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1.
Opt Lett ; 49(15): 4294-4297, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090917

ABSTRACT

To realize compact and denser photonic integrated circuits, three-dimensional integration has been widely accepted and researched. In this article, we demonstrate the operation of a 3D integrated silicon photonic platform fabricated through wafer bonding. Benefiting from the wafer bonding process, the material of all layers is c-Si, which ensures that the mobility is high enough to achieve a nanosecond response via the p-i-n diode shifter. Optical components, including multimode interferences (MMIs), waveguide crossing, and Mach-Zehnder interferometer (MZI)-based switch, are fabricated in different layers and exhibit great performance. The interlayer coupler and crossing achieve a 0.98 dB coupling loss and <-43.58 dB cross talk, while the crossing fabricated in the same layer shows <-36.00 dB cross talk. A nanosecond-order switch response is measured in different layers.

2.
Sensors (Basel) ; 24(15)2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39123925

ABSTRACT

When an ultrasonic pulse propagates in a thin plate, nonlinear Lamb waves with higher harmonics and a zero-frequency component (ZFC) will be generated because of the nonlinearity of materials. The ZFC, also known as the static displacement or static component, has its unique application on the evaluation of early-stage damages in the elastic symmetrical undulated plate. In this study, analysis of the excitation mechanism of the ZFC and the second harmonic component (SHC) was theoretically and numerically investigated, and the material early-stage damage of a symmetrical undulated was characterized by studying the propagation of nonlinear Lamb waves. Both the ZFC and SHC can be effectively employed in monitoring the material damages of the undulated plate in its early stage. However, several factors must be considered for the propagation of the SHC in an undulated plate because of the geometric curvature and interference between the second harmonics during propagation, preventing efficient application of this technique. If the fundamental wave can propagate in the plate regardless of the plate boundary conditions, an accumulative effect always exists for the ZFC in a thin plate, indicating that the ZFC is independent of the structural geometry. This study reveals that the ZFC-based inspection technique is more efficient and powerful in characterizing the damages of a symmetrical undulated plate in the early stage of service compared to the second harmonic method.

3.
ISA Trans ; 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39098567

ABSTRACT

When maneuvering corners at high speeds, commercial vehicles experience significant sideslip angles and tire force saturation, which can lead to severe traffic accidents. Incorporating intelligent driving technology to develop a controllable scheme that surpasses stability constraints and maintains the vehicle in a drift state is crucial for enhancing driving safety. Therefore, based on the model characteristics of distributed drive three-axle(DDTA) commercial vehicles, a two-stage auxiliary drift controller is proposed. In the auxiliary drift stage, time-varying model predictive control (MPC) is employed to track the desired states and achieve steady-state drift path tracking under extreme working conditions. A two-stage controller switching strategy is implemented based on road information. In the yaw stability control stage, an advanced auxiliary system facilitates cooperative control to smoothly restore tire attachment and vehicle yaw. Simulation results demonstrate that the control strategy ensures consistent path tracking performance even when adhesion of the middle and rear axle saturates and peak vehicle sideslip angle reaches 32.09°. After completing the drifting, vehicle yaw successfully returns to a stable state. Subsequently, miniaturized vehicle tests qualitatively analyze relevant conclusions by elucidating transient instability evolution in vehicles subjected to steering and distributed drive. The controllable stability boundary of the vehicle is thus expanded, thereby enhancing the engineering feasibility of drift technology.

4.
J Anim Sci Biotechnol ; 15(1): 114, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39118186

ABSTRACT

Obesity is a prevalent chronic disease that has significant negative impacts on humans and our companion animals, including dogs and cats. Obesity occurs with multiple comorbidities, such as diabetes, hypertension, heart disease and osteoarthritis in dogs and cats. A direct link between lipid metabolism dysregulation and obesity-associated diseases has been implicated. However, the understanding of such pathophysiology in companion animals is limited. This review aims to address the role of lipid metabolism in various metabolic disorders associated with obesity, emphasizing the involvement of the gut microbiota. Furthermore, we also discuss the management of obesity, including approaches like nutritional interventions, thus providing novel insights into obesity prevention and treatment for canines and felines.

