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1.
Free Radic Biol Med ; 223: 413-429, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39155025

ABSTRACT

Postmenopausal osteoporosis (PMO) is characterized by bone loss and microstructural damage, and it is most common in older adult women. Currently, there is no cure for PMO. The flavonoid chemical 7,8-dihydroxyflavone (7,8-DHF) specifically activates tropomyosin receptor kinase B (TRKB). Furthermore, 7,8-DHF has various biological characteristics, including anti-inflammatory and antioxidant effects. However, the specific implications and fundamental mechanisms of 7,8-DHF in PMO remain unclear. We used protein imprinting, flow cytometry, tissue staining, and other methods to estimate the preventive mechanisms of 7,8-DHF against hydrogen peroxide (H2O2)-induced apoptosis in primary mouse bone marrow mesenchymal stem cells (BMSCs), osteogenic differentiation ability, and bone mass in ovariectomized (OVX) mice. We found that 7,8-DHF effectively prevented H2O2-induced reductions in the viability and osteogenic differentiation capacity of primary BMSCs. Mechanistically, 7,8-DHF induced the TRKB to activate the PI3K/AKT/NRF2 pathway. In vivo experiments with the OVX mouse model confirmed that 7,8-DHF can inhibit oxidative stress and promote bone formation, indicating that 7,8-DHF improves the viability and osteogenic differentiation ability of BMSCs stimulated via H2O2 by activating the TRKB/PI3K/AKT and NRF2 pathways, thereby improving PMO.


Subject(s)
Flavones , Hydrogen Peroxide , Mesenchymal Stem Cells , NF-E2-Related Factor 2 , Osteogenesis , Osteoporosis, Postmenopausal , Oxidative Stress , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Receptor, trkB , Signal Transduction , Animals , Oxidative Stress/drug effects , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Mice , Female , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Flavones/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Osteoporosis, Postmenopausal/metabolism , Osteoporosis, Postmenopausal/pathology , Osteoporosis, Postmenopausal/drug therapy , Osteogenesis/drug effects , Signal Transduction/drug effects , Hydrogen Peroxide/metabolism , Humans , Receptor, trkB/metabolism , Receptor, trkB/genetics , Cell Differentiation/drug effects , Apoptosis/drug effects , Membrane Glycoproteins/metabolism , Membrane Glycoproteins/genetics , Ovariectomy , Mice, Inbred C57BL
2.
Redox Biol ; 75: 103299, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39127016

ABSTRACT

Lung cancer is a leading cause of cancer death worldwide, with high incidence and poor survival rates. Cold atmospheric plasma (CAP) technology has emerged as a promising therapeutic approach for cancer treatment, inducing oxidative stress in malignant tissues without causing thermal damage. However, the role of CAP in regulating lung cancer cell ferroptosis remains unclear. Here, we observed that CAP effectively suppressed the growth and migration abilities of lung cancer cells, with significantly increased ferroptotic cell death, lipid peroxidation, and decreased mitochondrial membrane potential. Mechanistically, CAP regulates SLC7A11-mediated cell ferroptosis by modulating HOXB9. SLC7A11, a potent ferroptosis suppressor, was markedly reduced by HOXB9 knockdown, while it was enhanced by overexpressing HOXB9. The luciferase and ChIP assays confirmed that HOXB9 can directly target SLC7A11 and regulate its gene transcription. Additionally, CAP enhanced the acetylation modification level of HOXB9 by promoting its interaction with acetyltransferase p300/CBP-associated factor (PCAF). Acetylated HOXB9 affects its protein ubiquitination modification level, which in turn affects its protein stability. Notably, the upregulation of SLC7A11 and HOXB9 mitigated the suppressive effects of CAP on ferroptosis status, cell proliferation, invasion, and migration in lung cancer cells. Furthermore, animal models have also confirmed that CAP can inhibit the progression of lung cancer in vivo. Overall, this study highlights the significance of the downregulation of the HOXB9/SLC7A11 axis by CAP treatment in inhibiting lung cancer, offering novel insights into the potential mechanisms and therapeutic strategies of CAP for lung cancer.


