The glycolytic enzyme PFKFB3 drives kidney fibrosis through promoting histone lactylation-mediated NF-κB family activation.

Persistently elevated glycolysis in kidney has been demonstrated to promote chronic kidney disease (CKD). However, the underlying mechanism remains largely unclear. Here, we observed that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key glycolytic enzyme, was remarkably induced in kidney proximal tubular cells (PTCs) following ischemia-reperfusion injury (IRI) in mice, as well as in multiple etiologies of patients with CKD. PFKFB3 expression was positively correlated with the severity of kidney fibrosis. Moreover, patients with CKD and mice exhibited increased urinary lactate/creatine levels and kidney lactate, respectively. PTC-specific deletion of PFKFB3 significantly reduced kidney lactate levels, mitigated inflammation and fibrosis, and preserved kidney function in the IRI mouse model. Similar protective effects were observed in mice with heterozygous deficiency of PFKFB3 or those treated with a PFKFB3 inhibitor. Mechanistically, lactate derived from PFKFB3-mediated tubular glycolytic reprogramming markedly enhanced histone lactylation, particularly H4K12la, which was enriched at the promoter of NF-κB signaling genes like Ikbkb, Rela, and Relb, activating their transcription and facilitating the inflammatory response. Further, PTC-specific deletion of PFKFB3 inhibited the activation of IKKß, I κ B α, and p65 in the IRI kidneys. Moreover, increased H4K12la levels were positively correlated with kidney inflammation and fibrosis in patients with CKD. These findings suggest that tubular PFKFB3 may play a dual role in enhancing NF-κB signaling by promoting both H4K12la-mediated gene transcription and its activation. Thus, targeting the PFKFB3-mediated NF-κB signaling pathway in kidney tubular cells could be a novel strategy for CKD therapy.

Rapid Fingerprinting of Urinary Volatile Metabolites and Point-of-Care Diagnosis of Phenylketonuria on a Patterned Nanorod Sensor Array with Multiplexed Surface-Enhanced Raman Scattering Readouts.

Phenylketonuria (PKU) is one of the most common genetic metabolic diseases, especially among newborns. Traditional clinical examination of newborn blood samples for PKU is invasive, laborious, and limited to hospitals and healthcare facilities. We reported herein a SERS-based sensor array with three thiophenolic nanoreceptors built on a patterned nanorod vertical array for rapid and inexpensive detection of characteristic volatile biomarkers indicative of PKU in the urine and accurate classification of newborn baby patients all performed on a hand-held SERS spectrophotometer. The well-ordered array was generated from the volatility-driven assembly of gold nanorods (AuNRs) into an upright and closely packed hexagonal configuration. The uniformly distributed nanowells between AuNRs offered an intense and aspect-ratio-dependent plasmonic field for the molecular enhancement of SERS outputs. The SERS-based detector was integrated into a test chip for regular monitoring of volatile phenylketone bodies in the spiked solution or patients' urine within 5 min, allowing the quantification of a wide variety of normal or abnormal metabolites at their physiologically relevant concentration range. The detection limits for common biomarkers of PKU, including phenylpyruvic acid, 4-hydroxyphenylacetic acid, and phenylacetic acid, were at a few µM and well below the diagnostic thresholds. Moreover, the volatile headspace mixtures from a given urine sample could be fingerprinted by the sensor array and discriminated using machine-learning algorithms. Ultimately, the discrimination of baby patients among 26 cases of mild and classic PKU phenotypes and 17 cases of healthy volunteers could be realized with an overall accuracy of 97%. This hand-held SERS platform plays a pivotal role in advancing healthcare applications in quick screening of neonatal PKU through a facile urinary vapor test.

Smartphone-Based Fluorescent Profiling of Quaternary MicroRNAs in Urine for Rapid Diagnosis of Urological Cancers Using a Multiplexed Isothermal Exponential Amplification Reaction.

