Cellular senescence mediates retinal ganglion cell survival regulation post-optic nerve crush injury.

Traumatic optic neuropathy refers to optic nerve (ON) injury by trauma, including explosion and traffic accident. Retinal ganglion cell (RGC) death is the critical pathological cause of irreversible visual impairment and blindness in ON injury. We previously investigated the patterns of 11 modes of cell death in mouse retina post-ON injury. Here we aimed to identify additional signalling pathways regulating RGC survival in rodents post-ON injury. RNA sequencing analysis identified the upregulation of inflammation and cellular senescence-related genes in retina post-ON injury, which were confirmed by immunoblotting and immunofluorescence analyses. Increased expression of senescence-associated ß-galactosidase (SA-ßgal) in RGCs and activation of microglia were also found. Transforming growth factor-ß receptor type II inhibitor (LY2109761) treatment suppressed p15Ink4b and p21Cip1 protein and SA-ßgal expression and promoted RGC survival post-ON injury with decreasing the expression of cell death markers in retina. Consistently, senolytics (dasatinib and quercetin) treatments can promote RGC survival and alleviate the reduction of ganglion cell complex thickness and pattern electroretinography activity post-ON injury with reducing SA-ßgal, p15Ink4b, p21Cip1, microglial activation and cell death marker expression. In summary, this study revealed the activation of cellular senescence in rodent retina post-ON injury and contribute to RGC survival regulation. Targeting cellular senescence can promote RGC survival after ON injury, suggesting a potential treatment strategy for traumatic optic neuropathy.

Cost of lost productivity in inflammatory arthritis and osteoarthritis in the year before and after diagnosis: An inception cohort study.

AIM: Existing studies on the cost of inflammatory arthritis (IA) and osteoarthritis (OA) are often cross-sectional and/or involve patients with various disease durations, thus not providing a comprehensive perspective on the cost of illness from the time of diagnosis. In this study, we therefore assessed the cost of lost productivity in an inception cohort of patients with IA and OA in the year before and after diagnosis. METHODS: Employment status, monthly income, days absent from work, and presenteeism were collected at diagnosis and 1 year later to estimate the annual costs of unemployment, absenteeism, and presenteeism using human capital approach. Non-parametric bootstrapping was performed to account for the uncertainty of the estimated costs. RESULTS: Compared to patients with OA (n = 64), patients with IA (n = 102, including 48 rheumatoid arthritis, 19 spondyloarthritis, 23 psoriatic arthritis, and 12 seronegative IA patients) were younger (mean age: 52.3 vs. 59.5 years) with a greater proportion receiving treatment (99.0% vs. 67.2%) and a greater decrease in presenteeism score (median: 15% vs 10%) 1 year after diagnosis. Annual costs of absenteeism and presenteeism were lower in patients with IA than those with OA both in the year before (USD566 vs. USD733 and USD8,472 vs. USD10,684, respectively) and after diagnosis (USD636 vs. USD1,035 and USD6,866 vs. USD9,362, respectively). CONCLUSION: Both IA and OA impose substantial cost of lost productivity in the year before and after diagnosis. The greater improvement in productivity seen in patients with IA suggests that treatment for IA improves work productivity.

Management of Idiopathic Intracranial Hypertension: A Case Report.

ABSTRACT: BACKGROUND: Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by elevated intracranial pressure, affecting predominantly obese women of childbearing age. Early recognition and comprehensive management are vital for preventing severe complications, particularly vision loss. METHODS: This study reports a case of a 27-year-old woman who presented with chronic headaches and blurred vision. Notable findings included headaches that were intensified upon waking and exacerbated by activities that elevated intracranial pressure. The patient also reported nausea, vomiting, transient visual obscurations, and pulsatile tinnitus. After a clinical examination, she was given a diagnosis of IIH. RESULTS: The patient underwent a lumbar-peritoneal shunt procedure to alleviate her symptoms in conjunction with medication treatment. This case study highlights the importance of a multidisciplinary approach in diagnosing and treating IIH. In particular, weight management emerged as a crucial preventive measure against IIH recurrence. CONCLUSION: A multidisciplinary team strategy can enhance outcomes and quality of life, accentuating the need for continued research into IIH recurrence, treatments, and wider implications.

Fe(III)/peroxymonosulfate oxidation system for the degradation of rhein, a toxic component abundance in rhubarb residue.

