METAVISION: a novel system for quantifying metamorphopsia in patients with myopic traction maculopathy.

PURPOSE: To develop a novel system for quantifying metamorphopsia in patients with myopic traction maculopathy (MTM) and to explore the metamorphopsia pattern of MTM. DESIGN: Observational, cross-sectional study. METHODS: We designed a new system. RESULTS: Of the 445 eyes tested, 188 (42.25%) were deemed by patients to have metamorphopsia impacting their daily lives while 257 (57.75%) were considered to have no metamorphopsia symptoms. The Amsler grid, M-CHARTS and METAVISION tests displayed sensitivities for metamorphopsia of 95.74%, 89.89% and 100%, respectively. The specificities of the Amsler grid, M-CHARTS and METAVISION tests are 100%. The metamorphopsia questionnaire and METAVISION scores were highly consistent (average intraclass correlation coefficient=0.951, p<0.001) and strongly correlated (R=0.879, p<0.001). The METAVISION score was highly correlated with the stages of MTM (R=0.837, p<0.001), whereas there was a moderate correlation between the M-CHARTS M-score and the stages of MTM (R=0.679, p<0.001). CONCLUSIONS: Quantification of metamorphopsia is important and useful for MTM management. The METAVISION is a clinically applicable and comprehensive approach for quantifying metamorphopsia, which can be used in clinical settings.

Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract: a randomized clinical trial.

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

The landscape of angiogenesis and inflammatory factors in eyes with myopic choroidal neovascularization before and after anti-VEGF injection.

INTRODUCTION: To investigate the levels of angiogenesis and inflammatory cytokines in individuals with myopic choroidal neovascularization (mCNV) and the changes in these factors following intravitreal anti-VEGF injection. METHODS: Aqueous humor samples were gathered from eyes with mCNV, those with single macular bleeding (SMB) without mCNV in highly myopic eyes, and those with age-related cataracts. Using a multiplex bead immunoassay, we analyzed 28 angiogenesis and inflammatory factors in the aqueous humor. Furthermore, clinical data were documented for correlation analysis. RESULTS: In this study, the levels of vascular endothelial growth factor A (VEGF-A), interleukin 8 (IL-8), and fibroblast growth factors 1 (FGF-1) were significantly elevated in mCNV compared to SMB eyes (p < 0.05). Their odds ratios for mCNV occurrence were 1.05, 3.45, and 2.64, respectively. Hepatocyte growth factor (HGF) and VEGF-C were notably higher in mCNV than in cataract patients (p < 0.05), and VEGF-C correlated to the degree of myopic atrophic maculopathy (p = 0.024). Axial length exhibited a negative correlation with VEGF-A and positive correlations with VEGF-C, HGF, and MCP-1 (p < 0.01). Following anti-VEGF treatment, a reduction in VEGF-A, endothelin-1, and FGF-2 was noted in mCNV patients (p < 0.05), but MCP-1 levels increased. CONCLUSION: Our findings highlight the predominant role of angiogenesis and inflammation factors in mCNV pathogenesis. VEGF-C's correlation with axial length and atrophy suggests its involvement in the process of myopic atrophic maculopathy.

Unlocking the potential: phenylboronic acid as a nuclear-targeting boron agent for neutron capture therapy.

It has been proposed that boron neutron capture therapy (BNCT) holds promise as a treatment modality for melanoma. However, the effectiveness of boron agents in delivery remains a critical issue to be addressed for BNCT. To this end, phenylboronic acid, which exhibits good water solubility and low cytotoxicity similar to BPA, has been investigated as a potential nuclear-targeting boron agent. The boron concentration of phenylboronic acid was found to be 74.47 ± 12.17 ng/106 B16F10 cells and 45.77 ± 5.64 ng/106 cells in the nuclei. Molecular docking experiments were conducted to investigate the binding of phenylboronic acid to importin proteins involved in nuclear transport. The potential of phenylboronic acid to serve as a desirable nucleus-delivery boron agent for neutron capture therapy in melanoma warrants further exploration.