Subject(s)
Amino Acid Transport System y+ , Carcinoma, Non-Small-Cell Lung , Ferroptosis , Gene Expression Regulation, Neoplastic , Homeodomain Proteins , Lung Neoplasms , p300-CBP Transcription Factors , Humans , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Acetylation , p300-CBP Transcription Factors/metabolism , Animals , Mice , Homeodomain Proteins/metabolism , Homeodomain Proteins/genetics , Cell Line, Tumor , Cell Proliferation , Cell Movement
3.
Kidney Dis (Basel) ; 10(4): 284-294, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39131882

ABSTRACT

Introduction: Patients undergoing maintenance hemodialysis are vulnerable to coronavirus disease 2019 (COVID-19), exhibiting a high risk of hospitalization and mortality. Thus, early identification and intervention are important to prevent disease progression in these patients. Methods: This was a two-center retrospective observational study of patients on hemodialysis diagnosed with COVID-19 at the Lingang and Xuhui campuses of Shanghai Sixth People's Hospital. Patients were randomized into the training (130) and validation cohorts (54), while 59 additional patients served as an independent external validation cohort. Artificial intelligence-based parameters of chest computed tomography (CT) were quantified, and a nomogram for patient outcomes at 14 and 28 days was created by screening quantitative CT measures, clinical data, and laboratory examination items, using univariate and multivariate Cox regression models. Results: The median dialysis duration was 48 (interquartile range, 24-96) months. Age, diabetes mellitus, serum phosphorus level, lymphocyte count, and chest CT score were identified as independent prognostic indicators and included in the nomogram. The concordance index values were 0.865, 0.914, and 0.885 in the training, internal validation, and external validation cohorts, respectively. Calibration plots showed good agreement between the expected and actual outcomes. Conclusion: This is the first study in which a reliable nomogram was developed to predict short-term outcomes and survival probabilities in patients with COVID-19 on hemodialysis. This model may be helpful to clinicians in treating COVID-19, managing serum phosphorus, and adjusting the dialysis strategies for these vulnerable patients to prevent disease progression in the context of COVID-19 and continuous emergence of novel viruses.

4.
J Imaging Inform Med ; 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39037669

ABSTRACT

Adenomatous polyps, a common premalignant lesion, are often classified into villous adenoma (VA) and tubular adenoma (TA). VA has a higher risk of malignancy, whereas TA typically grows slowly and has a lower likelihood of cancerous transformation. Accurate classification is essential for tailored treatment. In this study, we develop a deep learning-based approach for the localization and classification of adenomatous polyps using endoscopic images. Specifically, a pre-trained EGE-UNet is first adopted to extract regions of interest from original images. Multi-level feature maps are then extracted by the feature extraction pipeline (FEP). The deep-level features are fed into the Pyramid Pooling Module (PPM) to capture global contextual information, and the squeeze body edge (SBE) module is then used to decouple the body and edge parts of features, enabling separate analysis of their distinct characteristics. The Group Aggregation Bridge (GAB) and Boundary Enhancement Module (BEM) are then applied to enhance the body features and edge features, respectively, emphasizing their structural and morphological characteristics. By combining the features of the body and edge parts, the final output can be obtained. Experiments show the proposed method achieved promising results on two private datasets. For adenoma vs. non-adenoma classification, It achieved a mIoU of 91.41%, mPA of 96.33%, mHD of 11.63, and mASD of 2.33. For adenoma subclassification (non-adenomas vs. villous adenomas vs. tubular adenomas), it achieved a mIoU of 91.21%, mPA of 94.83%, mHD of 13.75, and mASD of 2.56. These results demonstrate the potential of our approach for precise adenomatous polyp classification.

5.
Cancer Lett ; 597: 217062, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38878852

ABSTRACT

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet persistent challenges such as low response rate and significant heterogeneity necessitate attention. The pivotal role of the major histocompatibility complex (MHC) in ICI efficacy, its intricate impacts and potentials as a prognostic marker, warrants comprehensive exploration. This study integrates single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, and spatial transcriptomic analyses to unveil pan-cancer immune characteristics governed by the MHC transcriptional feature (MHC.sig). Developed through scRNA-seq analysis of 663,760 cells across diverse cohorts and validated in 30 solid cancer types, the MHC.sig demonstrates a robust correlation between immune-related genes and infiltrating immune cells, highlighting its potential as a universal pan-cancer marker for anti-tumor immunity. Screening the MHC.sig for therapeutic targets using CRISPR data identifies potential genes for immune therapy synergy and validates its predictive efficacy for ICIs responsiveness across diverse datasets and cancer types. Finally, analysis of cellular communication patterns reveals interactions between C1QC+macrophages and malignant cells, providing insights into potential therapeutic agents and their sensitivity characteristics. This comprehensive analysis positions the MHC.sig as a promising marker for predicting immune therapy outcomes and guiding combinatorial therapeutic strategies.