Rhubarb is widely used in health care, but causing a great amount of rhein-containing herbal residue. Rhein with several toxicities might pollute environment, damage ecology and even hazard human health if left untreated. In this study, the degradation effects of bisulfite- (BS) and peroxymonosulfate- (PMS) based oxidation systems on rhein in rhubarb residue were compared and investigated. The effects of BS and PMS with two valence states of ferric ion (Fe) on the degradation of rhein in rhubarb residue were optimized for the selection of optimal oxidation system. The influences of reaction temperature, reaction time and initial pH on the removal of rhein under the optimal oxidation system were evaluated. The chemical profiles of rhubarb residue with and without oxidation process were compared by UPLC-QTOF-MS/MS, and the degradation effects were investigated by PLS-DA and S plot/OPLS-DA analysis. The results manifested that PMS showed relative higher efficiency than BS on the degradation of rhein. Moreover, Fe(III) promoted the degradation effect of PMS, demonstrated that Fe(III)/PMS is the optimal oxidation system to degrade rhein in rhubarb residue. Further studies indicated that the degradation of rhein by the Fe(III)/PMS oxidation system was accelerated with the prolong of reaction time and the elevation of reaction temperature, and also affected by the initial pH. More importantly, Fe(III)/PMS oxidation system could degrade rhein in rhubarb residue completely under the optimal conditions. In conclusion, Fe(III)/PMS oxidation system is a feasible method to treat rhein in rhubarb residue.

Unraveling a Small Secreted Peptide SUBPEP3 That Positively Regulates Salt-Stress Tolerance in Pyrus betulifolia.

Small secreted peptides (SSPs) play important roles in regulating plants' growth and development in response to external stimulus, but the genes and functions of SSPs in many species are still unknown. Therefore, it is particularly significant to characterize and annotate SSP genes in plant genomes. As a widely used stock of pears, Pyrus betulifolia has strong resistance to biotic and abiotic stresses. In this study, we analyzed the SSPs genes in the genome of P. betulifolia according to their characteristics and homology. A total of 1195 SSP genes were identified, and most of them are signaling molecules. Among these, we identified a new SSP, subtilase peptide 3 (SUBPEP3), which derived from the PA region of preSUBPEP3, increasing the expression level under salt stress. Both adding synthetic peptide SUBPEP3 to the culture medium of pears and the overexpression of SUBPEP3 in tobacco can improve the salt tolerance of plants. In summary, we annotated the SSP genes in the P. betulifolia genome and identified a small secreted peptide SUBPEP3 that regulates the salt tolerance of P. betulifolia, which provides an important theoretical basis for further revealing the function of SSPs.

Biogated mesoporous silica nanoagents for inhibition of cell migration and combined cancer therapy.

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.

Integrating UPLC-QTOF-MS/MS and UPLC-DAD to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on the overall quality of three Si-Wu-Tang formulations.

INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

Adherence to the low-fat diet pattern reduces the risk of lung cancer in American adults aged 55 years and above: a prospective cohort study.

OBJECTIVES: There is little evidence on the association between low-fat dietary patterns and lung cancer risk among middle-aged and older adults. To fill this gap, we comprehensively investigated the association of adherence to a low-fat diet (LFD) and intake of different fat components including saturated, monounsaturated, and polyunsaturated fatty acids with incidence of lung cancer and its subtypes [non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] among adults aged 55 years and older. DESIGN: A prospective cohort study with a mean follow-up time of 8.8 years. SETTING AND PARTICIPANTS: This study used data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The study population included 98,459 PLCO participants age 55 and over at baseline who completed food frequency questionnaires providing detailed dietary information and had no history of cancer. METHODS: Dietary intake was assessed using a validated food frequency questionnaire at baseline. A LFD score was calculated based on fat, protein, and carbohydrate intake as a percentage of total calories. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LFD score and intake of fat components (in quartiles) and incident lung cancer and its subtypes over follow-up. Restricted cubic spline analyses were conducted to examine possible nonlinear relationships. Subgroup analyses were performed to evaluate potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. RESULTS: During a follow-up of 869,807.9 person-years, 1,642 cases of lung cancer were observed, consisting of 1,408 (85.75%) cases of NSCLC and 234 (14.25%) cases of SCLC. The highest versus the lowest quartiles of the LFD score were found to be associated with a reduced risk of lung cancer (HR, 0.76; 95% CI, 0.66-0.89), NSCLC (HR, 0.79; 95% CI, 0.67-0.93), and SCLC (HR, 0.59; 95% CI, 0.38-0.92). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of lung cancer as well as its subtypes. This risk reduction association for overall lung cancer was more pronounced in smokers (HR, 0.71; 95% CI, 0.60-0.84; P for interaction = 0.003). For fat components, high consumption of saturated fatty acids was associated with an increased lung cancer risk (HR, 1.35; 95% CI, 1.10-1.66), especially for SCLC (HR, 2.05; 95% CI, 1.20-3.53). No significant association was found between consumption of monounsaturated or polyunsaturated fatty acids and incident lung cancer and its subtypes. CONCLUSIONS: Our findings suggest that adherence to LFD may reduce the lung cancer risk, particularly in smokers; while high saturated fatty acids consumption may increase lung cancer risk, especially for SCLC, among middle-aged and older adults in the US population.

