MMP12 is a Potential Predictive and Prognostic Biomarker of Various Cancers Including Lung Adenocarcinoma.

OBJECTIVE: This study sought to explore the clinical value of matrix metalloproteinases 12 (MMP12) in multiple cancers, including lung adenocarcinoma (LUAD). METHODS: Using >10,000 samples, this retrospective study demonstrated the first pan-cancer analysis of MMP12. The expression of MMP12 between cancer groups and their control groups was analyzed using Wilcoxon rank-sum tests. The clinical significance of MMP12 expression in multiple cancers was assessed using receiver operating characteristic curves, Kaplan-Meier curves, and univariate Cox analysis. A further LUAD-related analysis based on 4565 multi-center and in-house samples was performed to verify the findings regarding MMP12 in pan-cancer analysis partly. RESULTS: MMP12 mRNA is highly expressed in 13 cancers compared to their controls, and the MMP12 protein level is elevated in some of these cancers (e.g., colon adenocarcinoma) (P < .05). MMP12 expression makes it feasible to distinguish 21 cancer tissues from normal tissues (AUC = 0.86). A high MMP12 expression is a prognosis risk factor in eight cancers, such as adrenocortical carcinoma (hazard ratio >1, P < .05). The elevated MMP12 expression is also a prognosis protective factor in breast-invasive carcinoma and colon adenocarcinoma (hazard ratio <1, P < .05). Some pan-cancer findings regarding MMP12 are verified in LUAD-MMP12 expression is upregulated in LUAD at both the mRNA and protein levels (P < .05), has the potential to distinguish LUAD with considerable accuracy (AUC = .91), and plays a risk prognosis factor for patients with the disease (P < .05). CONCLUSIONS: MMP12 is highly expressed in most cancers and may serve as a novel biomarker for the prediction and prognosis of numerous cancers.

Retraction notice to "Berberine ameliorates renal injury in diabetic C57BL/6 mice: Involvement of suppression of SphK-S1P signaling pathway" [Arch. Biochem. Biophys. 502(2010) 112-120].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. This article shows significant data duplication and overlap with Liu, Weihua et al., Effects of berberine on matrix accumulation and NF-kappa B signal pathway in alloxan-induced diabetic mice with renal injury. European Journal of Pharmacology. 2010 Jul 25; 638(1-3):150-5 (https://doi.org/10.1016/j.ejphar.2010.04.033) without adequate referencing. Although there is a slight difference in the methodology section regarding alloxan-induced diabetes models in the two articles, there is a clear overlap between Table 2 of Lan, Tian et al. (2010); and Tables 1 and 2 of Liu, Weihua et al. (2010). The two manuscripts were submitted from the same laboratory in the same year.

Prognostic value of EBV DNA and platelet-to-lymphocyte ratio in patients with non-metastatic nasopharyngeal carcinoma: a retrospective study.

PURPOSE: Analyzing the prognostic value of Epstein-Barr virus (EBV) DNA load and platelet-to-lymphocyte ratio (PLR) in non-metastatic nasopharyngeal carcinoma (NPC) patients, thereby developing a reliable and effective marker. METHODS: We compared survival rates among different groups using the Kaplan-Meier method and the Log-rank test. The factors affecting the prognosis of NPC patients were determined using univariate and multivariate cox regression analysis. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. RESULTS: The ROC curve indicated a cut-off value of 775 copies/ml for EBV DNA and 203.3 for PLR. Kaplan-Meier and Log-rank tests showed that 3-year overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) of NPC patients in high risk group (HRG) were significantly poorer than those in medium risk group (MRG) and low risk group (LRG). The 3-year OS of NPC patients was significantly correlated with age, N stage and EBV DNA-PLR. The 3-year LRFS were significantly correlated with sex, N stage, histology type, and EBV DNA-PLR. The 3-year DMFS were correlated with histology type. The ROC curve showed that area under the curve (AUC) values of EBV DNA-PLR of 3-year OS, LRFS and DMFS in NPC were higher than those of PLR and EBV DNA. CONCLUSION: EBV DNA-PLR is an independent risk factor for the prognosis of NPC. Compared with PLR or EBV DNA alone, the combination of EBV DNA and PLR may be more accurate in predicting the prognosis of NPC patients.

