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1.
J Hypertens ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38973536

ABSTRACT

BACKGROUND: DNA methylation is an important epigenetic mechanism that may influence blood pressure (BP) regulation and hypertension risk. Obesity, a major lifestyle factor associated with hypertension, may interact with DNA methylation to affect BP. However, the indirect effect of DNA methylation on 24-hBP measurements mediated by obesity-related phenotypes such as BMI has not been investigated. METHODS: Causal mediation analysis was applied to examine the mediating role of BMI in the relation between DNA methylation and 24-h BP phenotypes, including SBP, DBP and mean arterial blood pressure (MAP), in 281 African American participants. RESULTS: Analysis of 38 215 DNA methylation regions, derived from 1,549,368 CpG sites across the genome, identified up to 138 methylation regions that were significantly associated with 24-h BP measurements through BMI mediation. Among them, 38 (19.2%) methylation regions were concurrently associated with SBP, DBP and MAP. Genes associated with BMI-mediated methylation regions are potentially involved in various chronic diseases such as coronary artery disease and renal disease, which are often caused or exacerbated by hypertension. Notably, three genes (CDH4, NOTCH1 and COLGALT1) showed both direct associations with 24-h BP measurements and indirect associations through BMI after adjusting for age and sex covariates. CONCLUSION: Our findings suggest that DNA methylation may contribute to the regulation of 24-h BP in African Americans both directly and indirectly through BMI mediation.

2.
bioRxiv ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38979303

ABSTRACT

Complex behavior entails a balance between taking in sensory information from the environment and utilizing previously learned internal information. Experiments in behaving mice have demonstrated that the brain continually alternates between outward and inward modes of cognition, switching its mode of operation every few seconds. Further, each state transition is marked by a stereotyped cascade of neuronal spiking that pervades most forebrain structures. Here we analyzed large fMRI datasets to demonstrate that a similar switching mechanism governs the operation of the human brain. We found that human brain activity was punctuated every several seconds by coherent, propagating waves emerging in the exteroceptive sensorimotor regions and terminating in the interoceptive default mode network. As in the mouse, the issuance of such events coincided with fluctuations in pupil size, indicating a tight relationship with arousal fluctuations, and this phenomenon occurred across behavioral states. Strikingly, concurrent measurement of human performance in a visual memory task indicated that each cycle of propagating fMRI waves sequentially promoted the encoding of semantic information and self-directed retrieval of memories. Together, these findings indicate that human cognitive performance is governed by autonomous switching between exteroceptive and interoceptive states. This apparently conserved feature of mammalian brain physiology bears directly on the integration of sensory and mnemonic information during everyday behavior.

3.
Sci Adv ; 10(28): eado0873, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38985869

ABSTRACT

Patterned arrays of perovskite single crystals can avoid signal cross-talk in optoelectronic devices, while precise crystal distribution plays a crucial role in enhancing device performance and uniformity, optimizing photoelectric characteristics, and improving optical management. Here, we report a strategy of droplet-assisted self-alignment to precisely assemble the perovskite single-crystal arrays (PSCAs). High-quality single-crystal arrays of hybrid methylammonium lead bromide (MAPbBr3) and methylammonium lead chloride (MAPbCl3), and cesium lead bromide (CsPbBr3) can be precipitated under a formic acid vapor environment. The crystals floated within the suspended droplets undergo movement and rotation for precise alignment. The strategy allows us to deposit PSCAs with a pixel size range from 200 to 500 micrometers on diverse substrates, including indium tin oxide, glass, quartz, and poly(dimethylsiloxane), and the area can reach up to 10 centimeters by 10 centimeters. The PSCAs exhibit excellent photodetector performance with a large responsivity of 24 amperes per watt.