Neuromodulation techniques in poststroke motor impairment recovery: Efficacy, challenges, and future directions.

Cerebrovascular accidents, also known as strokes, represent a major global public health challenge and contribute to substantial mortality, disability, and socioeconomic burden. Multidisciplinary approaches for poststroke therapies are crucial for recovering lost functions and adapting to new limitations. This review discusses the potential of neuromodulation techniques, repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, spinal cord stimulation (SCS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS), as innovative strategies for facilitating poststroke recovery. Neuromodulation is an emerging adjunct to conventional therapies that target neural plasticity to restore lost function and compensate for damaged brain areas. The techniques discussed in this review have different efficacies in enhancing neural plasticity, optimizing motor recovery, and mitigating poststroke impairments. Specifically, rTMS has shown significant promise in enhancing motor function, whereas SCS has shown potential in improving limb movement and reducing disability. Similarly, VNS, typically used to treat epilepsy, has shown promise in enhancing poststroke motor recovery, while DBS may be used to improve poststroke motor recovery and symptom mitigation. Further studies with standardized protocols are warranted to elucidate the efficacy of these methods and integrate them into mainstream clinical practice to optimize poststroke care.

Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

Prediction of atrazine degradation in soil based on XGBoost model.

We established the optimal model by using the automatic machine learning method to predict the degradation efficiency of herbicide atrazine in soil, which could be used to assess the residual risk of atrazine in soil. We collected 494 pairs of data from 49 published articles, and selected seven factors as input features, including soil pH, organic matter content, saturated hydraulic conductivity, soil moisture, initial concentration of atrazine, incubation time, and inoculation dose. Using the first-order reaction rate constant of atrazine in soil as the output feature, we established six models to predict the degradation efficiency of atrazine in soil, and conducted comprehensive analysis of model performance through linear regression and related evaluation indicators. The results showed that the XGBoost model had the best performance in predicting the first-order reaction rate constant (k). Based on the prediction model, the feature importance ranking of each factor was in an order of soil moisture > incubation time > pH > organic matter > initial concentration of atrazine > saturated hydraulic conductivity > inoculation dose. We used SHAP to explain the potential relationship between each feature and the degradation ability of atrazine in soil, as well as the relative contribution of each feature. Results of SHAP showed that time had a negative contribution and saturated hydraulic conductivity had a positive contribution. High values of soil moisture, initial concentration of atrazine, pH, inoculation dose and organic matter content were generally distributed on both sides of SHAP=0, indicating their complex contributions to the degradation of atrazine in soil. The XGBoost model method combined with the SHAP method had high accuracy in predicting the performance and interpretability of the k model. By using machine learning method to fully explore the value of historical experimental data and predict the degradation efficiency of atrazine using environmental parameters, it is of great significance to set the threshold for atrazine application, reduce the residual and diffusion risks of atrazine in soil, and ensure the safety of soil environment.

ZnMo-MOF as anti-CO hydrogen electrocatalyst enhance microbial electrosynthesis for CO/CO2 conversion.