5.
BMC Anesthesiol ; 24(1): 231, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987679

ABSTRACT

BACKGROUND: Patients who are recovering from general anesthesia commonly exhibit symptoms such as dry lips, throat irritation, and thirst, prompting a desire to drink water in the post-anesthesia care unit (PACU). In this study, we aimed to evaluate the therapeutic effects and any potential complications of administering varying quantities of water to such patients. The primary objectives are to assess the safety and feasibility of early water intake after general anesthesia, specifically in the context of daytime surgery. METHODS: A total of 200 nongastrointestinal patients who underwent outpatient surgery were randomly assigned to four groups: Group A (drinking < 1 ml/kg), Group B (drinking 1-2 ml/kg), Group C (drinking > 2 ml/kg), and Group D (no water intake). We monitored changes in the assessment parameters before and after water consumption, as well as the incidence of post-drinking nausea and vomiting, and compared these outcomes among the four groups. RESULTS: Water intake led to a significant reduction in thirst, oropharyngeal discomfort, and pain scores and a notable increase in the gastric antrum motility index (MI), exhibiting statistical significance compared to the values before drinking (p < 0.05). Remarkably, higher water consumption correlated with enhanced gastrointestinal peristalsis. There was a significant difference in the antral MI among groups B, C, and A (p < 0.05). The occurrence of nausea and vomiting did not significantly differ among groups A, B, C, and D (p > 0.05). Early water consumption enhanced patient satisfaction with medical care, significantly varying from Group D (p < 0.05). CONCLUSION: Non-gastrointestinal surgical patients who passed pre-drinking water assessments post GA(general anesthesia)recovery could safely ingest moderate amounts of water in the PACU. Early water intake is both safe and feasible, effectively fostering swift postoperative recovery.


Subject(s)
Ambulatory Surgical Procedures , Anesthesia Recovery Period , Anesthesia, General , Drinking Water , Feasibility Studies , Humans , Anesthesia, General/methods , Female , Male , Middle Aged , Ambulatory Surgical Procedures/methods , Drinking Water/administration & dosage , Adult , Drinking , Postoperative Nausea and Vomiting/epidemiology , Thirst/physiology , Aged
6.
Biomed Microdevices ; 26(3): 33, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023652

ABSTRACT

Stem cells are crucial in tissue engineering, and their microenvironment greatly influences their behavior. Among the various dental stem cell types, stem cells from the apical papilla (SCAPs) have shown great potential for regenerating the pulp-dentin complex. Microenvironmental cues that affect SCAPs include physical and biochemical factors. To research optimal pulp-dentin complex regeneration, researchers have developed several models of controlled biomimetic microenvironments, ranging from in vivo animal models to in vitro models, including two-dimensional cultures and three-dimensional devices. Among these models, the most powerful tool is a microfluidic microdevice, a tooth-on-a-chip with high spatial resolution of microstructures and precise microenvironment control. In this review, we start with the SCAP microenvironment in the regeneration of pulp-dentin complexes and discuss research models and studies related to the biological process.


Subject(s)
Dental Papilla , Lab-On-A-Chip Devices , Stem Cells , Humans , Stem Cells/cytology , Dental Papilla/cytology , Animals , Cellular Microenvironment , Dental Pulp/cytology , Tissue Engineering/instrumentation , Stem Cell Niche , Dentin/cytology
7.
Micromachines (Basel) ; 15(6)2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38930762

ABSTRACT

The mode rotator is an important component in a PLC-based mode-division multiplexing (MDM) system, which is used to implement high-order modes with vertical intensity peaks, such as LP11b mode conversions from LP11a in PLC chips. In this paper, an LP11 mode rotator based on a polymer/silica hybrid inverted ridge waveguide is demonstrated. The proposed mode rotator is composed of an asymmetrical waveguide with a trench. According to the simulation results, the broadband conversion efficiency between the LP11a and LP11b modes is greater than 98.5%, covering the C-band after optimization. The highest mode conversion efficiency (MCE) is 99.2% at 1550 nm. The large fabrication tolerance of the proposed rotator enables its wide application in on-chip MDM systems.