Therapeutic effect and study of human umbilical cord blood mononuclear cells in patients with ischaemic bowel disease.

Ischaemic bowel disease (ICBD) is a group of intestinal ischaemia syndromes caused by various aetiologies of reduced intestinal blood flow or vascular occlusion. ICBD can present as abdominal pain, bloody stool, and diarrhoea. This disease often occurs in middle-aged and elderly individuals with cardiovascular and cerebrovascular diseases. The incidence of ischaemic bowel disease has been increasing for decades, and it is difficult to diagnose, resulting in rapid disease progression and a high mortality rate. Therefore, fully understanding this disease, improving the diagnosis rate of this disease, and finding appropriate treatment methods are urgently needed to improve the condition and prognosis of patients. Umbilical cord blood stem cells are accessible, have weak immunogenicity, and have various biological functions, such as angiogenesis, inflammation and immune regulation. Many studies have confirmed that cord blood stem cells can relieve ischaemia, and these cells have attracted tremendous amounts of attention in regenerative medicine in recent years. In this paper, we discuss the clinical characteristics of ICBD, analyse the characteristics of human umbilical cord blood mononuclear cells (HUCB-MNCs), and use its to treat ischaemic bowel disease. Additionally, we compare the clinical manifestations and related indicators before and after treatment to evaluate the efficacy and safety of these methods.

Establishment and verification of the first prognostic nomograms in locally advanced thyroid cancer based on the analysis of clinical and follow-up information on 2396 patients.

Background and objectives: The purpose of this research was to develop and validate the first prognostic nomograms for 3-, 5-, and 10-year cancer-specific survival (CSS) and overall survival (OS) in patients diagnosed with locally advanced thyroid cancer (LATC) by evaluating independent predictors of prognosis in a population of LATC patients. Methods: Demographics, clinicopathologic characteristics, treatment, and follow-up of 2396 LATC patients in the surveillance, epidemiology, and end results database from 2004 to 2015 were retrospectively analyzed and compared with patients with LATC according to staging. We randomized all LATC patients into training and validation groups in a 7:3 ratio. Cox regression analyses helped us to derive independent prognostic factors for LATC patients. According to these results, we established and validated the first prognostic nomograms and risk stratification. Results: In our research, the clinical information of LATC patients was compared and significant differences were found in the relevant variables including CSS and OS (P < 0.05), with CSS of 82.0 % and 49.0 %, and OS of 70.6 % and 40.0 %, respectively. Cox regression analyses showed that age at diagnosis, tumor diameter, presence of DM, extrathyroidal extension sites, histological type, thyroidectomy scope, radiotherapy status, and chronological sequence of radiotherapy and surgery were observably correlated with CSS in LATC patients, and in addition to the above factors, gender, marital status, and chemotherapy status were also observably correlated with OS in LATC patients. The prognostic predictive power of the above factors is visualized by the Kaplan-Meier survival curve. The concordance index of nomograms for CSS and OS were 0.933, 0.925, and 0.926 (CSS), 0.918, 0.909, and 0.906 (OS), respectively, and the time-dependent receiver operating characteristic curve, area under curve, calibration curve and decision curve analysis curve indicate that the nomograms have good discriminatory ability, accuracy and clinical applicability in both the training and validation groups. Conclusions: In these findings, we drawed a conclusion that there were significant differences in clinical information between patients with T4a and T4b LATC, and we established and validated the first prognostic nomograms and risk stratification of CSS and OS for LATC patients at 3, 5, and 10 years, which will help clinicians to individualize their postoperative treatment and individualized follow-up.

Biomimetic Responsive Nanoconverters with Immune Checkpoint Blockade Plus Antiangiogenesis for Advanced Hepatocellular Carcinoma Treatment.

