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1.
J Colloid Interface Sci ; 672: 12-20, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38824684

ABSTRACT

Photoelectrochemical (PEC) water splitting on semiconductor electrodes is considered to be one of the important ways to produce clean and sustainable hydrogen fuel, which is a great help in solving energy and environmental problems. Bismuth vanadate (BiVO4) as a promising photoanode for photoelectrochemical water splitting still suffers from poor charge separation efficiency and photo-induced self-corrosion. Herein, we develop heterojunction-rich photoanodes composed of BiVO4 and iron vanadate (FeVO4), coated with nickel iron oxide (NiFeOx/FeVO4/BiVO4). The formation of the interface between BiVO4 and FeVO4 (Bi-VO4-Fe bridges) enhances the interfacial interaction, resulting in improved performance. Meanwhile, high-conductivity FeVO4 and NiFeOx oxygen evolution co-catalysts effectively enhance bulk electron/hole separation, interface water's kinetics and photostability. Concurrently, the optimized NiFeOx/FeVO4/BiVO4 possesses a remarkable photocurrent density of 5.59 mA/cm2 at 1.23 V versus reversible hydrogen electrode (vs RHE) under AM 1.5G (Air Mass 1.5 Global) simulated sunlight, accompanied by superior stability without any decreased of its photocurrent density after 14 h. This work not only reveals the crucial role of built-in electric field in BiVO4-based photoanode during PEC water splitting, but also provides a new guide to the design of efficient photoanode for PEC.

2.
Chemphyschem ; : e202400053, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38706399

ABSTRACT

The study of fluid absorption, particularly that of water, into nanoporous materials has garnered increasing attention in the last decades across a broad range of disciplines. However, most investigation approaches to probe such behaviors are limited by characterization conditions. In this study, a combined MRI and MAS NMR method was used to study a nanoporous silica glass to acquire information about its structural framework and interactions with confined water. Specifically, MRI was used for a quantitative analysis of water extent. While MAS NMR techniques provided structural information of silicate materials, including interactive surface area and framework packing. Analysis of water spin-spin relaxation times (T2) suggested differences in water confinement within the characterized framework. Subsequent unsuccessful delivery of paramagnetic molecule into the pores enabled a quantitative assessment of the dimensions that "bottleneck" the pores. Finally, pore sizes were derived from the molecular size, density function theory (DFT) simulation and characterizations on standard samples. Our result matches with Brunauer-Emmett-Teller (BET) analysis.. The use of a paramagnetic probe for pore size determination introduces a new approach of characterization in the liquid phase, offering an alternative to the conventional BET analysis that uses gas molecule as probes.

3.
Anal Chem ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816678

ABSTRACT

The PD-L1 protein on extracellular vesicles (EVs) is a promising biomarker for tumor immunotherapy. However, PD-L1+ EVs have various cell origins, so further analysis of the subpopulations is essential to help understand better their relationship with tumor immunotherapy. Different from the previous work which focus on the level of total PD-L1+ EVs expression, we, herein, report a dual-recognition mediated autocatalytic amplification (DRMAA) assay to detect the PD-L1 derived from tumors (EpCAM+), immune T cells (CD3+), and total (Lipids) EVs, respectively. The DRMAA assay employed proximity hybridization to construct a complete trigger sequence and then catalyzed the cross-hybridization of three hairpin probes, producing a three-way DNA junction (3-WJ) structure carrying the newly exposed trigger sequence. The 3-WJ complex subsequently initiated an autocatalytic amplification reaction and higher sensitivity than the traditional catalytic hairpin assembly assay was obtained. It was found that the EpCAM+ and PD-L1+ EVs were more effective than others in distinguishing lung cancer patients from healthy people. Surprisingly, the CD3+ and PD-L1+ EVs in lung cancer patients were also upregulated, indicating that immune cell-derived PD-L1+ EVs are also non-negligible marker in a tumor microenvironment. Our results suggested that the DRMAA assay would improve the study of subpopulations of PD-L1+ EVs to provide new insights for cancer immunotherapies.