Urological cancers such as bladder or prostate cancer represent one of the most malignant tumors that accounts for an extremely high mortality. However, conventionally standard diagnostics for urological cancers are hardly available in low-resource settings. We developed herein a hand-held fluorescent imaging platform by integrating a multiplexed isothermal exponential amplification reaction (EXPAR) with a microgel-enriched methodology for sensitive profiling of quaternary microRNAs (miRNAs) in urine and quick diagnosis of urological cancers at the early stage. The target miRNA mixtures in the urine underwent four parallel EXPARs without cross-reactivity, followed by surface concentration and hybridization by the encoded polyacrylamide microgels. This mix-and-read strategy allowed for one-pot analysis of several key miRNAs simultaneously and provided 5-fold enhancement in fluorescent detection sensitivities compared to the individual EXPAR-based assays. Four urinary miRNAs (let-7a, miRNA-155, -223, and -143) could be quantitatively determined in a wide linear range from 50 fM to 30 nM, with the limits of detection at femtomolar levels. Using a smartphone-based imaging microreader, healthy and cancerous cohorts with prostate, bladder, and renal cell cancers could be discriminated in 30 min with the accuracy >83% using linear discriminant analysis. The developed detection platform has proven to be a portable, noninvasive, and useful complement to the toolbox for miRNA-based liquid biopsies, which holds immense potential and advantage for regular and large-scale applications in early cancer diagnosis.

Clinicopathological phenotype and outcomes of NCAM-1+ membranous lupus nephritis.

INTRODUCTION: No studies explored the long-term outcomes of neural cell adhesion molecule 1 (NCAM1) associated membranous lupus nephritis (MLN) patients. METHOD: We performed immunohistochemical studies on kidney biopsy specimens against NCAM1 in consecutive MLN patients. The clinical and histopathological characteristics and outcomes of cases of NCAM1 associated MLN patients are described and compared with NCAM1 negative patients. In addition, we detected serum circulating anti-NCAM1 antibodies through western blotting and indirect immunofluorescence assays. RESULTS: Among 361 MLN cases, 18 (5.0%) were glomerular NCAM1-positive. NCAM1 positive MLN patients were older [35 years (IQR 27-43) versus 28 (22-37); P = 0.050) and had lower systemic lupus erythematosus disease activity index [11 (IQR 8-12) versus 14 (10-18); P = 0.007], serum creatinine [60 µmol/L (IQR 50-70) versus 70 (54-114); P = 0.029], activity index [3 (IQR 2-6) versus 6 (3-9); P = 0.045] at kidney biopsy compared with NCAM1 negative patients. The percentage of positive anti-Sjogren's syndrome related antigen A antibodies in NCAM1 positive patients was significantly greater (83.3% versus 58.2%; P = 0.035) than in the NCAM1 negative patients. However, no evidence of neuropsychiatric disorders was found in these 18 patients. There were no significant differences in the treatment response and the risk of end stage renal diseases between NCAM1 positive and negative groups (P = 0.668 and P = 0.318, respectively). But the risk of death was much higher in the NCAM1 positive group than the NCAM1 negative group (27.8% vs. 8.1%, P = 0.007). Moreover, the risk of death was also much higher in the NCAM1 positive group than the matched NCAM1 negative group (Log-rank P = 0.013). Additionally, circulating anti-NCAM1 antibodies can be detected in 1/5 (20%) patients who had serum available. CONCLUSION: The prevalence of NCAM1 positivity was 5.0% in our cohort of MLN and the high mortality in these subgroup patients are needed to validate in future studies.

A Perspective on the Controversy over Global Emission Fluxes of Microplastics from Ocean into the Atmosphere.

