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1.
Comput Biol Chem ; 113: 108223, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39340962

ABSTRACT

BACKGROUND AND OBJECTIVE: The reconstruction of gene regulatory networks (GRNs) stands as a vital approach in deciphering complex biological processes. The application of nonlinear ordinary differential equations (ODEs) models has demonstrated considerable efficacy in predicting GRNs. Notably, the decay rate and time delay are pivotal in authentic gene regulation, yet their systematic determination in ODEs models remains underexplored. The development of a comprehensive optimization framework for the effective estimation of these key parameters is essential for accurate GRN inference. METHOD: This study introduces GRNMOPT, an innovative methodology for inferring GRNs from time-series and steady-state data. GRNMOPT employs a combined use of decay rate and time delay in constructing ODEs models to authentically represent gene regulatory processes. It incorporates a multi-objective optimization approach, optimizing decay rate and time delay concurrently to derive Pareto optimal sets for these factors, thereby maximizing accuracy metrics such as AUROC (Area Under the Receiver Operating Characteristic curve) and AUPR (Area Under the Precision-Recall curve). Additionally, the use of XGBoost for calculating feature importance aids in identifying potential regulatory gene links. RESULTS: Comprehensive experimental evaluations on two simulated datasets from DREAM4 and three real gene expression datasets (Yeast, In vivo Reverse-engineering and Modeling Assessment [IRMA], and Escherichia coli [E. coli]) reveal that GRNMOPT performs commendably across varying network scales. Furthermore, cross-validation experiments substantiate the robustness of GRNMOPT. CONCLUSION: We propose a novel approach called GRNMOPT to infer GRNs based on a multi-objective optimization framework, which effectively improves inference accuracy and provides a powerful tool for GRNs inference.

2.
Article in English | MEDLINE | ID: mdl-39250369

ABSTRACT

Vision-based Bird's Eye View (BEV) representation is an emerging perception formulation for autonomous driving. The core challenge is to construct BEV space with multi-camera features, which is a one-to-many ill-posed problem. Diving into all previous BEV representation generation methods, we found that most of them fall into two types: modeling depths in image views or modeling heights in the BEV space, mostly in an implicit way. In this work, we propose to explicitly model heights in the BEV space, which needs no extra data like LiDAR and can fit arbitrary camera rigs and types compared to modeling depths. Theoretically, we give proof of the equivalence between height-based methods and depth-based methods. Considering the equivalence and some advantages of modeling heights, we propose HeightFormer, which models heights and uncertainties in a self-recursive way. Without any extra data, the proposed Height-Former could estimate heights in BEV accurately. Benchmark results show that the performance of HeightFormer achieves SOTA compared with those camera-only methods.

3.
Brain Behav ; 14(9): e70016, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39236111

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) is characterized by hippocampal volume reduction, impacting cognitive function. Inflammation, particularly elevated tumor necrosis factor-alpha (TNF-α) levels, is consistently implicated in MDD pathophysiology. This study investigates the relationships between TNF-α levels, hippocampal volume, beta-amyloid (Aß) burden, and cognitive abilities in MDD patients, aiming to illuminate the complex interplay among inflammatory markers, pathology indicators, structural brain alterations, and cognitive performance in non-demented MDD individuals. METHOD: Fifty-two non-demented MDD patients, comprising 25 with mild cognitive impairment (MCI), were recruited along with 10 control subjects. Each participant underwent a thorough assessment encompassing TNF-α blood testing, 18F-florbetapir positron emission tomography, magnetic resonance imaging scans, and neuropsychological testing. Statistical analyses, adjusted for age and education, were performed to investigate the associations between TNF-α levels, adjusted hippocampal volume (HVa), global Aß burden, and cognitive performance. RESULTS: MCI MDD patients displayed elevated TNF-α levels and reduced HVa relative to controls. Correlation analyses demonstrated inverse relationships between TNF-α level and HVa in MCI MDD, all MDD, and all subjects groups. Both TNF-α level and HVa exhibited significant correlations with processing speed across all MDD and all subjects. Notably, global 18F-florbetapir standardized uptake value ratio did not exhibit significant correlations with TNF-α level, HVa, and cognitive measures. CONCLUSION: This study highlights elevated TNF-α levels and reduced hippocampal volume in MCI MDD patients, indicating a potential association between peripheral inflammation and structural brain alterations in depression. Furthermore, our results suggest that certain cases of MDD may be affected by non-amyloid-mediated process, which impacts their TNF-α and hippocampal volume. These findings emphasize the importance of further investigating the complex interplay among inflammation, neurodegeneration, and cognitive function in MDD.


