A real-world comparison of circulating tumor cells in breast cancer from China: Novel device, CTC counts and its overall survival.

Background: Both CellSearch and CellCollector have been accepted as the proper devices to capture CTC by domestic approval department. However, there is little article about the comparison between these two devices around the world. Herein, we conducted the real-world study to compare with these two devices and to re-verify the efficacy of CTC counts. Methods: Patients who meet the following points should be included in the analysis. 1. Female, aged 18 years or older; 2. Eastern Cooperative Oncology Group (ECOG) score 0-2; 3. With at least one measurable tumor lesion; 4. Clear immunohistochemistry result; 5. Accept at least one CTC test. Patients were excluded in the analysis if they had a history of malignant tumors, incomplete follow-up information. Results: 536 metastatic breast cancer patients who had been detected for CTC at least once by CellSearch or CellCollector were included in the analysis. CellCollector in vivo CTC detection technology has a higher detection rate than the CellSearch system (69.2% vs 57.4%, P = 0.009). However, the proportion of CTC≥5 detected by CellSearch was higher than CellCollector (37.4% vs 16.3%, P < 0.001). There was a statistically significant difference in overall survival of patients with CTC negative and CTC positive (mOS:49.8 months vs 26.9 months). After 4 weeks of treatment, when CTC decreased by more than 50%, there was a significant difference in survival between the two groups (40.1 months vs 25.8 months, HR = 0.588, 95% CI: 0.350-0.933). In addition, for HER2-positive patients, Patients with CTC HER2 positive had longer overall survival than patients with CTC HER2 negative (median OS: 26.7 months vs 17.3 month, HR = 0.528, 95% CI: 0.269-0.887). Conclusions: Real-world data indicate that CTC is an independent prognostic factor, and CellCollector and CellSearch have their own advantages in CTC detection.

Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management.

Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans.

Acyl carrier protein OsMTACP2 confers rice cold tolerance at the booting stage.

Low temperatures occurring at the booting stage in rice (Oryza sativa L.) often result in yield loss by impeding male reproductive development. However, the underlying mechanisms by which rice responds to cold at this stage remain largely unknown. Here, we identified MITOCHONDRIAL ACYL CARRIER PROTEIN 2 (OsMTACP2), the encoded protein of which mediates lipid metabolism involved in the cold response at the booting stage. Loss of OsMTACP2 function compromised cold tolerance, hindering anther cuticle and pollen wall development, resulting in abnormal anther morphology, lower pollen fertility and seed setting. OsMTACP2 was highly expressed in tapetal cells and microspores during anther development, with the encoded protein localizing to both mitochondria and the cytoplasm. Comparative transcriptomic analysis revealed differential expression of genes related to lipid metabolism between the wild type and the Osmtacp2-1 mutant in response to cold. Through a lipidomic analysis, we demonstrated that wax esters, which are the primary lipid components of the anther cuticle and pollen walls, function as cold-responsive lipids. Their levels increased dramatically in the wild type but not in Osmtacp2-1 when exposed to cold. Additionally, mutants of two cold induced genes of wax ester biosynthesis, ECERIFERUM1 and WAX CRYSTAL-SPARSE LEAF2, showed decreased cold tolerance. These results suggest that OsMTACP2-mediated wax ester biosynthesis is essential for cold tolerance in rice at the booting stage.

Electroactive nanofibrous membrane with antibacterial and deodorizing properties for air filtration.

Water vapor from respiration can severely accelerate the charge dissipation of the face mask, reducing filtration efficiency. Moreover, the foul odor from prolonged mask wear tends to make people remove their masks, leading to the risk of infection. In this study, an electro-blown spinning electroactive nanofibrous membrane (Zn/CB@PAN) with antibacterial and deodorization properties was prepared by adding zinc (Zn) and carbon black (CB) nanoparticles to the polyacrylonitrile (PAN) nanofibers, respectively. The filtration efficiency of Zn/CB@PAN for PM0.3 was > 99% and could still maintain excellent durability within 4 h in a high-humidity environment (25 â„ƒ and RH = 95%). Moreover, the bacterial interception rate of the Zn/CB@PAN could reach 99.99%, and it can kill intercepted bacteria. In addition, the deodorization rate of Zn/CB@PAN in the moist state for acetic acid was 93.75% and ammonia was 95.23%, respectively. The excellent filtering, antibacterial, and deodorizing performance of Zn/CB@PAN can be attributed to the synergistic effect of breath-induced Zn/CB galvanic couples' electroactivity, released metal ions, and generated reactive oxygen species. The developed Zn/CB@PAN could capture and kill airborne environmental pathogens under humid environments and deodorize odors from prolonged wear, holding promise for broad applications as personal protective masks.