Since the transfer of microplastic across the sea-air interface was first reported in 2020, numerous studies have been conducted on its emission flux estimation. However, these studies have shown significant discrepancies in the estimated contribution of oceanic sources to global atmospheric microplastics, with evaluations ranging from predominant to negligible, varying by 4 orders of magnitude from 7.7 × 10-4 to 8.6 megatons per year, thereby creating considerable confusion in the research on the microplastic cycle. Here, we provide a perspective by applying the well-established theory of particulate transfer through the sea-air interface. The upper limit of global sea-air emission flux microplastics was calculated, aiming to constrain the controversy in the previously reported fluxes. Specifically, the flux of sub-100 µm microplastic cannot exceed 0.01 megatons per year, and for sub-0.1 µm nanoplastics, it would not exceed 3 × 10-7 megatons per year. Bridging this knowledge gap is crucial for a comprehensive understanding of the sea-air limb in the "plastic cycle", and facilitates the management of future microplastic pollution.

Exposure to microcystin-LR promotes the progression of colitis-associated colorectal cancer by inducing barrier disruption and gut microbiota dysbiosis.

Microcystins (MCs) are secondary metabolites generated by cyanobacterial blooms, among which microcystin-LR (MC-LR) stands out as the most widely distributed variant in aquatic environments. However, the effects of MC-LR on the colorectum and its role in promoting colorectal tumor progression remain unclear. Therefore, this study aims to scrutinize the impact of MC-LR on a mice model of colitis-associated colorectal cancer and elucidate the potential underlying molecular mechanisms. In this study, we used AOM/DSS mice and orally administered MC-LR at doses of 40 µg/kg or 200 µg/kg. Exposure to MC-LR increased tumor burden, promoted tumor growth, shortened colon size, and decreased goblet cell numbers and tight junction protein levels in intestinal tissues. Additionally, exposure to MC-LR induced alterations in the structure of gut microbiota in the mouse colon, characterized by an increase in the relative abundance of Escherichia_coli and Shigella_sonnei, and a decline in the relative abundance of Akkermansia_muciniphila. Transcriptomic analysis revealed that MC-LR exposure activated the IL-17 signaling pathway in mouse colorectal tissues and participated in inflammation regulation and immune response. Immunofluorescence results demonstrated an increase in T-helper 17 (Th17) cell levels in mouse colorectal tumors following MC-LR exposure. The results from RT-qPCR revealed that MC-LR induced the upregulation of IL-6, IL-1ß, IL-10, IL-17A, TNF-α, CXCL1, CXCL2, CXCL5 and CCL20. The novelty of this study lies in its comprehensive approach to understanding the mechanisms by which MC-LR may contribute to CRC progression, offering new perspectives and valuable reference points for establishing guidance standards regarding MC-LR in drinking water. Our findings suggest that even at guideline value, MC-LR can have profound effects on susceptible mice, emphasizing the need for a reevaluation of guideline value and a deeper understanding of the role of environmental toxins in cancer progression.

Influence of freeze-thaw process on As migration and microorganisms in aggregates of paddy soil.

A natural phenomenon known as the seasonal freeze-thaw (FT) cycle happens in cold temperature zone such as high latitude and high altitude regions where the soil frequently freezes and thaws in response to temperature variations. Global warming would increase the number of FT cycles in FT regions. However, the influence of FT process on arsenic (As) migration in paddy soil is seldom investigated. Herein, indoor simulation experiment was conducted to investigate the influence of FT process (60 cycles) on As migration from surface to deep soil and microorganisms in paddy soil column. Compared to non FT treatment groups, the concentrations of As in microaggregates of 8-10 cm depth and 18-20 cm depth in soil column of FT treatment group increased by 3.69 mg/kg and 4.16 mg/kg, respectively; the concentrations of As in macroaggregates of 8-10 cm depth and 18-20 cm depth in soil column of FT treatment group increased by 3.34 mg/kg and 3.94 mg/kg, respectively, indicating that FT process accelerated the As migration from surface to deep soil. FT process affected the microbial community structure by changing the physicochemical properties of the soil, which decreased the diversity and uniformity of bacterial community distribution in the soil. The relative abundance of two As-resistant bacteria, e.g., Sphingomonas and Lysobacter, increased by 8.2% and 11.35% after 60 cycles, respectively; moreover, total As in the soil was significantly (p < 0.05) negatively correlated with the alpha index of the soil microorganisms. This study would provide basic data for future study on determining environmental behavior and risk of metals in farm soils in seasonal FT aeras.