Subject(s)
Major Histocompatibility Complex , Neoplasms , Single-Cell Analysis , Humans , Neoplasms/genetics , Neoplasms/immunology , Single-Cell Analysis/methods , Major Histocompatibility Complex/genetics , Major Histocompatibility Complex/immunology , Sequence Analysis, RNA/methods , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , RNA-Seq
6.
PLoS One ; 19(5): e0299230, 2024.
Article in English | MEDLINE | ID: mdl-38787887

ABSTRACT

As a basic parameter of rock, the rock bridge angle plays an important role in maintaining the stability of rock masses. To study the size effect of rock bridge angle on the uniaxial compressive strength of rocks, this paper adopts the principle of regression analysis and combines numerical simulation to carry out relevant research. The research results indicate that: (1) the uniaxial compressive strength decreases with the increase of the rock bridge angle, showing a power function relationship; (2) The uniaxial compressive strength decreases with the increase of rock size and tends to stabilize when the rock size is greater than 350 mm, showing a significant size effect. (3) The fluctuation coefficient of compressive strength increases with the increase of rock bridge angle and decreases with the increase of rock size; When the rock size is 350 mm, the fluctuation coefficient is less than 5%; (4) The characteristic compressive strength and characteristic size both increase with the increase of the rock bridge angle.


Subject(s)
Compressive Strength , Regression Analysis , Models, Theoretical
7.
Artif Intell Med ; 152: 102871, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38685169

ABSTRACT

For the diagnosis and outcome prediction of gastric cancer (GC), machine learning methods based on whole slide pathological images (WSIs) have shown promising performance and reduced the cost of manual analysis. Nevertheless, accurate prediction of GC outcome may rely on multiple modalities with complementary information, particularly gene expression data. Thus, there is a need to develop multimodal learning methods to enhance prediction performance. In this paper, we collect a dataset from Ruijin Hospital and propose a multimodal learning method for GC diagnosis and outcome prediction, called GaCaMML, which is featured by a cross-modal attention mechanism and Per-Slide training scheme. Additionally, we perform feature attribution analysis via integrated gradient (IG) to identify important input features. The proposed method improves prediction accuracy over the single-modal learning method on three tasks, i.e., survival prediction (by 4.9% on C-index), pathological stage classification (by 11.6% on accuracy), and lymph node classification (by 12.0% on accuracy). Especially, the Per-Slide strategy addresses the issue of a high WSI-to-patient ratio and leads to much better results compared with the Per-Person training scheme. For the interpretable analysis, we find that although WSIs dominate the prediction for most samples, there is still a substantial portion of samples whose prediction highly relies on gene expression information. This study demonstrates the great potential of multimodal learning in GC-related prediction tasks and investigates the contribution of WSIs and gene expression, respectively, which not only shows how the model makes a decision but also provides insights into the association between macroscopic pathological phenotypes and microscopic molecular features.


Subject(s)
Machine Learning , Stomach Neoplasms , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Humans , Image Interpretation, Computer-Assisted/methods , Prognosis , Gene Expression Profiling/methods
8.
BMC Musculoskelet Disord ; 25(1): 270, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38589862