Rhizosphere-Associated Anammox Bacterial Diversity and Abundance of Nitrogen Cycle-Related Functional Genes of Emergent Macrophytes in Eutrophic Wetlands.

Rhizospheric microbial community of emergent macrophytes plays an important role in nitrogen removal, especially in the eutrophic wetlands. The objective of this study was to identify the differences in anammox bacterial community composition among different emergent macrophytes and investigate revealed the the main factors affecting on the composition, diversity, and abundance of anammox bacterial community. Results showed that the composition, diversity, and abundance of the anammox community were significantly different between the vegetated sediments of three emergent macrophytes and unvegetated sediment. The composition of the anammox bacterial community was different in the vegetated sediments of different emergent macrophytes. Also, the abundance of nitrogen cycle-related functional genes in the vegetated sediments was found to be higher than that in the unvegetated sediment. Canonical correspondence analysis (CCA) and structural equation models analysis (SEM) showed that salinity and pH were the main environmental factors influencing the composition and diversity of the anammox bacterial community and NO2--N indirectly affected anammox bacterial community diversity by affecting TOC. nirK-type denitrifying bacteria abundance had significant effects on the bacterial community composition, diversity, and abundance of anammox bacteria. The community composition of anammox bacteria varies with emergent macrophyte species. The rhizosphere of emergent macrophytes provides a favorable environment and promotes the growth of nitrogen cycling-related microorganisms that likely accelerate nitrogen removal in eutrophic wetlands.

Estimation of wheat protein content and wet gluten content based on fusion of hyperspectral and RGB sensors using machine learning algorithms.

The protein content (PC) and wet gluten content (WGC) are crucial indicators determining the quality of wheat, playing a pivotal role in evaluating processing and baking performance. Original reflectance (OR), wavelet feature (WF), and color index (CI) were extracted from hyperspectral and RGB sensors. Combining Pearson-competitive adaptive reweighted sampling (CARs)-variance inflation factor (VIF) with four machine learning (ML) algorithms were used to model accuracy of PC and WGC. As a result, three CIs, six ORs, and twelve WFs were selected for PC and WGC datasets. For single-modal data, the back-propagation neural network exhibited superior accuracy, with estimation accuracies (WF > OR > CI). For multi-modal data, the random forest regression paired with OR + WF + CI showed the highest validation accuracy. Utilizing the Gini impurity, WF outweighed OR and CI in the PC and WGC models. The amalgamation of MLs with multimodal data harnessed the synergies among various remote sensing sources, substantially augmenting model precision and stability.

A Modified Arthroscopic Triple-row Repair Technique for L-shaped Delaminated Rotator Cuff Tears.