4.
ACS Appl Mater Interfaces ; 16(20): 26217-26225, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38733352

ABSTRACT

Among various anode materials, SiOx is regarded as the next generation of promising anode due to its advantages of high theoretical capacity with 2680 mA h g-1, low lithium voltage platform, and rich natural resources. However, the pure SiOx-based materials have slow lithium storage kinetics attributed to their low electron/ion conductive properties and the large volume change during lithiation/delithiation, restricting their practical application. Optimizing the SiOx material structures and the fabricating methods to mitigate these fatal defects and adapt to the market demand for energy density is critical. Hence, SiOx material with TiO1-xNx phase modification has been prepared by simple, low-cost, and scalable ball milling and then combined with nitridation. Consequently, based on the TiO1-xNx modified layer, which boosts high ionic/electronic conductivity, chemical stability, and excellent mechanical properties, the SiOx@TON-10 electrode shows highly stable lithium-ion storage performance for lithium-ion half/full batteries due to a stable solid-electrolyte interface layer, fast Li+ transport channel, and alleviative volumetric expansion, further verifying its practical feasibility and universal applicability.

5.
Updates Surg ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38568357

ABSTRACT

PURPOSE: To compare the surgical safety and postoperative quality of life (QOL) between side overlap anastomosis (SOA) and double-tract anastomosis (DTA) after laparoscopic proximal gastrectomy (LPG). METHODS: This retrospective cohort study included 43 patients with proximal gastric cancer (PGC) who underwent LPG and were admitted to the Second Affiliated Hospital of Fujian Medical University between August 2020 and December 2022 were in. Their clinical and follow-up data were collected. The patients were divided into the modified SOA (mSOA) (n = 20) and DTA (n = 23) groups based on the anastomosis methods used. The main outcome measures included the QOL of patients 1 year after surgery, and the evaluation criteria were based on the postgastrectomy syndrome assessment scale. Secondary outcome measures included intraoperative and postoperative conditions, postoperative long-term complications and nutritional status 3, 6 and 12 months after surgery. RESULTS: No significant differences were observed in intraoperative and postoperative conditions (P > 0.05) between the mSOA and DTA groups. The mSOA group showed a decreased incidence of reflux esophagitis 1 year after surgery compared with the DTA group (P < 0.05), and no statistically significant differences were noticed between the two groups in terms of other postoperative complications (P > 0.05). The mSOA group showed better QOL when compared with the DTA group (P < 0.05). No significant differences were recorded in postoperative nutritional status between the two groups (P > 0.05). CONCLUSION: The efficacy and safety of LPG with mSOA for PGC were comparable. When compared with the DTA group, the mSOA group seems to show reduced incidence of gastroesophageal reflux and improved QOL, which makes mSOA one of the ideal surgical methods for PGC.

6.
BMC Genomics ; 25(1): 354, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594645

ABSTRACT

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.


Subject(s)
Actinidia , Homeodomain Proteins , Homeodomain Proteins/genetics , Genome, Plant , Phylogeny , Actinidia/genetics , Leucine Zippers/genetics , Gene Expression Regulation, Plant , Plant Proteins/genetics , Gene Expression Profiling
7.
BMC Genomics ; 25(1): 356, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38600443

ABSTRACT

BACKGROUND: Centromeres play a crucial and conserved role in cell division, although their composition and evolutionary history in green algae, the evolutionary ancestors of land plants, remains largely unknown. RESULTS: We constructed near telomere-to-telomere (T2T) assemblies for two Trebouxiophyceae species, Chlorella sorokiniana NS4-2 and Chlorella pyrenoidosa DBH, with chromosome numbers of 12 and 13, and genome sizes of 58.11 Mb and 53.41 Mb, respectively. We identified and validated their centromere sequences using CENH3 ChIP-seq and found that, similar to humans and higher plants, the centromeric CENH3 signals of green algae display a pattern of hypomethylation. Interestingly, the centromeres of both species largely comprised transposable elements, although they differed significantly in their composition. Species within the Chlorella genus display a more diverse centromere composition, with major constituents including members of the LTR/Copia, LINE/L1, and LINE/RTEX families. This is in contrast to green algae including Chlamydomonas reinhardtii, Coccomyxa subellipsoidea, and Chromochloris zofingiensis, in which centromere composition instead has a pronounced single-element composition. Moreover, we observed significant differences in the composition and structure of centromeres among chromosomes with strong collinearity within the Chlorella genus, suggesting that centromeric sequence evolves more rapidly than sequence in non-centromeric regions. CONCLUSIONS: This study not only provides high-quality genome data for comparative genomics of green algae but gives insight into the composition and evolutionary history of centromeres in early plants, laying an important foundation for further research on their evolution.


