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1.
Mediators Inflamm ; 2024: 4465592, 2024.
Article En | MEDLINE | ID: mdl-38707705

Objective: This study aims to evaluate the impact and predictive value of the preoperative NPRI on short-term complications and long-term prognosis in patients undergoing laparoscopic radical surgery for colorectal cCancer (CRC). Methods: A total of 302 eligible CRC patients were included, assessing five inflammation-and nutrition-related markers and various clinical features for their predictive impact on postoperative outcomes. Emphasis was on the novel indicator NPRI to elucidate its prognostic and predictive value for perioperative risks. Results: Multivariate logistic regression analysis identified a history of abdominal surgery, prolonged surgical duration, CEA levels ≥5 ng/mL, and NPRI ≥ 3.94 × 10-2 as independent risk factors for postoperative complications in CRC patients. The Clavien--Dindo complication grading system highlighted the close association between preoperative NPRI and both common and severe complications. Multivariate analysis also identified a history of abdominal surgery, tumor diameter ≥5 cm, poorly differentiated or undifferentiated tumors, and NPRI ≥ 2.87 × 10-2 as independent risk factors for shortened overall survival (OS). Additionally, a history of abdominal surgery, tumor maximum diameter ≥5 cm, tumor differentiation as poor/undifferentiated, NPRI ≥ 2.87 × 10-2, and TNM Stage III were determined as independent risk factors for shortened disease-free survival (DFS). Survival curve results showed significantly higher 5-year OS and DFS in the low NPRI group compared to the high NPRI group. The incorporation of NPRI into nomograms for OS and DFS, validated through calibration and decision curve analyses, attested to the excellent accuracy and practicality of these models. Conclusion: Preoperative NPRI independently predicts short-term complications and long-term prognosis in patients undergoing laparoscopic colorectal cancer surgery, enhancing predictive accuracy when incorporated into nomograms for patient survival.


Colorectal Neoplasms , Laparoscopy , Neutrophils , Postoperative Complications , Prealbumin , Humans , Colorectal Neoplasms/surgery , Male , Female , Middle Aged , Aged , Prognosis , Prealbumin/metabolism , Risk Factors , Disease-Free Survival , Adult , Multivariate Analysis , Logistic Models
2.
Pract Lab Med ; 39: e00379, 2024 Mar.
Article En | MEDLINE | ID: mdl-38715657

Background: Hemoglobin A1c has been widely used to diagnose and monitor diabetes. However, the accuracy of HbA1c analysis can be significantly affected by hemoglobin variants, leading to falsely low or elevated levels and misdiagnosis or inappropriate diabetes management. Case report: In this study, we present the case of a 23-year-old man with undetectable HbA1c levels during his annual checkup by high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). To investigate the reason for HbA1c absence, Sanger sequencing, multiplex ligation-dependent probe amplification assay (MLPA), long-read single molecule real-time sequencing (SMRT) and MALDI-TOF mass spectrometry (MS) were performed, and the proband was identified as compound heterozygous of ß-thalassemia with Hb G-Taipei (HBB:c.68A > G) and Hb Lepore-Boston-Washington (NG_000007.3:g.63632_71046del). Conclusion: The combination of these molecular technologies including MLPA, long-read SMRT sequencing and MALDI-TOF MS is beneficial for identifying rare hemoglobin variants. This case also provides essential evidence for uncovering the effect of compound heterozygosity for Hb Lepore-Boston-Washington and Hb G-Taipei on hematological phenotypes and HbA1c analysis.

3.
Article En | MEDLINE | ID: mdl-38724321

BACKGROUND: Regulatory B cells (Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs (miRNAs), miR-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and miR-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs (mBregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. METHODS: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce miR-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. RESULTS: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of mBregs in the circulating blood were significantly impaired. miR-29a-3p was found to be a regulator of mBregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5 (NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of mBregs. The inhibition of miR-29a-3p in CD19+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into mBregs. In addition, the observed enhancement of differentiation and immunosuppressive function of mBregs upon miR-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. CONCLUSIONS: miR-29a-3p was found to be a crucial regulator for mBregs differentiation and immunosuppressive function. Silencing miR-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.

