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Mangrove wetlands are highly productive ecosystems in tropical and subtropical coastal zones, play crucial roles in water purification, biodiversity maintenance, and carbon sequestration. Recent years have seen the implementation of pond return initiatives, which have facilitated the gradual recovery of mangrove areas in China. However, the implications of these initiatives for soil aggregate stability, microbial community structure, and network interactions remain unclear. This study assesses the impacts of converting ponds to mangroves-both in natural and artificially restored settings-on soil aggregate stability and microbial networks at typical mangrove restoration sites along China's southeastern coast. Our observations confirmed our hypothesis that pond-to-mangrove conversions resulted in an increase in the proportion of large aggregates (>0.25 mm), improved soil aggregate structural stability, and increased carbon sequestration. However, mangrove recovery led to a decrease in the abundance and diversity of soil fungi communities. In terms of co-occurrence networks, naturally restored mangrove wetlands exhibited more nodes and edges. The naturally recovered mangrove wetlands demonstrated a higher level of community symbiosis compared to those that were manually restored. Conversely, bacterial networks showed a different pattern, with significant shifts in key taxa related to carbon sequestration functions. For instance, the proportion of bacterial Desulfobacterota and fungi Basidiomycota in natural recovery mangrove increased by 15.03 % and 7.82 %, respectively, compared with that in aquaculture ponds. Soil fungi and bacteria communities, as well as carbon sequestration by aggregates, were all positively correlated with soil total carbon content (P < 0.05). Both bacterial and fungal communities contributed to soil aggregate stability. Our study highlights the complex relationships between soil microbial communities, aggregate stability, and the carbon cycle before and after land-use changes. These findings underscore the potential benefits of restoring mangrove wetlands, as such efforts can enhance carbon storage capacity and significantly contribute to climate change mitigation.
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Swin Transformer is an important work among all the attempts to reduce the computational complexity of Transformers while maintaining its excellent performance in computer vision. Window-based patch self-attention can use the local connectivity of the image features, and the shifted window-based patch self-attention enables the communication of information between different patches in the entire image scope. Through in-depth research on the effects of different sizes of shifted windows on the patch information communication efficiency, this article proposes a Dual-Scale Transformer with double-sized shifted window attention method. The proposed method surpasses CNN-based methods such as U-Net, AttenU-Net, ResU-Net, CE-Net by a considerable margin (Approximately 3% â¼ 6% increase), and outperforms the Transformer based models single-scale Swin Transformer(SwinT)(Approximately 1% increase), on the datasets of the Kvasir-SEG, ISIC2017, MICCAI EndoVisSub-Instrument and CadVesSet. The experimental results verify that the proposed dual scale shifted window attention benefits the communication of patch information and can enhance the segmentation results to state of the art. We also implement an ablation study on the effect of the shifted window size on the information flow efficiency and verify that the dual-scale shifted window attention is the optimized network design. Our study highlights the significant impact of network structure design on visual performance, providing valuable insights for the design of networks based on Transformer architectures.
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Among refractive errors, astigmatism is the most common optical aberration, where refraction changes in different meridians of the eye. It causes blurred vision at any distance and includes corneal, lenticular, and retinal astigmatism. Cataract surgery used to cause a progressive increase in the pre-exisiting corneal astigmatism because of creating a surgically induced astigmatism, for example, a large size surgery incision. The development of surgical techniques during last decades has made cataract surgery interchange to treat preoperative corneal astigmatism at time of surgery. Nowadays, three surgical approaches can be used. By placing a sutureless clear corneal incision on the steep meridian of the cornea, a preoperative corneal astigmatism less than 1.0 D can be corrected. Single or paired peripheral corneal relaxing incisions (PCRIs) provide 1.0-3.0 D corneal astigmatism correction. PCRIs are typically used for treating 1.0-1.5 D of regular corneal astigmatism, if more than 2.0 D, the risk of overcorrection and irregular astigmatism is increased. When toric intraocular lenses (IOLs) are unavailable in markets, PCRIs are still a reasonable option for patients with up to 3.0 D of pre-existing corneal astigmatism. Toric IOLs implantation can correct 1.0-4.5 D of corneal astigmatism. Several IOLs are approved to correct a high degree of corneal astigmatism with cylinder power up to 12.0 D. These approaches can be used alone or in combination.