4.
J Transl Med ; 22(1): 636, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978022

ABSTRACT

BACKGROUND: Prompt and precise differential diagnosis of biliary atresia (BA) among cholestatic patients is of great importance. Matrix metalloproteinase-7 (MMP-7) holds great promise as a diagnostic marker for BA. This study aimed to investigate the accuracy of age-specific serum MMP-7 for discriminating BA from other cholestatic pediatric patients. METHODS: This was a single center diagnostic accuracy and validation study including both retrospective and prospective cohorts. Serum MMP-7 concentrations were measured using an ELISA kit, the trajectory of which with age was investigated in a healthy infants cohort aged 0 to 365 days without hepatobiliary diseases (n = 284). Clinical BA diagnosis was based on intraoperative cholangiography and subsequent histological examinations. The diagnostic accuracy of age-specific cutoffs of serum MMP-7 were assessed in a retrospective cohort of cholestatic patients (n = 318, with 172 BA) and validated in a prospective cohort (n = 687, including 395 BA). RESULTS: The MMP-7 concentration declines non-linearly with age, showing higher levels in healthy neonates as well as higher cutoff value in neonatal cholestasis. The area under the ROC curve (AUROC) was 0.967 (95% confidence interval [CI]: 0.946-0.988) for the retrospective cohort, and the cutoff of 18 ng/mL yielded 93.0% (95%CI: 88.1-96.3%), 93.8% (95%CI: 88.6-97.1%), 94.7% (95%CI: 90.1-97.5%), and 91.9% (95%CI: 86.4-95.8%) for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. The performance of MMP-7 was successfully validated in the larger prospective cohort, resulting in a diagnostic sensitivity of 95.9% (379/395; 95% CI: 93.5-97.7%), a specificity of 87.3% (255/292; 95% CI: 83.0-90.9%), a PPV of 91.1% (379/416; 95% CI: 87.9-93.7%), and a NPV of 94.1% (255/271; 95% CI: 90.6-96.6%), respectively. Besides, higher cutoff value of 28.1 ng/mL achieved the best sensitivity, specificity, PPV, and NPV for infants aged 0-30 days, which was 86.4% (95% CI: 75.0-94.0%), 95.5% (95% CI: 77.2-99.9%), 98.1% (95% CI: 89.7-100%), and 72.4% (95% CI: 52.8-87.3%), respectively. CONCLUSIONS: The serum MMP-7 is accurate and reliable in differentiating BA from non-BA cholestasis, showing its potential application in the diagnostic algorithm for BA and significant role in the future research regarding pathogenesis of BA.


Subject(s)
Biliary Atresia , Matrix Metalloproteinase 7 , ROC Curve , Humans , Biliary Atresia/blood , Biliary Atresia/diagnosis , Matrix Metalloproteinase 7/blood , Infant , Male , Female , Infant, Newborn , Reproducibility of Results , Retrospective Studies , Diagnosis, Differential , Child, Preschool , Cholestasis/blood , Cholestasis/diagnosis , Prospective Studies
5.
Arch Virol ; 169(8): 164, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990242

ABSTRACT

Upregulation of ADAMTS-4 has been reported to have an important role in lung injury, and ADAMTS-4 expression is regulated by miR-126a-5p in abdominal aortic aneurysms. The aim of this study was to investigate whether miR-126a-5p/ADAMTS-4 plays a role in influenza-virus-induced lung injury. Lung fibroblasts were infected with H1N1 influenza virus to detect changes in miR-126a-5p and ADAMTS-4 expression, and cell viability was measured by CCK-8 assay. Inflammatory factors and matrix protease levels were examined using ELISA kits, and cell apoptosis was assessed by measuring the levels of apoptosis-related proteins. A dual luciferase assay was used to verify the regulatory relationship between miR-126a-5p and ADAMTS-4. H1N1 influenza virus reduced fibroblast viability, inhibited miR-126a-5p expression, and promoted ADAMTS-4 expression. Overexpression of miR-126a-5p attenuated the cellular inflammatory response, apoptosis, matrix protease secretion, and virus replication. Luciferase reporter assays revealed that miR-126a-5p inhibited ADAMTS-4 expression by targeting ADAMTS-4 mRNA. Further experiments showed that overexpression of ADAMTS-4 significantly reversed the inhibitory effects of miR-126a-5p on fibroblast inflammation, apoptosis, matrix protease secretion, and virus replication. Upregulation of miR-126a-5p inhibits H1N1-induced apoptosis, inflammatory factors, and matrix protease secretion, as well as virus replication in lung fibroblasts.


