TGFß1-Induced Fibrotic Responses of Conjunctival Fibroblasts through the Wnt/ß-Catenin/CRYAB Signaling Pathway.

Conjunctival fibrosis is a common postoperative complication of glaucoma filtration surgery, resulting in uncontrolled intraocular pressure and surgery failure. Therefore, it is urgent to understand the molecular mechanisms underlying conjunctival fibrosis and to explore novel pharmacologic anti-fibrosis therapies for glaucoma filtration surgery. The 4D-DIA quantitative proteomic results, coupled with experimental data, revealed the activation of the Wnt/ß-catenin pathway in transforming growth factor (TGF)-ß1-induced human conjunctival fibroblasts (HConFs). Treatment with ICG-001, a Wnt/ß-catenin inhibitor, effectively inhibited cell proliferation and migration in TGFß1-treated HConFs. ICG-001 treatment alleviated the increased generation of extracellular matrix proteins induced by TGFß1. In addition, ICG-001 reduced the expression level of α smooth muscle actin (α-SMA) and inhibited cell contractility in TGFß1-treated HConFs. Proteomics data further suggested that αB-crystallin (CRYAB) was a downstream target of Wnt/ß-catenin, which was up-regulated by TGFß1 and down-regulated by ICG-001. Immunoblotting assay also indicated that ICG-001 reduced the expressions of ubiquitin and ß-catenin in TGFß1-treated HConFs, implying that CRYAB stabilized ß-catenin by inhibiting its ubiquitination degradation. Exogenous CRYAB promoted cell viability, increased extracellular matrix protein levels, and up-regulated α-SMA expression of HConFs under TGFß1 stimulation. CRYAB rescued TGFß1-induced fibrotic responses that were suppressed by ICG-001. In conclusion, this study elucidates the regulatory mechanism of the Wnt/ß-catenin/CRYAB pathway in conjunctival fibrosis, offering promising therapeutic targets for mitigating bleb scarring after glaucoma filtration surgery.

In-Induced Electronic Structure Modulations of Bi─O Active Sites for Selective Carbon Dioxide Electroreduction to Liquid Fuel in Strong Acid.

The formation of carbonate in neutral/alkaline solutions leads to carbonate crossover, severely reducing carbon dioxide (CO2 ) single pass conversion efficiency (SPCE). Thus, CO2 electrolysis is a prospective route to achieve high CO2 utilization under acidic environment. Bimetallic Bi-based catalysts obtained utilizing metal doping strategies exhibit enhanced CO2 -to-formic acid (HCOOH) selectivity in alkaline/neutral media. However, achieving high HCOOH selectivity remains challenging in acidic media. To this end, Indium (In) doped Bi2O2CO3 via hydrothermal method is prepared for in-situ electroreduction to In-Bi/BiOx nanosheets for acidic CO2 reduction reaction (CO2RR). In doping strategy regulates the electronic structure of Bi, promoting the fast derivatization of Bi2O2CO3 into Bi-O active sites to enhance CO2RR catalytic activity. The optimized Bi2 O2 CO3 -derived catalyst achieves the maximum HCOOH faradaic efficiency (FE) of 96% at 200 mA cm-2 . The SPCE for HCOOH production in acid is up to 36.6%, 2.2-fold higher than the best reported catalysts in alkaline environment. Furthermore, in situ Raman and X-ray photoelectron spectroscopy demonstrate that In-induced electronic structure modulation promotes a rapid structural evolution from nanobulks to Bi/BiOx nanosheets with more active species under acidic CO2 RR, which is a major factor in performance improvement.

Synergistic Effects of PtRhNiFeCu High Entropy Alloy Nanocatalyst for Hydrogen Evolution and Oxygen Reduction Reactions.