4.
J Gene Med ; 26(5): e3689, 2024 May.
Article En | MEDLINE | ID: mdl-38676365

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy characterized by a poor prognosis and closely linked to tumor stemness. However, the key molecules that regulate ICC stemness remain elusive. Although Y-box binding protein 1 (YBX1) negatively affects prognosis in various cancers by enhancing stemness and chemoresistance, its effect on stemness and cisplatin sensitivity in ICC remains unclear. METHODS: Three bulk and single-cell RNA-seq datasets were analyzed to investigate YBX1 expression in ICC and its association with stemness. Clinical samples and colony/sphere formation assays validated the role of YBX1 in stemness and sensitivity to cisplatin. AZD5363 and KYA1979K explored the interaction of YBX1 with the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) and WNT/ß-catenin pathways. RESULTS: YBX1 was significantly upregulated in ICC, correlated with worse overall survival and shorter postoperative recurrence time, and was higher in chemotherapy-non-responsive ICC tissues. The YBX1-high group exhibited significantly elevated stemness scores, and genes linked to YBX1 upregulation were enriched in multiple stemness-related pathways. Moreover, YBX1 expression is significantly correlated with several stemness-related genes (SOX9, OCT4, CD133, CD44 and EPCAM). Additionally, YBX1 overexpression significantly enhanced the colony- and spheroid-forming abilities of ICC cells, accelerated tumor growth in vivo and reduced their sensitivity to cisplatin. Conversely, the downregulation of YBX1 exerted the opposite effect. The transcriptomic analysis highlighted the link between YBX1 and the PI3K/AKT and WNT/ß-catenin pathways. Further, AZD5363 and KYA1979K were used to clarify that YBX1 promoted ICC stemness through the regulation of the AKT/ß-catenin axis. CONCLUSIONS: YBX1 is upregulated in ICC and promotes stemness and cisplatin insensitivity via the AKT/ß-catenin axis. Our study describes a novel potential therapeutic target for improving ICC prognosis.


Cholangiocarcinoma , Cisplatin , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Y-Box-Binding Protein 1 , beta Catenin , Animals , Female , Humans , Male , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , beta Catenin/metabolism , beta Catenin/genetics , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation , Cholangiocarcinoma/genetics , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/pathology , Cholangiocarcinoma/mortality , Cisplatin/pharmacology , Cisplatin/therapeutic use , Drug Resistance, Neoplasm/genetics , Neoplastic Stem Cells/metabolism , Prognosis , Proto-Oncogene Proteins c-akt/metabolism , Wnt Signaling Pathway , Xenograft Model Antitumor Assays , Y-Box-Binding Protein 1/metabolism , Y-Box-Binding Protein 1/genetics
5.
Org Lett ; 26(17): 3519-3523, 2024 May 03.
Article En | MEDLINE | ID: mdl-38651932

An efficient method for remote radical C(sp3)-H azidation at unactivated sites is described. C-H functionalization proceeds via intramolecular 1,5-hydrogen atom transfer to N-centered radicals that are generated via azido group transfer and/or fragmentation. The readily installed sulfamoyl azide serves as both an amidyl radical precursor and an azido source. This reaction features excellent site selectivity for tertiary, secondary, primary, and benzylic C(sp3)-H bonds and exhibits broad functional group compatibility.

6.
Opt Lett ; 49(8): 2189-2192, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38621108

Multiplexing orbital angular momentum (OAM) modes enable high-capacity optical communication. However, the highly similar speckle patterns of adjacent OAM modes produced by strong mode coupling in common fibers prevent the utility of OAM channel demultiplexing. In this paper, we propose a machine learning-supported fractional OAM-multiplexed data transmission system to sort highly scattered data from up to 32 multiplexed OAM channels propagating through a commercial multi-mode fiber parallelly with an accuracy of >99.92%, which is the largest bit number of OAM superstates reported to date (to the best of our knowledge). Here, by learning limited samples, unseen OAM superstates during the training process can be predicted precisely, which reduces the explosive quantity of the dataset. To verify its application, both gray and colored images, encoded by the given system, have been successfully transmitted with error rates of <0.26%. Our work might provide a promising avenue for high-capacity OAM optical communication in scattering environments.