Subject(s)
Chlorella , Humans , Chlorella/genetics , Centromere/genetics , Plants/genetics , DNA Transposable Elements , Telomere/genetics
8.
Adv Healthc Mater ; : e2304648, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38597827

ABSTRACT

Drug-resistant and metastatic cancer cells such as a small population of cancer stem cells (CSCs) play a crucial role in metastasis and relapse. Conventional small-molecule chemotherapeutics, however, are unable to eradicate drug-resistant CSCs owing to limited interface inhibitory effects. Herein, it is reported that enhanced interfacial inhibition leading to eradication of drug-resistant CSCs can be dramatically induced by self-insertion of bioactive graphene quantum dots (GQDs) into DNA major groove (MAG) sites in cancer cells. Since transcription factors regulate gene expression at the MAG site, MAG-targeted GQDs exert greatly enhanced interfacial inhibition, downregulating the expression of a collection of cancer stem genes such as ALDH1, Notch1, and Bmi1. Moreover, the nanoscale interface inhibition mechanism reverses cancer multidrug resistance (MDR) by inhibiting MDR1 gene expression when GQDs are used at a nontoxic concentration (1/4 × half-maximal inhibitory concentration (IC50)) as the MDR reverser. Given their high efficacy in interfacial inhibition, CSC-mediated migration, invasion, and metastasis of cancer cells can be substantially blocked by MAG-targeted GQDs, which can also be harnessed to sensitize clinical cytotoxic agents for improved efficacy in combination chemotherapy. These findings elucidate the inhibitory effects of the enhanced nano-bio interface at the MAG site on eradicating CSCs, thus preventing cancer metastasis and recurrence.

9.
World J Gastrointest Oncol ; 16(3): 819-832, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38577440

ABSTRACT

BACKGROUND: The study on predicting the differentiation grade of colorectal cancer (CRC) based on magnetic resonance imaging (MRI) has not been reported yet. Developing a non-invasive model to predict the differentiation grade of CRC is of great value. AIM: To develop and validate machine learning-based models for predicting the differentiation grade of CRC based on T2-weighted images (T2WI). METHODS: We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023. Patients were randomly assigned to a training cohort (n = 220) or a validation cohort (n = 95) at a 7:3 ratio. Lesions were delineated layer by layer on high-resolution T2WI. Least absolute shrinkage and selection operator regression was applied to screen for radiomic features. Radiomics and clinical models were constructed using the multilayer perceptron (MLP) algorithm. These radiomic features and clinically relevant variables (selected based on a significance level of P < 0.05 in the training set) were used to construct radiomics-clinical models. The performance of the three models (clinical, radiomic, and radiomic-clinical model) were evaluated using the area under the curve (AUC), calibration curve and decision curve analysis (DCA). RESULTS: After feature selection, eight radiomic features were retained from the initial 1781 features to construct the radiomic model. Eight different classifiers, including logistic regression, support vector machine, k-nearest neighbours, random forest, extreme trees, extreme gradient boosting, light gradient boosting machine, and MLP, were used to construct the model, with MLP demonstrating the best diagnostic performance. The AUC of the radiomic-clinical model was 0.862 (95%CI: 0.796-0.927) in the training cohort and 0.761 (95%CI: 0.635-0.887) in the validation cohort. The AUC for the radiomic model was 0.796 (95%CI: 0.723-0.869) in the training cohort and 0.735 (95%CI: 0.604-0.866) in the validation cohort. The clinical model achieved an AUC of 0.751 (95%CI: 0.661-0.842) in the training cohort and 0.676 (95%CI: 0.525-0.827) in the validation cohort. All three models demonstrated good accuracy. In the training cohort, the AUC of the radiomic-clinical model was significantly greater than that of the clinical model (P = 0.005) and the radiomic model (P = 0.016). DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process. CONCLUSION: In this study, we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC. This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.