The unique properties of high entropy alloy (HEA) catalysts, particularly their severe lattice distortion and the synergistic effect of multiple components, endow them with exceptional multifunctional catalytic performance. Herein, it is revealed for the first time, that the ultrasmall PtRhNiFeCu HEA nanoparticles catalyst shows outstanding catalytic activity for both hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR). The catalyst exhibits an impressively low overpotential of 13 mV at 10 mA cm-2, a Tafel slope of 29.6 mV dec-1, and high mass activity of 7.6 A mgPt -1 at -50 mV in alkaline media, and long-term stability of at least 20 h. Moreover, the catalyst also demonstrates effective catalytic activity for acidic ORR with a commendable performance of 1.23 A mgPt -1, much exceeding the commercial Pt/C catalyst. Density functional theory (DFT) calculations unveil that the efficient electrocatalytic performance for HER and ORR can be primarily attributed to the synergistic effect between components tailors and optimizes the electronic structure of PtRhNiFeCu/C HEA, which not only enhances the HER activity through increasing water capture capability, decreasing energetic barrier for water dissociation, and optimizing hydrogen absorption but also initiates non-platinum active sites with high ORR activity, achieving the improved ORR performance.

lncTIMP3 promotes osteogenic differentiation of bone marrow mesenchymal stem cells via miR-214/Smad4 axis to relieve postmenopausal osteoporosis.

BACKGROUND: Promoting the balance between bone formation and bone resorption is the main therapeutic goal for postmenopausal osteoporosis (PMOP), and bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation plays an important regulatory role in this process. Recently, several long non-coding RNAs (lncRNAs) have been reported to play an important regulatory role in the occurrence and development of OP and participates in a variety of physiological and pathological processes. However, the role of lncRNA tissue inhibitor of metalloproteinases 3 (lncTIMP3) remains to be investigated. METHODS: The characteristics of BMSCs isolated from the PMOP rat model were verified by flow cytometry assay, alkaline phosphatase (ALP), alizarin red and Oil Red O staining assays. Micro-CT and HE staining assays were performed to examine histological changes of the vertebral trabeculae of the rats. RT-qPCR and western blotting assays were carried out to measure the RNA and protein expression levels. The subcellular location of lncTIMP3 was analyzed by FISH assay. The targeting relationships were verified by luciferase reporter assay and RNA pull-down assay. RESULTS: The trabecular spacing was increased in the PMOP rats, while ALP activity and the expression levels of Runx2, Col1a1 and Ocn were all markedly decreased. Among the RNA sequencing results of the clinical samples, lncTIMP3 was the most downregulated differentially expressed lncRNA, also its level was significantly reduced in the OVX rats. Knockdown of lncTIMP3 inhibited osteogenesis of BMSCs, whereas overexpression of lncTIMP3 exhibited the reverse results. Subsequently, lncTIMP3 was confirmed to be located in the cytoplasm of BMSCs, implying its potential as a competing endogenous RNA for miRNAs. Finally, the negative targeting correlations of miR-214 between lncTIMP3 and Smad4 were elucidated in vitro. CONCLUSION: lncTIMP3 may delay the progress of PMOP by promoting the activity of BMSC, the level of osteogenic differentiation marker gene and the formation of calcium nodules by acting on the miR-214/Smad4 axis. This finding may offer valuable insights into the possible management of PMOP.

Impact of LDLR polymorphisms on lipid levels and atorvastatin's efficacy in a northern Chinese adult Han cohort with dyslipidemia.