OBJECTIVE: To compare the clinical outcomes of a modified arthroscopic triple-row (TR) repair technique with the suture bridge (SB) repair technique in treating L-shaped delaminated rotator cuff tears. Various surgical techniques for L-shaped delaminated rotator cuff tears have been reported, many of which aid in increasing the contact area and pressure of the rotator cuff. However, there is still debate over which technique yields superior results. METHODS: From January 2017 to March 2020, 61 cases of L-shaped delaminated rotator cuff tears were included in this study. Of these, 34 cases underwent the modified arthroscopic triple-row repair technique, while 27 cases were addressed with the suture bridge repair technique. Functional assessment was conducted using the American Shoulder and Elbow Surgeons (ASES) score, the University of California Los Angeles (UCLA) shoulder score, the Constant score (CS), and the visual analogue scale (VAS) score. Magnetic Resonance Imaging (MRI) assessments for rotator cuff healing were performed at the 24-month postoperative mark. Statistical evaluations were conducted using SPSS for Windows (Version 25.0, IBM, Armonk, NY, USA), employing the Wilcoxon signed-rank test to compare preoperative and postoperative data and ROM differences, and the Mann-Whitney U test for statistical differences in clinical outcome scores between the two groups. A p-value of less than 0.05 was considered statistically significant. RESULTS: Comparative analysis of the preoperative and final follow-up scores revealed a substantial enhancement in shoulder function, as indicated by the ASES, UCLA, CS, and VAS scores, with statistical significance (p < 0.001). At both the preoperative stage and final follow-up, no notable differences were observed in ASES, UCLA, CS, and VAS scores between the two groups. However, the TR repair group exhibited lower VAS scores than the SB group at 1 and 3 months postoperatively. Active range of motion (ROM) showed significant improvement in both groups. No significant differences in ROM were noted between the two groups either before the surgery or at the final follow-up. CONCLUSION: The study demonstrates that both the modified arthroscopic TR and SB techniques for L-shaped delaminated cuff tears yield satisfactory outcomes, with no significant differences in overall clinical performance. Notably, early postoperative pain management appears more effective with the modified TR technique, suggesting its potential for enhanced early recovery experiences. This technique's design, promoting securer fixation and optimal contact conditions, is implied to facilitate superior long-term healing, warranting further investigation into its long-term benefits.

Enhanced Artificial Intelligence Strategies in Renal Oncology: Iterative Optimization and Comparative Analysis of GPT 3.5 Versus 4.0.

BACKGROUND: The rise of artificial intelligence (AI) in medicine has revealed the potential of ChatGPT as a pivotal tool in medical diagnosis and treatment. This study assesses the efficacy of ChatGPT versions 3.5 and 4.0 in addressing renal cell carcinoma (RCC) clinical inquiries. Notably, fine-tuning and iterative optimization of the model corrected ChatGPT's limitations in this area. METHODS: In our study, 80 RCC-related clinical questions from urology experts were posed three times to both ChatGPT 3.5 and ChatGPT 4.0, seeking binary (yes/no) responses. We then statistically analyzed the answers. Finally, we fine-tuned the GPT-3.5 Turbo model using these questions, and assessed its training outcomes. RESULTS: We found that the average accuracy rates of answers provided by ChatGPT versions 3.5 and 4.0 were 67.08% and 77.50%, respectively. ChatGPT 4.0 outperformed ChatGPT 3.5, with a higher accuracy rate in responses (p < 0.05). By counting the number of correct responses to the 80 questions, we then found that although ChatGPT 4.0 performed better (p < 0.05), both versions were subject to instability in answering. Finally, by fine-tuning the GPT-3.5 Turbo model, we found that the correct rate of responses to these questions could be stabilized at 93.75%. Iterative optimization of the model can result in 100% response accuracy. CONCLUSION: We compared ChatGPT versions 3.5 and 4.0 in addressing clinical RCC questions, identifying their limitations. By applying the GPT-3.5 Turbo fine-tuned model iterative training method, we enhanced AI strategies in renal oncology. This approach is set to enhance ChatGPT's database and clinical guidance capabilities, optimizing AI in this field.

Efficacy, Safety, and Population Pharmacokinetics of MW032 Compared With Denosumab for Solid Tumor-Related Bone Metastases: A Randomized, Double-Blind, Phase 3 Equivalence Trial.

