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1.
Nat Immunol ; 17(3): 241-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26692175

ABSTRACT

The gene encoding PTEN is one of the most frequently mutated tumor suppressor-encoding genes in human cancer. While PTEN's function in tumor suppression is well established, its relationship to anti-microbial immunity remains unknown. Here we found a pivotal role for PTEN in the induction of type I interferon, the hallmark of antiviral innate immunity, that was independent of the pathway of the kinases PI(3)K and Akt. PTEN controlled the import of IRF3, a master transcription factor responsible for IFN-ß production, into the nucleus. We further identified a PTEN-controlled negative phosphorylation site at Ser97 of IRF3 and found that release from this negative regulation via the phosphatase activity of PTEN was essential for the activation of IRF3 and its import into the nucleus. Our study identifies crosstalk between PTEN and IRF3 in tumor suppression and innate immunity.


Subject(s)
Immunity, Innate/immunology , Interferon Regulatory Factor-3/immunology , Interferon Type I/immunology , PTEN Phosphohydrolase/immunology , Respirovirus Infections/immunology , Rhabdoviridae Infections/immunology , Animals , Cell Line , Cell Line, Tumor , Cell Nucleus , Cell Proliferation , Cytokines/immunology , Dendritic Cells/immunology , Electrophoresis, Polyacrylamide Gel , Fluorescent Antibody Technique , Gene Transfer Techniques , HEK293 Cells , Humans , Immunoblotting , Immunoprecipitation , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-7/genetics , MCF-7 Cells , Macrophages/immunology , Mass Spectrometry , Mice , Microscopy, Confocal , Mutagenesis, Site-Directed , PTEN Phosphohydrolase/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sendai virus , Vesiculovirus
2.
Proc Natl Acad Sci U S A ; 120(23): e2300953120, 2023 Jun 06.
Article in English | MEDLINE | ID: mdl-37253015

ABSTRACT

Self-healing is a bioinspired strategy to repair damaged conductors under repetitive wear and tear, thereby largely extending the life span of electronic devices. The self-healing process often demands external triggering conditions as the practical challenges for the widespread applications. Here, a compliant conductor with electrically self-healing capability is introduced by combining ultrahigh sensitivity to minor damages and reliable recovery from ultrahigh tensile deformations. Conductive features are created in a scalable and low-cost fabrication process comprising a copper layer on top of liquid metal microcapsules. The efficient rupture of microcapsules is triggered by structural damages in the copper layer under stress conditions as a result of the strong interfacial interactions. The liquid metal is selectively filled into the damaged site for the instantaneous restoration of the metallic conductivity. The unique healing mechanism is responsive to various structural degradations including microcracks under bending conditions and severe fractures upon large stretching. The compliant conductor demonstrates high conductivity of ∼12,000 S/cm, ultrahigh stretchability of up to 1,200% strain, an ultralow threshold to activate the healing actions, instantaneous electrical recovery in microseconds, and exceptional electromechanical durability. Successful implementations in a light emitting diode (LED) matrix display and a multifunctional electronic patch demonstrate the practical suitability of the electrically self-healing conductor in flexible and stretchable electronics. The developments provide a promising approach to improving the self-healing capability of compliant conductors.

3.
Plant Physiol ; 194(4): 2549-2563, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38235827

ABSTRACT

Gene duplications have long been recognized as a driving force in the evolution of genes, giving rise to novel functions. The soybean (Glycine max) genome is characterized by a large number of duplicated genes. However, the extent and mechanisms of functional divergence among these duplicated genes in soybean remain poorly understood. In this study, we revealed that 4 MYB genes (GmMYBA5, GmMYBA2, GmMYBA1, and Glyma.09g235000)-presumably generated by tandem duplication specifically in the Phaseoleae lineage-exhibited a stronger purifying selection in soybean compared to common bean (Phaseolus vulgaris). To gain insights into the diverse functions of these tandemly duplicated MYB genes in anthocyanin biosynthesis, we examined the expression, transcriptional activity, induced metabolites, and evolutionary history of these 4 MYB genes. Our data revealed that Glyma.09g235000 is a pseudogene, while the remaining 3 MYB genes exhibit strong transcriptional activation activity, promoting anthocyanin biosynthesis in different soybean tissues. GmMYBA5, GmMYBA2, and GmMYBA1 induced anthocyanin accumulation by upregulating the expression of anthocyanin pathway-related genes. Notably, GmMYBA5 showed a lower capacity for gene induction compared to GmMYBA2 and GmMYBA1. Metabolomics analysis further demonstrated that GmMYBA5 induced distinct anthocyanin accumulation in Nicotiana benthamiana leaves and soybean hairy roots compared to GmMYBA2 and GmMYBA1, suggesting their functional divergence leading to the accumulation of different metabolites accumulation following gene duplication. Together, our data provide evidence of functional divergence within the MYB gene cluster following tandem duplication, which sheds light on the potential evolutionary directions of gene duplications during legume evolution.