BACKGROUND: Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia. METHODS: In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3' untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P < 0.05 indicating statistical significance. Assessment of linkage disequilibrium patterns and haplotype structures was conducted utilizing Haploview. RESULTS: Eleven distinct polymorphisms at LDLR 3' UTR were identified. Seven polymorphisms (rs1433099, rs14158, rs2738466, rs5742911, rs17249057, rs55971831, and rs568219285) were correlated with the baseline serum lipid levels (P < 0.05). In particular, four polymorphisms (rs14158, rs2738466, rs5742911, and rs17249057) were in strong linkage disequilibrium (r2 = 1), and patients with the AGGC haplotype had higher TC and LDL-C levels at baseline. Three polymorphisms (rs1433099, rs2738467, and rs7254521) were correlated with the therapeutic efficacy of atorvastatin (P < 0.05). Furthermore, carriers of the rs2738467 T allele demonstrated a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) levels post-atorvastatin treatment (P = 0.03), indicating a potentially crucial genetic influence on therapeutic outcomes. Two polymorphisms (rs751672818 and rs566918949) were neither correlated with the baseline serum lipid levels nor atorvastatin's efficacy. CONCLUSIONS: This research outlined the complex genetic architecture surrounding LDLR 3' UTR polymorphisms and their role in lipid metabolism and the response to atorvastatin treatment in adult Han Chinese patients with dyslipidemia, highlighting the importance of genetic profiling in enhancing tailored therapeutic strategies. Furthermore, this investigation advocates for the integration of genetic testing into the management of dyslipidemia, paving the way for customized therapeutic approaches that could significantly improve patient care. TRIAL REGISTRATION: This multicenter study was approved by the Ethics Committee of Xiangya Hospital Central South University (ethics number K22144). It was a general ethic. In addition, this study was approved by The First Hospital of Hebei Medical University (ethics number 20220418).

Interaction between visual impairment and subjective cognitive complaints on physical activity impairment in U.S. older adults: NHANES 2005-2008.

BACKGROUND/AIM: To investigate the independent relationships of visual impairment (VI) and Subjective cognitive complaints (SCC) with physical function impairment (PFI) and the interaction effect between VI and SCC on PFI in American older adults. METHODS: The data of this cross-sectional study was obtained from the 2005-2008 National Health and Examination Survey (NHANES) conducted in the United States. The VI criterion included both subjective self-reported eyesight conditions and objective visual acuity test results. The self-reported questionnaires were utilized to determine PFI and SCC. According to the survey design of NHANS, original data were weighted to produce nationally representative estimates. Both the unweighted original data and weighted estimates underwent analysis. Crude and adjusted logistic models were employed to assess the pairwise associations among VI, SCC, and PFI. To assess the interactive effect, measures such as the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) were calculated. RESULTS: A total of 2,710 subjects (weighted n = 38,966,687) aged 60 years or older were included. Compared with subjects without subjective visual impairment (SVI), those with SVI had a significant positive association with PFI [weighted OR (95%CI): 3.11 (2.25, 4.31)]. After multi-variable adjusting, the relationship remained significant [weighted OR (95%CI): 1.90 (1.32, 2.72)]. Similarly, those with objective visual impairment (OVI) were positively associated with the risk of PFI in the crude model [weighted OR (95%CI): 2.35 (1.53, 3.61)] and adjusted model [weighted OR (95%CI): 1.84 (1.07, 3.17)]. Moreover, we found the association of SCC with an increased risk of FPI [crude weighted OR (95%CI): 5.02 (3.40, 7.40); adjusted weighted OR (95%CI): 3.29 (2.01, 5.38)]. Ultimately, the additive interaction showed there was a significant positive interaction term between SVI and SCC on PFI, while OVI and SCC did not. CONCLUSION: Both VI and SCC were significantly associated with PFI in elder adults. Besides, there was a significant synergistic interaction between SVI and SCC on PFI, which indicated the improvement of SVI and SCC may be beneficial for the prevention of PFI. For the elderly, especially those with multiple disabilities, comprehensive and targeted approaches are imperative to foster their overall well-being and health.

A Deep Learning Model for Detecting Rhegmatogenous Retinal Detachment Using Ophthalmologic Ultrasound Images.