Subject(s)
Amyloid beta-Peptides , Atrophy , Cognitive Dysfunction , Depressive Disorder, Major , Hippocampus , Magnetic Resonance Imaging , Positron-Emission Tomography , Tumor Necrosis Factor-alpha , Humans , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/metabolism , Depressive Disorder, Major/pathology , Hippocampus/diagnostic imaging , Hippocampus/pathology , Hippocampus/metabolism , Male , Female , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/blood , Aged , Amyloid beta-Peptides/metabolism , Atrophy/pathology , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/diagnostic imaging , Middle Aged , Neuropsychological Tests , Aniline Compounds , Ethylene Glycols
4.
Transplant Proc ; 56(8): 1766-1773, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39242315

ABSTRACT

OBJECTIVE: To assess the effectiveness of early bedside cycling training in enhancing recovery among patients following liver transplantation. METHODS: A total of 64 patients who underwent liver transplantation were randomly assigned to either an experimental group or a control group, with 32 patients in each group. Patients in the control group received routine rehabilitation training after postoperative consciousness recovery and tracheal extubation. The experimental group received supplemental lower limb bedside cycling training in addition to the routine rehabilitation. Differences in physical function, length of intensive care unit, and hospital stays were compared between the two groups. RESULTS: The experimental group showed significantly greater improvements in physical function, such as activities of daily living scores and Berg Balance Scale scores, compared to the control group (P < .05). While the experimental group also exhibited decreased length of intensive care unit and hospital stays compared to the control group, these differences lacked statistical significance. CONCLUSION: Early bedside cycling training contributes to enhanced physical function, such as balance function and activities of daily living, among patients undergoing liver transplantation.


Subject(s)
Activities of Daily Living , Intensive Care Units , Length of Stay , Liver Transplantation , Humans , Liver Transplantation/rehabilitation , Male , Female , Middle Aged , Bicycling , Adult , Exercise Therapy/methods , Recovery of Function
5.
Front Neurol ; 15: 1416945, 2024.
Article in English | MEDLINE | ID: mdl-39108661

ABSTRACT

Objective: Incomplete occlusion of cerebral dural arteriovenous fistula (DAVF) may lead to fistula recurrence and rebleeding, which may necessitate several embolizations and lead to worse clinical outcomes. Herein, we describe a grouting technique for endovascular embolization and its outcomes in a series of patients with complex intracranial DAVF. Methods: A total of 20 patients with aggressive type or symptomatic intracranial non-cavernous DAVF underwent endovascular transvenous embolization combining detachable coils and Onyx. Two microcatheters were positioned either in the distal segment of the involved sinus or near the draining veins. To achieve tight occlusion of the involved sinus, coils were carefully delivered through the first microcatheter, starting from the distal segment and then to the proximal segment. Next, Onyx was injected through the second microcatheter to reinforce and fill (grout) the interspace of coil mass and gradually refluxed to the mural channels and para-sinus cortical veins until the fistula was completely occluded. Results: Successful embolization was achieved in all 20 patients. The initial angiographic results revealed the achievement of complete occlusion in 19 patients (95%). At the postembolization follow-up, complete obliteration of the fistula was achieved in all patients (100%). No symptom or angiographic recurrence was observed at the 2- to 5-year follow-ups. No patient required additional embolization or stereotactic radiosurgery. Conclusion: The proposed grouting technique combining detachable coils and Onyx appears to be promising for the elimination of complex intracranial non-cavernous DAVFs.

