MSC-Derived Small Extracellular Vesicles Alleviate Diabetic Retinopathy by Delivering miR-22-3p to Inhibit NLRP3 Inflammasome Activation.

PURPOSE: This study aimed to investigate the effect of mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) on diabetic retinopathy (DR) and its underlying mechanism. METHODS: In vivo, MSC-sEVs were injected intravitreally into diabetic rats to determine the therapeutic efficacy. In vitro, MSC-sEVs with/without miR-22-3p inhibition were cocultured with advanced glycation end-products (AGEs)-induced microglia with/without NLRP3 overexpression to explore the molecular mechanism. RESULTS: In vivo, MSC-sEVs inhibited NLRP3 inflammasome activation, suppressed microglial activation, decreased inflammatory cytokines levels in the retina, and alleviated DR as evidenced by improved histological morphology and blood-retinal barrier function. Based on miRNA sequencing of MSC-sEVs, bioinformatic software, and dual-luciferase reporter assay, miR-22-3p stood out as the critical molecule for the role of MSC-sEVs in regulating NLRP3 inflammasome activation. Diabetic rats had lower level of miR-22-3p in their retina than those of control and sEV-treated rats. Confocal microscopy revealed that sEV could be internalized by microglia both in vivo and in vitro. In vitro, compared with sEV, the anti-inflammation effect of sEVmiR-22-3p(-) on AGEs-induced microglia was compromised, as they gave a lower suppression of NLRP3 inflammasome activation and inflammatory cytokines. In addition, NLRP3 overexpression in microglia damped the anti-inflammatory effect of sEV. CONCLUSION: These results indicated that MSC-sEVs alleviated DR via delivering miR-22-3p to inhibit NLRP3 inflammasome activation. Our findings indicate that MSC-sEVs might be a potential therapeutic method for DR.

Comprehensive Analysis of Sphingolipid Metabolism-Related Genes in Osteoarthritic Diagnosis and Synovial Immune Dysregulation.

BACKGROUND Osteoarthritis (OA) is a chronic degenerative disease characterized by synovitis and has been implicated in sphingolipid metabolism disorder. However, the role of sphingolipid metabolism pathway (SMP)-related genes in the occurrence of OA and synovial immune dysregulation remains unclear. MATERIAL AND METHODS In this study, we obtained synovium-related databases from GEO (n=40 for both healthy controls and OA) and analyzed the expression levels of SMP-related genes. Using 2 algorithms, we identified hub genes and developed a diagnostic model incorporating these hub genes to predict the occurrence of OA. Subsequently, the hub genes were further validated in peripheral blood samples from OA patients. Additionally, CIBERSORT and MCP-counter analyses were employed to explore the correlation between hub genes and immune dysregulation in OA synovium. WGCNA was used to determine enriched modules in different clusters. RESULTS Overall, the expression levels of SMP genes were upregulated in OA synovium. We identified 6 hub genes of SMP and constructed an excellent diagnostic model (AUC=0.976). The expression of re-confirmed hub genes showed associations with immune-related cell infiltration and levels of inflammatory cytokines. Furthermore, we observed heterogeneity in the expression patterns of hub genes across different clusters of OA. Notably, older patients displayed increased susceptibility to elevated levels of pain-related inflammatory cytokines and infiltration of immune cells. CONCLUSIONS The SMP-related hub genes have the potential to serve as diagnostic markers for OA patients. Moreover, the 4 hub genes of SMP demonstrate wide participation in immune dysregulation in OA synovium. The activation of different pathways is observed among different populations of patients with OA.

Cataract-linked serine mutations in the gap junction protein connexin50 expose a sorting signal that promotes its lysosomal degradation.