INTRODUCTION: Rhegmatogenous retinal detachment (RRD) is one of the most common fundus diseases. Many rural areas of China have few ophthalmologists, and ophthalmologic ultrasound examination is of great significance for remote diagnosis of RRD. Therefore, this study aimed to develop and evaluate a deep learning (DL) model, to be used for automated RRD diagnosis based on ophthalmologic ultrasound images, in order to support timely diagnosis of RRD in rural and remote areas. METHODS: A total of 6,000 ophthalmologic ultrasound images from 1,645 participants were used to train and verify the DL model. A total of 5,000 images were used for training and validating DL models, and an independent testing set of 1,000 images was used to test the performance of eight DL models trained using four different DL model architectures (fully connected neural network, LeNet5, AlexNet, and VGG16) and two preprocessing techniques (original, original image augmented). Receiver operating characteristic (ROC) curves were used to analyze their performance. Heatmaps were generated to visualize the process of the best DL model in the identification of RRD. Finally, five ophthalmologists were invited to diagnose RRD independently on the same test set of 1,000 images for performance comparison with the best DL model. RESULTS: The best DL model for identifying RRD achieved an area under the ROC curve (AUC) of 0.998 with a sensitivity and specificity of 99.2% and 99.8%, respectively. The best preprocessing method in each model architecture was the application of original image augmentation (average AUC = 0.982). The best model architecture in each preprocessing method was VGG16 (average AUC = 0.998). CONCLUSION: The best DL model determined in this study has higher accuracy, sensitivity, and specificity than the ophthalmologists' diagnosis in identifying RRD based on ophthalmologic ultrasound images. This model may provide support for timely diagnosis in locations without access to ophthalmologic care.

Novel Variants of HPS6 Cause Suspected Ocular Albinism: A Report of 2 Cases and the Profile of HPS6 Variants.

INTRODUCTION: Hermansky-Pudlak syndrome (HPS) is a rare autosomal-recessive disease characterized by ocular albinism (OA) or oculocutaneous albinism (OCA), platelet dysfunction, and other symptoms. This study aimed to analyze the molecular defect in two Chinese families with suspected OA, as well as to investigate the profile of HPS6 variants and their genotype-phenotype correlations. METHODS: Seven members from two families were recruited and underwent clinical ophthalmologic examinations. The genomic DNA was extracted from peripheral blood leukocytes. Whole-exome sequencing was performed on the proband of family JX. The single coding exon of HPS6 was directly Sanger sequenced based on PCR amplification in all available family members. An additional 46 probands from families or sporadic cases with the pathogenic variants of HPS6 reported in the literature were reviewed. RESULTS: We identified two different compound heterozygous truncating variants of HPS6 in probands with suspected OA from two independent families. The proband of family JX had c.1674dup and c.503-504del variants, and the other proband from family CZ had a nonsense variant of c.1114C>T and a frameshift variant of c.1556del. Among them, c.1674dup and c.1556del variants in HPS6 have not been reported previously. Therefore, our patients were diagnosed as HPS6 disease by molecular diagnostics. In the retrospective cohort of HPS6 patients, we delineated the profile of HPS6 variants and revealed a significant overlap between CpG islands and the variants of HPS6, suggesting a potential link between DNA methylation and HPS6 variants. We also observed a spatial aggregation of the variants in 3D structure of HPS6 protein, implying the possible functional significance of these structural regions. In addition, we did not find any significant genotype-phenotype correlation of HPS6, and neither did we observe a correlation between the truncation length of the HPS6 protein and the phenotype of HPS6 disease. CONCLUSION: Our research expands the spectrum of HPS6 variants, providing a comprehensive delineation of their profile and systematically investigating genotype-phenotype correlations in HPS6. These findings could offer potentially valuable clues for investigating the molecular mechanism underlying HPS6 pathogenesis, as well as aiding the clinical diagnosis of HPS6 patients and improving disease prognosis.

Clinical observation of phacoemulsification under the low perfusion pattern and low negative pressure in patients with low corneal endothelial cell density.