Aqueous-phase formation of N-containing secondary organic compounds affected by the ionic strength.

The reaction of carbonyl-to-imine/hemiaminal conversion in the atmospheric aqueous phase is a critical pathway to produce the light-absorbing N-containing secondary organic compounds (SOC). The formation mechanism of these compounds has been wildly investigated in bulk solutions with a low ionic strength. However, the ionic strength in the aqueous phase of the polluted atmosphere may be higher. It is still unclear whether and to what extent the inorganic ions can affect the SOC formation. Here we prepared the bulk solution with certain ionic strength, in which glyoxal and ammonium were mixed to mimic the aqueous-phase reaction. Molecular characterization by High-resolution Mass Spectrometry was performed to identify the N-containing products, and the light absorption of the mixtures was measured by ultraviolet-visible spectroscopy. Thirty-nine N-containing compounds were identified and divided into four categories (N-heterocyclic chromophores, high-molecular-weight compounds with N-heterocycle, aliphatic imines/hemiaminals, and the unclassified). It was observed that the longer reaction time and higher ionic strength led to the formation of more N-heterocyclic chromophores and the increasing of the light-absorbance of the mixture. The added inorganic ions were proposed to make the aqueous phase somewhat viscous so that the molecules were prone to undergo consecutive and intramolecular reactions to form the heterocycles. In general, this study revealed that the enhanced ionic strength and prolonged reaction time had the promotion effect on the light-absorbing SOC formation. It implies that the aldehyde-derived aqueous-phase SOC would contribute more light-absorbing particulate matter in the industrial or populated area where inorganic ions are abundant.

Interfacial Profiling of MicroRNAs at Patterned Nanogaps for an Integrated Microfluidic-SERS Liquid Biopsy.

A versatile microfluidic-SERS barcoding system is developed for sensitive and multiplexed imaging of circulating microRNAs through interfacial probing of encoded nanorod aggregates at diverse patterned nanogaps. The use of a single-layer, vertically oriented nanorod array creates a plasmonic coupling-based electromagnetic field with enormously enhanced Raman outputs. The introduction of the herringbone micromixer with circulated microflow sampling accelerates the hybridization and capture of nanorod aggregates on the plasmonic substrate. The method is able to achieve ideal sensitivities at subfemtomolar levels for four miRNAs, with multiplexed assay capability for an integrated liquid biopsy. The on-chip digital profiling of serum miRNAs in mapping and barcoding formats enable both clear discrimination of untreated cancer patients from the healthy cohort and precise classification of tumor stages, metastatic conditions, and subtypes, with an overall accuracy of 94%. The SERS-based microfluidic barcoding system therefore holds great promise in early cancer screening, diagnosis, and prognosis.

circMRPS35 promotes malignant progression and cisplatin resistance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNA, have been reported to be involved in the etiology of various malignancies. However, the underlying cellular mechanisms of circRNAs implicated in the pathogenesis of HCC remain unknown. In this study, we identified a functional RNA, hsa_circ_0000384 (circMRPS35), from public tumor databases using a set of computational analyses, and we further identified that circMRPS35 was highly expressed in 35 pairs of HCC from patients. Moreover, knockdown of the expression of circMRPS35 in Huh-7 and HCC-LM3 cells suppressed their proliferation, migration, invasion, clone formation, and cell cycle in vitro, and it suppressed tumor growth in vivo as well. Mechanically, circMRPS35 sponged microRNA-148a-3p (miR-148a), regulating the expression of Syntaxin 3 (STX3), which modulated the ubiquitination and degradation of phosphatase and tensin homolog (PTEN). Unexpectedly, we detected a peptide encoded by circMRPS35 (circMRPS35-168aa), which was significantly induced by chemotherapeutic drugs and promoted cisplatin resistance in HCC. These results demonstrated that circMRPS35 might be a novel mediator in HCC progress, and they raise the potential of a new biomarker for HCC diagnosis and prognosis, as well as a novel therapeutic target for HCC patients.