A hypothesis for robust polarization vision: an example from the Australian imperial blue butterfly, Jalmenus evagoras.

The Australian lycaenid butterfly Jalmenus evagoras has iridescent wings that are sexually dimorphic, spectrally and in their degree of polarization, suggesting that these properties are likely to be important in mate recognition. We first describe the results of a field experiment showing that free-flying individuals of J. evagoras discriminate between visual stimuli that vary in polarization content in blue wavelengths but not in others. We then present detailed reflectance spectrophotometry measurements of the polarization content of male and female wings, showing that female wings exhibit blue-shifted reflectance, with a lower degree of polarization relative to male wings. Finally, we describe a novel method for measuring alignment of ommatidial arrays: by measuring variation of depolarized eyeshine intensity from patches of ommatidia as a function of eye rotation, we show that (a) individual rhabdoms contain mutually perpendicular microvilli; (b) many rhabdoms in the array have their microvilli misaligned with respect to neighboring rhabdoms by as much as 45 deg; and (c) the misaligned ommatidia are useful for robust polarization detection. By mapping the distribution of the ommatidial misalignments in eye patches of J. evagoras, we show that males and females exhibit differences in the extent to which ommatidia are aligned. Both the number of misaligned ommatidia suitable for robust polarization detection and the number of aligned ommatidia suitable for edge detection vary with respect to both sex and eye patch elevation. Thus, J. evagoras exhibits finely tuned ommatidial arrays suitable for perception of polarized signals, likely to match sex-specific life history differences in the utility of polarized signals.

A Novel Unsupervised Video Anomaly Detection Framework Based on Optical Flow Reconstruction and Erased Frame Prediction.

Reconstruction-based and prediction-based approaches are widely used for video anomaly detection (VAD) in smart city surveillance applications. However, neither of these approaches can effectively utilize the rich contextual information that exists in videos, which makes it difficult to accurately perceive anomalous activities. In this paper, we exploit the idea of a training model based on the "Cloze Test" strategy in natural language processing (NLP) and introduce a novel unsupervised learning framework to encode both motion and appearance information at an object level. Specifically, to store the normal modes of video activity reconstructions, we first design an optical stream memory network with skip connections. Secondly, we build a space-time cube (STC) for use as the basic processing unit of the model and erase a patch in the STC to form the frame to be reconstructed. This enables a so-called "incomplete event (IE)" to be completed. On this basis, a conditional autoencoder is utilized to capture the high correspondence between optical flow and STC. The model predicts erased patches in IEs based on the context of the front and back frames. Finally, we employ a generating adversarial network (GAN)-based training method to improve the performance of VAD. By distinguishing the predicted erased optical flow and erased video frame, the anomaly detection results are shown to be more reliable with our proposed method which can help reconstruct the original video in IE. Comparative experiments conducted on the benchmark UCSD Ped2, CUHK Avenue, and ShanghaiTech datasets demonstrate AUROC scores reaching 97.7%, 89.7%, and 75.8%, respectively.

Connexin32 ameliorates epithelial-to-mesenchymal-transition in diabetic renal tubular via inhibiting NOX4.

Renal tubulointerstitial fibrosis (RIF), characterized by epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (TECs), is the main cause of diabetic renal fibrosis. Oxidative stress plays a pivotal role in the development of diabetic RIF. Connexin32 (Cx32), prominently expressed in renal TECs, has emerged as an important player in the regulation of oxidative stress. However, the role of Cx32 in diabetic RIF has not been explored yet. Here, we showed that adenovirus-mediated Cx32 overexpression suppressed EMT to ameliorate RIF and renal function in STZ-induced diabetic mice, while knockout (KO) of Cx32 exacerbated RIF in diabetic mice. Moreover, overexpression of Cx32 inhibited EMT and the production of extra cellular matrix (ECM) in high glucose (HG) induced NRK-52E cells, whereas knockdown of Cx32 showed the opposite effects. Furthermore, we showed that NOX4, the main source of ROS in renal tubular, was down-regulated by Cx32. Mechanistically, Cx32 down-regulated the expression of PKC alpha in a carboxyl-terminal-dependent manner, thereby inhibiting the phosphorylation at Thr147 of p22phox triggered by PKC alpha, which ultimately repressed the formation of the p22phox-NOX4 complex to reduce the protein level of NOX4. Thus, we establish Cx32 as a novel target and confirm the protection mechanism in RIF.