BACKGROUND: To observe the safety and effect of phacoemulsification combined with intraocular lens (IOL) implantation in patients with low corneal endothelial cell density (CD) under the low perfusion pattern with low negative pressure. METHODS: In this retrospective case series study, a total of 16 patients (17 eyes) were studied. They had all been diagnosed with low corneal endothelial (CD) and cataracts in the First Affiliated Hospital of Fujian Medical University from December 2019 to October 2021. They underwent phacoemulsification combined with IOL implantation under the low perfusion pattern with low negative pressure. The variations of corneal endothelial( CD), coefficient of variation (CV) of the cell area, central corneal thickness (CCT), visual acuity, and intraocular pressure before and after the operation were observed and assessed. Then a paired t-test, repeated measures analysis of variance, and Pearson correlation analysis were adopted for data analysis. RESULTS: The mean intraocular pressure of the 17 eyes was 16.88 ± 6.47 mmHg before the operation and 14.41 ± 3.10 mmHg after the operation, showing a statistically significant difference of t = 2.222, and p = 0.041. Before the operation, the mean visual acuity was 0.16 ± 0.09, and after the operation, it was 0.45 ± 0.16, displaying a statistically significant difference of t = -9.917, p < 0.001. Before and after the operation, four of the 17 eyes had no detectable CD. The mean CD of the other 13 eyes at one month after the operation (644.308 ± 106.24 cells/mm2) was lower than that before the operation (709.62 ± 119.19 cells/mm2), and the differences were statistically significant (F = 20.044, p < 0.001). However, no statistically significant differences were found in the mean CV before the operation (31.23 ± 4.21), and at one month after the operation (32.62 ± 3.80; F = 2.130, p = 0.157). Moreover, the mean CCT of 14 eyes at one month after the operation (562.72 ± 27.82 µm) was larger than that before the operation (534.79 ± 24.69 µm). CONCLUSIONS: The low perfusion pattern with low negative pressure is safe and effective for corneal endothelial dysfunction patients complicated with cataracts.

Monitoring lesion activity on primary teeth with CP-OCT and SWIR reflectance imaging.

OBJECTIVE: The purpose of this study was to use cross polarization optical coherence tomography (CP-OCT) and short wavelength infrared imaging (SWIR) reflectance imaging to monitor changes in the structure and activity of early occlusal caries on primary teeth over a period of 6 months during intervention with fluoride. METHODS: Participants (n = 29) aged 6-10 each with two suspected active occlusal lesions on primary teeth completed the study. Fluoride varnish was applied to tooth surfaces every 3-months and participants were instructed to brush twice daily with a fluoride toothpaste. Images were acquired using CP-OCT every 3 months for 6 months. SWIR reflectance images were acquired during forced air-drying of the lesions for 30 s at 0 and 6-months. RESULTS: Most of the 42 lesions appeared initially active at baseline. Only 6 lesions appeared arrested at baseline based on the presence of a highly mineralized transparent surface layer (TSL) in CP-OCT images. At 6 months, 14 of the lesions appeared arrested including the 6 initially arrested lesions and the TSL thickness increased significantly (p < 0.0001). The mean lesion depth (Ld) and the integrated reflectivity over the lesion depth (ΔR) increased significantly (p < 0.05) after 6 months for the 42 lesions analyzed. SWIR reflectance images showed that there was a significantly higher (p < 0.05) delay before changes in intensity were measured for active lesions versus arrested lesions during lesion drying. CONCLUSION: CP-OCT was able to monitor changes in lesion structure and activity including the formation of a highly mineralized TSL indicative of lesion arrest during nonsurgical intervention. Time-resolved SWIR reflectance imaging also shows that there are differences in the dehydration kinetics between active and arrested lesions. This study demonstrates two independent imaging methods that can be used to monitor changes in lesion activity over time.

Boosting Hydrogen Peroxide Electrosynthesis via Modulating the Interfacial Hydrogen-Bond Environment.

Designing highly efficient and stable electrode-electrolyte interface for hydrogen peroxide (H2 O2 ) electrosynthesis remains challenging. Inhibiting the competitive side reaction, 4 e- oxygen reduction to H2 O, is essential for highly selective H2 O2 electrosynthesis. Instead of hindering excessive hydrogenation of H2 O2 via catalyst modification, we discover that adding a hydrogen-bond acceptor, dimethyl sulfoxide (DMSO), to the KOH electrolyte enables simultaneous improvement of the selectivity and activity of H2 O2 electrosynthesis. Spectral characterization and molecular simulation confirm that the formation of hydrogen bonds between DMSO and water molecules at the electrode-electrolyte interface can reduce the activity of water dissociation into active H* species. The suitable H* supply environment hinders excessive hydrogenation of the oxygen reduction reaction (ORR), thus improving the selectivity of 2 e- ORR and achieving over 90 % selectivity of H2 O2 . This work highlights the importance of regulating the interfacial hydrogen-bond environment by organic molecules as a means of boosting electrochemical performance in aqueous electrosynthesis and beyond.