7.
Front Biosci (Landmark Ed) ; 29(4): 132, 2024 Mar 29.
Article En | MEDLINE | ID: mdl-38682202

BACKGROUND: The incidence of melanoma brain metastasis (MBM) is high and significantly compromises patient survival and quality of life. Effective treatment of MBM is made difficult by the blood-brain barrier (BBB), since it restricts the entry of drugs into the brain. Certain anti-psychotic drugs able to cross the BBB have demonstrated efficacy in suppressing brain metastasis in preclinical studies. However, the activity of zuclopenthixol against MBM is not yet clear. METHODS: Cell viability assays were employed to investigate the potential of zuclopenthixol in the treatment of MBM. Subsequently, the mechanism of action was investigated by RNA-sequencing (RNAseq), flow cytometry-based cell cycle and apoptosis assays, protein expression analysis, and autophagy flux detection. Additionally, the efficacy of zuclopenthixol against tumor growth was investigated in vivo, including MBM models. RESULTS: Zuclopenthixol inhibited the proliferation of various melanoma cell lines at minimal doses by causing cell cycle arrest in the G0/G1 phase and mitochondrial-mediated intrinsic apoptosis. Zuclopenthixol also induced cytoprotective autophagy, and inhibition of autophagy enhanced the anti-melanoma effects of zuclopenthixol. Furthermore, zuclopenthixol inhibited the growth of human melanoma tumors in nude mice, as well as the growth of intracranial metastases in a mouse model of MBM. CONCLUSIONS: These results demonstrate that zuclopenthixol has significant potential as an effective therapeutic agent for MBM.


Apoptosis , Brain Neoplasms , Cell Cycle Checkpoints , Cell Proliferation , Melanoma , Apoptosis/drug effects , Animals , Brain Neoplasms/drug therapy , Brain Neoplasms/secondary , Brain Neoplasms/pathology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Humans , Melanoma/drug therapy , Melanoma/pathology , Melanoma/metabolism , Cell Proliferation/drug effects , Mice , Antipsychotic Agents/pharmacology , Autophagy/drug effects , Xenograft Model Antitumor Assays , Mice, Nude , Cell Survival/drug effects
8.
Medicine (Baltimore) ; 103(14): e37730, 2024 Apr 05.
Article En | MEDLINE | ID: mdl-38579062

RATIONALE: Turner syndrome (TS) is a genetic disorder associated with partial or complete monosomy X abnormalities; some patients may have a higher risk of psychiatric symptoms. Catatonia is associated with a wide range of life-threatening complications with complex pathogenesis; However, It very rare for patients with TS to develop psychotic symptoms and eventually progress to catatonia. This case report describes the diagnostic and therapeutic course of catatonia-associated TS. PATIENT CONCERNS: In this study, we report the case of a patient with TS who initially developed sudden hallucinations, delusions, and emotional instability, followed by catatonia. DIAGNOSES: The patient was diagnosed with: unspecified catatonia; TS. INTERVENTIONS: Treatment included administering a combination of esazolam injections and olanzapine tablets, placing a gastric tube and urinary catheter, and providing nutritional support. OUTCOMES: After treatment, the patient's hallucinations, delusions, and catatonia disappeared, with no residual sequelae, and social functioning returned to normal. LESSONS: For patients with TS who present with psychotic symptoms and catatonia, a comprehensive evaluation is necessary, and treatment with antipsychotics and benzodiazepines is effective.


Antipsychotic Agents , Catatonia , Psychotic Disorders , Turner Syndrome , Humans , Catatonia/etiology , Catatonia/therapy , Catatonia/diagnosis , Turner Syndrome/complications , Psychotic Disorders/etiology , Psychotic Disorders/drug therapy , Antipsychotic Agents/therapeutic use , Hallucinations/complications
9.
Sports Med ; 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38687441

There are several modifiable factors that can be targeted to prevent and manage the occurrence and progression of cancer, and maintaining adequate exercise is a crucial one. Regular physical exercise has been shown to be a beneficial strategy in preventing cancer, potentially amplifying the effectiveness of established cancer therapies, alleviating certain cancer-related symptoms, and possibly mitigating side effects resulting from treatment. Nevertheless, the exact mechanisms by which exercise affects tumors, especially its impact on the tumor microenvironment (TME), remain uncertain. This review aims to present an overview of the beneficial effects of exercise in the context of cancer management, followed by a summary of the exercise parameters, especially exercise intensity, that need to be considered when prescribing exercise for cancer patients. Finally, we discuss the influence of exercise on the TME, including its effects on crucial immune cells (e.g., T cells, macrophages, neutrophils, natural killer cells, myeloid-derived suppressor cells, B cells), intratumor angiogenesis, and cancer metabolism. This comprehensive review provides up-to-date scientific evidence on the effects of exercise training on cancer and offers guidance to clinicians for the development of safe and feasible exercise training programs for cancer patients in clinical practice.