The first-line treatment for advanced hepatocellular carcinoma (HCC) combines immune checkpoint inhibitors and antiangiogenesis agents to prolong patient survival. Nonetheless, this approach has several limitations, including stringent inclusion criteria and suboptimal response rates that stem from the severe off-tumor side effects and the unfavorable pharmacodynamics and pharmacokinetics of different drugs delivered systemically. Herein, we propose a single-agent smart nanomedicine-based approach that mimics the therapeutic schedule in a targeted and biocompatible manner to elicit robust antitumor immunity in advanced HCC. Our strategy employed pH-responsive carriers, poly(ethylene glycol)-poly(ß-amino esters) amphiphilic block copolymer (PEG-PAEs), for delivering apatinib (an angiogenesis inhibitor), that were surface-coated with plasma membrane derived from engineered cells overexpressing PD-1 proteins (an immune checkpoint inhibitor to block PD-L1). In an advanced HCC mouse model with metastasis, these biomimetic responsive nanoconverters induced significant tumor regression (5/9), liver function recovery, and complete suppression of lung metastasis. Examination of the tumor microenvironment revealed an increased infiltration of immune effector cells (CD8+ and CD4+ T cells) and reduced immunosuppressive cells (myeloid-derived suppressor cells and T regulatory cells) in treated tumors. Importantly, our nanomedicine selectively accumulated in both small and large HCC occupying >50% of the liver volume to exert therapeutic effects with minimal systemic side effects. Overall, these findings highlight the potential of such multifunctional nanoconverters to effectively reshape the tumor microenvironment for advanced HCC treatment.

An NIR-emitting cyanine dye with pyridinium groups: the impact of regio-bond connection on the photophysical properties.

Two ESIPT-based isomeric cyanines were synthesized with significant bathochromic shift in the optical absorption λabs and emission λem, along with a very large Stokes shift. Probe 2 exhibited a longer conjugation and better photostability. Both compounds exhibited good selectivity for labeling the plasma membrane of prokaryotic cells and the hair cells of zebrafish.

Buffer solution induced highly crystalline sodium-rich Prussian blue for sodium storage.

In this work, we have developed an efficient method to synthesize Prussian blue by self-decomposition of sodium ferrocyanide in acetic acid-sodium acetate buffer solution. This buffer solution-based proton pool provides a relatively low and stable concentration of protons for the slow decomposition of sodium ferrocyanide to get highly crystalline and sodium rich Prussian blue, which can be used as the cathode for high-performance sodium-ion batteries.

Josephin domain containing 2 (JOSD2) promotes lung cancer by inhibiting LKB1 (Liver kinase B1) activity.

Non-small cell lung cancer (NSCLC) ranks as one of the leading causes of cancer-related deaths worldwide. Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment, these drugs are suitable for and beneficial to a mere ~30% of NSCLC patients. Consequently, the need for novel strategies addressing NSCLC remains pressing. Deubiquitinases (DUBs), a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic targets. Nevertheless, the mechanisms by which DUBs promote NSCLC remain poorly understood. Through a global analysis of the 97 DUBs' contribution to NSCLC survival possibilities using The Cancer Genome Atlas (TCGA) database, we found that high expression of Josephin Domain-containing protein 2 (JOSD2) predicted the poor prognosis of patients. Depletion of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in vivo. Mechanically, we found that JOSD2 restricts the kinase activity of LKB1, an important tumor suppressor generally inactivated in NSCLC, by removing K6-linked polyubiquitination, an action vital for maintaining the integrity of the LKB1-STRAD-MO25 complex. Notably, we identified the first small-molecule inhibitor of JOSD2, and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo. Our findings highlight the vital role of JOSD2 in hindering LKB1 activity, underscoring the therapeutic potential of targeting JOSD2 in NSCLC, especially in those with inactivated LKB1, and presenting its inhibitors as a promising strategy for NSCLC treatment.

The novel prognostic nomograms for predicting cancer-specific survival and overall survival in mixed medullary and follicular cell carcinoma: A SEER-based study.