Importance: The bioequivalence of denosumab biosimilar has yet to be studied in a 53-week, multicenter, large-scale, and head-to-head trial. A clinically effective biosimilar may help increase access to denosumab in patients with solid tumor-related bone metastases. Objectives: To establish the biosimilarity of MW032 to denosumab in patients with solid tumor-related bone metastases based on a large-scale head-to-head study. Design, Setting, and Participants: In this 53-week, randomized, double-blind, phase 3 equivalence trial, patients with solid tumors with bone metastasis were recruited from 46 clinical sites in China. Overall, 856 patients were screened and 708 eligible patients were randomly allocated to receive either MW032 or denosumab. Interventions: Patients were randomly assigned (1:1) to receive MW032 or reference denosumab subcutaneously every 4 weeks until week 49. Main Outcomes and Measures: The primary end point was percentage change from baseline to week 13 of natural logarithmic transformed urinary N-telopeptide/creatinine ratio (uNTx/uCr). Results: Among the 701 evaluable patients (350 in the MW032 group and 351 in the denosumab group), the mean (range) age was 56.1 (22.0-86.0) years and 460 patients were women (65.6%). The mean change of uNTx/uCr from baseline to week 13 was -72.0% (95% CI, -73.5% to -70.4%) in the MW032 group and -72.7% (95% CI, -74.2% to -71.2%) in the denosumab group. These percent changes corresponded to mean logarithmic ratios of -1.27 and -1.30, or a difference of 0.02. The 90% CI for the difference (-0.04 to 0.09) was within the equivalence margin (-0.13 to 0.13); the mean changes of uNTx/uCr and bone-specific alkaline phosphatase (s-BALP) at each time point were also similar during 53 weeks. The differences of uNTx/uCr change were 0.015 (95% CI, -0.06 to 0.09), -0.02 (95% CI, -0.09 to 0.06), -0.05 (95% CI, -0.13 to 0.03) and 0.001 (95% CI, -0.10 to 0.10) at weeks 5, 25, 37, and 53, respectively. The differences of s-BALP change were -0.006 (95% CI, 0.06 to 0.05), 0.00 (95% CI, -0.07 to 0.07), -0.085 (95% CI, -0.18 to 0.01), -0.09 (95% CI, -0.20 to 0.02), and -0.13 (95% CI, -0.27 to 0.004) at weeks 5, 13, 25, 37 and 53, respectively. No significant differences were observed in the incidence of skeletal-related events (-1.4%; 95% CI, -5.8% to 3.0%) or time to first on-study skeletal-related events (unadjusted HR, 0.86; P = .53; multiplicity adjusted HR, 0.87; P = .55) in the 2 groups. Conclusions and Relevance: MW032 and denosumab were biosimilar in efficacy, population pharmacokinetics, and safety profile. Availability of denosumab biosimilars may broaden the access to denosumab and reduce the drug burden for patients with advanced tumors. Trial Registration: ClinicalTrials.gov Identifier: NCT04812509.

Electroacupuncture attenuates middle cerebral artery occlusion-induced learning and memory impairment by regulating microglial polarization in hippocampus.

BACKGROUND: As a traditional medical therapy, electroacupuncture (EA) has been demonstrated to have beneficial effects on ischemic stroke-induced cognitive impairment. However, the underlying mechanism is largely unclear. METHODS: Adult rats received occlusion of the middle cerebral artery and reperfusion (MCAO/R) to establish the ischemic stroke model. Morris water maze test was performed following EA stimulation at the GV20, PC6, and KI1 acupoints in rats to test the learning and memory ability. Western blot, immunofluorescent staining, and enzyme-linked immunosorbent assay were conducted to assess the cellular and molecular mechanisms. RESULTS: EA stimulation attenuated neurological deficits. In the Morris water maze test, EA treatment ameliorated the MCAO/R-induced learning and memory impairment. Moreover, we observed that MCAO/R induced microglial activation and polarization in the ischemic hippocampus, whereas, EA treatment dampened microglial activation and inhibited M1 microglial polarization but enhanced M2 microglial polarization. EA treatment inhibited the increased expression of proinflammatory cytokines and enhanced the increased expression of anti-inflammatory cytokines. Finally, we found that EA treatment dampened microglial p38 mitogen-activated protein kinase (MAPK) phosphorylation. CONCLUSION: Collectively, our data suggested that EA treatment ameliorated cognitive impairment induced by MCAO/R and the underlying mechanism may be p38-mediated microglia polarization and neuroinflammation.

Green Printing for Scalable Organic Photovoltaic Modules by Controlling the Gradient Marangoni Flow.

Despite the rapid development in the performances of organic solar cells (OSCs), high-performance OSC modules based on green printing are still limited. The severe Coffee-ring effect (CRE) is considered to be the primary reason for the nonuniform distribution of active layer films. To solve this key printing problem, the cosolvent strategy is presented to deposit the active layer films. The guest solvent Mesitylene with a higher boiling point and a lower surface tension is incorporated into the host solvent o-XY to optimize the rheological properties, such as surface tension and viscosity of the active layer solutions. And the synergistic effect of inward Marangoni flow generation and solution thickening caused by the cosolvent strategy can effectively restrain CRE, resulting in highly homogeneous large-area active layer films. In addition, the optimized crystallization and phase separation of active layer films effectively accelerate the charge transport and exciton dissociation of devices. Consequently, based on PM6:BTP-eC9 system, the device prepared with the co-solvent strategy shows the a power conversion efficiency of 17.80%. Moreover, as the effective area scales to 1 and 16.94 cm2 , the recorded performances are altered to 16.71% and 14.58%. This study provides a universal pathway for the development of green-printed high-efficiency organic photovoltaics.