A web-based database server using 43,710 public RNA-seq samples for the analysis of gene expression and alternative splicing in livestock animals.

BACKGROUND: Livestock animals is of great significance in agricultural production. However, the role of specific gene expression, especially alternative splicing in determining phenotype, is not well understood. The livestock research community needs a gene expression and alternative splicing database contributing to livestock genetic improvement. DESCRIPTION: We report the construction of LivestockExp ( https://bioinfo.njau.edu.cn/livestockExp ), a web-based database server for the exploration of gene expression and alternative splicing using 43,710 uniformly processed RNA-seq samples from livestock animals and several relative species across six orders. The database is equipped with basic querying functions and multiple online analysis modules including differential/specific expression analysis, co-expression network analysis, and cross-species gene expression conservation analysis. In addition to the re-analysis of public datasets, users can upload personal datasets to perform co-analysis with public datasets. The database also offers a wide range of visualization tools and diverse links to external databases enabling users to efficiently explore the results and to gain additional insights. CONCLUSION: LivestockExp covers by far the largest number of livestock animal species and RNA-seq samples and provides a valuable data resource and analysis platform for the convenient utilization of public RNA-seq datasets.

Dynamically Formed Surfactant Assembly at the Electrified Electrode-Electrolyte Interface Boosting CO2 Electroreduction.

Electrocatalytic reactions occur in the nanoscale space at the electrified electrode-electrolyte interface. It is well known that the electrode-electrolyte interface, also called as interfacial microenvironment, is difficult to investigate due to the interference of bulk electrolytes and its dynamic evolution in response to applied bias potential. Here, we employ electrochemical co-reduction of CO2 and H2O on commercial Ag electrodes as a model system, in conjunction with quaternary ammonium cationic surfactants as electrolyte additives. We probe bias-potential-driven dynamic response of the interfacial microenvironment as well as the mechanistic origin of catalytic selectivity. By virtue of comprehensive in situ vibrational spectroscopy, electrochemical impedance spectroscopy, and molecular dynamics simulations, it is revealed that the structure of surfactants is dynamically changed from a random distribution to a nearly ordered assembly with increasing bias potential. The nearly ordered surfactant assembly regulates the interfacial water environment by repelling isolated water and suppressing water orientation into an ordered structure as well as promotes CO2 enrichment at the electrified interface. Eventually, the formed hydrophobic-aerophilic interface microenvironment reduces the activity of water dissociation and increases the selectivity of CO2 electroreduction to CO. These results highlight the importance of regulating the interfacial microenvironment by organic additives as a means of boosting the electrochemical performance in electrosynthesis and beyond.

Stable Bismuth-Doped Lead Halide Perovskite Core-Shell Nanocrystals by Surface Segregation Effect.

Lead halide perovskite nanocrystals (NCs) exhibit excellent optoelectronic performance, however, the broad application is limited by their poor stability. Herein, a strategy for stable core-shell structured bismuth-doped lead halide perovskite NCs is reported. The stable core-shell perovskite NCs are prepared based on heterovalent substitutions and surface segregation effect. Core-shell features are revealed through advanced characterization and structure analyses. Meanwhile, the transfer of carriers between the core and the shell is observed by ultrafast transient absorption spectroscopy. The core-shell structured perovskite NCs exhibit outstanding structure stability and retain 97% of the original photocatalytic efficiency after cycle experiments under moisture ambient and light irradiation. Such a core-shell structure constructs gradient energy levels. These findings are expected to facilitate the development of stable lead halide perovskite devices.