BACKGROUND: The aim of this study was to evaluate independent predictors of prognosis in patients with mixed medullary and follicular cell carcinoma (MMFCC) and to establish the novel prognostic nomograms in the academic community for 3-, 5-, and 10 year CSS and OS in patients with MMFCC. METHODS: Demographic information, clinicopathological characteristics, treatment information, and survival status information of 200 patients with MMFCC and 6615 patients with medullary thyroid carcinoma (MTC) from 2000 to 2020 in the SEER database were retrospectively analyzed. Independent predictors of prognosis in MMFCC patients were derived using univariate and multivariate Cox regression analyses after relevant comparisons based on pathologic typing. On this basis, we developed and validated clinical prognostic nomograms and risk-stratified the patient population. RESULTS: In this study, the clinical information of 200 patients with MMFCC was compared with that of 5947 patients with MTC (NOS) and 668 patients with MTC with amyloid stroma, and there was a significant difference in the relevant variables among the three, with the CSS being 88.5%, 87.5%, and 90.9%, and the OS being 76.5%, 75.4%, and 83.8%. Univariate and multivariate Cox regression analyses yielded that age at diagnosis, presence of distant metastases, thyroidectomy scope, and lymph node dissection status were significantly correlated with the prognosis of patients (P < 0.05), and were independent predictors of CSS and OS for patients with MMFCC, and the Kaplan-Meier survival curves plotted by these factors demonstrated their predictive power for the prognosis of patients with MMFCC. The concordance index of the prognostic nomograms of CSS and OS established on this basis was 0.838 and 0.794, respectively, and the time-dependent area under curve, calibration curve, and decision curve analysis curve showed that the model had good discriminative ability, accuracy, and clinical applicability. CONCLUSIONS: In this study, we concluded that there are large differences between MMFCC and MTC in terms of demographic information, clinicopathological characteristics, treatment information, and survival status information, and we constructed the novel prognostic nomograms for 3-, 5-, and 10 year CSS and OS for patients with MMFCC with risk stratification, which will help clinicians to develop individualized protocols for their postoperative treatments and follow-ups.

A Hierarchical Graph V-Net With Semi-Supervised Pre-Training for Histological Image Based Breast Cancer Classification.

Numerous patch-based methods have recently been proposed for histological image based breast cancer classification. However, their performance could be highly affected by ignoring spatial contextual information in the whole slide image (WSI). To address this issue, we propose a novel hierarchical Graph V-Net by integrating 1) patch-level pre-training and 2) context-based fine-tuning, with a hierarchical graph network. Specifically, a semi-supervised framework based on knowledge distillation is first developed to pre-train a patch encoder for extracting disease-relevant features. Then, a hierarchical Graph V-Net is designed to construct a hierarchical graph representation from neighboring/similar individual patches for coarse-to-fine classification, where each graph node (corresponding to one patch) is attached with extracted disease-relevant features and its target label during training is the average label of all pixels in the corresponding patch. To evaluate the performance of our proposed hierarchical Graph V-Net, we collect a large WSI dataset of 560 WSIs, with 30 labeled WSIs from the BACH dataset (through our further refinement), 30 labeled WSIs and 500 unlabeled WSIs from Yunnan Cancer Hospital. Those 500 unlabeled WSIs are employed for patch-level pre-training to improve feature representation, while 60 labeled WSIs are used to train and test our proposed hierarchical Graph V-Net. Both comparative assessment and ablation studies demonstrate the superiority of our proposed hierarchical Graph V-Net over state-of-the-art methods in classifying breast cancer from WSIs. The source code and our annotations for the BACH dataset have been released at https://github.com/lyhkevin/Graph-V-Net.

The rate-limiting procedure of 3D DNA walkers and their applications in tandem technology.