Continuous genetic monitoring of transient mesenchymal gene activities in distal tubule and collecting duct epithelial cells during renal fibrosis.

Epithelial cells (ECs) have been proposed to contribute to myofibroblasts or fibroblasts through epithelial-mesenchymal transition (EMT) during renal fibrosis. However, since EMT may occur dynamically, transiently, and reversibly during kidney fibrosis, conventional lineage tracing based on Cre-loxP recombination in renal ECs could hardly capture the transient EMT activity, yielding inconsistent results. Moreover, previous EMT research has primarily focused on renal proximal tubule ECs, with few reports of distal tubules and collecting ducts. Here, we generated dual recombinases-mediated genetic lineage tracing systems for continuous monitoring of transient mesenchymal gene expression in E-cadherin+ and EpCAM+ ECs of distal tubules and collecting ducts during renal fibrosis. Activation of key EMT-inducing transcription factor (EMT-TF) Zeb1 and mesenchymal markers αSMA, vimentin, and N-cadherin, were investigated following unilateral ureteral obstruction (UUO). Our data revealed that E-cadherin+ and EpCAM+ ECs did not transdifferentiate into myofibroblasts, nor transiently expressed these mesenchymal genes during renal fibrosis. In contrast, in vitro a large amount of cultured renal ECs upregulated mesenchymal genes in response to TGF-ß, a major inducer of EMT.

Cepharanthine suppresses APC-mutant colorectal cancers by down-regulating the expression of ß-catenin.

The aberrant activation of the Wnt/ß-catenin signaling pathway is closely associated with the development of various carcinomas, especially colorectal cancers (CRCs), where adenomatous colorectal polyposis (APC) mutations are the most frequently observed, which limits the anti-tumor efficiency of inhibitors targeting the upstream of Wnt/ß-catenin pathway. The anti-tumor activity of the naturally occurring alkaloid cepharanthine (CEP) extracted from the plant Stephania cepharantha Hayata has been reported in various types of tumors. We previously observed that its derivatives inhibited the Wnt/ß-catenin signaling in liver cancer; however, the specific mechanism remains unknown. In this study, we confirmed CEP can effectively inhibit APC-mutant CRC cell lines (SW480, SW620, LoVo) through disturbing of the Wnt/ß-catenin signaling and elucidated the underlying mechanisms. Here, we demonstrate that CEP attenuates the Wnt/ß-catenin signaling by decreasing the ß-catenin, subsequently impeding the proliferation of APC-mutant CRCs. Moreover, CEP induced ß-catenin transcription inhibition rather than the instability of ß-catenin protein and mRNA contributes to reduction of ß-catenin. Taken together, our findings identify CEP as the first ß-catenin transcriptional inhibitor in the modulation of Wnt/ß-catenin signaling and indicate CEP as a potential therapeutic option for the treatment of APC-mutated CRCs.

Prevalence and causes of vision impairment in elderly Chinese people living in suburban Shanghai.