8.
Article in English | MEDLINE | ID: mdl-38832960

ABSTRACT

CU traits, characterized by shallow affect, lack of fear, and absence of remorse, have been moderately associated with childhood maltreatment in a recent meta-analysis. However, the potential impact of brain structures remains undetermined. This paper examines the relationship between callous-unemotional (CU) traits, childhood maltreatment, and amygdala volumes. In this study, we used a region-of-interest (ROI) analysis to explore the interaction between the volumes of the amygdala, childhood maltreatment, and the manifestation of CU traits in adolescents diagnosed with conduct disorder (CD, N = 67), along with a comparison group of healthy-control youths (HCs, N = 89). The ROI analysis revealed no significant group differences in the bilateral amygdalar volumes. Significant positive correlation was discovered between all forms of child maltreatment (except for physical neglect) and CU traits across subjects. But the interaction of physical abuse and amygdala volumes was only significant within CD patients. Notably, a sensitivity analysis suggested that gender significantly influences these findings. These results contribute critical insights into the etiology of CU traits, emphasizing the need for customized clinical assessment tools and intervention strategies.

9.
Chemistry ; 30(41): e202401426, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38757380

ABSTRACT

The fabrication of supramolecular light-harvesting systems (LHS) with sequential energy transfer is of significance in utilizing light energy. In this study, we report the non-covalent self-assembly of a sequential LHS by pillar[5]arene-based host-guest interaction in water and its applications in white light-emitting diode (LED) device and latent fingerprint imaging. The host-guest complex WP5 ⊃ ${ \supset }$ G self-assembles into nanoparticles in water and shows enhanced aggregation-induced emission (AIE) effect. The nanoparticles can be further used to construct sequential LHS with fluorescent dyes 4,7-di(2-thienyl)-benzo[2,1,3]thiadiazole (DBT) and sulforhodamine 101 (SR101). Impressively, the system shows white-light emission when the molar ratio of WP5 ⊃ ${ \supset }$ G/DBT/SR101 is 1100/2/16. The material can be coated on a LED bulb to achieve white-light emission. In addition, the sequential LHS exhibit multicolor fluorescence including red emission, which have been successfully applied to high-resolution imaging of latent fingerprints. Therefore, we demonstrated a general strategy for the construction of sequential LHS in water based on macrocyclic host-guest interaction and explored its multi-functional applications in white-light LED device and imaging of latent fingerprints, which will promote future development and application of supramolecular LHSs.

10.
J Dent ; 146: 105028, 2024 07.
Article in English | MEDLINE | ID: mdl-38719135

ABSTRACT

AIM: Three-dimensional (3D) cell culture systems perform better in resembling tissue or organism structures compared with traditional 2D models. Organs-on-chips (OoCs) are becoming more efficient 3D models. This study aimed to create a novel simplified dentin-on-a-chip using microfluidic chip technology and tissue engineering for screening dental materials. METHODOLOGY: A microfluidic device with three channels was designed for creating 3D dental tissue constructs using stem cells from the apical papilla (SCAP) and gelatin methacrylate (GelMA). The study investigated the effect of varying cell densities and GelMA concentrations on the layer features formed within the microfluidic chip. Cell viability and distribution were evaluated through live/dead staining and nuclei/F-actin staining. The osteo/odontogenic potential was assessed through ALP staining and Alizarin red staining. The impact of GelMA concentrations (5 %, 10 %) on the osteo/odontogenic differentiation trajectory of SCAP was also studied. RESULTS: The 3D tissue constructs maintained high viability and favorable spreading within the microfluidic chip for 3-7 days. A cell seeding density of 2 × 104 cells/µL was found to be the most optimal choice, ensuring favorable cell proliferation and even distribution. GelMA concentrations of 5 % and 10 % proved to be most effective for promoting cell growth and uniform distribution. Within the 5 % GelMA group, SCAP demonstrated higher osteo/odontogenic differentiation than that in the 10 % GelMA group. CONCLUSION: In 3D culture, GelMA concentration was found to regulate the osteo/odontogenic differentiation of SCAP. The study recommends a seeding density of 2 × 104 cells/µL of SCAP within 5 % GelMA for constructing simplified dentin-on-a-chip. CLINICAL SIGNIFICANCE: This study built up the 3D culture protocol, and induced odontogenic differentiation of SCAP, thus forming the simplified dentin-on-a-chip and paving the way to be used as a well-defined biological model for regenerative endodontics. It may serve as a potential testing platform for cell differentiation.