Subject(s)
Genes, myb , Glycine max , Glycine max/genetics , Anthocyanins/genetics , Gene Duplication , Multigene Family , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism
4.
Nano Lett ; 24(19): 5904-5912, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38700588

ABSTRACT

Stretchable electroluminescent devices represent an emerging optoelectronic technology for future wearables. However, their typical construction on sub-millimeter-thick elastomers has limited moisture permeability, leading to discomfort during long-term skin attachment. Although breathable textile displays may partially address this issue, they often have distinct visual appearances with discrete emissions from fibers or fiber junctions. This study introduces a convenient procedure to create stretchable, permeable displays with continuous luminous patterns. The design utilizes ultrathin nanocomposite devices embedded in a porous elastomeric microfoam to achieve high moisture permeability. These displays also exhibit excellent deformability, low-voltage operation, and excellent durability. Additionally, the device is decorated with fluorinated silica nanoparticles to achieve self-cleaning and washable capabilities. The practical implementation of these nanocomposite devices is demonstrated by creating an epidermal counter display that allows intimate integration with the human body. These developments provide an effective design of stretchable and breathable displays for comfortable wearing.

5.
Eur J Neurosci ; 59(7): 1428-1440, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38151046

ABSTRACT

Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high-risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol-O-methyltransferase (COMT) genes, and paranoid and motor-impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor-impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor-impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high-risk psychotic symptoms in MAUD patients.


Subject(s)
Methamphetamine , Polymorphism, Single Nucleotide , Humans , Catechol O-Methyltransferase/genetics , Dopamine , Methamphetamine/adverse effects , Genotype , Methylation
6.
Pharm Res ; 41(3): 531-546, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38366235

ABSTRACT

PURPOSE: Traditional eye drops exhibit a modest bioavailability ranging from 1 to 5%, necessitating recurrent application. Thus, a contact lens-based drug delivery system presents substantial benefits. Nonetheless, pharmaceutical agents exhibiting poor solubility may compromise the quintessential characteristics of contact lenses and are, consequently, deemed unsuitable for incorporation. To address this issue, the present study has engineered a novel composite drug delivery system that amalgamates micellar technology with contact lenses, designed specifically for the efficacious conveyance of timolol and brinzolamide. METHODS: Utilizing mPEG-PCL as the micellar material, this study crafted mPEG-PCL micelles loaded with brinzolamide and timolol through the film hydration technique. The micelle-loaded contact lens was fabricated employing the casting method; a uniform mixture of HEMA and EGDMA with the mPEG-PCL micelles enshrouding brinzolamide and timolol was synthesized. Following the addition of a photoinitiator, 50 µL of the concoction was deposited into a contact lens mold. Subsequently, the assembly was subjected to polymerization under 365 nm ultraviolet light for 35 min, resulting in the formation of the micelle-loaded contact lenses. RESULTS: In the present article, we delineate the construction of a micelle-loaded contact lens designed for the administration of brinzolamide and timolol in the treatment of glaucoma. The study characterizes crucial properties of the micelle-loaded contact lenses, such as transmittance and ionic permeability. It was observed that these vital attributes meet the standard requirements for contact lenses. In vitro release studies revealed that timolol and brinzolamide could be gradually liberated over periods of up to 72 and 84 h, respectively. In vivo pharmacodynamic evaluation showed a significant reduction in intraocular pressure and a relative bioavailability of 10.84 times that of commercially available eye drops. In vivo pharmacokinetic evaluation, MRT was significantly increased, and the bioavailability of timolol and brinzolamide was 2.71 and 1.41 times that of eye drops, respectively. Safety assessments, including in vivo irritation, histopathological sections, and protein adsorption studies, were conducted as per established protocols, confirming that the experiments were in compliance with safety standards. IN CONCLUSION: The manuscript delineates the development of a safe and efficacious micelle-loaded contact lens drug delivery system, which presents a novel therapeutic alternative for the management of glaucoma.