Optimal encephalitis/meningitis roadmap via precise diagnosis and treatment (IMPROVE): a study protocol for a randomized controlled trial.

BACKGROUND: Encephalitis/meningitis brings a heavy disease burden, and the origin of disease remains unknown in 30-40% of patients. It is greatly significant that combinations of nucleic acid amplification and autoimmune antibody testing improves the diagnosis and treatment of encephalitis/meningitis. Moreover, though several diagnostic methods are in clinical use, a recognized and unified diagnosis and treatment process for encephalitis management remains unclear. METHODS: IMPROVE is a multicenter, open label, randomized controlled clinical trial that aims to evaluate the diagnostic performance, applications, and impact on patient outcomes of a new diagnostic algorithm that combines metagenomic next-generation sequencing (mNGS), multiplex polymerase chain reaction (PCR) and autoimmune antibody testing. The enrolled patients will be grouped into two parallel groups, multiplex PCR test plus autoimmune antibody group (Group I) or the mNGS plus autoimmune antibody group (Group II) with a patient ratio of 1:1. Both groups will be followed up for 12 months. The primary outcomes include the initial time of targeted treatment and the modified Rankin scale score on the 30th day of the trial. The secondary outcomes are the cerebrospinal fluid index remission rate on the 14th day, mortality rate on the 30th day, and an evaluation of diagnostic efficacy. The two groups are predicted to comprise of 484 people in total. DISCUSSION: To optimize the roadmap of encephalitis/meningitis, precise diagnosis, and treatment are of great significance. The effect of rapid diagnosis undoubtedly depends on the progression of new diagnostic tests, such as the new multiplex PCR, mNGS, and examination of broad-spectrum autoimmune encephalitis antibodies. This randomized-controlled study could allow us to obtain an accurate atlas of the precise diagnostic ability of these tests and their effect on the treatment and prognosis of patients. Trial registration ClinicalTrial.gov, NCT04946682. Registered 29 June 2021, 'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT04946682?term=NCT04946682&draw=2&rank=1.

Host feces, olfactory beacon guiding aggregation of intestinal parasites Gasterophilus pecorum (Diptera: Gasterophilidae).

The aim of this study was to identify the aggregation sites and transmission characteristics of Gasterophilus pecorum, the dominant pathogen of endangered equines in desert steppe. Therefore, we tested with a four-arm olfactometer the olfactory response of the G. pecorum adults to the odors that have a great impact on their life cycle, and also investigated the occurrence sites of the adults in the area where the Przewalski's horse (Equus przewalskii) roam frequently during the peak period of G. pecorum infection. The results of four-directional olfactory test showed that the fresh horse feces had a stronger attraction rate on both male (50.4%) and female flies (38.2%). Stipa caucasica, the only oviposition plant where G. pecorum lay eggs, had a better attraction effect on females than that on males. And the attraction rates of S. caucasica to G. pecorum females in the early growth stage (Stipa I) and mid-growth stage (Stipa II) were 32.8% and 36.8%, respectively. In addition, the two-directional olfactory test showed that the attraction rate of males to fresh horse feces (68.90%) was higher than that to Stipa II (31.10%), and females also showed similar olfactory responses. Moreover, in our field investigation, 68.29% of G. pecorum adults were collected from around the horse feces. The results of laboratory test and field investigation implied that the location mechanism of G. pecorum aggregation for mating is related to the orientation of horse feces. The horse feces and the vicinity are the key contamination areas of G. pecorum, and it is also the areas where horses are seriously infected with G. pecorum. Those fresh feces, which gather abundant information about the host, naturally had the greatest chance of contacting with the host; G. pecorum adults create the opportunity to enter directly into the host's mouth and infect the host by laying eggs on S. caucasica, which is the most favorite plant of the host in this area. These characteristics are one of the main reasons why G. pecorum has become the dominant species under the condition of sparse vegetation in desert steppe.

Gene expression pattern analysis using dual-color RT-MLPA and integrative genome-wide association studies of eQTL for tuberculosis suscepitibility.