Subject(s)
Cell Differentiation , Cell Proliferation , Cell Survival , Dental Papilla , Dentin , Gelatin , Lab-On-A-Chip Devices , Tissue Engineering , Tissue Engineering/methods , Humans , Dental Papilla/cytology , Stem Cells/cytology , Odontogenesis , Osteogenesis/physiology , Methacrylates , Cell Culture Techniques , Microfluidics/methods , Microfluidics/instrumentation , Cell Culture Techniques, Three Dimensional/methods , Cell Culture Techniques, Three Dimensional/instrumentation , Cells, Cultured
11.
Research (Wash D C) ; 7: 0390, 2024.
Article in English | MEDLINE | ID: mdl-38812530

ABSTRACT

Recent advancements in spatial transcriptomics (ST) technologies offer unprecedented opportunities to unveil the spatial heterogeneity of gene expression and cell states within tissues. Despite these capabilities of the ST data, accurately dissecting spatiotemporal structures (e.g., spatial domains, temporal trajectories, and functional interactions) remains challenging. Here, we introduce a computational framework, PearlST (partial differential equation [PDE]-enhanced adversarial graph autoencoder of ST), for accurate inference of spatiotemporal structures from the ST data using PDE-enhanced adversarial graph autoencoder. PearlST employs contrastive learning to extract histological image features, integrates a PDE-based diffusion model to enhance characterization of spatial features at domain boundaries, and learns the latent low-dimensional embeddings via Wasserstein adversarial regularized graph autoencoders. Comparative analyses across multiple ST datasets with varying resolutions demonstrate that PearlST outperforms existing methods in spatial clustering, trajectory inference, and pseudotime analysis. Furthermore, PearlST elucidates functional regulations of the latent features by linking intercellular ligand-receptor interactions to most contributing genes of the low-dimensional embeddings, as illustrated in a human breast cancer dataset. Overall, PearlST proves to be a powerful tool for extracting interpretable latent features and dissecting intricate spatiotemporal structures in ST data across various biological contexts.

12.
Int J Mol Sci ; 25(5)2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38474320

ABSTRACT

Recent mechanistic studies have indicated that combinations of radiotherapy (RT) plus immunotherapy (via CSF-1R inhibition) can serve as a strategy to overcome RT resistance and improve the survival of glioma mice. Given the high mortality rate for glioma, including low-grade glioma (LGG) patients, it is of critical importance to investigate the mechanism of the combination of RT and immunotherapy and further translate the mechanism from mouse studies to improve survival of RT-treated human glioma patients. Using the RNA-seq data from a glioma mouse study, 874 differentially expressed genes (DEGs) between the group of RT-treated mice at glioma recurrence and the group of mice with combination treatment (RT plus CSF-1R inhibition) were translated to the human genome to identify significant molecular pathways using the KEGG enrichment analysis. The enrichment analysis yields statistically significant signaling pathways, including the phosphoinositide 3-kinase (PI3K)/AKT pathway, Hippo pathway, and Notch pathway. Within each pathway, a candidate gene set was selected by Cox regression models as genetic biomarkers for resistance to RT and response to the combination of RT plus immunotherapies. Each Cox model is trained using a cohort of 295 RT-treated LGG patients from The Cancer Genome Atlas (TCGA) database and validated using a cohort of 127 RT-treated LGG patients from the Chinese Glioma Genome Atlas (CGGA) database. A four-DEG signature (ITGB8, COL9A3, TGFB2, JAG1) was identified from the significant genes within the three pathways and yielded the area under time-dependent ROC curve AUC = 0.86 for 5-year survival in the validation set, which indicates that the selected DEGs have strong prognostic value and are potential intervention targets for combination therapies. These findings may facilitate future trial designs for developing combination therapies for glioma patients.