Subject(s)
Contact Lenses , Glaucoma , Polyesters , Polyethylene Glycols , Sulfonamides , Thiazines , Humans , Timolol/pharmacokinetics , Timolol/therapeutic use , Micelles , Antihypertensive Agents/pharmacokinetics , Glaucoma/drug therapy , Drug Delivery Systems , Ophthalmic Solutions/therapeutic use
7.
J Clin Gastroenterol ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38896424

ABSTRACT

OBJECTIVE: The diagnosis of RGERD in patients typically involves 24-hour esophageal pH monitoring, but due to its invasiveness and low patient compliance, new screening methods are needed. In this study, a lactulose breath test (LBT) was conducted to detect the growth of small intestine bacteria (SIBO) and explore the potential relationship between LBT and RGERD to identify a new treatment method for RGERD. METHODS: A total of 178 patients with gastroesophageal reflux were enrolled from June 2020 to December 2022 in the Gastroenterology Department, Building 3, the First Affiliated Hospital of Kunming Medical University; these patients included 96 patients with nonrefractory GERD (NRGERD) and 82 patients with RGERD. The Gerd Q score, reflux symptom index (RSI) score, gastroscopy results, clinical symptoms, and other related indicators were collected. Statistical methods were used to analyze the gathered data. RESULTS: The incidence of acid reflux and heartburn in patients with RGERD was significantly greater than that in patients with NRGERD (67.10% vs. 42.70%, P<0.01 and 65.00% vs. 34.40%, P<0.01). The CH4 values of patients with RGERD were significantly greater than those of patients with NRGERD at each time point, and there was a correlation between the CH4 values at 60 min and RGERD (P<0.05). For patients with RGERD, the incidence of abdominal pain, acid regurgitation, and heartburn was greater in the CH4-positive group than in the CH4-negative group (61.90% vs. 57.50%, 69.05% vs. 65.00%, 69.05% vs. 57.50%, P>0.05). The incidence of nausea was also greater in the CH4-positive group than in the CH4-negative group (61.90% vs. 35.00%, P<0.05). CONCLUSION: Increased CH4 levels are correlated with RGERD. In addition, patients with RGERD may develop SIBO after long-term use of PPIs, and interventions involving SIBO could provide new ideas for the treatment of RGERD.

8.
Environ Sci Technol ; 58(10): 4716-4726, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38412378

ABSTRACT

The mechanism and kinetics of reactive oxygen species (ROS) formation when atmospheric secondary organic aerosol (SOA) is exposed to solar radiation are poorly understood. In this study, we combined an in situ UV-vis irradiation system with electron paramagnetic resonance (EPR) spectroscopy to characterize the photolytic formation of ROS in aqueous extracts of SOA formed by the oxidation of isoprene, α-pinene, α-terpineol, and toluene. We observed substantial formation of free radicals, including •OH, superoxide (HO2•), and organic radicals (R•/RO•) upon irradiation. Compared to dark conditions, the radical yield was enhanced by a factor of ∼30 for •OH and by a factor of 2-10 for superoxide radicals, and we observed the emergence of organic radicals. Total peroxide measurements showed substantial decreases of peroxide contents after photoirradiation, indicating that organic peroxides can be an important source of the observed radicals. A liquid chromatography interfaced with high-resolution mass spectrometry was used to detect a number of organic radicals in the form of adducts with a spin trap, BMPO. The types of detected radicals and aqueous photolysis of model compounds indicated that photolysis of carbonyls by Norrish type I mechanisms plays an important role in the organic radical formation. The photolytic ROS formation serves as the driving force for cloud and fog processing of SOA.