BACKGROUND: When infected with Mycobacterium tuberculosis, only a small proportion of the population will develop active TB, and the role of host genetic factors in different TB infection status was not fully understood. METHODS: Forty-three patients with active tuberculosis and 49 with latent tuberculosis were enrolled in the prospective cohort. Expressing levels of 27 candidate mRNAs, which were previously demonstrated to differentially expressed in latent and active TB, were measured by dual color reverse transcription multiplex ligation dependent probe amplification assay (dcRT-MLPA). Using expression levels of these mRNAs as quantitative traits, associations between expression abundance and genome-wild single nucleotide polymorphisms (SNPs) were calculated. Finally, identified candidate SNPs were further assessed for their associations with TB infection status in a validation cohort with 313 Chinese Han cases. RESULTS: We identified 9 differentially expressed mRNAs including il7r, il4, il8, tnfrsf1b, pgm5, ccl19, il2ra, marco and fpr1 in the prospective cohort. Through expression quantitative trait loci mapping, we screened out 8 SNPs associated with these mRNAs. Then, CG genotype of the SNP rs62292160 was finally verified to be significantly associated with higher transcription levels of IL4 in LTBI than in TB patients. CONCLUSION: We reported that the SNP rs62292160 in Chinese Han population may link to higher expression of il4 in latent tuberculosis. Our findings provided a new genetic variation locus for further exploration of the mechanisms of TB and a possible target for TB genetic susceptibility studies, which might aid the clinical decision to precision treatment of TB.

CKIP-1 acts downstream to Cx43 on the activation of Nrf2 signaling pathway to protect from renal fibrosis in diabetes.

We previously reported that both Cx43 and CKIP-1 attenuated diabetic renal fibrosis via the activation of Nrf2 signaling pathway. However, whether CKIP-1, a scaffold protein, participates in regulating the activation of Nrf2 signaling pathway by Cx43 remains to be elucidated. In this study, the effect of adenovirus-mediated Cx43 overexpression on renal fibrosis in CKIP-1-/- diabetic mice was investigated. We found that overexpression of Cx43 could significantly alleviate renal fibrosis by activating the Nrf2 pathway in diabetic mice, but have no obvious effect in CKIP-1-/- diabetic mice. Cx43 overexpressed plasmid and CKIP-1 small interfering RNA were simultaneously transfected into glomerular mesangial cells and the result demonstrated that the effect of activation of Nrf2 signaling pathway by Cx43 was blocked by CKIP-1 depletion. The interaction between Cx43 and CKIP-1 was analyzed by immunofluorescence and immunoprecipitation assays. We found that Cx43 interacted with CKIP-1, and the interaction was weakened by high glucose treatment. Moreover, Cx43 regulated the expression of CKIP-1 and the interaction of CKIP-1 with Nrf2 via Cx43 carboxyl terminus (CT) domain, thereby activating Nrf2 signaling pathway. According to the results, we preliminary infer that CKIP-1 acts downstream to CX43 on the activation of Nrf2 signaling pathway to protect from renal fibrosis in diabetes, the mechanism of which might be related to the interaction of CKIP-1 with Nrf2 through Cx43 CT. Our study provides further experimental basis for targeting the Cx43-CKIP-1-Nrf2 axis to resist diabetic renal fibrosis.

Artemisinin co-delivery system based on manganese oxide for precise diagnosis and treatment of breast cancer.

Tumor microenvironment (TME) responsive intelligent system can realize the specific release and uniform distribution of chemotherapy drugs in tumor tissues, to achieve high-efficiency and low-toxic treatment of tumors. In this paper, drug delivery system TKD@RBCm-Mn2O3-ART with the above characteristics was constructed. We synthesized hollow mesoporous manganese trioxide (Mn2O3) nanoparticles and firstly found that they owned time-dependent size transformation feature in simulated TME. The particle size decreased from 318 nm to 50 nm and 6 nm at 1 h and 4 h in simulated TME, respectively. Then artemisinin (ART) was loaded into Mn2O3to realize the co-delivery of Mn2+and ART. The modification of homologous red cell membrane (RBCm) and TKD peptide was aimed at long circulation and tumor targeting in the body.In vitroresults demonstrated that in the presence of GSH, the cumulative drug release percentage could achieve 97.5%. Meanwhile, Mn2O3exhibited a good imaging capability in tumor, with the relaxation rate of 6.3113 mM-1s-1. After entering into MCF-7 cells, TKD@RBCm-Mn2O3/ART synchronously released Mn2+and ART to generate large amount of ROS and induce DNA damage.In vivoresults proved TKD@RBCm-Mn2O3/ART could arrive the deep area of solid tumors and achieve accurate diagnosis and treatment of breast cancer.