PURPOSE: To investigate the current prevalence and causes of moderate and severe visual impairment (MSVI) and blindness in elderly people in suburban Shanghai, China. METHODS: A cross-sectional study based on the population was conducted, which involved 5846 individuals (11,692 eyes) aged 65 years or older. Thorough eye examinations were performed to assess the prevalence and leading factors of MSVI (BCVA <20/63 to ≥20/400) and blindness (BCVA <20/400). RESULTS: The standardized prevalence of bilateral MSVI and blindness was 3.3% and 0.6%, correspondingly. The standardized prevalence of monocular MSVI and blindness was 7.4% and 2.0%, correspondingly. Cataract (47.9% and 20.7%, correspondingly) and myopic macular degeneration (MMD, 25.7% and 31.1%, correspondingly) were the principal causes of bilateral MSVI and blindness. As for monocular MSVI, the primary causes were cataract (39.4%), age-related macular degeneration (AMD, 16.6%), and MMD (16.6%). The primary causes of monocular blindness were other posterior segment eye diseases (30.1%) and MMD (14.2%). In adults aged 65-74 years, MMD was the foremost factor causing bilateral vision impairment. Conversely, cataract was identified as the primary cause of bilateral and monocular vision impairment among adults aged ≥ 75 years. AMD accounts for a significant proportion of individuals across all age groups. CONCLUSIONS: The significant prevalence of MSVI and blindness among Chinese adults represents a critical public health issue. In addition to cataract, the vision impairment caused by MMD and AMD become an important issue in the elderly Chinese people.

Evaluation of suitable reference genes for expression profile analyses of target genes in the coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae).

The coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae), is a major destructive insect pest of coffee, which impacts the coffee crops negatively. As a draft genome has been completed for this insect, most molecular studies on gene transcriptional levels under different experimental conditions will be conducted using real-time reverse-transcription quantitative polymerase chain reactions (RT-qPCR). However, the lack of suitable internal reference genes will affect the accuracy of RT-qPCR results. In this study, the expression stability of nine candidate reference genes was evaluated under different developmental stages, temperature stress, and Beauveria bassiana infection. Data analyses were completed by four commonly used programs, BestKeeper, NormFinder, geNorm, and RefFinder. The result showed that RPL3 and EF1α combination were recommended as the most stable reference genes for developmental stages. EF1α and RPS3a combination were the top two stable reference genes for B. bassiana infection. RPS3a and RPL3 combination performed as the optimal reference genes both in temperature stress and all samples. Our results should provide a good foundation for the expression profile analyses of target genes in the future, especially for molecular studies on insect genetic development, temperature adaptability, and immune mechanism to entomogenous fungi in H. hampei.

Reduction of ETV1 is Identified as a Prominent Feature of Age-Related Cataract.

PURPOSE: To identify the inactive genes in cataract lenses and explore their function in lens epithelial cells (LECs). METHODS: Lens epithelium samples obtained from both age-related cataract (ARC) patients and normal donors were subjected to two forms of histone H3 immunoprecipitation: H3K9ac and H3K27me3 chromatin immunoprecipitation (ChIP), followed by ChIP-seq. The intersection set of "active genes in normal controls" and "repressed genes in cataract lenses" was identified. To validate the role of a specific gene, ETV1, within this set, quantitative polymerase chain reaction (qPCR), western blot, and immunofluorescence were performed using clinical lens epithelium samples. Small interference RNA (siRNA) was utilized to reduce the mRNA level of ETV1 in cultured LECs. Following this, transwell assay and western blot was performed to examine the migration ability of the cells. Furthermore, RNA-seq analysis was conducted on both cell samples with ETV1 knockdown and control cells. Additionally, the expression level of ETV1 in LECs was examined using qPCR under H2O2 treatment. RESULTS: Six genes were identified in the intersection set of "active genes in normal controls" and "repressed genes in ARC lenses". Among these genes, ETV1 showed the most significant fold-change decrease in the cataract samples compared to the control samples. After ETV1 knockdown by siRNA in cultured LECs, reduced cell migration was observed, along with a decrease in the expression of ß-Catenin and Vimentin, two specific genes associated with cell migration. In addition, under the oxidative stress induced by H2O2 treatment, the expression level of ETV1 in LECs significantly decreased. CONCLUSIONS: Based on the findings of this study, it can be concluded that ETV1 is significantly reduced in human ARC lenses. The repression of ETV1 in ARC lenses appears to contribute to the disrupted differentiation of lens epithelium, which is likely caused by the inhibition of both cell differentiation and migration processes.

Targeting DAD1 gene with CRISPR-Cas9 system transmucosally delivered by fluorinated polylysine nanoparticles for bladder cancer intravesical gene therapy.