DNA walkers, artificial dynamic DNA nanomachines, can mimic actin to move rapidly along a predefined nucleic acid track. They can generally be classified as one- (1D), two- (2D), and three-dimensional (3D) DNA walkers. In particular, 3D DNA walkers demonstrate amazing sustainable walking ability, strong enrichment ability, and fantastic signal amplification ability. In light of these, 3D DNA walkers have been widely used in fields such as biosensors, bioanalysis and cell imaging. Most notably, the strong compatibility of 3D DNA walkers allows their integration with a range of amplification strategies, effectively enhancing signal transduction and amplifying biosensor sensing signals. Herein, we first systematically expound the walking principle of the 3D walkers in this review. Then, by presenting representative examples, the research direction of 3D walkers in recent years is discussed. Furthermore, we also categorize and evaluate diverse tandem signal amplification strategies in 3D walkers. Finally, the challenges and development trends of 3D DNA walkers in the emerging field of analysis are carefully discussed. It is believed that this work can provide new ideas for researchers to quickly understand 3D DNA walkers and their applications in diverse biosensors.

Development and validation of nomograms for predicting the risk of central lymph node metastasis of solitary papillary thyroid carcinoma of the isthmus.

BACKGROUND: This study was conducted to develop nomograms and validate them by assessing risk factors for the development of central lymph node metastasis (CLNM) in patients with solitary papillary thyroid carcinoma of the isthmus (PTCI) for predicting the probability of CLNM. METHODS: Demographic and clinicopathological variables of patients with solitary papillary thyroid carcinoma (PTC) from May 2018 to May 2023 at the First Hospital of Shanxi Medical University were retrospectively analyzed, and the lobar group and the isthmus group were divided according to tumor location. Patients with the same sex, age difference of less than 3 years, and equal gross tumor diameter were selected from the lobar group and compared with the paraisthmic tumor group. Independent risk factors were determined using univariate and multivariate logistic regression analysis. On this basis, clinical predictive nomograms were developed and validated. RESULTS: Clinical data from 326 patients with solitary PTCI and 660 cases of solitary lobar PTC were used for analysis in our study. The incidence of solitary tumors CLNM located in the median isthmus, paracentral isthmus, and lobes was 69.8%, 40.9%, and 33.6%, respectively. Statistical analysis revealed that gender, age, isthmus location, maximum nodal diameter, the presence of possible CLNM in advance on preoperative ultrasound, chronic lymphocytic thyroiditis, and the lymphocyte/monocyte ratio were independent risk factors for preoperative CLNM in patients with solitary PTCI. Age, isthmus location, chronic lymphocytic thyroiditis, gross tumor diameter, presence of intraoperative extrathyroidal extension, and presence of metastasis in the Delphian lymph node on frozen section were independent risk factors for intraoperative CLNM. The concordance indices of nomograms for preoperative and intraoperative are 0.871 and 0.894 in the training set and 0.796 and 0.851 in the validation set, calibration curve and decision curve analysis also demonstrated the strong reliability and clinical applicability of this clinical prediction model. CONCLUSION: In this study, we concluded that solitary PTCI is more aggressive compared to solitary lobar PTC, and we constructed nomograms and risk stratification to accurately identify patients with solitary PTCI who are at high risk of developing CLNM, which will help clinicians in personalized decision making.

Development and validation of a nomogram for risk of pulmonary metastasis in non-papillary thyroid carcinoma: A SEER-based study.

In this study, a nomogram was established and validated by assessing the risk factors for the development of pulmonary metastases in patients with non-papillary thyroid carcinoma (NPTC) and was used to predict the risk of developing pulmonary metastases. Demographic and clinicopathological variables of patients with NPTC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed, and independent risk factors were identified using χ2 tests and full subset regression analysis. Based on this, a nomogram was developed and validated for predicting the risk of pulmonary metastasis in patients with NPTC. The predictive performance of the nomogram was calculated using the consistency index, and the clinical application value of the nomogram was evaluated using calibration curve and decision curve analyses. In addition, risk stratification of patients with NPTC based on these results was performed to facilitate early diagnosis and treatment of patients with pulmonary metastases in the clinic. Data from 1435 patients with NPTC were used for the analysis based on the inclusion and exclusion criteria. Statistical analysis yielded a high risk of pulmonary metastasis in patients with older age, high T-stage, poorly differentiated, undifferentiated thyroid carcinoma, follicular thyroid carcinoma (NOS), and the presence of other distant metastases. We further developed a nomogram with a consistency index of 0.898 (95% confidence interval: 0.880-0.920) in the training cohort and 0.895 (95% confidence interval: 0.862-0.927) in the validation cohort. The calibration curve and decision curve analyses also demonstrated the strong reliability and accuracy of this clinical prediction model. In this study, a nomogram was constructed to accurately identify patients with NPTC at a high risk of pulmonary metastasis, which will help clinicians in personalized decision-making.