Microbial electrosynthesis (MES) is an electrically driven technology that can be used for converting CO/CO2 into chemicals. The unique electronic and substrate properties of CO make it an important research target for MES. However, CO can poison the cathode and increase the overpotential of hydrogen evolution reaction (HER), thus reducing the electron transfer rate via H2. This work evaluated the effect of an anti-CO HER catalyst on the performance of MES for CO/CO2 conversion. ZnMo-metal-organic framework (MOF) materials with different calcination temperatures were synthesized. ZnMo-MOF-800 with Mo2C nanoparticles as active centers exhibited excellent resistance to CO toxicity. It also obtained the highest hydrogen evolution and enhanced electron transfer rate in CO atmosphere. MES with ZnMo-MOF-800 cathode and Clostridium ljungdahlii as biocatalyst obtained 0.31 g L-1 d-1 acetate yield, 0.1 g L-1 d-1 butyrate yield, and 0.09 g L-1 d-1 2,3-butanediol yield in CO/CO2, while Pt/C only get 0.076 g L-1 d-1 acetate yield, 0.05 g L-1 d-1 butyrate yield and 0.02 g L-1 d-1 2,3-butanediol yield. ZnMo-MOF-800 was conducive to biofilm formation, enabling it to better resist CO toxicity. This work provides new opportunities for constructing a highly efficient cathode with an anti-CO hydrogen evolution catalyst to enhance CO/CO2 conversion in MES.

Ultralow Background Membrane Editors for Spatiotemporal Control of Phosphatidic Acid Metabolism and Signaling.

Phosphatidic acid (PA) is a multifunctional lipid with important metabolic and signaling functions, and efforts to dissect its pleiotropy demand strategies for perturbing its levels with spatiotemporal precision. Previous membrane editing approaches for generating local PA pools used light-mediated induced proximity to recruit a PA-synthesizing enzyme, phospholipase D (PLD), from the cytosol to the target organelle membrane. Whereas these optogenetic PLDs exhibited high activity, their residual activity in the dark led to undesired chronic lipid production. Here, we report ultralow background membrane editors for PA wherein light directly controls PLD catalytic activity, as opposed to localization and access to substrates, exploiting a light-oxygen-voltage (LOV) domain-based conformational photoswitch inserted into the PLD sequence and enabling their stable and nonperturbative targeting to multiple organelle membranes. By coupling organelle-targeted LOVPLD activation to lipidomics analysis, we discovered different rates of metabolism for PA and its downstream products depending on the subcellular location of PA production. We also elucidated signaling roles for PA pools on different membranes in conferring local activation of AMP-activated protein kinase signaling. This work illustrates how membrane editors featuring acute, optogenetic conformational switches can provide new insights into organelle-selective lipid metabolic and signaling pathways.

Serum exosomal miR-3662 down-regulates the expression of RBMS3 to promote malignant progression and gemcitabine resistance of breast cancer cells.

Breast cancer (BC) is a prevalent malignancy among women worldwide. As an anticancer drug of pyrimidine nucleoside analogs, gemcitabine can be used to treat BC, but its clinical application is restricted due to drug resistance. This study investigated the effect of serum exosomal microRNA-3662 (miR-3662) on gemcitabine resistance in BC cells by targeting RNA-Binding Motif Single-Stranded Interacting Protein 3 (RBMS3) and related molecular mechanisms. We performed the bioinformatics analyses on the differential miRNAs in BC and predicted the downstream regulators. Quantitative real-time polymerase chain reaction was conducted to determine miR-3662 and RBMS3 expression, while dual luciferase was conducted to confirme the regulatory relationship between them. Flow cytometry, cell counting kit-8, and transwell assays were applied to assess apoptosis, cell viability, invasion, and migration. The expression of marker proteins (TSG101, CD63, and CD81) in patients' serum exosomes was evaluated through western blot, and exosomes were observed using transmission electron microscopy. miR-3662 expression was significantly upregulated in BC, and miR-3662 knockdown significantly reduced BC cell viability and gemcitabine resistance. As the downstream gene of miR-3662, RBMS3 was significantly downregulated in BC, and dual luciferase assay verified the binding of RBMS3-3'UTR to miR-3662. Rescue experiments revealed that silencing RBMS3 reversed the inhibitory effect of miR-3662 knockdown on BC cells. Besides, we also found that miR-3662 expression was significantly low in serum exosome samples from BC patients and could be transmitted to tumor cells. miR-3662 was upregulated in serum exosomes and promoted BC cell progression and gemcitabine resistance by targeting RBMS3.

Carbohydrate quality, not quantity, linked to reduced colorectal cancer incidence and mortality in US populations: evidence from a prospective study.