Model-Free Adaptive Positioning Control of the Bidirectional Stick-Slip Piezoelectric Actuator with Coupled Asymmetric Flexure-Hinge Mechanisms.

A model-free adaptive positioning control strategy for piezoelectric stick-slip actuators (PSSAs) with uncertain disturbance is proposed. The designed controller consists of a data-driven self-learning feedforward controller and a model-free adaptive feedback controller with a radial basis function neural network (RBFNN)-based observer. Unlike the traditional model-based control methods, the model-free adaptive control (MFAC) strategy avoids the complicated modeling process. First, the nonlinear system of the PSSA is dynamically linearized into a data model. Then, the model-free adaptive feedback controller based on a data model is designed to avoid the complicated modeling process and enhance the robustness of the control system. Simultaneously, the data-driven self-learning feedforward controller is improved to realize the high-precision control performance. Additionally, the convergence of the tracking error and the boundedness of the control output signal are proved. Finally, the experimentally obtained results illustrate the advantages and effectiveness of the developed control methodology on the bidirectional stick-slip piezoelectric actuator with coupled asymmetric flexure-hinge mechanisms. The positioning error through the proposed controller reaches 30 nm under the low-frequency condition and 200 nm under the high-frequency condition when the target position is set to 100 µm. In addition, the target position can be accurately tracked in less than 0.5 s in the presence of a 100 Hz frequency.

Construction of durable superhydrophobic and anti-icing coatings via incorporating boroxine cross-linked silicone elastomers with good self-healability.

The fragility of the micro-nano structure makes superhydrophobic coatings highly susceptible to stress, resulting in a decrease in their superhydrophobic and anti-icing performance. In this work, we proposed a new insight to improve durability by incorporating a thin layer of self-healable elastomer with a dynamic network on the micro-nano structure. We constructed superhydrophobic coatings (EP/SiO2/BFVSE) with a three-layered structure of the epoxy resin/silica nanoparticle/silicon elastomer. The silicon elastomer (BFVES) with a B-O dynamic cross-linked network and fluorinated moieties was synthesized by graft polymerization on vinyl silicon oil. The preparation route is facile and convenient for mass production. BFVES has rapid self-healing properties for scratches at room-temperature, underwater and at -18 °C. EP/SiO2/BFVSE preserved apparently higher CAs after being immersed in pH = 1, pH = 13, and NaCl solutions for 96 h as compared with the EP/SiO2 coating. In a water striking environment, the CA of EP/SiO2/BFVSE was slightly decreased to 153°. SEM images further reveal that the recovery of superhydrophobicity and icephobicity is attributed to the self-healing behavior of the boroxine-containing silicon elastomer. The EP/SiO2/BFVSE coating also possesses additional self-healing ability under chemical oxidation. The high durability of the self-healable superhydrophobic coating enables great application potential in aircraft, marine vessels, and outdoor facilities in harsh environments.

Correction: Construction of durable superhydrophobic and anti-icing coatings via incorporating boroxine cross-linked silicone elastomers with good self-healability.

Correction for 'Construction of durable superhydrophobic and anti-icing coatings via incorporating boroxine cross-linked silicone elastomers with good self-healability' by Hengfei Liang et al., Soft Matter, 2022, https://doi.org/10.1039/d2sm01106a.

Absorption Enhancement of Black Carbon Aerosols Constrained by Mixing-State Heterogeneity.

Atmospheric black carbon (BC) has a large yet highly uncertain contribution to global warming. When mixed with non-BC/coating material during atmospheric aging, the BC light absorption can be enhanced through the lensing effect. Laboratory and modeling studies have consistently found strong BC absorption enhancement, while the results in ambient measurements are conflicting, with some reporting weak absorption enhancement even for particles with large bulk coating amounts. Here, from our direct field observations, we report both large and minor absorption enhancement factors for different BC-containing particle populations with large bulk non-BC-to-BC mass ratios. By gaining insights into the measured coating material distribution across each particle population, we find that the level of absorption enhancement is strongly dependent on the particle-resolved mixing state. Our study shows that the greater mixing-state heterogeneity results in the larger difference between observed and predicted absorption enhancement. We demonstrate that by considering the variability in coating material thickness in the optical model, the previously observed model measurement discrepancy of absorption enhancement can be reconciled. The observations and improved optical models reported here highlight the importance of mixing-state heterogeneity on BC's radiative forcing, which should be better resolved in large-scale models to increase confidence when estimating the aerosol radiation effect.