Many human connexin50 (Cx50) mutants have been linked to cataracts including two carboxyl terminus serine mutants that are known phosphorylation sites in the lens (Cx50S258F and Cx50S259Y). To examine the behavior of these mutants and the role of phosphorylation at these positions, we stably transfected HeLa cells with cataract-linked and phosphorylation-mimicking (Cx50S258D and Cx50S259D) Cx50 mutants. We observed that gap junctional plaques were rarely detected in Cx50S258F-expressing and Cx50S259Y-expressing cells compared with wild-type cells. In contrast, gap junction abundance and size were greatly increased for Cx50S258D and Cx50S259D mutants. Cx50S258F and Cx50S259Y supported very low levels of gap junctional coupling, whereas Cx50S258D and Cx50S259D supported extensive intercellular communication. Furthermore, Cx50 levels as detected by immunoblotting were lower in Cx50S258F and Cx50S259Y mutants than in the wild-type or the aspartate substitution mutants, and chloroquine or ammonium chloride treatment significantly increased Cx50S258F and Cx50S259Y protein levels, implying participation of the lysosome in their increased degradation. Alanine substitution of amino acids within a predicted tyrosine-based sorting signal in Cx50S258F and Cx50S259Y increased levels of gap junctional plaques and intercellular transfer of neurobiotin. These results suggest that the absence of phosphorylatable serines at these positions exposes a sorting signal leading to lysosomal degradation of Cx50, whereas phosphorylation at these sites conceals this signal and allows targeting of Cx50 to the plasma membrane and stabilization of gap junction plaques. We propose that in the lens, degradation of Cx50S258F and Cx50S259Y decreases Cx50 levels at the plasma membrane and consequently Cx50 function, leading to cataracts.

Adult-Onset Focal Segmental Glomerulosclerosis With Steroid-Dependent Nephrotic Syndrome Caused by a Novel TBC1D8B Variant: A Case Report and Literature Review.

Focal segmental glomerulosclerosis (FSGS) is a histological lesion with a variety of potential causes, including rare variants of podocyte-related genes. Recently, it has been found that variants in the TBC1D8B gene on the X chromosome can lead to early-onset focal segmental glomerulosclerosis and steroid-resistant nephrotic syndrome by affecting endocytosis and recycling of nephrin. Here, we report a 19-year-old Chinese patient with nephrotic syndrome and normal kidney function. He had a complete remission of nephrotic syndrome after full-dose prednisone and cyclosporine treatment. Unfortunately, a relapse of nephrotic syndrome occurred during prednisone tapering. Focal segmental glomerulosclerosis was proven by a kidney biopsy, and a hemizygous pathogenic variant located in the TBC (Tre-2-Bub2-Cdc16) domain of TBC1D8B was detected by whole-exome sequencing. By comparing our case with reports of other patients with TBC1D8B variants, we suggest possible genotype-phenotype correlations. To our knowledge, this is the first report identifying a pathogenetic variant in the TBC domain of TBC1D8B in an adult-onset focal segmental glomerulosclerosis patient with steroid-dependent NS. With this report, we broaden the clinical and genetic spectrum of X-linked genetic FSGS.

The impact of an online educational game on breast cancer awareness among university female students, Malaysia: a pilot study.

BACKGROUND: Breast cancer is one of the world's most prevalent cancer and the most common type of cancer in Malaysia. Interestingly, breast cancer in young women is more aggressive compared to older women and the survival rate among these groups of individuals is poor. Thus, breast cancer awareness is essential among young women as early detection is possible and treatment will be effective during which the disease is curable. Hence, the purpose of this study is to design and evaluate the impact of an educational game on breast cancer awareness among female university students in Malaysia. METHODS: This is a one-group pre-and post-intervention pilot study. It was conducted in Private and public higher education institutions around Malaysia. An online education game was created and used as the intervention. A self-administered questionnaire was administered to the participants during the pre-and post-intervention test to evaluate the online educational game on breast cancer awareness. RESULTS: A total of 52 responses were collected. The mean age of the participants was 21.98 (SD = 1.896) years. The findings showed a statistically significant median increase (p < 0.05) in breast cancer knowledge scores among participants in the post-intervention. A median increase in breast cancer knowledge score of 6 was shown when participants were exposed to the online education game (24.00) compared to before they were exposed to it (17.00). CONCLUSION: Using online educational games effectively raised awareness of breast cancer among university students. Online games can be used as a health educational tool to promote awareness of a topic of interest, as digital games can be accessed easily, game content can be tailored made or updated, and improve participant engagement in learning.