10.
Genome Biol ; 25(1): 107, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38671502

ABSTRACT

Long-read sequencing data, particularly those derived from the Oxford Nanopore sequencing platform, tend to exhibit high error rates. Here, we present NextDenovo, an efficient error correction and assembly tool for noisy long reads, which achieves a high level of accuracy in genome assembly. We apply NextDenovo to assemble 35 diverse human genomes from around the world using Nanopore long-read data. These genomes allow us to identify the landscape of segmental duplication and gene copy number variation in modern human populations. The use of NextDenovo should pave the way for population-scale long-read assembly using Nanopore long-read data.


Subject(s)
DNA Copy Number Variations , Genome, Human , Humans , High-Throughput Nucleotide Sequencing/methods , Software , Nanopore Sequencing/methods , Sequence Analysis, DNA/methods , Genomics/methods
11.
Acta Biomater ; 180: 323-336, 2024 May.
Article in English | MEDLINE | ID: mdl-38561075

ABSTRACT

Peripheral nerve injuries (PNIs) can cause neuropathies and significantly affect the patient's quality of life. Autograft transplantation is the gold standard for conventional treatment; however, its application is limited by nerve unavailability, size mismatch, and local tissue adhesion. Tissue engineering, such as nerve guidance conduits, is an alternative and promising strategy to guide nerve regeneration for peripheral nerve repair; however, only a few conduits could reach the high repair efficiency of autografts. The healing process of PNI is frequently accompanied by not only axonal and myelination regeneration but also angiogenesis, which initializes nerve regeneration through vascular endothelial growth factor A (VEGF-A). In this study, a composite nerve conduit with a poly (lactic-co-glycolic acid) (PLGA) hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with VEGF-A transfected Schwann cells (SCs) as the inner layer was established to evaluate its promising ability for peripheral nerve repair. A rat model of peripheral nerve defect was used to examine the efficiency of PLGA/GelMA-SC (VA) conduits, whereas autograft, PLGA, PLGA/GelMA, and PLGA/GelMA-SC (NC) were used as controls. VEGF-A-transfected SCs can provide a stable source for VEGF-A secretion. Furthermore, encapsulation in GelMA cannot only promote proliferation and tube formation of human umbilical vein endothelial cells but also enhance dorsal root ganglia and neuronal cell extension. Previous animal studies have demonstrated that the regenerative effects of PLGA/GelMA-SC (VA) nerve conduit were similar to those of autografts and much better than those of other conduits. These findings indicate that combination of VEGF-A-overexpressing SCs and PLGA/GelMA conduit-guided peripheral nerve repair provides a promising method that enhances angiogenesis and regeneration during nerve repair. STATEMENT OF SIGNIFICANCE: Nerve guidance conduits shows promise for peripheral nerve repair, while achieving the repair efficiency of autografts remains a challenge. In this study, a composite nerve conduit with a PLGA hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with vascular endothelial growth factor A (VEGF-A)-transfected Schwann cells (SCs) as the inner layer was established to evaluate its potential ability for peripheral nerve repair. This approach preserves growth factor bioactivity and enhances material properties. GelMA insertion promotes Schwann cell proliferation and morphology extension. Moreover, transfected SCs serve as a stable VEGF-A source and fostering angiogenesis. This study offers a method preserving growth factor efficacy and safeguarding SCs, providing a comprehensive solution for enhanced angiogenesis and nerve regeneration.


Subject(s)
Neovascularization, Physiologic , Nerve Regeneration , Polylactic Acid-Polyglycolic Acid Copolymer , Rats, Sprague-Dawley , Schwann Cells , Vascular Endothelial Growth Factor A , Schwann Cells/metabolism , Schwann Cells/cytology , Animals , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/pharmacology , Nerve Regeneration/drug effects , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Neovascularization, Physiologic/drug effects , Rats , Transfection , Gelatin/chemistry , Male , Tissue Scaffolds/chemistry , Humans , Peripheral Nerve Injuries/therapy , Peripheral Nerve Injuries/pathology , Angiogenesis
12.
ACS Biomater Sci Eng ; 10(5): 3136-3147, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38663028