Subject(s)
Air Pollutants , Peroxides , Peroxides/chemistry , Reactive Oxygen Species , Photolysis , Superoxides , Aerosols
9.
J Asian Nat Prod Res ; 26(1): 4-17, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37888783

ABSTRACT

Seven new monoterpene alkaloids (1 - 7), along with 16 known analogues, were isolated from an aqueous decoction of the hook-bearing stems of Uncaria rhynchophylla (Gou-teng). Their structures were determined by spectroscopic data analysis, single crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are stereoisomers belonging to a novel type of pseudoindoxyl monoterpene alkaloids, 3 is the first monoterpene furoindole alkaloid from nature, and 4 - 7 are derivatives of the known monoterpene alkaloids featuring different structures.


Subject(s)
Alkaloids , Uncaria , Indole Alkaloids/chemistry , Uncaria/chemistry , Monoterpenes
10.
Nano Lett ; 23(23): 11174-11183, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38047765

ABSTRACT

Stretchable conductive nanocomposites are essential for deformable electronic devices. These conductors currently face significant limitations, such as insufficient deformability, significant resistance changes upon stretching, and drifted properties during cyclic deformations. To tackle these challenges, we present an electrically self-healing and ultrastretchable conductor in the form of bilayer silver nanowire/liquid metal microcapsule nanocomposites. These nanocomposites utilize silver nanowires to establish their initial excellent conductivity. When the silver nanowire networks crack during stretching, the microcapsules are ruptured to release the encased liquid metal for recovering the electrical properties. This self-healing capability allows the nanocomposite to achieve ultrahigh stretchability for both uniaxial and biaxial strains, minor changes in resistance during stretching, and stable resistance after repetitive deformations. The conductors have been used to create skin-attachable electronic patches and stretchable light-emitting diode arrays with enhanced robustness. These developments provide a bioinspired strategy to enhance the performance and durability of conductive nanocomposites.

11.
Genes Dev ; 30(4): 460-70, 2016 Feb 15.
Article in English | MEDLINE | ID: mdl-26848046

ABSTRACT

The CRISPR (clustered regularly interspaced short palindromic repeat) system is an RNA-guided immune system that protects prokaryotes from invading genetic elements. This system represents an inheritable and adaptable immune system that is mediated by multisubunit effector complexes. In the Type III-B system, the Cmr effector complex has been found to cleave ssRNA in vitro. However, in vivo, it has been implicated in transcription-dependent DNA targeting. We show here that the Cmr complex from Thermotoga maritima can cleave an ssRNA target that is complementary to the CRISPR RNA. We also show that binding of a complementary ssRNA target activates an ssDNA-specific nuclease activity in the histidine-aspartate (HD) domain of the Cmr2 subunit of the complex. These data suggest a mechanism for transcription-coupled DNA targeting by the Cmr complex and provide a unifying mechanism for all Type III systems.


Subject(s)
CRISPR-Cas Systems/physiology , DNA Cleavage , Thermotoga maritima/genetics , Thermotoga maritima/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Deoxyribonucleases/metabolism , Enzyme Activation , Protein Binding , Protein Structure, Tertiary , RNA, Bacterial/metabolism
12.
J Xray Sci Technol ; 32(1): 17-30, 2024.
Article in English | MEDLINE | ID: mdl-37980594

ABSTRACT

BACKGROUND: Alberta stroke program early CT score (ASPECTS) is a semi-quantitative evaluation method used to evaluate early ischemic changes in patients with acute ischemic stroke, which can guide physicians in treatment decisions and prognostic judgments. OBJECTIVE: We propose a method combining deep learning and radiomics to alleviate the problem of large inter-observer variance in ASPECTS faced by physicians and assist them to improve the accuracy and comprehensiveness of the ASPECTS. METHODS: Our study used a brain region segmentation method based on an improved encoding-decoding network. Through the deep convolutional neural network, 10 regions defined for ASPECTS will be obtained. Then, we used Pyradiomics to extract features associated with cerebral infarction and select those significantly associated with stroke to train machine learning classifiers to determine the presence of cerebral infarction in each scored brain region. RESULTS: The experimental results show that the Dice coefficient for brain region segmentation reaches 0.79. Three radioactive features are selected to identify cerebral infarction in brain regions, and the 5-fold cross-validation experiment proves that these 3 features are reliable. The classifier trained based on 3 features reaches prediction performance of AUC = 0.95. Moreover, the intraclass correlation coefficient of ASPECTS between those obtained by the automated ASPECTS method and physicians is 0.86 (95% confidence interval, 0.56-0.96). CONCLUSIONS: This study demonstrates advantages of using a deep learning network to replace the traditional template registration for brain region segmentation, which can determine the shape and location of each brain region more precisely. In addition, a new brain region classifier based on radiomics features has potential to assist physicians in clinical stroke detection and improve the consistency of ASPECTS.