6.
J Control Release ; 374: 50-60, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39111599

ABSTRACT

Corneal neovascularization (CNV) is a major cause of blindness worldwide. However, the recent drug treatment is limited by repeated administration and low drug bioavailability. In this work, SU6668 (an inhibitor of receptor tyrosine kinases) and indocyanine green (ICG) are loaded onto poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and then coated with anti-VEGFR2 single chain antibody (AbVr2 scFv) genetically engineered cell membrane vesicles. The nanomedicine is delivered via eye drops, and the hyperthermia induced by laser irradiation could block the blood vessels. Meanwhile, the photothermal effect can also cause the degradation of nanomaterials and release chemotherapeutic drugs in the blocked area, thereby continuously inhibit the neovascularization. Furthermore, SU6668 could inhibit the expression of heat shock protein 70 (HSP70), promoting the cell death induced by photothermal effect. In conclusion, the combination of photothermal and chemotherapy drugs provides a novel, effective and safe approach for the treatment of CNV.


Subject(s)
Corneal Neovascularization , Indocyanine Green , Nanoparticles , Polylactic Acid-Polyglycolic Acid Copolymer , Theranostic Nanomedicine , Animals , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Indocyanine Green/administration & dosage , Indocyanine Green/pharmacokinetics , Theranostic Nanomedicine/methods , Humans , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Biomimetic Materials/administration & dosage , Biomimetic Materials/chemistry , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/pharmacokinetics , Drug Liberation , HSP70 Heat-Shock Proteins , Biomimetics , Photothermal Therapy/methods
7.
Commun Biol ; 7(1): 1007, 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39154094

ABSTRACT

Biological invasions pose a significant threat to ecosystems, disrupting local biodiversity and ecosystem functions. The genomic underpinnings of invasiveness, however, are still largely unknown, making it difficult to predict and manage invasive species effectively. The common reed (Phragmites australis) is a dominant grass species in wetland ecosystems and has become particularly invasive when transferred from Europe to North America. Here, we present a high-quality gap-free, telomere-to-telomere genome assembly of Phragmites australis consisting of 24 pseudochromosomes and a B chromosome. Fully phased subgenomes demonstrated considerable subgenome dominance and revealed the divergence of diploid progenitors approximately 30.9 million years ago. Comparative genomics using chromosome-level scaffolds for three other lineages and a previously published draft genome assembly of an invasive lineage revealed that gene family expansions in the form of tandem duplications may have contributed to the invasiveness of the lineage. This study sheds light on the genome evolution of Arundinoideae grasses and suggests that genetic drivers, such as gene family expansions and tandem duplications, may underly the processes of biological invasion in plants. These findings provide a crucial step toward understanding and managing the genetic basis of invasiveness in plant species.


Subject(s)
Chromosomes, Plant , Evolution, Molecular , Genome, Plant , Introduced Species , Poaceae , Poaceae/genetics , Chromosomes, Plant/genetics , Phylogeny , Genomics/methods
8.
Ocul Surf ; 34: 247-261, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39111696

ABSTRACT

Fuchs endothelial corneal dystrophy (FECD) stands as the most prevalent primary corneal endothelial dystrophy worldwide, posing a significant risk to corneal homeostasis and clarity. Corneal endothelial cells exhibit susceptibility to oxidative stress, suggesting a nuanced relationship between oxidant-antioxidant imbalance and FECD pathogenesis, irrespective of FECD genotype. Given the constrained availability of corneal transplants, exploration into non-surgical interventions becomes crucial. This encompasses traditional antioxidants, small molecule compounds, biologics, and diverse non-drug therapies, such as gene-related therapy, hydrogen therapy and near infrared light therapy. This review concentrates on elucidating the mechanisms behind oxidant-antioxidant imbalance and the evolution of strategies to restore oxidant-antioxidant balance in FECD. It provides a comprehensive overview of both conventional and emerging therapeutic approaches, offering valuable insights for the advancement of non-surgical treatment modalities. The findings herein might establish a robust foundation for future research and the therapeutic strategy of FECD.