ABSTRACT

BACKGROUND: Fractures of hands and feet are common in children, but relevant epidemiological studies are currently lacking. We aim to study the epidemiological characteristics of hand and foot fractures and growth plate injuries in children and provide a theoretical basis for their prevention, diagnosis, and treatment. METHODS: We retrospectively analyzed the data of children with hand and foot fractures who were hospitalized at Shenzhen Children's Hospital between July 2015 and December 2020. Data on demographic characteristics, fracture site, treatment method, etiology of injury, and accompanying injuries were collected. The children were divided into four age groups: infants, preschool children, school children, and adolescents. The fracture sites were classified as first-level (the first-fifth finger/toe, metacarpal, metatarsal, carpal, and tarsal) and second-level (the first-fifth: proximal phalanx, middle phalanx, distal phalanx, metacarpal, and metatarsal) sites. The changing trends in fracture locations and injury causes among children in each age group were analyzed. RESULTS: Overall, 1301 children (1561 fractures; 835 boys and 466 girls) were included. The largest number of fractures occurred in preschool children (n = 549, 42.20%), with the distal phalanx of the third finger being the most common site (n = 73, 15.57%). The number of fractures in adolescents was the lowest (n = 158, 12.14%), and the most common fracture site was the proximal phalanx of the fifth finger (n = 45, 29.61%). Of the 1561 fractures, 1143 occurred in the hands and 418 in the feet. The most and least common first-level fracture sites among hand fractures were the fifth (n = 300, 26.25%) and first (n = 138, 12.07%) fingers, respectively. The most and least common first-level foot fracture locations were the first (n = 83, 19.86%) and fourth (n = 26, 6.22%) toes, respectively. The most common first-level and second level etiologies were life related injuries (n = 1128, 86.70%) and clipping injuries (n = 428, 32.90%), respectively. The incidence of sports injuries gradually increased with age, accounting for the highest proportion in adolescents (26.58%). Hand and foot fractures had many accompanying injuries, with the top three being nail bed injuries (570 cases, 36.52%), growth plate injuries (296 cases, 18.96%), and distal severed fracture (167 cases, 10.70%). Among the 296 growth plate injuries, 246 occurred on the hands and 50 on the feet. CONCLUSIONS: In contrast to previous epidemiological studies on pediatric hand and foot fractures, we mapped the locations of these fractures, including proximal, shaft, distal, and epiphyseal plate injuries. We analyzed the changing trends in fracture sites and injury etiologies with age. Hand and foot fractures have many accompanying injuries that require attention during diagnosis and treatment. Doctors should formulate accident protection measures for children of different ages, strengthen safety education, and reduce the occurrence of accidental injuries.


Subject(s)
Foot Injuries , Fractures, Bone , Hand Injuries , Metacarpal Bones , Salter-Harris Fractures , Male , Child, Preschool , Infant , Female , Adolescent , Child , Humans , Retrospective Studies , Salter-Harris Fractures/complications , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Fractures, Bone/diagnosis , Hand Injuries/epidemiology , Hand Injuries/etiology , Hand Injuries/therapy , Metacarpal Bones/injuries , Foot Injuries/epidemiology , Foot Injuries/etiology , Foot Injuries/therapy
9.
Mol Cancer ; 23(1): 59, 2024 03 21.
Article in English | MEDLINE | ID: mdl-38515149

ABSTRACT

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure. METHODS: The whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids (n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335). RESULTS: Anlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels. CONCLUSIONS: CircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.


Subject(s)
Colorectal Neoplasms , Indoles , MicroRNAs , Quinolines , Humans , Animals , Mice , RNA, Circular/genetics , Tumor Suppressor Protein p53 , Prospective Studies , MicroRNAs/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Cell Proliferation/genetics , Biomarkers , Ubiquitin Thiolesterase/metabolism , Cyclins/metabolism
10.
Acta Biomater ; 177: 456-471, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38331131

