this study, rubidium chloride (RbCl) was introduced as the interface modification layer between the perovskite layer and the S n O 2 electron transport layer to enhance the PCE of PSCs. The research showed that the RbCl interface modification layer effectively passivated the under-coordinated defects of Sn ions and optimized the energy level alignment between the perovskite layer and the S n O 2 film. Moreover, the fabricated PSCs exhibited an open-circuit voltage of 1.11 V and a power conversion efficiency of 21.64%. Furthermore, the device maintained 80% of initial efficiency after storage for 30 days in an inert gas environment and 60% of the value after storage for 30 days in ambient air.