BACKGROUND: Carbohydrates have been implicated in colorectal cancer (CRC) risk, but the specific impact of carbohydrate quality and quantity on CRC susceptibility in US populations remains unclear. METHODS: We followed 101,694 participants from Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The carbohydrate quality index (CQI) and low-carbohydrate diet score (LCDs) were used to evaluate the daily carbohydrate quality and quantity separately, where higher scores indicated greater adherence. Cox proportional hazards regression was used to compute HRs and 95% CIs for incident CRC and related death. Subgroup analyses were conducted to identify potential effect modifiers. RESULTS: During follow-up, we documented 1085 incident cases of CRC, of whom 311 died from CRC. Individuals in the highest compared with the lowest quartiles of CQI had a lower CRC incidence (Q4 vs Q1: HR 0.80, 95% CI 0.67-0.96, Ptrend = 0.012) and mortality (Q4 vs Q1: HR 0.61, 95% CI 0.44-0.86, Ptrend = 0.004). The inverse association between CQI and CRC risk was observed for distal colon and rectum but not for proximal colon cancer. Regarding mortality, this association was only significant for rectum cancer. Subgroup analyses indicated this inverse association of CQI with CRC risk was only observed in participants with lower LCDs. No significant associations were found between LCDs and CRC incidence or mortality. CONCLUSIONS: Our findings suggest focusing on higher quality, rather than restricting the quantity, of carbohydrate consumption may be an effective approach to reduce the risk of CRC in the US population, particularly for distal colon and rectal cancers.

Establishing language and ethnic equivalence for health-related quality of life item banks and testing their efficiency via computerised adaptive testing simulations.

PURPOSE: We aimed to (1) establish linguistic and ethnic equivalence (i.e. lack of bias) for the items in the English and Chinese versions of the Singapore Health and Well Being (SHAWS) Physical Functioning (PF), Positive Mindset (PM) and Social Relationship (SR) item banks (IBs); and (2) evaluate the preliminary efficiency of these IBs using Computer Adaptive Testing (CAT) simulations. METHODS: In this cross-sectional study, 671, 670, and 672 subjects answered 55, 48 and 30 items of the PF, PM, and SR IBs, respectively. Rasch analysis was conducted to assess each IB's psychometric properties, particularly the presence of differential item functioning (DIF) for language and ethnicity. A set of performance criteria related to removing items that displayed notable DIF were employed. CAT simulations determined the mean number of items for high, moderate, and moderate-low measurement precisions (stopping rule: SEM 0.300, 0.387. 0.521, respectively). RESULTS: Half of subjects were >50 years old (40.9% PF, 42.1% PM, 41.4% SR), Chinese (50.7% PF, 51.0% PM, 50.6% SR) and female (50.0% PF. 49.4% PM, 52.8% SR) respectively. Rasch analysis revealed 4 items with DIF for the PF IB, 9 items with DIF for the PM IB and 2 items with DIF for the SR IB. In CAT simulations, the mean number of items administered was 8.5, 21.6 and 14.5 for the PF, PM and SR IBs, respectively (SEM 0.300), 5.1, 13.0, 8.0 for PF, PM and SR IBs, respectively (SEM 0.387) and 3.1, 5.3 and 4.1 for PF, PM and SR IBs, respectively (SEM 0.521). CONCLUSION: The PF, PM and SR IBs to measure health-related quality of life revealed minimal DIF for language and ethnicity after remedial efforts. CAT simulations demonstrated that these IBs were efficient, especially when the stopping rule was set at moderate precision, and support the implementation of the SHAWS IBs into routine clinical care.

Core-shell "loading-type" nanomaterials enabling glucometer readout for portable and sensitive detection of p-aminophenol in real samples.

A one-target-many-trigger signal model sensing strategy is proposed for quickly, sensitive and on-site detection of the environmental pollutant p-aminophenol (PAP) by use of a commercial personal glucose meter (PGM) for signal readout with the core-shell "loading-type" nanomaterial MSNs@MnO2 as amplifiable nanoprobes. In this design, the mesoporous silica nanoparticles (MSNs) nanocontainer with entrapped signal molecule glucose is coated with redoxable manganese dioxide (MnO2) nanosheets to form the amplifiable nanoprobes (Glu-MSNs@MnO2). When encountered with PAP, the redox reaction between the MnO2 and PAP can induce the degradation of the outer layer of MSNs@MnO2, liberating multiple copies of the loaded glucose to light up the PGM signal. Owing to the high loading capability of nanocarriers, a "one-to-many" relationship exists between the target and the signal molecule glucose, which can generate adequate signal outputs to achieve the requirement of on-site determination of environmental pollutants. Taking advantage of this amplification mode, the developed PAP assay owns a dynamic linear range of 10.0-400 µM with a detection limit of 2.78 µM and provides good practical application performance with above 96.7 ± 4.83% recovery in environmental water and soil samples. Therefore, the PGM-based amplifiable sensor for PAP proposed can accommodate these requirements of environment monitoring and has promising potential for evaluating pollutants in real environmental samples.