ABSTRACT

Cetuximab (Cet) and oxaliplatin (OXA) are used as first-line drugs for patients with colorectal carcinoma (CRC). In fact, the heterogeneity of CRC, mainly caused by K-ras mutations and drug resistance, undermines the effectiveness of drugs. Recently, a hydrophobic prodrug, (1E,4E)-6-((S)-1-(isopentyloxy)-4-methylpent-3-en-1-yl)-5,8-dimethoxynaphthalene-1,4­dione dioxime (DMAKO-20), has been shown to undergo tumor-specific CYP1B1-catalyzed bioactivation. This process results in the production of nitric oxide and active naphthoquinone mono-oximes, which exhibit specific antitumor activity against drug-resistant CRC. In this study, a Cet-conjugated bioresponsive DMAKO-20/PCL-PEOz-targeted nanocodelivery system (DMAKO@PCL-PEOz-Cet) was constructed to address the issue of DMAKO-20 dissolution and achieve multitargeted delivery of the cargoes to different subtypes of CRC cells to overcome K-ras mutations and drug resistance in CRC. The experimental results demonstrated that DMAKO@PCL-PEOz-Cet efficiently delivered DMAKO-20 to both K-ras mutant and wild-type CRC cells by targeting the epidermal growth factor receptor (EGFR). It exhibited a higher anticancer effect than OXA in K-ras mutant cells and drug-resistant cells. Additionally, it was observed that DMAKO@PCL-PEOz-Cet reduced the expression of glutathione peroxidase 4 (GPX4) in CRC cells and significantly inhibited the growth of heterogeneous HCT-116 subcutaneous tumors and patient-derived tumor xenografts (PDX) model tumors. This work provides a new strategy for the development of safe and effective approaches for treating CRC. STATEMENT OF SIGNIFICANCE: (1) Significance: This work reports a new approach for the treatment of colorectal carcinoma (CRC) using the bioresponsible Cet-conjugated PCL-PEOz/DMAKO-20 nanodelivery system (DMAKO@PCL-PEOz-Cet) prepared with Cet and PCL-PEOz for the targeted transfer of DMAKO-20, which is an anticancer multitarget drug that can even prevent drug resistance, to wild-type and K-ras mutant CRC cells. DMAKO@PCL-PEOz-Cet, in the form of nanocrystal micelles, maintained stability in peripheral blood and efficiently transported DMAKO-20 to various subtypes of colorectal carcinoma cells, overcoming the challenges posed by K-ras mutations and drug resistance. The system's secure and effective delivery capabilities have also been confirmed in organoid and PDX models. (2) This is the first report demonstrating that this approach simultaneously overcomes the K-ras mutation and drug resistance of CRC.


Subject(s)
Antineoplastic Agents , Colorectal Neoplasms , Humans , Cetuximab/pharmacology , Cetuximab/therapeutic use , Nanoparticle Drug Delivery System , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , Drug Resistance, Neoplasm , Mutation , Hydrogen-Ion Concentration
11.
Dalton Trans ; 53(4): 1735-1745, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38168804

ABSTRACT

The synthesis of highly efficient NiFe-layered double hydroxides (NiFe-LDHs) to catalyze the oxygen evolution reaction (OER) is urgent and challenging. Herein, NiFe-FeCl3-x and NiFe-FeCl2-x samples (where FeCl3 and FeCl2 represent the Fe sources and x represents the imposed reaction time: 6, 12, and 24 h) were prepared via one-pot hydrothermal synthesis using Fe sources characterized by Fe(III) or Fe(II) valence states. In the presence of triethanolamine, when FeCl3 was used as the Fe source, pure NiFe-LDH was obtained, whose crystallinity increased with increasing hydrothermal treatment time. In contrast, when FeCl2 was used as the Fe source, a mixture of NiFe-LDH, Fe2O3, and trace amounts of Fe3O4 was obtained. The content of NiFe-LDH in the mixture increased under longer hydrothermal treatment and NiFe-FeCl3-x catalysts exhibited better OER performance than NiFe-FeCl2-x catalysts. Specifically, NiFe-FeCl3-6 afforded the highest OER performance with an overpotential of 246.8 mV at 10 mA cm-2 and a Tafel slope of 46.1 mV dec-1. Herein, we investigated the effects of the valence state of Fe precursors on the structures and OER activities of the prepared catalysts; the mechanism of NiFe-LDH formation via hydrothermal synthesis in the presence of triethanolamine was also proposed.