Subject(s)
Brain Ischemia , Deep Learning , Ischemic Stroke , Stroke , Humans , Brain Ischemia/diagnostic imaging , Alberta , Radiomics , Tomography, X-Ray Computed/methods , Stroke/diagnostic imaging , Cerebral Infarction/diagnostic imaging , Retrospective Studies
13.
Yi Chuan ; 46(2): 92-108, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38340001

ABSTRACT

Fluorescent RNA is a kind of emerging RNA labeling technique that can be used for in situ labeling and imaging of RNA in live cells, which plays an important role in understanding the function and regulation mechanism of RNA. Biosensing technology based on fluorescent RNA can be applied in dynamic detection of small molecule metabolites and proteins in real time, offering valuable tools for basic life science research and biomedical sensing technology development. In this review, we introduce the development of genetically encoded fluorescent RNA, and the application of fluorescent RNA in RNA imaging and biosensing technology based on fluorescent RNA in biosensing in live cell. Meanwhile, we discuss the direction and challenge of future development of fluorescent RNA technology to provide valuable insights for further development and application of this technology in relevant fields.


Subject(s)
Biosensing Techniques , RNA , Biosensing Techniques/methods , Proteins , Fluorescent Dyes
14.
Virol J ; 20(1): 233, 2023 10 13.
Article in English | MEDLINE | ID: mdl-37833806

ABSTRACT

BACKGROUND: As the HIV epidemic continues to grow, transmitted drug resistance(TDR) and determining relationship of HIV transmission are major barriers to reduce the risk of HIV transmissions.This study aimed to examine the molecular epidemiology and TDR and evaluated the transmission pattern among newly diagnosed people living with HIV/AIDS(PLWHA) in Ningbo city, which could contribute to the development of targeted precision interventions. METHODS: Consecutive cross-sectional surveys were conducted in Ningbo City between January 2018 and December 2021. The HIV-1 pol gene region was amplified and sequenced for drug resistance and genetic transmission network analysis. TDR was determined using the Stanford University HIV Drug Resistance Database. Genetic transmission network was visualized using Cytoscape with the genetic distance threshold of 0.013. RESULTS: A total of 1006 sequences were sequenced successfully, of which 61 (6.1%) showed evidence of TDR. The most common mutations were K103N (2.3%), E138A/G/Q (1.7%) and V179D/E (1.2%). 12 HIV-1 genotypes were identified, with CRF07_BC being the major genotype (43.3%, 332/767), followed by CRF01_AE (33.7%, 339/1006). 444 (44.1%) pol sequences formed 856 links within 120 transmission clusters in the network. An increasing trend in clustering rate between 2018 and 2021(χ2 = 9.546, P = 0.023) was observed. The odds of older age (≥ 60 years:OR = 2.038, 95%CI = 1.072 ~ 3.872, compared to < 25 years), HIV-1 genotypes (CRF07_BC: OR = 2.147, 95%CI = 1.582 ~ 2.914; CRF55_01B:OR = 2.217, 95%CI = 1.201 ~ 4.091, compared to CRF01_AE) were significantly related to clustering. Compared with CRF01_AE, CRF07_BC were prone to form larger clusters. The largest cluster with CRF07_BC was increased from 15 cases in 2018 to 83 cases in 2021. CONCLUSIONS: This study revealed distribution of HIV-1 genotypes, and genetic transmission network were diverse and complex in Ningbo city. The prevalence of TDR was moderate, and NVP and EFV were high-level NNRTI resistance. Individuals aged ≥ 60 years old were more easily detected in the networks and CRF07_BC were prone to form rapid growth and larger clusters. These date suggested that surveillance and comprehensive intervention should be designed for key rapid growth clusters to reduce the potential risk factors of HIV-1 transmission.


Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , HIV Seropositivity , HIV-1 , Humans , Middle Aged , HIV-1/genetics , HIV Infections/epidemiology , Cross-Sectional Studies , Phylogeny , Genotype , China/epidemiology , Drug Resistance, Viral/genetics
15.
J Vasc Interv Radiol ; 34(6): 991-998, 2023 06.
Article in English | MEDLINE | ID: mdl-36739086

ABSTRACT

PURPOSE: To investigate the clinical relevance of serum chemokine ligand 14 (sCCL14) in patients with hepatocellular carcinoma (HCC) and the effect of transarterial chemoembolization (TACE) on the expression level of sCCL14 and the immune microenvironment. MATERIALS AND METHODS: In this prospective single-center observational study, 52 patients with HCC were recruited from January 2019 to December 2021, their clinical data and blood samples were collected, and the relationship between sCCL14 and progression-free survival (PFS) and TACE treatment response was analyzed. RESULTS: Among the 52 patients with HCC (Barcelona Clinic Liver Cancer [BCLC] Stage A, 25.0%; BCLC Stage B, 44.2%; and BCLC Stage C, 30.8%), patients with BCLC Stage C HCC had significantly lower sCCL14 levels than those of patients with BCLC Stages A and B HCC (P = .001). sCCL14 levels were significantly higher in the first week after treatment than before TACE treatment (P = .024). Baseline sCCL14 levels in patients who showed complete response after TACE treatment were significantly higher than those in other groups, and lower baseline sCCL14 values were associated with shorter PFS times. Multivariate Cox regression analysis showed that sCCL14 level (hazard ratio, 1.855; 95% CI, 1.039-3.311; P = .037) was an independent prognostic factor of PFS. sCCL14 levels negatively correlated with the proportion of B lymphocytes and regulatory T cells in circulating blood and positively correlated with the absolute T-lymphocyte count. CONCLUSIONS: sCCL14 may be a predictive biomarker of TACE effectiveness. Further studies are needed to validate and outline the role of combination immunotherapy.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Ligands , Prospective Studies , Chemoembolization, Therapeutic/adverse effects , Neoplasm Staging , Lymphocytes , Retrospective Studies , Treatment Outcome , Tumor Microenvironment
16.
Mol Biol Rep ; 50(4): 3379-3387, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36729208

ABSTRACT

BACKGROUND: Normalization of the expression profiling of target genes, in a tissue-specific manner and under different experimental conditions, requires stably expressed gene(s) to be used as internal reference(s). However, to study the molecular regulation of oocyte meiosis initiation during ovary development in chicken embryos, stable reference gene(s) still need to be compared and confirmed. METHODS AND RESULTS: Six candidate genes previously used as internal references for the chicken embryo (Actb, Cvh, Dazl, Eef1a, Gapdh and Rpl15) were chosen, and their expression profiles in left ovaries dissected at five chicken embryonic days (E12.5, E15.5, E17.5, E18.5 and E20.5) were evaluated, respectively. Separately, GeNorm, NormFinder, BestKeeper and Comparative ΔCt methods were used to assess the stability of candidate reference genes, and all results were combined to give the final rank by RefFinder. All methods identified that Eef1a and Rpl15 were the two most stable internal reference genes, whereas Cvh is the most unstable one. Moreover, expression levels of three marker genes for chicken oocyte meiosis entry (Stra8, Scp3 and Dmc1) were normalized, based on Eef1a, Rpl15, or their combinations, respectively. CONCLUSION: Our findings provide the most suitable internal reference genes (Eef1a and Rpl15), to investigate further molecular regulation of ovary development and oocyte meiosis initiation in chicken embryos.


Subject(s)
Chickens , Gene Expression Profiling , Animals , Female , Chick Embryo , Chickens/genetics , Gene Expression Profiling/methods , Ovary , Real-Time Polymerase Chain Reaction/methods , Reference Standards
17.
Surg Endosc ; 37(3): 1672-1682, 2023 03.
Article in English | MEDLINE | ID: mdl-36220988