ABSTRACT

Treatment with immune checkpoint inhibitors (ICIs) has shown efficacy in some patients with Lynch syndrome-associated colon cancer, but some patients still do not benefit from it. In this study, we adopted a combination strategy of tumor vaccines and ICIs to maximize the benefits of immunotherapy. Here, we obtained tumor-antigen-containing cell lysate (TCL) by lysing MC38Mlh1 KD cells and prepared liposome nanoparticles (Lipo-PEG) with a typical spherical morphology by thin-film hydration. Anti-PD-L1 was coupled to the liposome surface by the amidation reaction. As observed, anti-PD-L1/TCL@Lipo-PEG was not significantly toxic to mouse intestinal epithelial cells (MODE-K) in the safe concentration range and did not cause hemolysis of mouse red blood cells. In addition, anti-PD-L1/TCL@Lipo-PEG reduced immune escape from colon cancer cells (MC38Mlh1 KD) by the anti-PD-L1 antibody, restored the killing function of CD8+ T cells, and targeted more tumor antigens to bone marrow-derived dendritic cells (BMDCs), which also expressed PD-L1, to stimulate BMDC antigen presentation. In syngeneic transplanted Lynch syndrome-associated colon cancer mice, the combination of anti-PD-L1 and TCL provided better cancer suppression than monoimmunotherapy, and the cancer suppression effect of anti-PD-L1/TCL@Lipo-PEG treatment was even better than that of the free drug. Meanwhile anti-PD-L1/TCL@Lipo-PEG enhanced the immunosuppressive tumor microenvironment. In vivo fluorescence imaging and H&E staining showed that the nanomedicine was mainly retained in the tumor site and had no significant toxic side effects on other major organs. The anti-PD-L1/TCL@Lipo-PEG prepared in this study has high efficacy and good biosafety in alleviating the progression of Lynch syndrome-associated colon cancer, and it is expected to be a therapeutic candidate for Lynch syndrome-associated colon cancer.


Subject(s)
B7-H1 Antigen , Colonic Neoplasms , Colorectal Neoplasms, Hereditary Nonpolyposis , Liposomes , Animals , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , Colonic Neoplasms/pathology , Colonic Neoplasms/drug therapy , Mice , B7-H1 Antigen/metabolism , Nanomedicine , Cell Line, Tumor , Cancer Vaccines/therapeutic use , Cancer Vaccines/immunology , Humans , Mice, Inbred C57BL , Female , Dendritic Cells/immunology , Dendritic Cells/drug effects , Dendritic Cells/metabolism , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Disease Progression , Polyethylene Glycols/chemistry , Polyethylene Glycols/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Antigens, Neoplasm/immunology
13.
Nat Biotechnol ; 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38519720

ABSTRACT

Long-read-based de novo and somatic structural variant (SV) discovery remains challenging, necessitating genomic comparison between samples. We developed SVision-pro, a neural-network-based instance segmentation framework that represents genome-to-genome-level sequencing differences visually and discovers SV comparatively between genomes without any prerequisite for inference models. SVision-pro outperforms state-of-the-art approaches, in particular, the resolving of complex SVs is improved, with low Mendelian error rates, high sensitivity of low-frequency SVs and reduced false-positive rates compared with SV merging approaches.

14.
J Hazard Mater ; 469: 133990, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38460261

ABSTRACT

Heavy metal migration in soil poses a serious threat to the soil and groundwater. Understanding the migration pattern of heavy metals (HMs) under different factors could provide a more reasonable position for pollution evaluation and targetoriented treatment of soil heavy metal. In this study, the migration behavior of Pb and Cd in co-contaminated soil under different pH and ionic strength (NaCl concentration) was simulated using convective dispersion equation (CDE). We predicted the migration trends of Pb and Cd in soils after 5, 10, and 20 years via PHREEQC. The results showed that the migration time of Cd in the soil column experiment was about 60 days faster than that of Pb, and the migration trend was much steeper. The CDE was proved to describe the migration behavior of Pb and Cd (R2 > 0.75) in soil. The predicted results showed that Cd migrated to 15-20 cm of soil within 7 years and Pb stayed mainly in the top 0-6 cm of soil within 5 years as the duration of irrigation increased. Overall, our study is expected to provide new insight into the migration of heavy metal in soil ecosystems and guidance for reducing risk of heavy metal in the environment.