Enhancing Channel Contention Efficiency in IEEE 802.15.4 Wireless Networks.

Numerous Internet of Things (IoT) devices adopt the IEEE 802.15.4 standard, which targets low data rate wireless networks. With the explosive growth in the use of IoT devices, it is essential to design effective and efficient channel access schemes for the 802.15.4 networks. In order to improve channel contention efficiency (CCE), which is defined as the number of times of successfully gaining the channel per unit of backoff time whereby throughput is improved, the scheme of enhancing channel contention efficiency (ECCE) has been proposed to jointly optimize the three key parameters of macMinBe, macMaxBe and macMaxCsmaBackoffs in the carrier sense multiple access with collision avoidance (CSMA-CA) mechanism in the 802.15.4 standard. A novel Markov chain was developed to model the CSMA-CA mechanism, which yielded the expected number of failures in gaining the channel, the expected number of backoff periods and the expected number of backoffs when a node intended to transmit a packet. These statistics resulted in CCE. An optimization problem that maximized the CCE with respect to the above-mentioned three key parameters was formulated. The solution to the optimization problem led to the optimal parameter values, which were applied in the ECCE scheme. The simulation results show that the proposed ECCE scheme outperformed the CSMA-CA mechanism in terms of CCE, delay and throughput.

Super-Coordinated Nickel N4 Ni1 O2 Site Single-Atom Catalyst for Selective H2 O2 Electrosynthesis at High Current Densities.

Electrochemical production of hydrogen peroxide (H2 O2 ) from O2 on single-atom catalysts has attracted great attention, yet the quest for robust catalysts is driven by achieving >90 % Faradaic efficiency (FE) under industrial-relevant current densities (>100 mA cm-2 ). Herein we synthesize a catalyst that contains single nickel site coordinated by four nitrogen and two oxygen atoms (i.e., N4 Ni1 O2 ) via involving carboxyl functionalized multiwall carbon nanotubes as a substrate to provide extra O coordination to the regular NiN4 site. It has a cathodic energy efficiency of approximately 82 % and a H2 O2 FE of around 96 % at 200 mA cm-2 current density, outperforming the reported single-atom catalysts for H2 O2 electrosynthesis.

The exosomes derived from CAR-T cell efficiently target mesothelin and reduce triple-negative breast cancer growth.

Genetically engineered T cells expressing a chimeric antigen receptor (CAR) have rapidly developed into a powerful and innovative therapeutic modality for cancer patients. However, the problem of dose-dependent systemic toxicity cannot be ignored. In this study, exosomes derived from mesothelin (MSLN)-targeted CAR-T cells were isolated, and we found that they maintain most characteristics of the parental T cells, including surface expression of the CARs and CD3. Furthermore, CAR-carrying exosomes significantly inhibited the growth of both endogenous and exogenous MSLN-positive triple-negative breast cancer (TNBC) cells. The expression of the effector molecules perforin and granzyme B may be a mechanism of tumor killing. More importantly, a highly effective tumor inhibition rate without obvious side effects was observed with the administration of CAR-T cell exosomes in vivo. Thus, the use of CAR-T cell exosomes has great therapeutic potential against MSLN-expressing TNBC.

Forkhead domain inhibitory-6 attenuates subconjunctival fibrosis in rabbit model with trabeculectomy.