DMBT1 Alleviates Nasal Airway Inflammatory Response in the LPS-Induced Nasal Polyp Model.

INTRODUCTION: The aim of this study was to investigate the effects and mechanism of deleted in malignant brain tumors 1 (DMBT1) protein on the mouse model of nasal polyps. METHODS: The mouse model of nasal polyps was induced by intranasal drip intervention of lipopolysaccharide (LPS) 3 times a week for 12 weeks. A total of 42 mice were randomly divided into blank group, LPS group, and LPS+DMBT1 group. DMBT1 protein was applied by intranasal drip intervention in each nostril after LPS. After 12 weeks, 5 mice in each group were randomly picked for the mouse olfactory disorder experiment, 3 mice were randomly picked for histopathological observation of nasal mucosa, 3 mice for olfactory marker protein (OMP) immunofluorescence analysis and the last 3 mice were grabbed for nasal lavage, and the levels of cytokines interleukin (IL)-4, IL-5, IL-13, and phosphatidylinositide 3-kinases (PI3K) in the nasal lavage fluid were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the blank group, mice in LPS group had olfactory dysfunction, the level of OMP was significantly reduced, the nasal mucosa was swollen, discontinuous, and contained a large number of inflammatory cells. The levels of IL-4, IL-5, IL-13, and PI3K in the nasal lavage fluid were significantly increased in LPS group (p < 0.01). Compared with the LPS group, the number of mice with olfactory dysfunction in the LPS+DMBT1 group was less, the infiltration of inflammatory cells was reduced, the OMP-positive cells were significantly increased, and the IL-4, IL-5, IL-13, and PI3K in the nasal lavage fluid were significantly increased, p < 0.01. CONCLUSIONS: DMBT1 protein alleviates the nasal airway inflammatory response in the mouse nasal polyp model, and the mechanism may be through the PI3K-AKT signaling pathway.

Mutation in XPO5 causes adult-onset autosomal dominant familial focal segmental glomerulosclerosis.

BACKGROUND: Focal and segmental glomerulosclerosis (FSGS) is a histological pathology that characterizes a wide spectrum of diseases. Many genes associated with FSGS have been studied previously, but there are still some FSGS families reported in the literature without the identification of known gene mutations. The aim of this study was to investigate the new genetic cause of adult-onset FSGS. METHODS: This study included 40 FSGS families, 77 sporadic FSGS cases, 157 non-FSGS chronic kidney disease (CKD) families and 195 healthy controls for analyses. Whole-exome sequencing (WES) and Sanger sequencing were performed on probands and family members of all recruited families and sporadic FSGS cases. RESULTS: Using WES, we have identified a novel heterozygous missense variant (c.T1655C:p.V552A) in exportin 5 gene (XPO5) in two families (FS-133 and CKD-05) affected with FSGS and CKD. Sanger sequencing has confirmed the co-segregation of this identified variant in an autosomal dominant pattern within two families, while this variant was absent in healthy controls. Furthermore, the identified mutation was absent in 195 ethnically matched healthy controls by Sanger sequencing. Subsequently, in silico analysis demonstrated that the identified variant was highly conservative in evolution and likely to be pathogenic. CONCLUSIONS: Our study reports an adult-onset autosomal dominant inheritance of the XPO5 variant in familial FSGS for the first time. Our study expanded the understanding of the genotypic, phenotypic and ethnical spectrum of mutation in this gene.

Tunable Optical Frequency Comb Generated Using Periodic Windows in a Laser and Its Application for Distance Measurement.