12.
Int J Surg ; 109(12): 4221-4237, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37988410

ABSTRACT

Since the advent of conventional multiport laparoscopic surgery, the prosperity of minimally invasive surgery has been thriving on the advancement of endoscopic techniques. Cosmetic superiority, recovery benefits, and noninferior surgical outcomes weigh single-incision laparoscopic surgery as a promising modality. Although there are surgical challenges posed by steep learning curve and technological difficulties, such as instruments collision, triangulation loss and limited retraction, the establishment of robotic surgical platform as a solution to all is inspiring. Furthermore, with enhanced instrument maneuverability and stability, robotic ergonomic innovations adopt the advantages of single-incision laparoscopic surgery and surmount its recognized barriers by introducing a novel combination, single-incision robotic-assisted surgery. As was gradually diffused in general surgery and other specialties, single-incision robotic-assisted surgery manifests privileges in noninferior clinical outcomes an satisfactory cosmetic effect among strictly selected patients, and has the potential of a preferable surgical option for minimally invasive surgery.


Subject(s)
Laparoscopy , Robotic Surgical Procedures , Robotics , Surgical Wound , Humans , Robotic Surgical Procedures/methods , Laparoscopy/methods , Minimally Invasive Surgical Procedures
14.
Adv Sci (Weinh) ; 10(34): e2303091, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37863665

ABSTRACT

Erlotinib, an EGFR tyrosine kinase inhibitor, is used for treating patients with cancer exhibiting EGFR overexpression or mutation. However, the response rate of erlotinib is low among patients with gastric cancer (GC). The findings of this study illustrated that the overexpression of bromodomain PHD finger transcription factor (BPTF) is partially responsible for erlotinib resistance in GC, and the combination of the BPTF inhibitor AU-1 with erlotinib synergistically inhibited tumor growth both in vivo and in vitro. AU-1 inhibited the epigenetic function of BPTF and decreased the transcriptional activity of c-MYC on PLCG1 by attenuating chromosome accessibility of the PLCG1 promoter region, thus decreasing the expression of p-PLCG1 and p-Erk and eventually improving the sensitivity of GC cells to erlotinib. In patient-derived xenograft (PDX) models, AU-1 monotherapy exhibited remarkable tumor-inhibiting activity and is synergistic anti-tumor effects when combined with erlotinib. Altogether, the findings illustrate that BPTF affects the responsiveness of GC to erlotinib by epigenetically regulating the c-MYC/PLCG1/pErk axis, and the combination of BPTF inhibitors and erlotinib is a viable therapeutic approach for GC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Stomach Neoplasms , Humans , Erlotinib Hydrochloride/pharmacology , Erlotinib Hydrochloride/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , ErbB Receptors/genetics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor , Phospholipase C gamma/pharmacology
15.
EBioMedicine ; 89: 104451, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36738481

ABSTRACT

BACKGROUND: Vacuolar protein sorting-associated protein 35 (VPS35) is a core component of the retromer complex which mediates intracellular protein transport. It is well known that dysfunctional VPS35 functions in the accumulation of pathogenic proteins. In our previous study, VPS35 was found to be a potential gene related to poor prognosis in gastric cancer. However, the biological functions of VPS35 in gastric cancer remain unclear. METHODS: Cell viability assays were performed to examine whether VPS35 affected cell proliferation. Immunoprecipitation and biotin assays showed that VPS35 bound to epidermal growth factor receptor (EGFR) in the cytoplasm and recycled it to the cell surface. Patient-derived xenografts and organoids were used to evaluate the effect of VPS35 on the response of gastric cancer to EGFR inhibitors. FINDINGS: VPS35 expression levels were upregulated in tumour tissues and correlated with local tumour invasion and poor survival in patients with gastric cancer. VPS35 promoted cell proliferation and increased tumour growth. Mechanistically, VPS35 selectively bound to endocytosed EGFR in early endosomes and recycled it back to the cell surface, leading to the downstream activation of the ERK1/2 pathway. We also found that high VPS35 expression levels increased the sensitivity of the xenograft and organoid models to EGFR inhibitors. INTERPRETATION: VPS35 promotes cell proliferation by recycling EGFR to the cell surface, amplifying the network of receptor trafficking. VPS35 expression levels are positively correlated with gastric cancer sensitivity to EGFR inhibitors, which offers a potential method to stratify patients for EGFR inhibitor utilisation. FUNDING: National Natural Science Foundation of China.