Subject(s)
Brain Neoplasms , Glioma , Radiation Oncology , Humans , Animals , Mice , Phosphatidylinositol 3-Kinases , Phosphatidylinositol 3-Kinase , Immunotherapy
13.
J Hypertens ; 42(5): 801-808, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38164953

ABSTRACT

OBJECTIVES: Renal denervation (RDN) has been proven to be effective in lowering blood pressure (BP) in patients, but previous studies have had short follow-ups and have not examined the effects of RDN on major cardiovascular outcomes. This study aimed to demonstrate the effectiveness and safety of RDN in the long-term treatment of hypertension and to determine if it has an effect on cardiovascular outcomes. METHODS: All patients with resistant hypertension who underwent RDN between 2011 and 2015 at Tianjin First Central Hospital were included in the study. Patients were followed up at 1,5 and 10 years and the longest follow-up was 12 years. Data were collected on office BP, home BP, ambulatory BP monitoring (ABPM), renal function, antihypertensive drug regimen, major adverse events (including acute myocardial infarction, stroke, cardiovascular death and all cause death) and safety events. RESULTS: A total of 60 participants with mean age 50.37 ±â€Š15.19 years (43.33% female individuals) completed long-term follow-up investigations with a mean of 10.02 ±â€Š1.72 years post-RDN. Baseline office SBP and DBP were 179.08 ±â€Š22.05 and 101.17 ±â€Š16.57 mmHg under a mean number of 4.22 ±â€Š1.09 defined daily doses (DDD), with a reduction of -35.93/-14.76 mmHg as compared with baseline estimates ( P  < 0.0001). Compared with baseline, ambulatory SBP and DBP after 10-years follow-up were reduced by 14.31 ±â€Š10.18 ( P  < 0.001) and 9 ±â€Š4.35 ( P  < 0.001) mmHg, respectively. In comparison to baseline, participants were taking fewer antihypertensive medications ( P  < 0.001), and their mean heart rate had decreased ( P  < 0.001). Changes in renal function, as assessed by estimated glomerular filtration rate (eGFR) and creatinine, were within the expected rate of age-related decline. No major adverse events related to the RDN procedure were observed in long-term consequences. All-cause mortality and cardiovascular mortality rates were 10 and 8.34%, respectively, for the 10-year period. CONCLUSION: The BP-lowering effect of RDN was safely sustained for at least 10 years post-procedure. More importantly, to the best of my knowledge, this is the first study to explore cardiovascular and all-cause mortality at 10 years after RDN.


Subject(s)
Hypertension , Humans , Female , Adult , Middle Aged , Aged , Male , Follow-Up Studies , Blood Pressure/physiology , Treatment Outcome , Kidney , Sympathectomy/methods , Antihypertensive Agents/therapeutic use , Blood Pressure Monitoring, Ambulatory , Denervation
14.
Neuropsychopharmacology ; 49(5): 806-813, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38218921

ABSTRACT

Sex-specific neurobiological changes have been implicated in Major Depressive Disorder (MDD). Dysfunctions of the default mode network (DMN), salience network (SN) and frontoparietal network (FPN) are critical neural characteristics of MDD, however, the potential moderating role of sex on resting-state network dynamics in MDD has not been sufficiently evaluated. Thus, resting-state functional magnetic resonance imaging (fMRI) data were collected from 138 unmedicated patients with first-episode MDD (55 males) and 243 healthy controls (HCs; 106 males). Recurring functional network co-activation patterns (CAPs) were extracted, and time spent in each CAP (the total amount of volumes associated to a CAP), persistence (the average number of consecutive volumes linked to a CAP), and transitions across CAPs involving the SN, DMN and FPN were quantified. Relative to HCs, MDD patients exhibited greater persistence in a CAP involving activation of the DMN and deactivation of the FPN (DMN + FPN-). In addition, relative to the sex-matched HCs, the male MDD group spent more time in two CAPs involving the SN and DMN (i.e., DMN + SN- and DMN-SN + ) and transitioned more frequently from the DMN + FPN- CAP to the DMN + SN- CAP relative to the male HC group. Conversely, the female MDD group showed less persistence in the DMN + SN- CAP relative to the female HC group. Our findings highlight that the imbalance between SN and DMN could be a neurobiological marker supporting sex differences in MDD. Moreover, the dominance of the DMN accompanied by the deactivation of the FPN could be a sex-independent neurobiological correlate related to depression.