15.
J Hepatol ; 80(6): 928-940, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38336346

ABSTRACT

BACKGROUND & AIMS: Men are more prone to develop and die from liver fibrosis than women. In this study, we aim to investigate how sex-determining region Y gene (SRY) in hepatocytes promotes liver fibrosis. METHODS: Hepatocyte-specific Sry knock-in (KI), Sry knockout (KO), and Sry KI with platelet-derived growth factor receptor α (Pdgfrα) KO mice were generated. Liver fibrosis was induced in mice by bile duct ligation for 2 weeks or carbon tetrachloride treatment for 6 weeks. In addition, primary hepatocytes, hepatic stellate cells (HSCs), and immortalized cell lines were used for in vitro studies and mechanistic investigation. RESULTS: Compared to females, the severity of toxin- or cholestasis-induced liver fibrosis is similarly increased in castrated and uncastrated male mice. Among all Y chromosome-encoded genes, SRY was the most significantly upregulated and consistently increased gene in fibrotic/cirrhotic livers in male patients and in mouse models. Sry KI mice developed exacerbated liver fibrosis, whereas Sry KO mice had alleviated liver fibrosis, compared to age- and sex-matched control mice after bile duct ligation or administration of carbon tetrachloride. Mechanistically, both our in vivo and in vitro studies illustrated that SRY in hepatocytes can transcriptionally regulate Pdgfrα expression, and promote HMGB1 (high mobility group box 1) release and subsequent HSC activation. Pdgfrα KO or treatment with the SRY inhibitor DAX1 in Sry KI mice abolished SRY-induced HMGB1 secretion and liver fibrosis. CONCLUSIONS: SRY is a strong pro-fibrotic factor and accounts for the sex disparity observed in liver fibrosis, suggesting its critical role as a potentially sex-specific therapeutic target for prevention and treatment of the disease. IMPACT AND IMPLICATION: We identified that a male-specific gene, sex-determining region Y gene (SRY), is a strong pro-fibrotic gene that accounts for the sex disparity observed in liver fibrosis. As such, SRY might be an appropriate target for surveillance and treatment of liver fibrosis in a sex-specific manner. Additionally, SRY might be a key player in the sexual dimorphism observed in hepatic pathophysiology more generally.


Subject(s)
Hepatic Stellate Cells , Hepatocytes , Liver Cirrhosis , Mice, Knockout , Sex-Determining Region Y Protein , Animals , Male , Female , Mice , Liver Cirrhosis/genetics , Liver Cirrhosis/metabolism , Liver Cirrhosis/physiopathology , Humans , Hepatocytes/metabolism , Sex-Determining Region Y Protein/genetics , Sex-Determining Region Y Protein/metabolism , Hepatic Stellate Cells/metabolism , Sex Characteristics , Receptor, Platelet-Derived Growth Factor alpha/genetics , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Carbon Tetrachloride/toxicity , Carbon Tetrachloride/adverse effects , Cholestasis/genetics , Cholestasis/metabolism , Cholestasis/physiopathology , Disease Models, Animal
16.
Cancer Med ; 13(3): e7006, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38400680

ABSTRACT

PURPOSE: In the present study, we aimed to evaluate the efficacy and safety of camrelizumab combined with oxaliplatin plus S-1 in patients with resectable gastric or gastroesophageal junction cancer. METHODS: In this single-arm, phase II clinical trial, patients with locally advanced gastric or gastroesophageal junction adenocarcinoma were enrolled to receive three cycles of neoadjuvant camrelizumab and oxaliplatin plus S-1 every 3 weeks, followed by surgical resection and adjuvant therapy with the same regimen. The primary endpoint was pathological complete response (pCR) (ypT0) rate and secondary endpoints were R0 resection rate, total pCR (tpCR, ypT0N0) rate, major pathological response (MPR) rate, downstaging, objective response rate (ORR), disease control rate (DCR), event-free survival (EFS), overall survival (OS), and safety. RESULTS: Between September, 2020 and January, 2022, a total of 29 patients were enrolled in the present study, all of whom completed neoadjuvant therapy and underwent surgery. Three (10.3%) (95% CI: 2.2-27.4) patients achieved pCR as well as tpCR, 20 (69.0%) patients had MPR and 28 (96.6%) patients achieved R0 resection. Treatment-emergent adverse events (AEs) of any grade were observed in 24 (82.8%) patients. Immune-related adverse events of any grade were reported in 13 (44.8%) patients, whereas no grade 3 or higher adverse events occurred. CONCLUSION: The neoadjuvant therapy with camrelizumab in combination with oxaliplatin and S-1 showed a modest pCR rate, and favorable MPR rate and safety profile in patients with gastric or gastroesophageal junction cancer.