ABSTRACT

BACKGROUND: With advancements in the field of laparoscopic and endoscopic techniques leading to improved patient outcomes, open resection has become increasingly outdated for the treatment of gastric gastrointestinal stromal tumours (GIST). This is further superseded with the advent of laparoscopic and endoscopic cooperative surgery (LECS), an amalgamation of the two techniques to further improve results garnered while overcoming prior limitations each had individually. METHODS: The electronic databases MEDLINE, Embase and PubMed were reviewed up to August 2021, using terms relating to LECS and gastric GIST. Relevant in-article references not returned in the searches were also considered. RESULTS: Advancements in the field of laparoscopic and endoscopic techniques has led to improved patient outcomes, making open resection a thing of the past for gastric GIST. This has become even more apparent with the advent of LECS, coupling two cutting edge techniques to further improve results garnered while overcoming prior limitations each had individually. LECS has gained much favour by reducing surgical margins due to endoscopic visualisation without being limited to smaller tumours, allowing for better anatomical and functional preservation of prior anatomy. Furthermore, hybrid approaches have improved perioperative outcomes, with reduction in procedure time, post-procedure hospital stay and lesser complications. Additionally, subtypes of LECS such as inverted LECS, closed LECS, non-exposed endoscopic wall-inversion surgery (NEWS) and laparoscopy-assisted endoscopic full-thickness resection (LAEFR) have been developed that allows the abdominal cavity to not be exposed to tumour cells and gastric contents by extracting the lesion transorally. CONCLUSIONS: LECS and its subtypes being a combination of two advanced techniques shows a synergistic effect that is promising. However, despite all these advantages of enhanced safety and certainty, there remains areas that require further improvement.


Subject(s)
Endoscopic Mucosal Resection , Gastrointestinal Stromal Tumors , Laparoscopy , Stomach Neoplasms , Humans , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/pathology , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Laparoscopy/methods , Endoscopic Mucosal Resection/methods
18.
Surg Endosc ; 37(8): 6402-6407, 2023 08.
Article in English | MEDLINE | ID: mdl-36932187

ABSTRACT

BACKGROUND: Colonoscopies have long been the gold standard for detection of pre-malignant neoplastic lesions of the colon. Our previous study tried real-time artificial intelligence (AI)-aided colonoscopy over a three-month period and found significant improvements in collective and individual endoscopist's adenoma detection rates compared to baseline. As an expansion, this study evaluates the 1-year performance of AI-aided colonoscopy in the same institution. METHODS: A prospective cohort study was conducted in a single institution in Singapore. The AI software used was GI Genius™ Intelligent Endoscopy Module, US-DG-2000309 © 2021 Medtronic. Between July 2021 and June 2022, polypectomy rates in non-AI-aided colonoscopies and AI-aided colonoscopies were calculated and compared. Some of the AI-aided colonoscopies were recorded and video reviewed. A "hit" was defined as a sustained detection of an area by the AI. If a polypectomy was performed for a "hit," its histology was reviewed. Additional calculations for polyp detection rate (PDR), adenoma detection rate (ADR), and adenoma detection per colonoscopy (ADPC) were performed. Cost analysis was performed to determine cost effectiveness of subscription to the AI program. RESULTS: 2433 AI-aided colonoscopies were performed between July 2021 and June 2022 and compared against 1770 non-AI-aided colonoscopies. AI-aided colonoscopies yielded significantly higher rates of polypectomies (33.6%) as compared with non-AI-aided colonoscopies (28.4%) (p < 0.001). Among the AI-aided colonoscopies, 1050 were reviewed and a final 843 were included for additional analysis. The polypectomy to "hit" ratio was 57.4%, PDR = 45.6%, ADR = 32.4%, and ADPC = 2.08. Histological review showed that 25 polyps (3.13%) were sessile-serrated adenomas. Cost analysis found that the increased polypectomy rates in AI-aided colonoscopes led to an increase in revenue, which covered the subscription cost with an excess of USD 20,000. CONCLUSION: AI-aided colonoscopy is a cost effective means of improving colonoscopy quality and may help advance colorectal cancer screening in Singapore.


Subject(s)
Adenoma , Colonic Polyps , Colorectal Neoplasms , Polyps , Humans , Artificial Intelligence , Prospective Studies , Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathology , Polyps/diagnosis , Adenoma/diagnosis , Adenoma/surgery , Adenoma/pathology , Colonic Polyps/diagnosis , Colonic Polyps/surgery , Colonic Polyps/pathology
19.
Surg Endosc ; 37(9): 7128-7135, 2023 09.
Article in English | MEDLINE | ID: mdl-37322360