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Dysregulation of apoptosis occurs in different types of malignant tumors and is likely to influence the tumor evolution, as well as clinical prognosis. However, the limited number of studies investigating the predictive power of apoptosis-related genes (ARGs) in gastric cancer indicates a gap in the current research. 174 ARGs who differentially expressed were screened using public databases, including the Gene Expression Omnibus and the Molecular Signatures Database. Univariate and LASSO regression analyses were rigorous approaches to recognize the 12 optimal genes (CTHRC1, PDGFRL, VCAN, GJA1, LOX, UPP1, ANGPT2, CRIM1, HIF1A, APOD, RNase1, and ID1) that make up the prognostic risk model. Molecular mutations, related signaling pathways, and immune system characteristics in different subgroups defined by the risk model were analyzed using different R packages. Moreover, based on the database of Genomics of Drug Sensitivity in Cancer, chemotherapy sensitivity was predicted among the risk subgroups. As a result, there were differences in mutation profiles, signaling pathways, and infiltrated immune cells between patients in various risk groups. Moreover, the low-risk group displayed greater sensitivity to chemotherapy than the high-risk group. Risk model provided a better prognostic value than the T, N, and M stages, according to the receiver operating characteristic curve. Finally, in a nomogram, the risk model and clinical factors were combined to visualize the survival rates of patients with GC. In response to the differential expression of apoptosis-related genes, a novel model for predicting the prognosis of GC patients was developed. This model may be highly valuable for guiding doctors to deliver treatment plans tailored to the need of patients with GC.
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Northern peatlands contain ~30% of terrestrial carbon (C) stores, but in recent decades, 14% to 20% of the stored C has been lost because of conversion of the peatland to cropland. Microorganisms are widely acknowledged as primary decomposers, but the keystone taxa within the bacterial community regulating C loss from cultivated peatlands remain largely unknown. In this study, we investigated the bacterial taxa driving peat C mineralization during rice cultivation. Cultivation significantly decreased concentrations of soil organic C, dissolved organic C (DOC), carbohydrates, and phenolics but increased C mineralization rate (CMR). Consistent with the classic theory that phenolic inhibition creates a "latch" that reduces peat C decomposition, phenolics were highly negatively correlated with CMR in cultivated peatlands, indicating that elimination of inhibitory phenolics can accelerate soil C mineralization. Bacterial communities were significantly different following peatland cultivation, and co-occurrence diagnosis analysis revealed substantial changes in network clusters of closely connected nodes (modules) and bacterial keystone taxa. Specifically, in cultivated peatlands, bacterial modules were significantly negatively correlated with phenolics, carbohydrates, and DOC. While keystone taxa Xanthomonadales, Arthrobacter, and Bacteroidetes_vadinHA17 can regulate bacterial modules and promote carbon mineralization. Those observations indicated that changes in bacterial modules can promote phenolic decomposition and eliminate phenolic inhibition of labile C decomposition, thus accelerating soil organic C loss during rice cultivation. Overall, the study provides deeper insights into microbe-driven peat C loss during rice cultivation and highlights the crucial role of keystone bacterial taxa in the removal of phenolic constraints on peat C preservation.
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BACKGROUND: The programmed death 1 inhibitor toripalimab plus the angio-immuno kinase inhibitor surufatinib revealed a tolerable safety profile and preliminary efficacy in patients with advanced solid tumours in a phase I study. PATIENTS AND METHODS: This was an open-label, single-arm, multi-cohort phase II study in China. Patients with advanced neuroendocrine tumours (NETs) or neuroendocrine carcinomas (NECs) or mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) who had failed or were intolerable of standard treatment were given surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every 3 weeks). Primary end-point was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end-points included duration of response (DoR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty patients were enrolled into two cohorts by tumour types (NET, n = 19; NEC-MiNEN, n = 21). ORRs (95% CIs) were 21.1% (6.1-45.6) and 23.8% (8.2-47.2) in the NET and NEC-MiNEN cohorts, respectively. Median DoR was 7.1 months (6.9-not evaluable [NE]) and 4.1 months (3.0-NE), respectively. Median PFS was 9.6 months (4.1-NE) and 4.1 months (1.5-5.5); median OS was 27.3 (15.3-NE) and 10.9 months (9.1-14.6), respectively. Overall, grade ≥ 3 treatment-related adverse events occurred in 18 (45.0%) patients. CONCLUSIONS: Surufatinib plus toripalimab showed antitumour activity and a tolerable safety profile in patients with previously treated NETs/NECs/MiNENs. Further study of this combination regimen is ongoing for advanced NECs, for which current therapeutic options remain limited. CLINICALTRIALS: gov: NCT04169672.