Background: Intravesical chemotherapy is highly recommended after transurethral resection of bladder tumor for patients with bladder cancer (BCa). However, this localized adjuvant therapy has drawbacks of causing indiscriminate damage and inability to penetrate bladder mucosal. Methods: Fluorinated polylysine micelles (PLLF) were synthesized by reacting polylysine (PLL) with heptafluorobutyrate anhydride. Anti-apoptotic gene defender against cell death 1 (DAD1) was selected by different gene expression analysis between BCa patients and healthy individuals and identified by several biological function assays. The gene transfection ability of PLLF was verified by multiple in vitro and in vivo assays. The therapeutic efficiency of PLLF nanoparticles (NPs) targeting DAD1 were confirmed by intravesical administration using an orthotopic BCa mouse model. Results: Decorated with fluorinated chains, PLL can self-assemble to form NPs and condense plasmids with excellent gene transfection efficiency in vitro. Loading with the CRISPR-Cas9 system designed to target DAD1 (Cas9-sgDAD1), PLLF/Cas9-sgDAD1 NPs strongly inhibited the expression of DAD1 in BCa cells and induced BCa cell apoptosis through the MAPK signaling pathway. Furthermore, intravesical administration of PLLF/Cas9-sgDAD1 NPs resulted in significant therapeutic outcomes without systemic toxicity in vivo. Conclusion: The synthetized PLLF can transmucosally deliver the CRISPR-Cas9 system into orthotopic BCa tissues to improve intravesical instillation therapy for BCa. This work presents a new strategy for targeting DAD1 gene in the intravesical therapy for BCa with high potential for clinical applications.

Programmable Compartment Networks by Unraveling the Stress-Dependent Deformation of Polymer Vesicles.

Nanocontainers that can sense and respond to environmental stimuli like cells are desirable for next-generation delivery systems. However, it is still a grand challenge for synthetic nanocontainers to mimic or even surpass the shape adaption of cells, which may produce novel compartments for cargo loading. Here, this work reports the engineering of compartment network with a single polymer vesicle by unraveling osmotic stress-dependent deformation. Specifically, by manipulating the way in exerting the stress, sudden increase or gradual increase, polymer vesicles can either undergo deflation into the stomatocyte, a bowl-shaped vesicle enclosing a new compartment, or tubulation into the tubule of varied length. Such stress-dependent deformation inspired us to program the shape transformation of polymer vesicles, including tubulation, deflation, or first tubulation and then deflation. The coupled deformation successfully transforms the polymer vesicle into the stomatocyte with tubular arms and a network of two or three small stomatocytes connected by tubules. To the author's knowledge, these morphologies are still not accessed by synthetic nanocontainers. This work envisions that the network of stomatocytes may enable the loading of different catalysts to construct novel motile systems, and the well-defined morphology of vesicles helps to define the effect of morphology on cellar uptake.

Unilateral Biportal Endoscopic Posterior Cervical Foraminotomy: An Outcome Comparison With the Full-endoscopic Posterior Cervical Foraminotomy.

STUDY DESIGN: Retrospective control study. OBJECTIVE: To compare the curative effects of unilateral biportal endoscopic posterior cervical foraminotomy (UBE-PCF) with full-endoscopic posterior cervical foraminotomy (FPCF). SUMMARY OF BACKGROUND DATA: There are few studies directly comparing outcomes between UBE-PCF and FPCF. The objective of this study was to compare outcomes between UBE-PCF and FPCF. METHODS: A retrospective control study was conducted for 69 patients of cervical radiculopathy from July 2019 to December 2021. Clinical outcomes scores, including neck disability index, visual analog scale (VAS)-arm, and VAS-neck were evaluated. Serum creatine kinase levels and the size of the operating hole were measured. RESULTS: Postoperative neck disability index, VAS-neck, and VAS-arm scores showed statistically significant improvement over preoperative scores ( P <0.01). The operating time was significantly shorter in the UBE-PCF group ( P <0.001). No significant differences were found in serum creatine kinase levels between the 2 groups ( P >0.05). The mean area of the operating hole was 1.47+0.05 cm 2 in the FPCF group and 1.79+0.11 cm 2 in the UBE-PCF group. The difference was statistically significant ( P <0.001). CONCLUSIONS: Both UBE-PCF and FPCF are safe and effective procedures for cervical radiculopathy. Predictable and sufficient decompression could be achieved by UBE-PCF in a shorter operation time. LEVEL OF EVIDENCE: Treatment Benefits Level III.