Subject(s)
ADAMTS4 Protein , Apoptosis , Fibroblasts , Inflammation , Influenza A Virus, H1N1 Subtype , Lung , MicroRNAs , MicroRNAs/genetics , MicroRNAs/metabolism , Fibroblasts/virology , Fibroblasts/metabolism , Humans , Lung/virology , Lung/pathology , ADAMTS4 Protein/genetics , ADAMTS4 Protein/metabolism , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/physiology , Inflammation/genetics , Cell Survival , Virus Replication , Influenza, Human/virology , Influenza, Human/genetics , Influenza, Human/metabolism , Cell Line
6.
Toxics ; 12(6)2024 May 30.
Article in English | MEDLINE | ID: mdl-38922079

ABSTRACT

Polyvinyl chloride microplastics (PVC-MPs) are microplastic pollutants widely present in the environment, but their potential risks to human lung health and underlying toxicity mechanisms remain unknown. In this study, we systematically analyzed the effects of PVC-MPs on the transcriptome and metabolome of BEAS-2B cells using high-throughput RNA sequencing and untargeted metabolomics technologies. The results showed that exposure to PVC-MPs significantly reduced the viability of BEAS-2B cells, leading to the differential expression of 530 genes and 3768 metabolites. Further bioinformatics analyses showed that PVC-MP exposure influenced the expression of genes associated with fluid shear stress, the MAPK and TGF-ß signaling pathways, and the levels of metabolites associated with amino acid metabolism. In particular, integrated pathway analysis showed that lipid metabolic pathways (including glycerophospholipid metabolism, glycerolipid metabolism, and sphingolipid metabolism) were significantly perturbed in BEAS-2B cells following PVC-MPs exposure. This study provides new insights and targets for a deeper understanding of the toxicity mechanism of PVC-MPs and for the prevention and treatment of PVC-MP-associated lung diseases.

7.
8.
J Thorac Dis ; 16(5): 3317-3324, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38883619

ABSTRACT

Background: Open thoracotomy has been the traditional surgical approach for patients with bronchogenic cysts (BCs). This study aimed to evaluate the safety and efficacy of video-assisted thoracoscopic surgery (VATS) compared to open surgery for the treatment of BCs in adults. Methods: This single-institution, retrospective cohort study included 117 consecutive adult patients who underwent VATS (group A) or open surgery (group B) for BC resection between February 2019 and January 2023. Data regarding clinical history, operation duration, length of hospital stay, 30-day mortality, and recurrence during follow-up were collected and analyzed. Results: Of the total cohort, 103 (88.0%) patients underwent VATS, while 14 (12.0%) patients underwent open surgery. Patients' age in group B were much older than group A (P=0.014), and no significant differences in other demographic and baseline clinical characteristics were observed between the groups. The VATS group had shorter median operation duration (96 vs. 149.5 min, P<0.001) and shorter mean length of hospital stay (5.0±5.5 vs. 8.6±4.0 days, P<0.001). One death occurred in the open surgery group. During a median follow-up of 34 (interquartile range, 20.8-42.5) months, no instances of BC recurrence were observed in either group. Conclusions: Compared to open surgery, VATS is also a safe and efficacious approach for treating BCs in adults. What's more, VATS offered shorter operative times and hospital stays. Considering the minimally invasive, VATS may be a better choice in most patients with bronchial cysts.