Effect of stearic and oleic acid-based lipophilic emulsifiers on the crystallization of the fat blend and the stability of whipped cream.

Effect of stearic acid-based lipophilic emulsifiers (sorbitan monostearate (Span-60), sucrose ester S-170, and lactic acid esters of monoglycerides (LACTEM)) and oleic acid-based lipophilic emulsifiers (sorbitan monooleate (Span-80) and sucrose ester O-170) on the crystallization of fat blend and the stability of whipped cream were studied. Span-60 and S-170 possessed strong nucleation inducing ability and good emulsifying properties. Thus, tiny and uniform crystals were formed in fat blends, small and ordered fat globules were distributed in emulsions, and air bubbles were effectively wrapped in firmly foam structures. The crystallization of the fat blend and the stability of whipped cream were slightly modified by LACTEM due to its poor nucleation inducing ability and moderate emulsifying characteristic. Span-80 and O-170 had weak nucleation inducing ability and poor emulsifying properties, therefore, loose crystals were formed in fat blends and some big fat globules were separated in emulsions, thereby decreasing the stability of whipped creams.

Multi-Scale Transformer Network With Edge-Aware Pre-Training for Cross-Modality MR Image Synthesis.

Cross-modality magnetic resonance (MR) image synthesis can be used to generate missing modalities from given ones. Existing (supervised learning) methods often require a large number of paired multi-modal data to train an effective synthesis model. However, it is often challenging to obtain sufficient paired data for supervised training. In reality, we often have a small number of paired data while a large number of unpaired data. To take advantage of both paired and unpaired data, in this paper, we propose a Multi-scale Transformer Network (MT-Net) with edge-aware pre-training for cross-modality MR image synthesis. Specifically, an Edge-preserving Masked AutoEncoder (Edge-MAE) is first pre-trained in a self-supervised manner to simultaneously perform 1) image imputation for randomly masked patches in each image and 2) whole edge map estimation, which effectively learns both contextual and structural information. Besides, a novel patch-wise loss is proposed to enhance the performance of Edge-MAE by treating different masked patches differently according to the difficulties of their respective imputations. Based on this proposed pre-training, in the subsequent fine-tuning stage, a Dual-scale Selective Fusion (DSF) module is designed (in our MT-Net) to synthesize missing-modality images by integrating multi-scale features extracted from the encoder of the pre-trained Edge-MAE. Furthermore, this pre-trained encoder is also employed to extract high-level features from the synthesized image and corresponding ground-truth image, which are required to be similar (consistent) in the training. Experimental results show that our MT-Net achieves comparable performance to the competing methods even using 70% of all available paired data. Our code will be released at https://github.com/lyhkevin/MT-Net.

Engineering Trichoderma reesei for the hyperproduction of cellulose induced protein 1 (Cip1) on a sophorose-containing inducer to efficiently saccharify alkali-pretreated corn stover.