A novel method for the generation of an optical frequency comb (OFC) is presented. The proposed approach uses a laser diode with optical feedback and operating at a specific nonlinear dynamic state named periodic window. In this case, the laser spectrum exhibits a feature with a series of discrete, equally spaced frequency components, and the repetition rate can be flexibly adjusted by varying the system parameters (e.g., external cavity length), which can provide many potential applications. As an application example, a dual-OFC system for distance measurement is presented. The results demonstrate the system's ability to achieve target distance detection, underscoring its potential for real-world applications in this field.

Witnessing multi-observer steering on both sides simultaneously via weak measurements.

The quantum steering as an intermediate form of quantum correlations, has various peculiarities differing from the Bell nonlocality and the quantum entanglement. In a specific scenario, each side of the observer shares one of the two entangled qubits, steering can be witnessed simultaneously between any two observers from different sides by performing weak or projective measurements successively, with independently chosen and unbiased inputs. Here, we demonstrate this steering scenario experimentally to simultaneously witness quartic Einstein-Podolsky-Rosen steerings of two successive observers between each side with the entangled pair with a state fidelity of 97.6% compared with a maximally-entangled one.

Rhabdomyolysis-associated acute kidney injury: clinical characteristics and intensive care unit transfer analysis.

BACKGROUND: Information on rhabdomyolysis-associated acute kidney injury (AKI) in the emergency department or general ward is limited. AIM: To assess the risk factors, outcomes and clinical correlates with intensive care unit (ICU) transfer of patients with rhabdomyolysis-associated AKI. METHODS: Patients with rhabdomyolysis were divided into the rhabdomyolysis-associated AKI group and the rhabdomyolysis without AKI group. Inhospital outcomes, including ICU transfer, mortality, length of stay, daily cost and renal recovery were analysed. Multivariate regression analysis was performed to identify the association between rhabdomyolysis-associated AKI and ICU transfer. RESULTS: Among 149 patients with rhabdomyolysis, 68 (45.6%) developed AKI. Age and urine protein were important risk factors for incidence of rhabdomyolysis-associated AKI. Patients with rhabdomyolysis-associated AKI had higher levels of undergoing dialysis (19.1% vs 2.5%; P < 0.01), all-cause mortality (13.2% vs 1.2%; P < 0.01), cost of hospitalisation (10.8 1000 yuan, IQR (5.5, 3.5) vs 5.9 1000 yuan, IQR 5.9 (3.6, 9.9); P = 0.03), as well as longer length of hospital stay (8.0 days (5.0, 14.0)) versus (6.0 days (4.0, 11.0); P = 0.02). Additionally, the percentage of patients with AKI who transferred to ICU was higher than patients without AKI (33.8% vs 12.3%; P < 0.002) and rhabdomyolysis-associated AKI was an independent risk factor for ICU transfer (adjusted odds ratio = 2.58; 95% confidence interval, 1.12-6.8, P = 0.03). CONCLUSION: Rhabdomyolysis-associated AKI was common in the emergency department or general ward and led to more severe outcomes. It was also associated with an increased risk of ICU transfer.

Achieving Long Distance Sensing Using Semiconductor Laser with Optical Feedback by Operating at Switching Status.

In this study, a novel distance sensing method is presented by using a semiconductor laser (SL) with optical feedback (OF) and operating the SL at a switching status happened between two nonlinear dynamic states (stable state and period-one state). In this case, without the need for any electronic or optical modulation devices, the laser intensity can be modulated in a square wave form due to the switching via utilizing the inherent SL dynamics. The periodicity in the switching enables us to develop a new approach for long-distance sensing compared to other SL with OF-based distance measurement systems and lift the relevant restrictions that existed in the systems. Moreover, the impact of system controllable parameters on the duty cycle of the square wave signals generated was investigated on how to maintain the proposed system robustly operating at the switching status. Both simulation and experiment verified the proposed sensing approach.