10.
IEEE Trans Med Imaging ; PP2024 Mar 28.
Article En | MEDLINE | ID: mdl-38546999

Accurate myocardial segmentation is crucial in the diagnosis and treatment of myocardial infarction (MI), especially in Late Gadolinium Enhancement (LGE) cardiac magnetic resonance (CMR) images, where the infarcted myocardium exhibits a greater brightness. However, segmentation annotations for LGE images are usually not available. Although knowledge gained from CMR images of other modalities with ample annotations, such as balanced-Steady State Free Precession (bSSFP), can be transferred to the LGE images, the difference in image distribution between the two modalities (i.e., domain shift) usually results in a significant degradation in model performance. To alleviate this, an end-to-end Variational autoencoder based feature Alignment Module Combining Explicit and Implicit features (VAMCEI) is proposed. We first re-derive the Kullback-Leibler (KL) divergence between the posterior distributions of the two domains as a measure of the global distribution distance. Second, we calculate the prototype contrastive loss between the two domains, bringing closer the prototypes of the same category across domains and pushing away the prototypes of different categories within or across domains. Finally, a domain discriminator is added to the output space, which indirectly aligns the feature distribution and forces the extracted features to be more favorable for segmentation. In addition, by combining CycleGAN and VAMCEI, we propose a more refined multi-stage unsupervised domain adaptation (UDA) framework for myocardial structure segmentation. We conduct extensive experiments on the MSCMRSeg 2019, MyoPS 2020 and MM-WHS 2017 datasets. The experimental results demonstrate that our framework achieves superior performances than state-of-the-art methods.

11.
Molecules ; 29(6)2024 Mar 08.
Article En | MEDLINE | ID: mdl-38542857

To produce functional protective textiles with minimal environmental footprints, we developed durable superhydrophobic antimicrobial textiles. These textiles are characterized by a micro-pleated structure on polyester fiber surfaces, achieved through a novel plasma impregnation crosslinking process. This process involved the use of water as the dispersion medium, water-soluble nanosilver monomers for antimicrobial efficacy, fluorine-free polydimethylsiloxane (PDMS) for hydrophobicity, and polyester (PET) fabric as the base material. The altered surface properties of these fabrics were extensively analyzed using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectrometry (XPS), thermogravimetric analysis (TGA), and water contact angle (WCA) measurements. The antimicrobial performance of the strains was evaluated using Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. After treatment, the fabrics exhibited enhanced hydrophobic and antimicrobial properties, which was attributed to the presence of a micro-pleated structure and nanosilver. The modified textiles demonstrated a static WCA of approximately 154° and an impressive 99.99% inhibition rate against both test microbes. Notably, the WCA remained above 140° even after 500 washing cycles or 3000 friction cycles.


Anti-Infective Agents , Polyesters , Silver , Polyesters/chemistry , Textiles , Anti-Infective Agents/pharmacology , Hydrophobic and Hydrophilic Interactions , Water/chemistry
12.
ACS Synth Biol ; 13(4): 1365-1372, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38518262

Lactococcus cremoris (homotypic synonym: Lactococcus lactis) is receiving increasing attention as a prominent vehicle for the delivery of live vaccines. This can hardly be achieved without developing tools for the genetic manipulation of L. cremoris, and the paucity of studies on L. cremoris endogenous promoters has attracted our attention. Here, we report the discovery and characterization of 29 candidate promoters identified from L. cremoris subsp. cremoris NZ9000 by RNA sequencing analysis. Furthermore, 18 possible constitutive promoters were obtained by RT-qPCR screening from these 29 candidate promoters. Then, these 18 promoters were cloned and characterized by a reporter gene, gusA, encoding ß-glucuronidase. Eventually, eight endogenous constitutive promoters of L. cremoris were obtained, which can be applied to genetic manipulation of lactic acid bacteria.