Combined treatment of human mesenchymal stem cells and green tea extract on retinal ganglion cell regeneration in rats after optic nerve injury.

Retinal ganglion cell (RGC) death and axonal loss cause irreversible vision loss upon optic nerve (ON) injury. We have independently demonstrated that mesenchymal stem cells (MSCs) and green tea extract (GTE) promote RGC survival and axonal regeneration in rats with ON injury. Here we aimed to evaluate the combined treatment effect of human bone marrow-derived MSCs (hBM-MSCs) and GTE on RGC survival and axonal regeneration after ON injury. Combined treatment of hBM-MSCs and GTE promoted RGC survival and neurite outgrowth/axonal regeneration in ex vivo retinal explant culture and in rats after ON injury. GTE increased Stat3 activation in the retina after combined treatment, and enhanced brain-derived neurotrophic factor secretion from hBM-MSCs. Treatment of 10 µg/mL GTE would not induce hBM-MSC apoptosis, but inhibited their proliferation, migration, and adipogenic and osteogenic differentiation in vitro with reducing matrix metalloproteinase secretions. In summary, this study revealed that GTE can enhance RGC protective effect of hBM-MSCs, suggesting that stem cell priming could be a prospective strategy enhancing the properties of stem cells for ON injury treatment.

Dasatinib suppresses collective cell migration through the coordination of focal adhesion and E-cadherin in colon cancer cells.

Collective cell migration is an important process in cancer metastasis. Unlike single-cell migration, collective cell migration requires E-cadherin expression in the cell cohort. However, the mechanisms underlying cellular contact and focal adhesions remain unclear. In this study, Src was hypothesized to coordinate focal adhesion and Rab11-mediated E-cadherin distribution during collective cell migration. This study primarily used confocal microscopy to visualize the 3D structure of cell-cell contacts with associated molecules. These results demonstrate that the clinical Src inhibitor dasatinib was less toxic to HT-29 colon cancer cells; instead, the cells aggregated. 3D immunofluorescence imaging showed that Rab11 was localized with E-cadherin at the adherens junctions of the apical cell-cell contacts. In the transwell assay, Rab11 colocalized with a broad range of E-cadherin proteins in collectively migrated cells, and dasatinib treatment significantly suppressed collective cell migration. Transmission electron microscopy demonstrated that dasatinib treatment increased cell membrane protrusion contacts and generated spaces between cells, which may allow epidermal growth factor receptor activity at the cell-cell contacts. This study suggests that dasatinib treatment does not inhibit cell survival but targets Src at different cellular compartments in the coordination of focal adhesions and cell-cell contacts in collective cell migration through E-cadherin dynamics in colon cancer cells.

Identification of NADPH Oxidase Genes Crucial for Rice Multiple Disease Resistance and Yield Traits.

Reactive oxygen species (ROS) act as a group of signaling molecules in rice functioning in regulation of development and stress responses. Respiratory burst oxidase homologues (Rbohs) are key enzymes in generation of ROS. However, the role of the nine Rboh family members was not fully understood in rice multiple disease resistance and yield traits. In this study, we constructed mutants of each Rboh genes and detected their requirement in rice multiple disease resistance and yield traits. Our results revealed that mutations of five Rboh genes (RbohA, RbohB, RbohE, RbohH, and RbohI) lead to compromised rice blast disease resistance in a disease nursery and lab conditions; mutations of five Rbohs (RbohA, RbohB, RbohC, RbohE, and RbohH) result in suppressed rice sheath blight resistance in a disease nursery and lab conditions; mutations of six Rbohs (RbohA, RbohB, RbohC, RbohE, RbohH and RbohI) lead to decreased rice leaf blight resistance in a paddy yard and ROS production induced by PAMPs and pathogen. Moreover, all Rboh genes participate in the regulation of rice yield traits, for all rboh mutants display one or more compromised yield traits, such as panicle number, grain number per panicle, seed setting rate, and grain weight, resulting in reduced yield per plant except rbohb and rbohf. Our results identified the Rboh family members involved in the regulation of rice resistance against multiple pathogens that caused the most serious diseases worldwide and provide theoretical supporting for breeding application of these Rbohs to coordinate rice disease resistance and yield traits.