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Carcinoma Neuroendócrino , Indóis , Tumores Neuroendócrinos , Pirimidinas , Sulfonamidas , Humanos , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Neuroendócrino/tratamento farmacológicoRESUMO
The homeostasis of the intestinal epithelium heavily relies on the self-renewal and differentiation of intestinal stem cells (ISCs). Although the orchestration of these processes by signaling pathways such as the Wnt, BMP, Notch, and MAPK signals has been extensively studied, the dynamics of their regulation remains unclear. Our study explores how the Wnt signaling pathway temporally regulates the differentiation of ISCs into various cell types in an intestinal organoid system. We report that the duration of Wnt exposure following Notch pathway inactivation significantly influences the differentiation direction of intestinal epithelial cells toward multiple secretory cell types, including goblet cells, enteroendocrine cells (EECs), and Paneth cells. This temporal regulation of Wnt signaling adds another layer of complexity to the combination of niche signals that govern cell fate. By manipulating this temporal signal, we have developed optimized protocols for the efficient in vitro differentiation of ISCs into EECs and goblet cells. These findings provide critical insights into the dynamic regulation of ISC differentiation and offer a robust platform for future investigations into intestinal biology and potential therapeutic applications.
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Mucosa Intestinal , Intestinos , Diferenciação Celular/fisiologia , Mucosa Intestinal/metabolismo , Células-Tronco , Via de Sinalização Wnt/fisiologia , OrganoidesRESUMO
Pleurotus placentodes (PPL) and Pleurotus cystidiosus (PCY) are economically valuable species. PPL grows on conifers, while PCY grows on broad-leaved trees. To reveal the genetic mechanism behind PPL's adaptability to conifers, we performed de novo genome sequencing and comparative analysis of PPL and PCY. We determined the size of the genomes for PPL and PCY to be 36.12 and 42.74 Mb, respectively, and found that they contain 10,851 and 15,673 protein-coding genes, accounting for 59.34% and 53.70% of their respective genome sizes. Evolution analysis showed PPL was closely related to P. ostreatus with the divergence time of 62.7 MYA, while PCY was distantly related to other Pleurotus species with the divergence time of 111.7 MYA. Comparative analysis of carbohydrate-active enzymes (CAZYmes) in PPL and PCY showed that the increase number of CAZYmes related to pectin and cellulose degradation (e.g., AA9, PL1) in PPL may be important for the degradation and colonization of conifers. In addition, geraniol degradation and peroxisome pathways identified by comparative genomes should be another factors for PPL's tolerance to conifer substrate. Our research provides valuable genomes for Pleurotus species and sheds light on the genetic mechanism of PPL's conifer adaptability, which could aid in breeding new Pleurotus varieties for coniferous utilization.
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OBJECTIVE: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Despite rapid progress in targeted therapy and immunotherapy for HCC over the past 10 years, the overall efficacy remains unsatisfactory. This is mainly due to the presence of an intrahepatic microenvironment of cirrhosis in HCC patients, leading to cancer recurrence and drug resistance. METHODS: In this study, we investigated the correlations between the Wnt-1/ß-catenin signaling pathway and the prognosis as well as liver function of HCC patients. Additionally, we conducted in vitro experiments using different concentrations of matrine on HuH-7 cells. Furthermore, we verified the associations between the Wnt-1/ß-catenin signaling pathway, inflammation, and epithelial-mesenchymal transition (EMT) in a rat model of pre-hepatocellular carcinoma. Finally, matrine was employed to treat pre-hepatocellular carcinoma in rats and patients with advanced hepatocellular carcinoma. RESULTS: The results demonstrated the activation of the Wnt-1/ß-catenin signaling pathway, the occurrence of EMT, and exacerbated inflammation in human HCC tissues. In HuH-7 cell experiments, matrine effectively downregulated the Wnt-1/ß-catenin pathway, reversed EMT, and suppressed migration and invasion of HCC cells. In the rat model of pre-hepatocellular carcinoma, matrine dose-dependently inhibited the activation of the Wnt-1/ß-catenin signaling pathway, reversed the occurrence of EMT, and alleviated liver inflammation. Matrine analogues exhibited promising hepatoprotective effects in patients with advanced HCC. CONCLUSIONS: Matrine can reverse EMT, alleviate intrahepatic inflammation, and counteract immune depletion by inhibiting the Wnt-1/ß-catenin signaling pathway in HCC.