Lactococcus lactis , Lactococcus , Lactococcus lactis/genetics , Lactococcus lactis/metabolism , Promoter Regions, Genetic/genetics , Genes, Reporter/genetics , Gene Expression
13.
Sci Rep ; 14(1): 6488, 2024 03 18.
Article En | MEDLINE | ID: mdl-38499636

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract and a leading cause of cancer-related death worldwide. Since many CRC patients are diagnosed already in the advanced stage, and traditional chemoradiotherapy is prone to drug resistance, it is important to find new therapeutic targets. In this study, the expression levels of ALDOA and p-AKT were detected in cancer tissues and paired normal tissues, and it was found that they were significantly increased in CRC tissues, and their high expression indicated poor prognosis. Moreover, a positive correlation between the expression of ALDOA and p-AKT was found in CRC tissues and paired normal tissues. In addition, the Kaplan-Meier analysis revealed that the group with both negative of ALDOA/p-AKT expression had longer five-year survival rates compared with the other group. Besides, the group with both high expression of ALDOA/p-AKT had a worse prognosis compared with the other group. Based on the expression of ALDOA and p-AKT in tumor tissues, we can effectively distinguish tumor tissues from normal tissues through cluster analysis. Furthermore, we constructed nomograms to predict 3-year and 5-year overall survival, showing that the expression of ALDOA/p-AKT plays a crucial role in predicting the prognosis of CRC patients. Therefore, ALDOA/p-AKT may act as a crucial role in CRC, which may provide new horizons for targeted therapies for CRC.


Colorectal Neoplasms , Proto-Oncogene Proteins c-akt , Humans , Prognosis , Kaplan-Meier Estimate , Colorectal Neoplasms/metabolism , Fructose-Bisphosphate Aldolase/metabolism
14.
Toxicol Appl Pharmacol ; 484: 116878, 2024 Mar.
Article En | MEDLINE | ID: mdl-38431229

Bladder cancer is a prevalent malignancy affecting the urinary system, which presents a significant global health concern. Although there are many treatments for bladder cancer, identifying more effective drugs and methods remains an urgent problem. As a pivotal component of contemporary medical practice, traditional Chinese medicine (TCM) assumes a crucial role in the realm of anti-tumor therapy, especially with the identification of active ingredients and successful exploration of pharmacological effects. Febrifugine, identified as a quinazoline-type alkaloid compound extracted from the Cytidiaceae family plant Huangchangshan, exhibits heightened sensitivity to bladder cancer cells in comparison to control cells (non-cancer cells) group. The proliferation growth of bladder cancer cells T24 and SW780 was effectively inhibited by Febrifugine, and the IC50 was 0.02 and 0.018 µM respectively. Febrifugine inhibits cell proliferation by suppressing DNA synthesis and induces cell death by reducing steroidogenesis and promoting apoptosis. Combined with transcriptome analysis, Febrifugine was found to downregulate low density lipoprotein receptor-associated protein, lanosterol synthase, cholesterol biosynthesis second rate-limiting enzyme, 7-dehydrocholesterol reductase, flavin adenine dinucleotide dependent oxidoreductase and other factors to inhibit the production of intracellular steroids in bladder cancer T24 cells. The results of animal experiments showed that Febrifugine could inhibit tumor growth. In summary, the effect of Febrifugine on bladder cancer is mainly through reducing steroid production and apoptosis. Therefore, this study contributes to the elucidation of Febrifugine's potential as an inhibitor of bladder cancer and establishes a solid foundation for the future development of novel therapeutic agents targeting bladder cancer.


Piperidines , Urinary Bladder Neoplasms , Animals , Cell Line, Tumor , Cell Proliferation , Urinary Bladder Neoplasms/pathology , Quinazolines/pharmacology , Quinazolines/therapeutic use , Apoptosis
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 313: 124124, 2024 May 15.
Article En | MEDLINE | ID: mdl-38460230

Derivative spectroscopy is used to separate the small absorption peaks superimposed on the main absorption band, which is widely adopted in modern spectral analysis to increase both the valid spectral information and the identification accuracy. In this study, a method based on attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) with first-order derivative (FD) processing combined with chemometrics is proposed for rapid qualitative and quantitative analysis of Panax ginseng polysaccharides (PGP), Panax notoginseng polysaccharides (PNP), and Panax quinquefolius polysaccharides (PQP). First, ATR-FTIR with FD processing was used to establish the discriminant model combined with principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and linear discriminant analysis (LDA). After that, two-dimensional ATR-FTIR based on single-characteristic temperature as external interference (2D-sATR-FTIR) was established using ATR-FTIR with FD processing. Then, ATR-FTIR with FD processing was combined with PLS to establish and optimize the quantitative regression model. Finally, the established discriminant model and 2D-sATR-FTIR successfully distinguished PGP, PNP and PQP, and the optimal PLS regression model had a good prediction ability for the Panax polysaccharide extracts content. This strategy provides an efficient, economical and nondestructive method for the distinction and quantification of PGP, PNP and PQP in a short detection time.