9.
Insect Sci ; 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39135329

ABSTRACT

Aedes albopictus is an important vector of arboviruses and prefers small containers of stagnant water as oviposition sites. One of the mechanisms mosquitoes use to search for suitable oviposition sites is relying on odor cues from prospective sites and their surroundings. The genetic and molecular bases of this behavior are not known for Ae. albopictus. Oviposition site-searching behavior can be separated into 2 stages: container location and water detection. We applied a glue compound to the antennae and the maxillary palps of adult females to mask their ability to detect molecules that may guide them to preferred oviposition sites. Treatment of the antennae significantly reduces the location index (P < 0.001), indicating a decreased ability to find oviposition sites, whereas no significant difference was observed in mosquitoes with maxillary palps treated with the same glue compound (P > 0.05). The detection time, measured as the duration from contact with the water surface to the deposition of the first egg, was extended in mosquitoes with treated antennae or maxillary palps, supporting the conclusion that olfaction is involved in the detection of oviposition site. Transcriptomic analysis identified differentially expressed olfactory-related genes, including obp67, obp56d-like, obp19d-like and obp67-like. RNA interference (RNAi)-mediated knockdown of obp67 and obp56d-like significantly affected the location index and detection time, respectively. Cas9/guide RNA-mediated knockout of obp56d-like resulted in a prolonged detection time, compared with the wild type (P < 0.05). These findings help to elucidate aspects of the olfactory mechanisms involved in Ae. albopictus oviposition site selection, and provide a basis for the development of mosquito surveillance and control strategies.

10.
Article in English | MEDLINE | ID: mdl-39178083

ABSTRACT

The rapid growth of the Internet of Things (IoT) has led to the widespread adoption of the IoT networks in numerous digital applications. To counter physical threats in these systems, automatic modulation classification (AMC) has emerged as an effective approach for identifying the modulation format of signals in noisy environments. However, identifying those threats can be particularly challenging due to the scarcity of labeled data, which is a common issue in various IoT applications, such as anomaly detection for unmanned aerial vehicles (UAVs) and intrusion detection in the IoT networks. Few-shot learning (FSL) offers a promising solution by enabling models to grasp the concepts of new classes using only a limited number of labeled samples. However, prevalent FSL techniques are primarily tailored for tasks in the computer vision domain and are not suitable for the wireless signal domain. Instead of designing a new FSL model, this work suggests a novel approach that enhances wireless signals to be more efficiently processed by the existing state-of-the-art (SOTA) FSL models. We present the semantic-consistent signal pretransformation (ScSP), a parameterized transformation architecture that ensures signals with identical semantics exhibit similar representations. ScSP is designed to integrate seamlessly with various SOTA FSL models for signal modulation recognition and supports commonly used deep learning backbones. Our evaluation indicates that ScSP boosts the performance of numerous SOTA FSL models, while preserving flexibility.

11.
Cell Mol Immunol ; 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39164536

ABSTRACT

The preferable antigen delivery profile accompanied by sufficient adjuvants favors vaccine efficiency. Mitochondria, which feature prokaryotic characteristics and contain various damage-associated molecular patterns (DAMPs), are easily taken up by phagocytes and simultaneously activate innate immunity. In the current study, we established a mitochondria engineering platform for generating antigen-enriched mitochondria as cancer vaccine. Ovalbumin (OVA) and tyrosinase-related protein 2 (TRP2) were used as model antigens to synthesize fusion proteins with mitochondria-localized signal peptides. The lentiviral infection system was then employed to produce mitochondrial vaccines containing either OVA or TRP2. Engineered OVA- and TRP2-containing mitochondria (OVA-MITO and TRP2-MITO) were extracted and evaluated as potential cancer vaccines. Impressively, the engineered mitochondria vaccine demonstrated efficient antitumor effects when used as both prophylactic and therapeutic vaccines in murine tumor models. Mechanistically, OVA-MITO and TRP2-MITO potently recruited and activated dendritic cells (DCs) and induced a tumor-specific cell-mediated immunity. Moreover, DC activation by mitochondria vaccine critically involves TLR2 pathway and its lipid agonist, namely, cardiolipin derived from the mitochondrial membrane. The results demonstrated that engineered mitochondria are natively well-orchestrated carriers full of immune stimulants for antigen delivery, which could preferably target local dendritic cells and exert strong adaptive cellular immunity. This proof-of-concept study established a universal platform for vaccine construction with engineered mitochondria bearing alterable antigens for cancers as well as other diseases.