Subject(s)
Antibodies, Monoclonal, Humanized , Neoadjuvant Therapy , Stomach Neoplasms , Humans , Oxaliplatin , Esophagogastric Junction , Stomach Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects
17.
World J Gastrointest Surg ; 16(1): 113-123, 2024 Jan 27.
Article in English | MEDLINE | ID: mdl-38328314

ABSTRACT

BACKGROUND: With the increasing incidence of proximal gastric cancer, laparoscopic proximal gastrectomy has been applied. However, reflux esophagitis often occurs after traditional esophagogastric anastomosis. In order to solve this problem, several methods of digestive tract reconstruction have emerged, but the most satisfying method remains to be discussed. Therefore, we modified traditional Kamikawa anastomosis to investigate the appropriate digestive tract reconstruction in laparoscopic proximal gastrectomy. AIM: To discuss the clinical efficacy of modified Kamikawa anastomosis in laparoscopic proximal gastrectomy. METHODS: A retrospective case series was adopted. Clinicopathological data were collected from 26 patients who underwent laparoscopic proximal gastrectomy and modified Kamikawa anastomosis at our hospital from January 2020 to September 2022. The operation conditions, postoperative recovery, postoperative complications, and follow-up data were collected and analyzed. RESULTS: All the patients were successfully operated on without conversion to laparotomy. The duration of operation and digestive tract reconstruction were 203.500 (150-224) min and 87.500 (73-111) min, respectively. The intraoperative amount of bleeding was 20.500 mL ± 0.696 mL. The time of postoperative first flatus, the first postoperative fluid intake, and the postoperative length of stay were 2 (1-3) d, 4 (3-5) d, and 9 (8-10) d, respectively. All the patients were followed up for 12-23 months. The body mass index at 6 and 12 months after surgery were 22.577 kg/m2 ± 3.098 kg/m2 and 22.594 kg/m2 ± 3.207 kg/m2, respectively. The nutrition risk screening 2002 score, the patient-generated subjective global assessment score, and the gastroesophageal reflux disease scale score were good at 6 and 12 months after surgery. Reflux esophagitis and anastomotic stenosis were not observed in any of the patients during their 12-month postoperative gastroscopy or upper gastrointestinal tract visits. All the patients exhibited no tumor recurrence or metastasis. CONCLUSION: The modified Kamikawa anastomosis is safe and feasible for laparoscopic proximal gastrectomy and has good antireflux effects and nutritional status.

18.
Updates Surg ; 76(2): 513-520, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38245891

ABSTRACT

According to past and current literature, metastasis of the lymph nodes at the inferior mesenteric artery (IMA-LN), also known as 253LN of colorectal cancer has been seldom investigated. To date, there are still controversies on whether the 253LN need to be routinely cleaned. Using specific criteria, 347 patients who underwent radical resection for rectal cancer between April 2019 and July 2022 were selected for the study. Logistic regression was used to determine the likelihood that a patient may suffer 253LN metastasis, and a nomogram for 253LN metastasis subsequently developed. The c-index and calibration curve were used to evaluate precision and discrimination in the nomogram, and the appropriateness of the final nomogram for the clinical setting determined using decision curve analysis (DCA). 253LN metastases appeared in the pathological specimens of 29 (8.4%) of the selected patients. Logistic regression showed that preoperative parameters including serum carcinoembryonic antigen (CEA) value ( > 5 ng / ml, OR = 2.894, P = 0.023), distance from anal margin (> 9 cm, OR = 2.406, P = 0.045) and degree of differentiation (poor, OR = 9.712, P < 0.001) were significantly associated with 253LN metastasis. A nomogram to predict 253LN metastasis in rectal cancer was developed and showed considerable discrimination and good precision (c-index = 0.750). Furthermore, DCA confirmed that the nomogram has some feasibility for the clinical environment. Clinicopathological and radiological patient data can be pivotal for making surgical decisions relating to 253LN metastasis. A nomogram was developed using this data, providing an objective method that can significantly improve prognoses in colorectal cancer.