Subject(s)
Stomach Neoplasms , Vesicular Transport Proteins , Humans , Carrier Proteins/metabolism , Cell Proliferation , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , ErbB Receptors/metabolism , Protein Transport/drug effects , Protein Transport/genetics , Stomach Neoplasms/genetics , Vesicular Transport Proteins/genetics , Vesicular Transport Proteins/metabolism
16.
ACS Appl Mater Interfaces ; 15(4): 5301-5308, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36662503

ABSTRACT

The utilization of thermoelectric devices that directly convert waste heat to electricity is an effective approach to alleviate the global energy crisis. However, the low efficiency of thermoelectric materials has puzzled the widespread applications. The CoSb3-based skutterudites are favored by device integration due to the excellent thermal stability, while the development of pristine CoSb3 materials is limited by the ultra-high thermal conductivity and the poor Seebeck coefficient. In this work, we demonstrate that both structural improvement and strong phonon interaction are realized simultaneously in In-filled CoSb3 coordinated with excessive Sb. The extra Sb compensates the deficiency on the Sb4 ring, improving the Seebeck coefficient, and cooperates with In to further advance the carrier concentration. Therefore, the structure optimization and chemical potential regulation maximize the electrical properties. Thermally, the residual InSb nanoparticles and partial In/Sb-alloying, along with vibration of In in voids, jointly shorten the multi-frequency phonon relaxation time, leading to a dramatic decline in the lattice thermal conductivity. As a result, a maximum zTmax of ∼1.27 at 650 K and an average zTavg of ∼0.9 from 300 to 750 K was obtained in In1.4Co4Sb12 + 8%Sb, respectively. Our findings provide valuable guidance for the selection of CoSb3-based skutterudite dopants to achieve high-performance thermoelectric materials.

17.
J Colloid Interface Sci ; 629(Pt B): 610-619, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36179580

ABSTRACT

Water electrolysis is a promising technique for producing high-quality hydrogen, the application of which is impeded by the sluggish oxygen evolution reaction (OER) process. In this study, ultrathin nickel-iron layered double hydroxide (NiFe LDH) nanosheets were successfully synthesized through a facile hydrothermal reaction with the assistance of triethanolamine (TEA). Morphological and structural characterizations revealed that the presence of TEA modified the morphology of NiFe LDH, facilitated the synthesis of high-purity NiFe LDH, improved the crystallinity of NiFe LDH and resulted in a slight decrease in specific surface area. X-ray photoelectron spectroscopy (XPS) analysis demonstrated the modulation of the electronic structure engendered by the addition of TEA, with nickel and iron appearing in high valence state in the resulting NiFe LDH nanosheets. The as-prepared NiFe LDH nanosheets possessed outstanding OER activity with fast kinetics, exhibiting a low overpotential of 261 mV to achieve a current density of 10 mA cm-2 and a small Tafel slope of 32.5 mV dec-1 in 1 M KOH. The excellent OER performance and rapid OER kinetics are mainly attributed to the high-valence Ni and Fe rather than the modification in the morphology and microstructure.

18.
Arthroscopy ; 39(6): 1515-1525, 2023 06.
Article in English | MEDLINE | ID: mdl-36577618

ABSTRACT

PURPOSE: To compare the postoperative outcomes of 4 different femoral drilling techniques in anterior cruciate ligament reconstruction. METHODS: Three databases were searched for randomized controlled trials comparing any 2 or more of the following femoral drilling techniques in anterior cruciate ligament reconstruction: standard transtibial (sTT), anteromedial portal (AMP), outside-in (OI), or modified transtibial (mTT) technique. A Bayesian network meta-analysis was performed to assess postoperative stability and functional recovery in terms of the side-to-side difference (measured by arthrometry), Lachman test, pivot-shift test, International Knee Documentation Committee subjective and objective scores, Lysholm score, and Tegner score. The Fisher exact probability test and χ2 test were used to compare the incidences of infection and graft rupture, respectively. RESULTS: We included 20 randomized controlled trials involving 1,515 patients. The AMP technique showed a lower side-to-side difference (standardized mean difference, -0.33; 95% credible interval [CrI], -0.53 to -0.12), higher negative rate on the pivot-shift test (odds ratio, 2.19; 95% CrI, 1.38 to 3.44), and higher International Knee Documentation Committee objective score (odds ratio, 3.13; 95% CrI, 1.42 to 7.82) than the sTT technique. However, knee stability and functional outcomes did not differ significantly between the OI and sTT techniques. Safety outcomes of the mTT technique were unavailable. The incidence of graft rupture was 5.20% for the OI technique, 2.27% for the AMP technique, and 1.51% for the sTT technique. The OI technique had a significantly higher incidence of graft rupture than the sTT technique (χ2 = 4.421, P = .035). No significant difference in the incidence of infection was found between the sTT, AMP, and OI techniques (P = .281). CONCLUSIONS: The AMP technique, but not the OI technique, was superior to the sTT technique in knee stability and functional recovery. The OI technique had a higher incidence of graft rupture than the sTT technique. There was no significant difference between the AMP and OI techniques or between the mTT technique and any other femoral drilling technique. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and II studies.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Humans , Anterior Cruciate Ligament/surgery , Bayes Theorem , Network Meta-Analysis , Anterior Cruciate Ligament Injuries/surgery , Knee Joint/surgery , Femur/surgery , Anterior Cruciate Ligament Reconstruction/methods , Treatment Outcome
19.
J Hazard Mater ; 443(Pt B): 130346, 2023 02 05.
Article in English | MEDLINE | ID: mdl-36444060