Extracellular vesicles from human hepatic progenitor cells accelerate deep frostbite wound healing by promoting fibroblasts proliferation and inhibiting apoptosis.

Frostbites are cold tissue damages frequently observed at high altitudes and under extremely cold conditions. Though their incidence rate is low, the resulting impact in affected patients can be very serious, often leading to amputations. Clinical management and the prediction of outcome can be of utmost importance to frostbite patients. A possible use of stem cell-derived extracellular vesicles (EVs) has been suggested for cutaneous wound healing and we, therefore, tested their use for the treatment of deep frostbite wound. To this end, the impacts of hHPC-derived EVs were evaluated in an in vivo animal model comprising of Kunming female mice as well as studied in vitro for the mechanism. We first characterized the EVs and these hHPC-derived EVs, when applied to treat frostbite wounds, accelerated wound healing in the in vivo animal model, as assessed by wound closure, re-epithelization thickness, collagen density and the expression of Collagen I and α-SMA. The proliferation and migration of human skin fibroblasts was also found to be increased by EVs in the in vitro experiments. The H2O2-induced apoptosis cell model, established to simulate the post-frostbite injury, was inhibited by EVs, with concomitant increase in the expression of Bcl-2 and decreased expression of Bax, further confirming the findings. Our novel results indicate that the application of EVs might be a promising strategy for deep frostbite wound healing.

Molecular mechanisms underlying enhanced hemichannel function of a cataract-associated Cx50 mutant.

Connexin-50 (Cx50) is among the most frequently mutated genes associated with congenital cataracts. Although most of these disease-linked variants cause loss of function because of misfolding or aberrant trafficking, others directly alter channel properties. The mechanistic bases for such functional defects are mostly unknown. We investigated the functional and structural properties of a cataract-linked mutant, Cx50T39R (T39R), in the Xenopus oocyte system. T39R exhibited greatly enhanced hemichannel currents with altered voltage-gating properties compared to Cx50 and induced cell death. Coexpression of mutant T39R with wild-type Cx50 (to mimic the heterozygous state) resulted in hemichannel currents whose properties were indistinguishable from those induced by T39R alone, suggesting that the mutant had a dominant effect. Furthermore, when T39R was coexpressed with Cx46, it produced hemichannels with increased activity, particularly at negative potentials, which could potentially contribute to its pathogenicity in the lens. In contrast, coexpression of wild-type Cx50 with Cx46 was associated with a marked reduction in hemichannel activity, indicating that it may have a protective effect. All-atom molecular dynamics simulations indicate that the R39 substitution can form multiple electrostatic salt-bridge interactions between neighboring subunits that could stabilize the open-state conformation of the N-terminal (NT) domain while also neutralizing the voltage-sensing residue D3 as well as residue E42, which participates in loop gating. Together, these results suggest T39R acts as a dominant gain-of-function mutation that produces leaky hemichannels that may cause cytotoxicity in the lens and lead to development of cataracts.

Dynamic changes of functional fitness, antibodies to SARS-CoV-2 and immunological indicators within 1 year after discharge in Chinese health care workers with severe COVID-19: a cohort study.