9.
Parasit Vectors ; 17(1): 256, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867315

ABSTRACT

BACKGROUND: Human toxocariasis is a neglected parasitic disease characterised by the syndromes visceral, cerebral, and ocular larva migrans. This disease is caused by the migrating larvae of Toxocara roundworms from dogs and cats, affecting 1.4 billion people globally. Via extracellular vesicles (EVs), microRNAs have been demonstrated to play roles in host-parasite interactions and proposed as circulating biomarkers for the diagnosis and follow-up of parasitic diseases. METHODS: Small RNA-seq was conducted to identify miRNAs in the infective larvae of T. canis and plasma EV-containing preparations of infected BALB/c mice. Differential expression analysis and target prediction were performed to indicate miRNAs involved in host-parasite interactions and miRNAs associated with visceral and/or cerebral larva migrans in the infected mice. Quantitative real-time polymerase chain reaction (PCR) was used to amplify circulating miRNAs from the infected mice. RESULTS: This study reports host and parasite miRNAs in the plasma of BALB/c mice with visceral and cerebral larva migrans and demonstrates the alterations of these miRNAs during the migration of larvae from the livers through the lungs and to the brains of infected mice. After filtering unspecific changes in an irrelevant control, T. canis-derived miRNAs and T. canis infection-induced differential miRNAs are predicted to modulate genes consistently involved in mitogen-activated protein kinase (MAPK) signalling and pathways regulating axon guidance and pluripotency of stem in the infected mice with visceral and cerebral larva migrans. For these plasma circulating miRNAs predicted to be involved in host-parasite crosstalk, two murine miRNAs (miR-26b-5p and miR-122-5p) are experimentally verified to be responsive to larva migrans and represent circulating biomarker candidates for visceral and cerebral toxocariasis in BALB/c mice. CONCLUSIONS: Our findings provide novel insights into the crosstalk of T. canis and the mammalian host via plasma circulating miRNAs, and prime agents and indicators for visceral and cerebral larva migrans. A deep understanding of these aspects will underpin the diagnosis and control of toxocariasis in humans and animals.


Subject(s)
Circulating MicroRNA , Mice, Inbred BALB C , Toxocara canis , Toxocariasis , Animals , Toxocara canis/genetics , Toxocara canis/physiology , Mice , Toxocariasis/parasitology , Toxocariasis/blood , Circulating MicroRNA/blood , Circulating MicroRNA/genetics , Host-Parasite Interactions , Larva Migrans, Visceral/parasitology , Larva Migrans, Visceral/blood , Female , Larva Migrans/parasitology , Larva Migrans/blood , Larva/genetics , Dogs , MicroRNAs/blood , MicroRNAs/genetics , Biomarkers/blood , Brain/parasitology
10.
J Transl Med ; 22(1): 553, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858763

ABSTRACT

Gamma delta (γδ) T cells demonstrate strong cytotoxicity against diverse cancer cell types in an MHC-independent manner, rendering them promising contenders for cancer therapy. Although amplification and adoptive transfer of γδ T cells are being evaluated in the clinic, their therapeutic efficacy remains unsatisfactory, primarily due to the influence of the immunosuppressive tumor microenvironment (TME). Currently, the utilization of targeted therapeutic antibodies against inhibitory immune checkpoint (ICP) molecules is a viable approach to counteract the immunosuppressive consequences of the TME. Notably, PD-1/PD-L1 checkpoint inhibitors are considered primary treatment options for diverse malignancies, with the objective of preserving the response of αß T cells. However, γδ T cells also infiltrate various human cancers and are important participants in cancer immunity, thereby influencing patient prognosis. Hence, it is imperative to comprehend the reciprocal impact of the PD-1/PD-L1 axis on γδ T cells. This understanding can serve as a therapeutic foundation for improving γδ T cells adoptive transfer therapy and may offer a novel avenue for future combined immunotherapeutic approaches.