Subject(s)
Nomograms , Rectal Neoplasms , Humans , Retrospective Studies , Case-Control Studies , Mesenteric Artery, Inferior/surgery , Mesenteric Artery, Inferior/pathology , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Lymph Nodes/pathology , Lymphatic Metastasis/pathology
19.
Nat Commun ; 15(1): 41, 2024 01 02.
Article in English | MEDLINE | ID: mdl-38167806

ABSTRACT

Prospective evidence regarding the combination of programmed cell death (PD)-1 and angiogenesis inhibitors in treating locally advanced gastric cancer (LAGC) is limited. In this multicenter, randomized, phase 2 trial (NCT04195828), patients with gastric adenocarcinoma (clinical T2-4N + M0) were randomly assigned (1:1) to receive neoadjuvant camrelizumab and apatinib combined with nab-paclitaxel plus S-1 (CA-SAP) or chemotherapy SAP alone (SAP) for 3 cycles. The primary endpoint was the major pathological response (MPR), defined as <10% residual tumor cells in resection specimens. Secondary endpoints included R0 resection rate, radiologic response, safety, overall survival, and progression-free survival. The modified intention-to-treat population was analyzed (CA-SAP [n = 51] versus SAP [n = 53]). The trial has met pre-specified endpoints. CA-SAP was associated with a significantly higher MPR rate (33.3%) than SAP (17.0%, P = 0.044). The CA-SAP group had a significantly higher objective response rate (66.0% versus 43.4%, P = 0.017) and R0 resection rate (94.1% versus 81.1%, P = 0.042) than the SAP group. Nonsurgical grade 3-4 adverse events were observed in 17 patients (33.3%) in the CA-SAP group and 14 (26.4%) in the SAP group. Survival results were not reported due to immature data. Camrelizumab and apatinib combined with chemotherapy as a neoadjuvant regimen was tolerable and associated with favorable responses for LAGC.


Subject(s)
Neoplasms, Second Primary , Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Neoadjuvant Therapy , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
20.
Quant Imaging Med Surg ; 14(1): 579-591, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38223078

ABSTRACT

Background: Pneumonia can be anatomically classified into lobar, lobular, and interstitial types, with each type associated with different pathogens. Utilizing artificial intelligence (AI) to determine the anatomical classifications of pneumonia and assist in refining the differential diagnosis may offer a more viable and clinically relevant solution. This study aimed to develop a multi-classification model capable of identifying the occurrence of pneumonia in patients by utilizing case-specific computed tomography (CT) information, categorizing the pneumonia type (lobar, lobular, and interstitial pneumonia), and performing segmentation of the associated lesions. Methods: A total of 61 lobar pneumonia patients, 60 lobular pneumonia patients, and 60 interstitial pneumonia patients were consecutively enrolled at our local hospital from June 2020 and May 2022. All selected cases were divided into a training cohort (n=135) and an independent testing cohort (n=46). To generate the ground truth labels for the training process, manual segmentation and labeling were performed by three junior radiologists. Subsequently, the segmentations were manually reviewed and edited by a senior radiologist. AI models were developed to automatically segment the infected lung regions and classify the pneumonia. The accuracy of pneumonia lesion segmentation was analyzed and evaluated using the Dice coefficient. Receiver operating characteristic curves were plotted, and the area under the curve (AUC), accuracy, precision, sensitivity, and specificity were calculated to assess the efficacy of pneumonia classification. Results: Our AI model achieved a Dice coefficient of 0.743 [95% confidence interval (CI): 0.657-0.826] for lesion segmentation in the training set and 0.723 (95% CI: 0.602-0.845) in the test set. In the test set, our model achieved an accuracy of 0.927 (95% CI: 0.876-0.978), precision of 0.889 (95% CI: 0.827-0.951), sensitivity of 0.889 (95% CI: 0.827-0.951), specificity of 0.946 (95% CI: 0.902-0.990), and AUC of 0.989 (95% CI: 0.969-1.000) for pneumonia classification. We trained the model using labels annotated by senior physicians and compared it to a model trained using labels annotated by junior physicians. The Dice coefficient of the model's segmentation improved by 0.014, increasing from 0.709 (95% CI: 0.589-0.830) to 0.723 (95% CI: 0.602-0.845), and the AUC improved by 0.042, rising from 0.947 to 0.989. Conclusions: Our study presents a robust multi-task learning model with substantial promise in enhancing the segmentation and classification of pneumonia in medical imaging.

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