BACKGROUND: Few studies had described the health consequences of patients with coronavirus disease 2019 (COVID-19) especially in those with severe infections after discharge from hospital. Moreover, no research had reported the health consequences in health care workers (HCWs) with COVID-19 after discharge. We aimed to investigate the health consequences in HCWs with severe COVID-19 after discharge from hospital in Hubei Province, China. METHODS: We conducted an ambidirectional cohort study in "Rehabilitation Care Project for Medical Staff Infected with COVID-19" in China. The participants were asked to complete three physical examinations (including the tests of functional fitness, antibodies to SARS-CoV-2 and immunological indicators) at 153.4 (143.3, 164.8), 244.3 (232.4, 259.1), and 329.4 (319.4, 339.3) days after discharge, respectively. Mann-Whitney U test, Kruskal-Wallis test, t test, one-way ANOVA, χ2, and Fisher's exact test were used to assess the variance between two or more groups where appropriate. RESULTS: Of 333 HCWs with severe COVID-19, the HCWs' median age was 36.0 (31.0, 43.0) years, 257 (77%) were female, and 191 (57%) were nurses. Our research found that 70.4% (114/162), 48.9% (67/137), and 29.6% (37/125) of the HCWs with severe COVID-19 were considered to have not recovered their functional fitness in the first, second, and third functional fitness tests, respectively. The HCWs showed improvement in muscle strength, flexibility, and agility/dynamic balance after discharge in follow-up visits. The seropositivity of IgM (17.0% vs. 6.6%) and median titres of IgM (3.0 vs. 1.4) and IgG (60.3 vs. 45.3) in the third physical examination was higher than that in the first physical examination. In the third physical examination, there still were 42.1% and 45.9% of the HCWs had elevated levels of IL-6 and TNF-α, and 11.9% and 6.3% of the HCWs had decreased relative numbers of CD3+ T cells and CD4+ T cells. CONCLUSION: The HCWs with severe COVID-19 showed improvement in functional fitness within 1 year after discharge, active intervention should be applied to help their recovery if necessary. It is of vital significance to continue monitoring the functional fitness, antibodies to SARS-CoV-2 and immunological indicators after 1 year of discharge from hospital in HCWs with severe COVID-19.

A validation study of UCSD-Mayo risk score in predicting hospital-acquired acute kidney injury in COVID-19 patients.

INTRODUCTION: Acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients is associated with poor prognosis. Early prediction and intervention of AKI are vital for improving clinical outcome of COVID-19 patients. As lack of tools for early AKI detection in COVID-19 patients, this study aimed to validate the USCD-Mayo risk score in predicting hospital-acquired AKI in an extended multi-center COVID-19 cohort. METHODS: Five hundred seventy-two COVID-19 patients from Wuhan Tongji Hospital Guanggu Branch, Wuhan Leishenshan Hospital, and Wuhan No. Ninth Hospital was enrolled for this study. Patients who developed AKI or reached an outcome of recovery or death during the study period were included. Predictors were evaluated according to data extracted from medical records. RESULTS: Of all patients, a total of 44 (8%) developed AKI. The UCSD-Mayo risk score achieved excellent discrimination in predicting AKI with the C-statistic of 0.88 (95%CI: 0.84-0.91). Next, we determined the UCSD-Mayo risk score had good overall performance (Nagelkerke R2 = 0.32) and calibration in our cohort. Further analysis showed that the UCSD-Mayo risk score performed well in subgroups defined by gender, age, and several chronic comorbidities. However, the discrimination of the UCSD-Mayo risk score in ICU patients and patients with mechanical ventilation was not good which might be resulted from different risk factors of these patients. CONCLUSIONS: We validated the performance of UCSD-Mayo risk score in predicting hospital-acquired AKI in COVID-19 patients was excellent except for patients from ICU or patients with mechanical ventilation.

Hypophosphatemia is an independent risk factor for AKI among hospitalized patients with COVID-19 infection.

BACKGROUND: This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. METHODS: In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. RESULTS: In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14-1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p < .001) in subgroup analysis, indicating renal phosphate loss via proximal renal tubular dysfunction. CONCLUSION: The AKI incidence was very low in non-ICU patients as compared to ICU patients. Hypophosphatemia is an independent risk factor for AKI in patients hospitalized for COVID-19 infection.

New risk score for predicting steroid resistance in patients with focal segmental glomerulosclerosis or minimal change disease.