Subject(s)
Depressive Disorder, Major , Humans , Female , Male , Depressive Disorder, Major/diagnostic imaging , Magnetic Resonance Imaging/methods , Neural Pathways/diagnostic imaging , Brain/diagnostic imaging , Brain Mapping
15.
Colloids Surf B Biointerfaces ; 234: 113739, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38219640

ABSTRACT

Browning has many important implications with nutrition and the shelf life of foods. Mitigating browning is of particular interest in food chemistry. The addition of antioxidants has been a common strategy to extend shelf life of drug and food products. In this work, we report a microfluidic technology for encapsulation of three common food additives (potassium metathionite (PMS), curcumin (CCM), and ß-carotene (ß-Car)) into nano-formulations using low-cost and readily available materials such as shellac. The food additives encapsulated nanoparticles provide a microenvironment that can prevent oxidation during daily storage. The results showed that the produced nanoparticles had a narrow size distribution with an average size of around 100 nm, were stable at conventional storage conditions (4 ºC) for 18 weeks, and had sustained release ability at 37 ºC, pH= 7.8, 160 rpm. In addition, further experiments showed that the formulation of hydrophobic additives, such as CCM and ß-Car did not only improve their bioavailability but also allowed for the encapsulation of a combination of ingredients. In addition, the antioxidants loaded nanoparticles demonstrated good biocompatibility, low toxicity to human cells. The longer release time of encapsulated food additives increases shelf life of foods and enhances consumer purchase preferences, which not only saves costs but also reduces waste. In summary, this study shows that such antioxidant-loaded nanoparticles provide a promising strategy in extending the shelf life of food products.


Subject(s)
Antioxidants , Nanoparticles , Humans , Antioxidants/pharmacology , Antioxidants/chemistry , Food Additives , Microfluidics , Food , Nanoparticles/chemistry
16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1032022

ABSTRACT

Objective@#To evaluate the applicability of a modified U-shaped forearm flap for the repair of small- and medium-sized defects in the oral and maxillary areas to provide a reference for clinicians.@*Methods@#This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Ten patients with small- and medium-sized defects in the oral and maxillary areas underwent surgical repair using modified U-shaped forearm flaps. There were 8 males and 2 females aged 43-72 years. The donor site was apposed primarily after harvesting the modified U-shaped forearm skin flap. The flaps ranged from 6 cm × 4 cm to 8 cm × 5 cm in size. Six months after the operation, hand movements (finger extension, fist clenching, wrist rotation upward and wrist rotation downward), the forearm donor site, hand sensations and the satisfaction score for the postoperative quality of the scar at the donor site were evaluated (0 to 10; 0: very unattractive, 10: very satisfactory).@*Results@#A total of 10 patients with modified U-shaped forearm flaps survived. One patient developed venous crisis 24 hours after surgery and survived after surgical exploration. Delayed healing occurred at the donor site of the forearm in 1 patient, and the wounds at the donor site of the forearm in the other patients all healed in the first stage. One patient presented with dysesthesia in the hand 2 weeks after surgery and recovered within 3 months. Six months after surgery, all patients had no limited hand movement and no paresthesia at the forearm donor site or hand. The patients were basically satisfied with the appearance of the donor site,and the average satisfaction score of the subjective questionnaire was 8.4 points.@*Conclusion@#Modified U-shaped forearm flaps can directly close forearm donor site wounds, which avoids surgical trauma to the secondary donor site and significantly reduces related complications. Modified U-shaped forearm flaps provide an alternative to conventional forearm flaps for the repair of small- and medium-sized defects in the oral and maxillary areas.