12.
Cancers (Basel) ; 16(14)2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39061238

ABSTRACT

While low-dose computed tomography (LDCT) for lung cancer screening (LCS) has been recognized for its effectiveness in reducing lung cancer mortality, it often simultaneously leads to the detection of incidental findings (IFs) unrelated to the primary screening indication. These IFs present diagnostic and management challenges, potentially causing unnecessary anxiety and further invasive diagnostic procedures for patients. This review article provides an overview of IFs encountered in LDCT, emphasizing their clinical significance and recommended management strategies. We categorize IFs based on their anatomical locations (intrathoracic-intrapulmonary, intrathoracic-extrapulmonary, and extrathoracic) and discuss the most common findings. We highlight the importance of utilizing guidelines and standardized reporting systems by the American College of Radiology (ACR) to guide appropriate follow-ups. For each category, we present specific IF examples, their radiologic features, and the suggested management approach. This review aims to provide radiologists and clinicians with a comprehensive understanding of IFs in LCS for accurate assessment and management, ultimately enhancing patient care. Finally, we outline a few key aspects for future research and development in managing IFs.

13.
J Forensic Sci ; 69(5): 1871-1879, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38984820

ABSTRACT

Opium poppy, coca and cannabis are raw materials for three notorious illicit drugs. For a long time, drug lords have been growing and smuggling these drugs in a variety of ways and channels and are continually finding new ways of trafficking their wares, which has led to the increasing difficulty of global drug enforcement. In the present paper, we propose an innovative pollen identification system for these important drug plants, which provides a tool for screening and detection of the drugs to aid in drug enforcement. By utilizing the characteristics of these fine particles, their abundant production, and high resistance to decay, we believe this tool could be applied in the following scenarios: detecting and dynamically monitoring drug cultivation activities; determining whether a suspect has been to fields of drug plants and determining whether the site has ever been planted with a drug plant and/or was involved in drug production. In the future, combined with microscope automatic image acquisition technology and intelligent image recognition technology, this pollen identification system is expected to be used to screen three notorious illicit drug plants, thus enhancing the efficiency of drug related crime investigations.


Subject(s)
Cannabis , Coca , Drug Trafficking , Illicit Drugs , Papaver , Pollen , Humans , Coca/chemistry , Papaver/chemistry , Opium , Forensic Sciences/methods
14.
Genes (Basel) ; 15(6)2024 May 25.
Article in English | MEDLINE | ID: mdl-38927620

ABSTRACT

The incidence of ulcerative colitis (UC) has increased globally. As a complex disease, the genetic predisposition for UC could be estimated by the polygenic risk score (PRS), which aggregates the effects of a large number of genetic variants in a single quantity and shows promise in identifying individuals at higher lifetime risk of UC. Here, based on a cohort of 2869 UC cases and 2900 controls with genotype array datasets, we used PRSice-2 to calculate PRS, and systematically analyzed factors that could affect the power of PRS, including GWAS summary statistics, population stratification, and impact of variants. After leveraging a stepwise condition analysis, we eventually established the best PRS model, achieving an AUC of 0.713. Meanwhile, samples in the top 20% of the PRS distribution had a risk of UC more than ten times higher than samples in the lowest 20% (OR = 10.435, 95% CI 8.571-12.703). Our analyses demonstrated that including population-enriched, more disease-associated SNPs and using GWAS summary statistics from similar ethnic background can improve the power of PRS. Strictly following the principle of focusing on one population in all aspects of generating PRS can be a cost-effective way to apply genotype-array-derived PRS to practical risk estimation.