Trichoderma reesei was induced to produce cellulase by a combination of glucose and ß-disaccharide; however, lower levels of auxiliary proteins for degrading lignocellulosic biomass were detected by iTRAQ analysis compared with cellulose as an inducer, especially cellulose induced protein 1 (CIP1). In this study, A pdc1 promoter-driven overexpression of the endogenous Trcip1 gene was observed in T. reesei Rut C30, and the Trcip1 transcription levels of the two transformants, T. reesei OE-cip1-1 and OE-cip1-2, demonstrated 31.2- and 164.6-fold increases, respectively, but there was no significant change in cellobiohydrolase, endoglucanase and filter paper activity at 48 h. The crude enzyme was then used to hydrolyze corn stover. For T. reesei OE-cip1-1 and OE-cip1-2, the hydrolysis efficiency increased by 25.0 and 28.6% with a solid loading of 5% at 2 h, respectively. Simultaneously, 85.5 and 85.2 g/L glucose were released using a cellulase cocktail at high solid loading (20%), and these glucose release rates were significantly greater than that of T. reesei Rut C30 cellulase (77.4 g/L) at 120 h. Furthermore, scanning electron microscopy (SEM) and X-ray diffraction (XRD) showed that the enhanced hydrolysis efficiency was primarily triggered by the decrease in the crystallinity of lignocellulose, and the fiber structure had varying degrees of loosening and disintegration.

Multilabel Feature Selection With Constrained Latent Structure Shared Term.

High-dimensional multilabel data have increasingly emerged in many application areas, suffering from two noteworthy issues: instances with high-dimensional features and large-scale labels. Multilabel feature selection methods are widely studied to address the issues. Previous multilabel feature selection methods focus on exploring label correlations to guide the feature selection process, ignoring the impact of latent feature structure on label correlations. In addition, one encouraging property regarding correlations between features and labels is that similar features intend to share similar labels. To this end, a latent structure shared (LSS) term is designed, which shares and preserves both latent feature structure and latent label structure. Furthermore, we employ the graph regularization technique to guarantee the consistency between original feature space and latent feature structure space. Finally, we derive the shared latent feature and label structure feature selection (SSFS) method based on the constrained LSS term, and then, an effective optimization scheme with provable convergence is proposed to solve the SSFS method. Better experimental results on benchmark datasets are achieved in terms of multiple evaluation criteria.

SDHA/B reduction promotes hepatocellular carcinoma by facilitating the deNEDDylation of cullin1 and stabilizing YAP/TAZ.

BACKGROUND AND AIMS: Succinate dehydrogenase enzyme (SDH) is frequently diminished in samples from patients with hepatocellular carcinoma (HCC), and SDH reduction is associated with elevated succinate level and poor prognosis in patients with HCC. However, the underlying mechanisms of how impaired SDH activity promotes HCC remain unclear. APPROACH AND RESULTS: In this study, we observed remarkable downregulations of SDH subunits A and B (SDHA/B) in chronic liver injury-induced murine HCC models and patient samples. Subsequent RNA sequencing, hematoxylin and eosin staining, and immunohistochemistry analyses of HCC samples revealed that Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) were significantly upregulated in HCC, with their levels inversely correlating with that of SDHA/B. YAP/TAZ stability was greatly enhanced in SDHA/B-depleted HCC cells along with accumulation of succinate. Further mechanistic analyses demonstrated that impaired activity of SDHA/B resulted in succinate accumulation, which facilitated the deNEDDylation of cullin1 and therefore disrupted the E3 ubiquitin ligase SCF ß-TrCP complex, consequently leading to YAP/TAZ stabilization and activation in HCC cells. The accelerated in vitro cell proliferation and in vivo tumor growth caused by SDHA/B reduction or succinate exposure were largely dependent on the aberrant activation of YAP/TAZ. CONCLUSIONS: Our study demonstrated that SDHA/B reduction promotes HCC proliferation by preventing the proteasomal degradation of YAP/TAZ through modulating cullin1 NEDDylation, thus binding SDH-deficient HCC cells to YAP/TAZ pathway and rendering these cells vulnerable to YAP/TAZ inhibition. Our findings warrant further investigation on the therapeutic effects of targeting YAP/TAZ in patients with HCC displaying reduced SDHA/B or elevated succinate levels.