ABSTRACT

BACKGROUND: The Erector Spinae Plane (ESP) block is a recent development in the field of regional anaesthesia and has been increasingly explored for abdominal surgeries to reduce opioid use and improve pain control. Colorectal cancer is the commonest cancer in multi-ethnic Singapore and requires surgery for curative treatment. ESP is a promising alternative in colorectal surgeries, but few studies have evaluated its efficacy in such surgeries. Therefore, this study aims to evaluate the use of ESP blocks in laparoscopic colorectal surgeries to establish its safety and efficacy in this field. METHODS: A prospective two-armed interventional cohort study comparing T8-T10 ESP blocks with conventional multimodal intravenous analgesia for laparoscopic colectomies was conducted in a single institution in Singapore. The decision for doing an ESP block versus conventional multimodal intravenous analgesia was made by a consensus between the attending surgeon and anesthesiologist. Outcomes measured were total intra-operative opioid consumption, post-operative pain control and patient outcome. Post-operative pain control was measured by pain score, analgesia use, and amount of opioids consumed. Patient outcome was determined by presence of ileus. RESULTS: A total of 146 patients were included, of which 30 patients received an ESP block. Overall, the ESP group had a significantly lower median opioid usage both intra-operatively and post-operatively (p = 0.031). Fewer patients required patient-controlled analgesia and rescue analgesia post-operatively for pain control (p < 0.001) amongst the ESP group. Pain scores were similar and post-operative ileus was absent in both groups. Multivariate analysis found that the ESP block had an independent effect on reducing intra-opioid consumption (p = 0.014). Multivariate analysis of post-operative opioid use and pain scores did not yield statistically significant results. CONCLUSIONS: The ESP block was an effective alternative regional anaesthesia for colorectal surgery that reduced intra-operative and post-operative opioid use while attaining satisfactory pain control.


Subject(s)
Colorectal Neoplasms , Laparoscopy , Nerve Block , Humans , Analgesics, Opioid/therapeutic use , Anesthetics, Local , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Nerve Block/methods , Prospective Studies , Cohort Studies , Analgesia, Patient-Controlled , Colectomy , Colorectal Neoplasms/surgery , Ultrasonography, Interventional/methods
20.
Compr Psychiatry ; 122: 152368, 2023 04.
Article in English | MEDLINE | ID: mdl-36739835

ABSTRACT

BACKGROUND: Insomnia is a common problem among patients with major depressive disorder (MDD). According to previous studies, the development and severity of Insomnia are influenced by childhood trauma experience. Furthermore, negative life events and dysfunctional attitudes may also mediate the impact. So, this study aimed to examine the association between childhood trauma, negative life events, dysfunctional attitudes and insomnia and investigate how negative life events and dysfunctional attitudes mediate the relationship between childhood trauma and insomnia in MDD. METHOD: This cross-sectional study recruited 621 college students with MDD. The Childhood Trauma Questionnaire (CTQ), Life Event Scale (LES), Dysfunctional Attitude Scale (DAS), Insomnia Severity Index (ISI), and Hamilton Depression Scale-17 (HAMD-17) were used to assess participants' psychosocial factors. Descriptive analysis, Chi-square test, t-test, Pearson correlations, and serial mediation analyses were used in data analysis. In order to eliminate the influence of the severity of depression symptoms, severity of depression symptoms was used as a control variable in this study. RESULTS: There were 166 (26.7%) participants having clinical insomnia (ISI score > 14). After controlling for the effect of severity of depression symptoms, results of serial mediation analyses determined that childhood trauma has a direct (Estimate = 0.109, 95%CI: 0.023,0.190) and indirect (Estimate = 0.090, 95%CI: 0.054,0.137) impact to insomnia. The indirect impact of childhood trauma on insomnia through the pathways of negative life events alone (Estimate = 0.050, 95%CI: 0.024,0.093), dysfunctional attitudes alone (Estimate = 0.027, 95%CI: 0.008,0.050), and negative life events to dysfunctional attitudes (Estimate = 0.013, 95%CI: 0.006,0.024) were significant. CONCLUSIONS: This study demonstrates that screening for childhood trauma should be considered when treating insomnia in college students with MDD. Managing negative life events and dysfunctional attitudes may mitigate the negative impact of childhood trauma on insomnia in college students with MDD.


Subject(s)
Adverse Childhood Experiences , Depressive Disorder, Major , Sleep Initiation and Maintenance Disorders , Humans , Cross-Sectional Studies , Attitude , Students/psychology
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