Subject(s)
Colitis, Ulcerative , Genetic Predisposition to Disease , Genome-Wide Association Study , Multifactorial Inheritance , Polymorphism, Single Nucleotide , White People , Humans , Colitis, Ulcerative/genetics , Multifactorial Inheritance/genetics , Genome-Wide Association Study/methods , White People/genetics , Female , Male , Risk Factors , Case-Control Studies , Genotype
15.
Alzheimers Res Ther ; 16(1): 127, 2024 06 13.
Article in English | MEDLINE | ID: mdl-38872230

ABSTRACT

BACKGROUND: Our study aims to evaluate the genetic and phenotypic spectrum of Frontotemporal dementia (FTD) gene variant carriers in Chinese populations, investigate mutation frequencies, and assess the functional properties of TBK1 and OPTN variants. METHODS: Clinically diagnosed FTD patients underwent genetic analysis through exome sequencing, repeat-primed polymerase chain reaction, and Sanger sequencing. TBK1 and OPTN variants were biologically characterized in vitro using immunofluorescence, immunoprecipitation, and immunoblotting analysis. The frequencies of genes implicated in FTD in China were analyzed through a literature review and meta-analysis. RESULTS: Of the 261 Chinese FTD patients, 61 (23.4%) carried potential causative variants in FTD-related genes, including MAPT (n = 17), TBK1 (n = 7), OPTN (n = 6), GRN (n = 6), ANXA11 (n = 4), CHMP2B (n = 3), C9orf72 GGGGCC repeats (n = 2), CYLD (n = 2), PRNP (n = 2), SQSTM1 (n = 2), TARDBP (n = 2), VCP (n = 1), CCNF (n = 1), CHCHD10 (n = 1), SIGMAR1 (n = 1), CHCHD2 (n = 1), FUS (n = 1), TMEM106B (n = 1), and UBQLN2 (n = 1). 29 variants can be considered novel, including the MAPT p.D54N, p.E342K, p.R221P, p.T263I, TBK1 p.E696G, p.I37T, p.E232Q, p.S398F, p.T78A, p.Q150P, p.W259fs, OPTN p.R144G, p.F475V, GRN p.V473fs, p.C307fs, p.R101fs, CHMP2B p.K6N, p.R186Q, ANXA11 p.Q155*, CYLD p.T157I, SQSTM1 p.S403A, UBQLN2 p.P509H, CCNF p.S160N, CHCHD10 p.A8T, SIGMAR1 p.S117L, CHCHD2 p.P53fs, FUS p.S235G & p.S236G, and TMEM106B p.L144V variants. Patients with TBK1 and OPTN variants presented with heterogeneous clinical phenotypes. Functional analysis demonstrated that TBK1 I37T and E232Q mutants showed decreased autophosphorylation, and the OPTN phosphorylation was reduced by the TBK1 I37T mutant. The OPTN-TBK1 complex formation was enhanced by the TBK1 E696G mutant, while OPTN R144G and F475V mutants exhibited reduced recruitment to autophagosomes compared to the wild-type. The overall frequency of TBK1 and OPTN in Chinese FTD patients was 2.0% and 0.3%, respectively. CONCLUSIONS: Our study demonstrates the extensive genetic and phenotypic heterogeneity of Chinese FTD patients. TBK1 mutations are the second most frequent cause of clinical FTD after MAPT in the Chinese.


Subject(s)
Cell Cycle Proteins , Frontotemporal Dementia , Membrane Transport Proteins , Protein Serine-Threonine Kinases , Transcription Factor TFIIIA , Aged , Female , Humans , Male , Middle Aged , Cell Cycle Proteins/genetics , China/epidemiology , East Asian People/genetics , Frontotemporal Dementia/genetics , Genetic Predisposition to Disease/genetics , Membrane Transport Proteins/genetics , Mutation , Protein Serine-Threonine Kinases/genetics , Transcription Factor TFIIIA/genetics
16.
Zhongguo Zhen Jiu ; 44(5): 565-8, 2024 May 12.
Article in Chinese | MEDLINE | ID: mdl-38764107