Association between serum chloride levels with mortality in incident peritoneal dialysis patients.

BACKGROUND AND AIMS: Lower serum chloride (Cl) levels have been associated with excess mortality in pre-dialysis chronic kidney disease patients. However, the relationship between serum Cl levels and clinical outcomes in continuous ambulatory peritoneal dialysis (CAPD) patients is unclear. METHODS AND RESULTS: In this retrospective cohort study, we enrolled 1656 eligible incident patients undergoing CAPD from 2006 to 2013, and followed until December 2018. Cox regression analyses were used to examine the association between baseline and time-varying serum Cl levels and mortality. During a median follow-up of 46 months, 503 patients (30.4%) died. In analyses of baseline serum Cl, the adjusted hazard ratios (HR) for tertile 1 (<100.0 mmol/L), tertile 2 (100.0-103.0 mmol/L) versus tertile 3 (>103.0 mmol/L) were 2.34 [95% confidence interval (CI) 1.43-3.82] and 1.73 (95% CI 1.24-2.42) for all-cause mortality, 2.86 (95% CI 1.47-5.56) and 1.90 (95% CI 1.19-3.02) for cardiovascular disease (CVD) mortality, respectively. And a linear relationship was observed between serum Cl and mortality. Further, the inverse association between serum Cl and CVD mortality was particularly accentuated in the patients who were ≥50 years or with a history of diabetes. Similarly, lower time-varying serum Cl levels were also associated with a significant increased risk of all-cause and CVD death. CONCLUSION: Lower serum Cl levels predicted higher risk of all-cause and CVD mortality in CAPD patients.

Amplification-Free and Mix-and-Read Analysis of Multiplexed MicroRNAs on a Single Plasmonic Microbead.

In this work, a single microbead covered with a plasmonic layer is employed as the microreactor for the multiplexed miRNA analysis without nucleic acid amplification. On the plasmonic layer, the S9.6 antibody is adopted as the universal module for binding DNA/miRNA duplexes regardless of the sequence. Meanwhile, there is also a SERS reporter gold nanoparticle (GNP) pool, in which each group of GNPs is labeled with both a Raman coding molecule and a DNA probe for recognizing a given miRNA of interest. The target miRNAs will lead to the specific capture of the corresponding SERS reporter GNPs onto the plasmonic layer, which will enormously enhance the target miRNA-induced SERS signals. Finally, the enhanced SERS signals concentrated on the microbead will be mapped out by a confocal Raman microscope. The proposed method achieves the high-precision sensing of sub-pM target miRNA in a simple mix-and-read format and possesses multiplexed assay capability.

An overview of flood-induced transport disruptions on urban streets and roads in Chinese megacities: Lessons and future agendas.

Urban road transport disruptions caused by urban floods have become severe in the Chinese megacities due to climate change and urbanisation. Urban road planning, design, and land drainage systems are insufficiently coping with intense rainstorms, especially in the wet season. This is reflected in more research findings on urban flood impacts and road transport disruption over the past decade. Here we provide a critical overview of current research on urban road inundation, road traffic delays, and accessibility losses under flood conditions, and illustrate up-to-date practices with the relevant governmental institutions. Our review implies that urban flood management in road design is still at an embryonic stage in the Chinese megacities. Hence, we review the lessons and experiences of urban flood impacts on roads in the global context. We argue that it is essential to enhance better co-production practices on emergency responses and recovery measures between authorities, which is vital to improving flood resilience in uncertain climates.

High-flux nanofiltration membrane with modified highly dispersed MOF particles as nano filler.