Subject(s)
B7-H1 Antigen , Programmed Cell Death 1 Receptor , Tumor Microenvironment , Humans , Tumor Microenvironment/immunology , Programmed Cell Death 1 Receptor/metabolism , B7-H1 Antigen/metabolism , Animals , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Receptors, Antigen, T-Cell, gamma-delta/immunology , T-Lymphocytes/immunology , Neoplasms/immunology , Neoplasms/pathology , Neoplasms/therapy
11.
Front Aging Neurosci ; 16: 1400589, 2024.
Article in English | MEDLINE | ID: mdl-38934020

ABSTRACT

Background: Dementia is a progressive neurodegenerative condition, while metabolic syndrome (MetS) is characterized by a combination of metabolic abnormalities such as hypertension, high blood sugar, and obesity. There exists a connection and overlap between the two conditions in certain aspects, and both are influenced to varying degrees by the process of aging. This study presents an overview of the current research landscape regarding dementia and MetS through bibliometric analysis. Methods: A systematic search was conducted to retrieve relevant literature on dementia and MetS published between 1 January 2000, and 30 November 2023, from the Web of Science Core Collection database. Various bibliometric tools, including VOSviewer, CiteSpace, and the R software package "bibliometrix," were utilized for analysis. Results: A total of 717 articles were identified, showing an upward trend in annual publications. Leading contributors included the United States, Italy, and China, with institutions such as the University of California System at the forefront. The Journal of Alzheimer's Disease emerged as the top publisher, while research published in Neurology garnered significant citations. Noteworthy authors encompassed Panza, Francesco; Frisardi, Vincenza; and Feldman, Eva L, with Kristine Yaffe being the most cited author (280 citations). Recent studies have focused on themes like "gut microbiota," "neuroinflammation," "fatty acids," and "microglia." Conclusion: This bibliometric analysis summarizes the foundational knowledge structure in the realm of dementia and MetS from 2000 to 2023. By highlighting current research frontiers and trending topics, this analysis serves as a valuable reference for researchers in the field.

12.
Angew Chem Int Ed Engl ; : e202407277, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780892

ABSTRACT

Chiral multi-resonance thermally activated delayed fluorescence (CP-MR-TADF) materials hold promise for circularly polarized organic light-emitting diodes (CP-OLEDs) and 3D displays. 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 the frontier molecular orbitals. Due to the heavy-atom effect, sulfur atoms are introduced to accelerate the reverse intersystem crossing process and increase the efficiency of molecules. R/S-BDBF-BOH and R/S-BDBT-BOH manifest ultra-pure blue emission with a maximum at 458/459 nm with a full width at half maximum of 27 nm, 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 an external quantum efficiency of 30.1 % and |gEL| factors of 1.2×10-3.

13.
Water Res ; 258: 121752, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38761591

ABSTRACT

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.


Subject(s)
Hydrogen Peroxide , Iron , Membranes, Artificial , Hydrogen Peroxide/chemistry , Iron/chemistry , Oxidation-Reduction , Wastewater/chemistry , Hydrogen-Ion Concentration , Filtration , Waste Disposal, Fluid/methods
14.
Br J Haematol ; 205(1): 229-235, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38810989

ABSTRACT

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.


Subject(s)
Hematologic Diseases , Hematopoietic Stem Cell Transplantation , Spermatogonia , Humans , Male , Child , Spermatogonia/pathology , Child, Preschool , Hematologic Diseases/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Adolescent , Fertility Preservation/methods , Testis/pathology , Testis/radiation effects , Spermatogenesis/radiation effects , Infant , Myelodysplastic Syndromes/therapy
15.
Sleep Med ; 119: 499-504, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38796979

ABSTRACT

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.


Subject(s)
Shift Work Schedule , Stroke , Humans , Stroke/epidemiology , Stroke/etiology , Shift Work Schedule/adverse effects , Risk Factors , Work Schedule Tolerance , Sleep Deprivation/complications
16.
Heliyon ; 10(9): e30350, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707362

ABSTRACT

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(q>0.12) 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.

17.
Article in English | MEDLINE | ID: mdl-38805329

ABSTRACT

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.

18.
Am J Surg ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38777717

ABSTRACT

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€‹< â€‹0.001). 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€‹< â€‹0.001). 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.

20.
Expert Rev Clin Immunol ; : 1-13, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38752776

ABSTRACT

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.

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