17.
Comput Struct Biotechnol J ; 21: 5285-5295, 2023.
Article in English | MEDLINE | ID: mdl-37941656

ABSTRACT

Drug resistance is a prominent impediment to the efficacy of targeted therapies across various cancer types, including glioblastoma (GBM). However, comprehending the intricate intracellular and extracellular mechanisms underlying drug resistance remains elusive. Empirical investigations have elucidated that genetic aberrations, such as gene mutations, along with microenvironmental adaptation, notably angiogenesis, act as pivotal drivers of tumor progression and drug resistance. Nonetheless, mathematical models frequently compartmentalize these factors in isolation. In this study, we present a multiscale agent-based model of GBM, encompassing cellular dynamics, intricate signaling pathways, gene mutations, angiogenesis, and therapeutic interventions. This integrative framework facilitates an exploration of the interplay between genetic mutations and the vascular microenvironment in shaping the dynamic evolution of tumors during treatment with tyrosine kinase inhibitor. Our simulations unveil that mutations influencing the migration and proliferation of tumor cells expedite the emergence of phenotype heterogeneity, thereby exacerbating tumor invasion under both treated and untreated conditions. Moreover, angiogenesis proximate to the tumor fosters a protumoral milieu, augmenting mutation-induced drug resistance by increasing the survival rate of tumor cells. Collectively, our findings underscore the dual roles of intrinsic genetic mutations and extrinsic microenvironmental adaptations in steering tumor growth and drug resistance. Finally, we substantiate our model predictions concerning the impact of gene mutations and angiogenesis on the responsiveness of targeted therapies by integrating single-cell RNA-seq, spatial transcriptomics, bulk RNA-seq, and clinical data from GBM patients. The multidimensional approach enhances our understanding of the complexities governing drug resistance in glioma and offers insights into potential therapeutic strategies.

18.
Genome Res ; 33(10): 1788-1805, 2023 10.
Article in English | MEDLINE | ID: mdl-37827697

ABSTRACT

Cell-cell communication (CCC) is critical for determining cell fates and functions in multicellular organisms. With the advent of single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST), an increasing number of CCC inference methods have been developed. Nevertheless, a thorough comparison of their performances is yet to be conducted. To fill this gap, we developed a systematic benchmark framework called ESICCC to evaluate 18 ligand-receptor (LR) inference methods and five ligand/receptor-target inference methods using a total of 116 data sets, including 15 ST data sets, 15 sets of cell line perturbation data, two sets of cell type-specific expression/proteomics data, and 84 sets of sampled or unsampled scRNA-seq data. We evaluated and compared the agreement, accuracy, robustness, and usability of these methods. Regarding accuracy evaluation, RNAMagnet, CellChat, and scSeqComm emerge as the three best-performing methods for intercellular ligand-receptor inference based on scRNA-seq data, whereas stMLnet and HoloNet are the best methods for predicting ligand/receptor-target regulation using ST data. To facilitate the practical applications, we provide a decision-tree-style guideline for users to easily choose best tools for their specific research concerns in CCC inference, and develop an ensemble pipeline CCCbank that enables versatile combinations of methods and databases. Moreover, our comparative results also uncover several critical influential factors for CCC inference, such as prior interaction information, ligand-receptor scoring algorithm, intracellular signaling complexity, and spatial relationship, which may be considered in the future studies to advance the development of new methodologies.


Subject(s)
Single-Cell Analysis , Software , Ligands , Single-Cell Analysis/methods , Algorithms , Cell Communication/genetics , Sequence Analysis, RNA/methods
19.
J Org Chem ; 88(19): 13699-13711, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37747962

ABSTRACT

The selective C(sp3)-S bond cleavage of thioethers was first developed to prepare unsymmetrical disulfides by using electrophilic halogenation reagents. In this strategy, NBS (N-bromosuccinimide) achieves selective furfuryl C(sp3)-S bond cleavage of furfuryl alkylthioethers at room temperature. Meanwhile, NFSI (N-fluorobenzenesulfonimide) enables selective methyl C(sp3)-S bond cleavage of aryl and alkyl methylthioethers at an elevated temperature. Notably, the substrate scope investigation indicates that the order of selectivity of the C-S bond cleavage is furfuryl C(sp3)-S > benzyl C(sp3)-S > alkyl C(sp3)-S > C(sp2)-S bond. Moreover, this practical and operationally simple strategy also provides an important complementary way to access various unsymmetrical disulfides with excellent functional group tolerances and moderate to good yields.

20.
Chempluschem ; 88(10): e202300431, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37609789

ABSTRACT

A guest molecule containing a short alkyl spacer between the tetraphenylethylene group and the methylpyridinium group was designed and synthesized. After complexation with a water-soluble pillar[5]arene, the resulting host-guest complex can further self-assemble into fluorescence-emitting nanoparticles in water. By loading a commercially available dye Rhodamine 6G into the nanoparticles, an efficient artificial light-harvesting system with high donor/acceptor ratios (>400/1) was successfully constructed. The obtained systems show considerable antenna effects with values of more than 10 times. The system also exhibits tunable fluorescence emission behavior and can be used as a fluorescent ink for information encryption.

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