The synthesis of optimized thin film nanocomposite (TFN) membrane with no or few defects is an efficacious method which can improve nanofiltration performance. However, poor dispersion of fillers in the organic phase and wrong compatibility between fillers and polymerizate are still a serious problem. In this study, the particle size of metal organic framework (MOF), aluminum-based metal-organic frameworks (CAU-1) was modulated and for the first time, dodecyl aldehyde was used to modify the surface hydrophobicity of CAU-1, which improved the dispersibility and inhibited the aggregation in the trimesoyl chloride (TMC)/n-hexane solution; later CAU-1 and modified CAU-1 were incorporated into the polyamide (PA) selective layer to synthesize TFN membrane by interfacial polymerization (IP). The particle size modulation and modification of the CAU-1 were demonstrated by X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) characterization. The characterization showed that PA selective layer was synthesized on the top layer of polysulfone (PSF) substrate. The pure water flux of the TFN membrane was increased to 79.89 ± 1.24 L·m-2·h-1·bar-1 compared to the original thin film composite (TFC) membrane, which was due to the polymerization of 100 nm modified CAU-1 on the PA layer to form a new water molecular channel, thus increasing the water flux by about 70%.

The miRNA-15b/USP7/KDM6B axis engages in the initiation of osteoporosis by modulating osteoblast differentiation and autophagy.

Osteoporosis is a metabolic disease that results from oxidative stress or inflammation in renal disorders. microRNAs (miRNAs) are recently implicated to participate in osteoporosis, but the mechanism remains largely unexplored. Herein, we aimed to explore the potential role of miR-15b in osteoblast differentiation and autophagy in osteoporosis. We established osteoporosis models through ovariectomy and determined that miR-15b was highly expressed whereas USP7 and KDM6B were poorly expressed in tissue of osteoporosis mice. Treatment of silenced miR-15b resulted in the elevation of decreased bone mineral density (BMD), the maximum elastic stress and the maximum load of osteoporosis mice. In osteoblasts, miR-15 overexpression decreased proliferation but suppressed the cell differentiation and autophagy, accompanied with decreased expression of USP7. Mechanistically, miR-15 bound and inhibited USP7 expression, while overexpression of USP7 promoted autophagy of osteoblasts. USP7, importantly, strengthened the stability of KDM6B and promoted KDM6B expression. MG132 protease inhibitor increased KDM6B and USP7 expression in osteoblasts. Silencing of KDM6B reversed the promoting effect on autophagy and proliferation induced by overexpression of USP7. Taken altogether, miR-15b inhibits osteoblast differentiation and autophagy to aggravate osteoporosis by targeting USP7 to regulate KDM6B expression.

Multiplexed Analysis of Photochemical Oxidants Using a Nanoparticle-Based Optoelectronic Nose.

Photochemical pollutants pose a substantial threat to human health in both outdoor and indoor environments. Herein, we prepare a class of gold nanoparticle-based colorimetric sensor arrays on optimized hydrophobic substrates using a simple pin-printing method for accurate identification and quantification of various gas-phase oxidants, as these microdetectors are low cost, sensitive, and easy to fabricate. For an array of AuNP sensors modified with various thiol-terminated ligands, a unique and distinguishable change in color (i.e., red, green, and blue response patterns) was obtained for each specific pollutant for molecular fingerprinting. Remarkable discrimination among 15 gases at a fairly low vapor concentration (i.e., 500 ppb) was illustrated using standard chemometric methods. Using digital imaging, the AuNP colorimetric sensor array offers ultrasensitive dosimetric identification of gas-phase oxidants relevant to outdoor and indoor air pollution, with limits of detection generally at sub-ppb levels for 2 h measurement. As a practical application, the sensor array is able to predict the overall air quality in indoor office environments over 24 h. Such sensor array based on chemically induced sintering of nanoparticles has significant implications for the development of nanosensors used in continuous monitoring of potential airborne pollutants at low concentrations from a large number of locations in a cost-effective manner.