BACKGROUND: Glucocorticosteroid is used for patients with primary nephrotic syndrome. This study aims to identify and validate that biomarkers can be used to predict steroid resistance. METHODS: Our study contained two stages, discovery and validation stage. In discovery stage, we enrolled 51 minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) patients treated with full dose steroid. Five urinary biomarkers including ß2-microglobulin (ß2-MG) and α1-microglobulin (α1-MG) were tested and candidates' biomarkers were selected based on their associations with steroid response. In validation stage, candidates' biomarkers were validated in two prospectively enrolled cohorts. Validation cohort A included 157 FSGS/MCD patients. Validation cohort B included 59 membranous nephropathy (MN) patients. Patients were classified into response group (RG) or non-response group (NRG) based on their responses to steroid treatment. RESULTS: In discovery stage, higher urinary ß2-MG was independently associated with response to corticosteroid treatment in MCD/FSGS patients [OR = 1.89, 95% CI 1.02-3.53] after adjusted by age and gender. In validation cohort A, patients in NRG had a significant higher urinary ß2-MG [Ln (ß2-MG/uCr): 4.6 ± 1.7 vs 3.2 ± 1.5] compared to patients in RG. We then developed a 3-variable risk score in predicting steroid resistance in FSGS/MCD patients based on the best predictive model including Ln(ß2-MG/uCr) [OR = 1.76, 95% CI 1.30-2.37], age [OR = 1.005, 95% CI 0.98-1.03] and pathology [MCD vs FSGS, OR = 0.20, 95% CI 0.09-0.46]. The area under the ROC curves of the risk score in predicting steroid response was 0.80 (95% CI 0.65-0.85). However, no such association was found in MN patients. CONCLUSIONS: Our study identified a 3-variable risk score in predicting steroid resistance in patients with FSGS or MCD.

Low-cost biosensors based on a plasmonic random laser on fiber facet.

Low-cost and miniaturized biosensors are key factors leading to the possibility of portable and integrated biomedical system, which play an important role in clinical medicine and life sciences. Random lasers with simple structures provide opportunities for detecting biomolecules. Here, low-cost biosensors on fiber facet for label-free detecting biomolecules are demonstrated based on a plasmonic random laser. The random laser is achieved resorting to a self-assembled plasmonic scattering structure of Ag nanoparticles and polymer film on fiber facet. Refractive index sensitivity and near-surface sensitivity of the biosensor are systematically studied. Furthermore, the biosensor is used to detect IgG through specific binding to protein A, exhibiting the detecting limit of 0.68 nM. It is believed that this work may promote the applications of a plasmonic random laser bio-probe in portable or integrated medical diagnostic platforms, and provide fundamental understanding for the life science.

Tunable polymer lasing in chirped cavities.

Continuously tunable polymer lasing was achieved in one-dimensional, two-dimensional, and compound chirped cavities. The chirped cavity was simply fabricated by using interference lithography and spin coating. Two-dimensional and compound chirped cavities were obtained by employing oblique exposure and double exposure, respectively. The tunability range of two-dimensional chirped cavities was much wider than that of one-dimensional chirped cavities, which varied from 557 nm to 582 nm. The interaction between lasing modes was studied in the compound cavity by introducing an additional nanostructure into the two-dimensional chirped cavities. The threshold of the compound chirped cavities changed with the coupling strength between lasing modes. These results may be helpful for designing compact polymer laser sources.

Experimental demonstration of hidden nonlocality with local filters.

The violation of the Bell inequalities implies that quantum mechanics cannot be interpreted using any local hidden variable theory. However, particular quantum states that can originally be described using a local hidden variable model surprisingly exhibit nonlocality by employing local filters before a standard Bell test is performed. This is referred to as hidden nonlocality. In this study, we provide the experimental demonstration of hidden nonlocality through linear optics towards the local states which are put forword by Hirsch et al., PRL 111, 160402 (2013). A class of local states is generated through a spontaneous parametric down-conversion process, and the violation of the Clauser-Horne-Shimony-Holt (CHSH)-Bell inequality is observed by applying local filters. Our experimental results confirm the superiority of local filters, and throw light on deep understanding the intriguing phenomena of hidden nonlocality and local states.