ABSTRACT

The clinical experience of Shao's needling technique for post-stroke depression is introduced. Professor SHAO Jingming proposes that the main pathogenesis of this condition lies in the "imbalance of body and spirit," with its onset closely related to the heart, liver, spleen, and kidney. In clinical practice, based on the principle of "treating both the body and spirit", "three acupoints for treating the spirit" including Dazhui (GV 14), Fengchi (GB 20), and Baihui (GV 20) are selected, combined with back-shu points such as Xinshu (BL 15), Ganshu (BL 18), Pishu (BL 20), and Shenshu (BL 23). The nu-needle manipulation method is applied. The treatment focuses on both physical and mental aspects, achieving remarkable therapeutic effects.


Subject(s)
Acupuncture Points , Acupuncture Therapy , Depression , Stroke , Humans , Stroke/complications , Stroke/therapy , Acupuncture Therapy/methods , Depression/therapy , Depression/etiology , Female , Male , Middle Aged , Aged
18.
ACS Med Chem Lett ; 15(5): 646-652, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38746889

ABSTRACT

The potassium (K+) ion channel KCNK13 is specifically expressed in human microglia with elevated expression observed in post-mortem human brain tissue from patients with Alzheimer's disease. Modulation of KCNK13 activity by a small-molecule inhibitor is proposed as a potential treatment for neurodegenerative diseases. Herein, we describe the evolution of a series of KCNK13 inhibitors derived from a high-throughput screening campaign, resulting in CVN293, a potent, selective, and brain permeable clinical candidate molecule. CVN293 demonstrated a concentration-dependent inhibition of the NLRP3-inflammasome mediated production of IL-1ß from LPS-primed murine microglia. Cross-species pharmacokinetic data of CVN293 are also disclosed. These findings support the advancement of CVN293 in clinical trials.

19.
J Nanobiotechnology ; 22(1): 290, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802884

ABSTRACT

Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.


Subject(s)
Cornea , Corneal Neovascularization , Nanoparticles , Ophthalmic Solutions , Corneal Neovascularization/drug therapy , Animals , Nanoparticles/chemistry , Ophthalmic Solutions/chemistry , Cornea/metabolism , Cornea/drug effects , Mice , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/pharmacology , Particle Size , Humans , Male , Mice, Inbred C57BL , Rabbits
20.
Foodborne Pathog Dis ; 21(8): 467-477, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38757692

ABSTRACT

Vibrio parahaemolyticus is a common foodborne pathogenic bacterium. With the overuse of antibiotics, an increasing proportion of drug-resistant strains are emerging, which puts enormous pressure on public health. In this study, a V. parahaemolyticus-specific phage, VP41s3, was isolated. The head length, width, and tail length of the phage were 77.7 nm, 72.2 nm, and 17.5 nm, respectively. It remained active in the temperature range of 30-50°C and pH range of 4-11. The lytic curve of phage VP41s3 showed that the host bacteria did not grow until 11 h under phage treatment at MOI of 1000, indicating that the phage had good bacteriostatic ability. When it was added to shellfish contaminated with V. parahaemolyticus (15°C, 48 h), the number of bacteria in the experimental group was 2.11 log10 CFU/mL lower than that in the control group at 24 h. Furthermore, genomic characterization and phylogenetic analysis indicated that phage VP41s3 was a new member of the Podoviridae family. The genome contained 50 open reading frames (ORFs), in which the ORF19 (thymidine kinase) was an enzyme involved in the pyrimidine salvage pathway, which might lead to the accelerated DNA synthesis efficiency after phage entered into host cells. This study not only contributed to the improvement of phage database and the development of beneficial phage resources but also revealed the potential application of phage VP41s3 in food hygiene and safety.


Subject(s)
Bacteriophages , Genome, Viral , Shellfish , Vibrio parahaemolyticus , Vibrio parahaemolyticus/virology , Shellfish/microbiology , Bacteriophages/physiology , Bacteriophages/isolation & purification , Food Microbiology , Phylogeny , Podoviridae/isolation & purification , Podoviridae/genetics , Podoviridae/physiology , Animals , Open Reading Frames , Food Contamination/prevention & control
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