ABSTRACT

The present study applied the ozonation process to degrade 2,4-di-tert-butylphenol (2,4-DTBP), an emerging micropollutant detected in typical bamboo pulp and papermaking wastewater (BPPW). The effects of various influencing factors on the degradation performance and corresponding degradation mechanism were investigated. The results showed that ozone could degrade 2,4-DTBP rapidly with a reaction rate constant of (1.80 ± 0.05) × 105 M-1·s-1. The removal efficiency of 2,4-DTBP (5 mg/L) could reach 100% when the ozone dosage exceed 6 mg/L in a neutral medium. The presence of coexisting chemicals in BPPW such as Cl- and HCO3- promoted the removal performance of 2,4-DTBP. In contrast, NH4+ and humic acid presented inhibition on 2,4-DTBP removal. The ozonation of 2,4-DTBP was dominated by the ozone molecule, and this was primarily attributed to electrophilic substitution and 1,3-dipolar cycloaddition reactions. Twenty-seven kinds of intermediate products were identified by UPLC-Q-TOF/MS. The variations in their productions were based on the changes in ozone dosage. The degradation pathways were proposed. The toxicity of 2,4-DTBP was weakened after ozonation. As for the ozonation of actual biochemical effluent of BPPW, the desirable treatment performance was obtained. This study proved the feasibility of ozonation and provided data basis for subsequent pilot study.


Subject(s)
Ozone , Wastewater , Pilot Projects , Phenols
20.
Front Microbiol ; 13: 1035942, 2022.
Article in English | MEDLINE | ID: mdl-36274744

ABSTRACT

Ensiling has long been as a mainstream technology of preserving forage for ruminant production. This study investigated the effects of bioaugmented ensiling with laccase and Pediococcus pentosaceus on the fermentation quality, nutritive value, enzymatic hydrolysis, and bacterial community of alfalfa. The application of laccase and Pediococcus pentosaceus combination was more potent in modulating the fermentation quality of silage than laccase and Pediococcus pentosaceus alone, as indicated by higher lactic acid contents and lactic acid to acetic acid ratios, and lower pH, dry matter losses, and ammonia nitrogen contents. Moreover, treatments with additive enhanced protein preservation and structural carbohydrate degradation, while increasing true protein and water-soluble carbohydrate contents. By promoting lignin degradation, treatments containing laccase further facilitated the release of sugars from cellulose compared with treatment with Pediococcus pentosaceus alone. The additive treatments reduced the bacterial diversity and optimized the bacterial community composition of silage, with an increase in the relative abundance of desirable Lactobacillus and a decrease in the relative abundance of undesirable Enterobacter and Klebsiella. PICRUSt functional prediction based on Kyoto Encyclopedia of Genes and Genomes (KEGG) databases revealed that PL and LPL treatments increased the metabolism of membrane transport, carbohydrate, and terpenoids and polyketides related to fermentation activities. It can be concluded that bioaugmented ensiling with laccase and Pediococcus pentosaceus combination can be an effective and practical strategy to improve silage fermentation and nutrient preservation of alfalfa silage.

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