Panax notoginseng , Spectroscopy, Fourier Transform Infrared/methods , Discriminant Analysis , Least-Squares Analysis , Polysaccharides
16.
Opt Express ; 32(4): 5339-5352, 2024 Feb 12.
Article En | MEDLINE | ID: mdl-38439263

The orbital angular momentum (OAM) of light, possessing an infinite-dimensional degree of freedom, holds significant potential to enhance the capacity of optical communication and information processing in both classical and quantum regimes. Despite various methods developed to accurately measure OAM modes, the probing limit of the highest-order OAM remains an open question. Here, we report an accurate recognition of superhigh-order OAM using a convolutional neural network approach with an improved ResNeXt architecture, based on conjugated interference patterns. A type of hybrid beam carrying double OAM modes is utilized to provide more controllable degrees of freedom for greater recognition of the OAM modes. Our contribution advances the OAM recognition limit from manual counting to machine learning. Results demonstrate that, within our optical system, the maximum recognizable OAM modes exceed l = ±690 with an accuracy surpassing 99.93%, the highest achieved by spatial light modulator to date. Enlarging the active area of the CCD sensor extends the number of recognizable OAM modes to 1300, constrained only by the CCD resolution limit. Additionally, we explore the identification of fractional high-order OAM modes with a resolution of 0.1 from l = ±600.0 to l = ±600.9, achieving a high accuracy of 97.86%.

17.
Cancers (Basel) ; 16(5)2024 Feb 22.
Article En | MEDLINE | ID: mdl-38473249

The strategy of drug repurposing has gained traction in the field of cancer therapy as a means of discovering novel therapeutic uses for established pharmaceuticals. Paroxetine (PX), a selective serotonin reuptake inhibitor typically utilized in the treatment of depression, has demonstrated promise as an agent for combating cancer. Nevertheless, the specific functions and mechanisms by which PX operates in the context of triple-negative breast cancer (TNBC) remain ambiguous. This study aimed to examine the impact of PX on TNBC cells in vitro as both a standalone treatment and in conjunction with other pharmaceutical agents. Cell viability was measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, apoptosis was assessed through flow cytometry, and the effects on signaling pathways were analyzed using RNA sequencing and Western blot techniques. Furthermore, a subcutaneous tumor model was utilized to assess the in vivo efficacy of combination therapy on tumor growth. The results of our study suggest that PX may activate the Ca2+-dependent mitochondria-mediated intrinsic apoptosis pathway in TNBC by potentially influencing the PI3K/AKT/mTOR pathway as well as by inducing cytoprotective autophagy. Additionally, the combination of PX and chemotherapeutic agents demonstrated moderate inhibitory effects on 4T1 tumor growth in an in vivo model. These findings indicate that PX may exert its effects on TNBC through modulation of critical molecular pathways, offering important implications for improving chemosensitivity and identifying potential therapeutic combinations for clinical use.