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BACKGROUND: Rectal neuroendocrine neoplasms (NENs) are rare neoplasms with limited understanding of its genomic alterations and molecular typing. METHODS: The paraffin-embedded tissue specimens of 38 patients with rectal NENs after surgery were subjected to whole gene sequencing (WGS), and mutation profilings were drawn to identify high-frequency mutation genes, copy-number variations (CNVs), tumor mutation burden (TMB), signal pathways, mutation signatures, DNA damage repair (DDR) genes, and molecular types. The differences of mutated genes and signaling pathways in different pathological grades and metastatic/non-metastatic groups were compared. It helped to search for potential targets. RESULTS: C > T and T > C transitions are the most common base substitutions in rectal NENs. DNA mismatch repair deficiency, DNA base modifications, smoking and exposure to ultraviolet light might play a role in the occurrence of rectal NENs. DAXX, KMT2C, BCL2L1, LTK, MERTK, SPEN, PKN1, FAT3, and LRP2 mutations were found in only low-grade rectal NETs, whereas APC, TP53, NF1, SOX9, and BRCA1 mutations were common in high-grade rectal NECs/MiNENs. These genes helped in distinguishing poorly-differentiated or well-differentiated rectal NENs. Alterations in P53, Wnt and TGFß signaling pathways were more pronounced in rectal NECs and MiNENs. Alterations in Wnt, MAPK and PI3K/AKT signaling pathways promoted metastases. Rectal NENs were classified into two molecular subtypes by cluster analysis based on the mutant genes and signaling pathways combined with clinicopathological features. Patients with mutations in the LRP2, DAXX, and PKN1 gene showed a trend of well-differentiated and early-stage tumors with less metastasis (p = 0.000). CONCLUSIONS: This study evaluated risk factors for regional lymphatic and/or distant metastases, identified high-frequency mutated genes, mutation signatures, altered signaling pathways through NGS. Rectal NENs were divided into two molecular types. This helps to evaluate the likelihood of metastasis, formulate follow-up strategies for patients and provide a target for future research on precision treatment of rectal NENs. PARP inhibitors, MEK inhibitors, mTOR/AKT/PI3K and Wnt signaling pathway inhibitors may be effective drugs for the treatment of metastatic rectal NENs.
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Tumores Neuroendócrinos , Neoplasias Retais , Tumores Neuroendócrinos/classificação , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Neoplasias Retais/classificação , Neoplasias Retais/genética , Neoplasias Retais/patologia , Inclusão em Parafina , Mutação , Tipagem Molecular , Análise Mutacional de DNA , Estadiamento de Neoplasias , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
Background: Programmed cell death protein-1 inhibitors combined with lenvatinib have become a popular treatment option for patients with unresectable hepatocellular carcinoma. Transarterial chemoembolization combined with programmed cell death protein-1 inhibitors and lenvatinib has also shown preliminary efficacy in the unresectable hepatocellular carcinoma. We conducted this observational, retrospective, cohort study to compare the clinical outcomes and safety of transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib versus programmed cell death protein-1 inhibitors plus lenvatinib in patients with unresectable hepatocellular carcinoma. Methods: Between November 2019 and November 2021, patients who were diagnosed with unresectable hepatocellular carcinoma and received transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib or programmed cell death protein-1 inhibitors plus lenvatinib treatment were reviewed for eligibility. The primary endpoints included objective response rate, overall survival, and progression-free survival. The secondary endpoint was the frequency of key adverse events. Results: In total, 105 patients were eligible for the present study, and they were divided into the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group (n = 46) and the programmed cell death protein-1 inhibitors plus lenvatinib group (n = 59). The patient cohort after a one-to-one propensity score matching (n = 86) was also analyzed. The transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had a higher objective response rate both in the patient cohort before propensity score matching (54.3% vs 25.4%, P = .002) and after propensity score matching (55.8% vs 30.2%, P = .017). The patients in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had prolonged overall survival (median, 20.5 vs 12.6 months, P = .015) and progression-free survival (median, 10.2 vs 7.4 months, P = .035). For patient cohort- propensity score matching, the overall survival (20.5 vs 12.8 months, P = .013) and progression-free survival (12.1 vs 7.8 months, P = .030) were also significantly better in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group than in the programmed cell death protein-1 inhibitors plus lenvatinib group. There were no significant differences between the 2 groups concerning adverse reactions caused by immunotherapy and lenvatinib. The adverse reactions caused by transarterial chemoembolization were transient and were quickly reversed. Conclusions: Compared to programmed cell death protein-1 inhibitors plus lenvatinib, transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib may provide better treatment response and survival benefits for patients with unresectable hepatocellular carcinoma, and the adverse events were manageable.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Inibidores de Checkpoint Imunológico , Estudos de Coortes , Estudos Retrospectivos , Quimioembolização Terapêutica/efeitos adversos , Neoplasias Hepáticas/terapia , Proteínas Reguladoras de ApoptoseRESUMO
Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in the tumorigenesis and progression of diverse malignancies. However, the majority of circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined and the exact functions and underlying mechanisms of circRNAs in ESCC still need further exploration. In this study, we identified a novel onco-circRNA hsa_circ_0002938, derived from the exons of cysteine-rich transmembrane BMP regulator 1 (CRIM1) pre-mRNA, referred to as circCRIM1. We found that the expression of circCRIM1 was higher in ESCC tissues, compared to para-carcinoma tissues. Increased expression of circCRIM1 was positively correlated with clinical parameters of ESCC patients including tumor-node-metastasis (TNM) stage, tumor invasion range, and lymph node metastasis. Functionally, the results from the experiments in vitro showed that the knockdown of circCRIM1 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in ESCC cells. By conducting bioinformatics algorithms analyses and microRNA (miRNA) rescue experiments, we found that circCRIM1 could act as a competing endogenous RNA (ceRNA) to sponge miR-342-3p in ESCC cells, and thereby upregulated the expression of transcription factor 12 (TCF12), a key regulator promoting the EMT process. Taken together, circCRIM1 facilitates the progression of ESCC by sponging miR-342-3p to regulate TCF12 and promote EMT, and the circCRIM1/miR-342-3p/TCF12 axis may be regarded as a potential predictive biomarker and therapeutic target for treating ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genéticaRESUMO
The incorporation of post-harvest crop straw and application of industrial and agricultural wastes to paddy soils increase rice crop yields and soil fertility. However, the impacts of combined applications of straw and waste products on greenhouse gas (GHG) emissions and global warming potential (GWP) of paddy soils are unclear. Therefore, we conducted a field experiment in subtropical rice in China to test the effects of applications of straw, straw+biochar, straw+shell slag, straw+gypsum slag, straw+silicon, and straw+steel slag on rice yields, GWP, and greenhouse gas emission intensity (GHGI). The results showed that, compared to the control, cumulative emissions of carbon dioxide (CO2) from paddy soils were 15.2, 16.9, and 36.6 % lower following application of straw+steel slag, straw+silicon, and straw+gypsum, respectively, and cumulative emissions of methane (CH4) were 5.0 and 62.1 % lower following application of straw+steel slag and straw+gypsum, respectively. Meanwhile, relative to the addition of straw alone, application of straw+steel slag and straw+gypsum reduced GHG emissions largely due to reductions in CO2 emissions, further declining the GWP of CO2 and GHGI. In addition, temperature sensitivity (Q10) of CO2 emissions was highest following application of straw+silicon and lowest following application of straw+gypsum. There were no treatment effects on mean dissolved porewater concentrations of CO2, CH4, or nitrous oxide (N2O) and soil emissions of CO2 were negatively correlated with mean dissolved concentrations of CO2, CH4, and N2O. Rice yields were reduced following application of straw+gypsum and unaffected by the other treatments. Thus, relative to the addition of straw alone or control, we suggest the combined application of straw+steel slag may improve the sustainability of paddy rice production, because it reduces GWP, while maintaining yields.
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Gases de Efeito Estufa , Oryza , Agricultura/métodos , Sulfato de Cálcio , Dióxido de Carbono/análise , China , Aquecimento Global , Gases de Efeito Estufa/análise , Metano/análise , Óxido Nitroso/análise , Silício , Solo , Aço , TemperaturaRESUMO
Optical flow is widely used in medical image processing, such as image registration, segmentation, 3D reconstruction, and temporal super-resolution. However, high-precision optical flow training datasets for medical images are challenging to produce. The current optical flow estimation models trained on these non-medical datasets, such as KITTI, Sintel, and FlyingChairs are unsuitable for medical images. In this work, we propose a semi-supervised learning mechanism to estimate the optical flow of coronary angiography. Our proposed method only needs the original medical images, segmentation results of regions of interest, and pre-trained models based on other optical flow datasets to train a new optical flow estimation model suitable for medical images. First, we use the coronary segmentation results to perform image enhancement processing on the coronary vascular region to improve the image contrast between the vascular region and the surrounding tissues. Then, we extract the high-precision optical flow of coronary arteries based on the coronary-enhanced images and the pre-trained optical flow estimation model. After estimating the optical flow, we take it and its corresponding original coronary angiography images as the training dataset to train the optical flow estimation network. Furthermore, we generate a large-scale synthetic Flying-artery dataset based on coronary artery segmentation results and original coronary angiography images, which is used to improve and evaluate the accuracy of optical flow estimation for coronary angiography. The experimental results on the coronary angiography datasets demonstrate that our proposed method can significantly improve the optical flow estimation accuracy of coronary angiography sequences compared with other methods.