Antiproliferative therapies are crucially important for improving the success rate of the glaucoma filtration surgeries. In this study, we investigated the potential efficacy of Forkhead Domain Inhibitory-6 (FDI-6) in inhibiting post-trabeculectomy subconjunctival fibrosis. In vitro, the effect of FDI-6 (10 µM) on fibrotic response and its underlying mechanism were investigated in rabbit tenon's fibroblasts (RTFs) treated with or without transforming growth factor-ß1 (TGF-ß1, 20 ng/mL). In vivo, FDI-6 (40 µM) was injected subconjunctivally to a rabbit trabeculectomy model. Intraocular pressure (IOP) changes were monitored within the 14-day period post-surgery. Bleb morphology and subepithelial fibrosis at the operating area were evaluated with slit lamp and confocal microscopic examinations and with histologic examinations. The results showed that, in cell culture studies, FDI-6 suppressed the proliferation, migration, collagen gel contraction and the expression levels of fibronectin (FN) and α-smooth muscle actin (α-SMA) in RTFs with TGF-ß treatment by down-regulating the TGF-ß1/Smad2/3 signaling pathway. In animal studies, the IOPs of the FDI-6-treated group were significantly lower than those of the saline-treated group after trabeculectomy. The FDI-6-treated eyes showed a better bleb appearance with fewer blood vessels compared to the saline-treated eyes. The analysis of confocal microscopy in vivo and histopathology revealed that subconjunctival fibrosis after trabeculectomy was significantly attenuated in the FDI-6-treated group compared to the controls. In conclusion, our studies indicate that FDI-6 exerts an inhibitory effect on subconjunctival fibrosis caused by trabeculectomy, holding potentials as a new antiproliferative agent used in anti-glaucoma filtration surgeries in the future.

Upregulation of microRNA-155 Enhanced Migration and Function of Dendritic Cells in Three-dimensional Breast Cancer Microenvironment.

Background: Dendritic cells (DCs) play an essential role in the induction and regulation of immune responses, including the activation of effector T lymphocytes for the eradication of cancers. However, the tumor microenvironment (TME) often leads to DCs dysfunction due to their immature state. MicroRNA-155 (miR-155) has emerged as a typical multifunctional gene regulator associated with immune system development and immune cell activation and differentiation.Methods: In this study, a three-dimensional TME model that closely mimics the microenvironment of breast cancer was prepared. MiR-155 overexpression and control vectors were constructed using lentivirus. The relative expression of miR-155 was determined by qRT-PCR. Cell viability, antigen uptake and cell surface marker expression were analyzed by live-dead staining and flow cytometry. The migration ability of bone marrow-derived DCs (BMDCs) was qualified by transwell assay. A mixed lymphocyte culture assay was used to assess T cell-specific proliferation. Cytokine levels were determined by ELISA.Results: We found that the expression of miR-155 in DCs was inhibited by the TME. Furthermore, upregulation of miR-155 enhanced the migration ability, uptake of antigen and elevated the expression of the mature DCs markers CD80 and MHCII. More importantly, overexpression of miR-155 in DCs significantly induced T cell proliferation and IFN-γ and IL-2 secretion.Conclusion: MiR-155 is a potential molecular regulator that may improve the efficacy of DCs-based tumor immunotherapy.

Transcriptome analysis of lateral buds from Phyllostachys edulis rhizome during germination and early shoot stages.

BACKGROUND: The vegetative growth is an important stage for plants when they conduct photosynthesis, accumulate and collect all resources needed and prepare for reproduction stage. Bamboo is one of the fastest growing plant species. The rapid growth of Phyllostachys edulis results from the expansion of intercalary meristem at the basal part of nodes, which are differentiated from the apical meristem of rhizome lateral buds. However, little is known about the major signaling pathways and players involved during this rapid development stage of bamboo. To study this question, we adopted the high-throughput sequencing technology and compared the transcriptomes of Moso bamboo rhizome buds in germination stage and late development stage. RESULTS: We found that the development of Moso bamboo rhizome lateral buds was coordinated by multiple pathways, including meristem development, sugar metabolism and phytohormone signaling. Phytohormones have fundamental impacts on the plant development. We found the evidence of several major hormones participating in the development of Moso bamboo rhizome lateral bud. Furthermore, we showed direct evidence that Gibberellic Acids (GA) signaling participated in the Moso bamboo stem elongation. CONCLUSION: Significant changes occur in various signaling pathways during the development of rhizome lateral buds. It is crucial to understand how these changes are translated to Phyllostachys edulis fast growth. These results expand our knowledge on the Moso bamboo internodes fast growth and provide research basis for further study.