18.
Exp Cell Res ; 437(1): 113998, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38513962

Plasma saturated free fatty acid (FFA)-induced endothelial dysfunction (ED) contributes to the pathogenesis of atherosclerosis and cardiovascular diseases. However, the mechanism underlying saturated FFA-induced ED remains unclear. This study demonstrated that palmitic acid (PA) induced ED by activating the NADPH oxidase (NOX)/ROS signaling pathway to activate protein phosphatase 4 (PP4) and protein phosphatase 2A (PP2A), thereby reducing endothelial nitric oxide synthase (eNOS) phosphorylation at Ser633 and Ser1177, respectively. Okadaic acid (OA) and fostriecin (FST), which are inhibitors of PP2A, inhibited the PA-induced decreases in eNOS phosphorylation at Ser633 and Ser1177. The antioxidants N-acetylcysteine (NAC) and apocynin (APO) or knockdown of gp91phox or p67phox (NOX subunits) restored PA-mediated downregulation of PP4R2 protein expression and eNOS Ser633 phosphorylation. Knockdown of the PP4 catalytic subunit (PP4c) specifically increased eNOS Ser633 phosphorylation, while silencing the PP2A catalytic subunit (PP2Ac) restored only eNOS Ser1177 phosphorylation. Furthermore, PA dramatically decreased the protein expression of the PP4 regulatory subunit R2 (PP4R2) but not the other regulatory subunits. PP4R2 overexpression increased eNOS Ser633 phosphorylation, nitric oxide (NO) production, cell migration and tube formation but did not change eNOS Ser1177 phosphorylation levels. Coimmunoprecipitation (Co-IP) suggested that PP4R2 and PP4c interacted with the PP4R3α and eNOS proteins. In summary, PA decreases PP4R2 protein expression through the Nox/ROS pathway to activate PP4, which contributes to ED by dephosphorylating eNOS at Ser633. The results of this study suggest that PP4 is a novel therapeutic target for ED and ED-associated vascular diseases.


Nitric Oxide Synthase Type III , Phosphoprotein Phosphatases , Vascular Diseases , Humans , Phosphorylation , Nitric Oxide Synthase Type III/metabolism , Palmitic Acid/pharmacology , Serine/metabolism , Reactive Oxygen Species , Cells, Cultured , Protein Phosphatase 2/metabolism , Nitric Oxide/metabolism
19.
ACS Appl Mater Interfaces ; 16(8): 10813-10821, 2024 Feb 28.
Article En | MEDLINE | ID: mdl-38359411

Hydrogel, recognized as a promising biomaterial for tissue engineering, possesses notable characteristics, including high water uptake, an interconnected porous structure, and excellent permeability. However, the intricate task of fabricating a hierarchically macro-micronanoporous structure, essential for providing adequate space for nutrient diffusion and cell growth within hydrogels, remains a formidable challenge. In response to these challenges, this study introduces a sustainable and straightforward three-dimensional (3D) foaming printing strategy to produce hierarchically macro-micronanoporous hydrogels (HPHs) without the utilization of porogens and post-etching process. This method entails the controlled generation of air bubbles within the hydrogels through the application of optimal mechanical stirring rates. Subsequent ultraviolet (UV) cross-linking serves to effectively stabilize the macropores within the HPHs. The resulting hierarchically macro-micronanoporous structures demonstrate a substantial improvement in the viability, adhesion, and proliferation of human umbilical vein endothelial cells (HUVECs) when incubated with the hydrogels. These findings present a significant advancement in the fabrication of hierarchically macro-micronanoporous hydrogels, with potential applications in the fields of tissue engineering and organoid development.


Biomimetics , Hydrogels , Humans , Hydrogels/pharmacology , Hydrogels/chemistry , Tissue Engineering/methods , Human Umbilical Vein Endothelial Cells , Cell Proliferation , Printing, Three-Dimensional , Tissue Scaffolds/chemistry
20.
Article En | MEDLINE | ID: mdl-38356213

RGB-D salient object detection (SOD) has gained tremendous attention in recent years. In particular, transformer has been employed and shown great potential. However, existing transformer models usually overlook the vital edge information, which is a major issue restricting the further improvement of SOD accuracy. To this end, we propose a novel edge-aware RGB-D SOD transformer, called, which explicitly models the edge information in a dual-band decomposition framework. Specifically, we employ two parallel decoder networks to learn the high-frequency edge and low-frequency body features from the low-and high-level features extracted from a two-steam multimodal backbone network, respectively. Next, we propose a cross-attention complementarity exploration module to enrich the edge/body features by exploiting the multimodal complementarity information. The refined features are then fed into our proposed color-hint guided fusion module for enhancing the depth feature and fusing the multimodal features. Finally, the resulting features are fused using our deeply supervised progressive fusion module, which progressively integrates edge and body features for predicting saliency maps. Our model explicitly considers the edge information for accurate RGB-D SOD, overcoming the limitations of existing methods and effectively improving the performance. Extensive experiments on benchmark datasets demonstrate that is an effective RGB-D SOD framework that outperforms the current state-of-the-art models, both quantitatively and qualitatively. A further extension to RGB-T SOD demonstrates the promising potential of our model in various kinds of multimodal SOD tasks.

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