Design of Citrus Fruit Detection System Based on Mobile Platform and Edge Computer Device.

Citrus fruit detection can provide technical support for fine management and yield determination of citrus orchards. Accurate detection of citrus fruits in mountain orchards is challenging because of leaf occlusion and citrus fruit mutual occlusion of different fruits. This paper presents a citrus detection task that combines UAV data collection, AI embedded device, and target detection algorithm. The system used a small unmanned aerial vehicle equipped with a camera to take full-scale pictures of citrus trees; at the same time, we extended the state-of-the-art model target detection algorithm, added the attention mechanism and adaptive fusion feature method, improved the model's performance; to facilitate the deployment of the model, we used the pruning method to reduce the amount of model calculation and parameters. The improved target detection algorithm is ported to the edge computing end to detect the data collected by the unmanned aerial vehicle. The experiment was performed on the self-made citrus dataset, the detection accuracy was 93.32%, and the processing speed at the edge computing device was 180 ms/frame. This method is suitable for citrus detection tasks in the mountainous orchard environment, and it can help fruit growers to estimate their yield.

Connexin 43 prevents the progression of diabetic renal tubulointerstitial fibrosis by regulating the SIRT1-HIF-1α signaling pathway.

Hyperglycemia-induced renal epithelial-to-mesenchymal transition (EMT) is a key pathological factor in diabetic renal tubulointerstitial fibrosis (RIF). Our previous studies have shown that connexin 43 (Cx43) activation attenuated the development of diabetic renal fibrosis. However, whether Cx43 regulates the EMT of renal tubular epithelial cells (TECs) and the pathological process of RIF under the diabetic conditions remains to be elucidated. In the present study, we identified that Cx43 protein expression was down-regulated in the kidney tissues of db/db mice as well as in high glucose (HG)-induced NRK-52E cells. Overexpression of Cx43 improved renal function in db/db spontaneous diabetic model mice, increased SIRT1 levels, decreased hypoxia-inducible factor (HIF)-1α expression, and reduced production of EMT markers and extracellular matrix (ECM) components. Additionally, Cx43 overexpression inhibited the EMT process and reduced the expression of ECM components such as fibronectin (FN), Collagen I, and Collagen IV in HG-induced NRK-52E cells, whereas Cx43 deficiency had the opposite effects. Mechanistically, Cx43 in a carboxyl-terminal signal transduction-dependent manner could up-regulate SIRT1 expression and enhance SIRT1-dependent deacetylation of HIF-1α to reduce HIF-1α activity, which eventually ameliorated renal EMT and diabetic RIF. Our study indicates the essential role of Cx43 in regulating renal EMT and diabetic RIF via regulating the SIRT1-HIF-1α signaling pathway and provides an experimental basis for Cx43 as a potential target for diabetic nephropathy (DN).

Gentiopicroside activates the bile acid receptor Gpbar1 (TGR5) to repress NF-kappaB pathway and ameliorate diabetic nephropathy.

Our previous studies indicated that the G-protein-coupled bile acid receptor, Gpbar1 (TGR5), inhibits inflammation by inhibiting the NF-κB signalling pathway, eventually attenuating diabetic nephropathy (DN). Gentiopicroside (GPS), the main active secoiridoid glycoside of Gentiana manshurica Kitagawa, has been demonstrated to inhibit inflammation in various diseases via inhibiting the inflammatory signalling pathways. However, whether GPS inhibits the NF-κB signalling pathway by activating TGR5 and regulates the pathological progression of diabetic renal fibrosis requires further investigation. In this study, we found that GPS significantly reversed the downregulation of TGR5 and inhibited the overproduction of fibronectin (FN), transforming growth factor ß1 (TGF-ß1), intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) in glomerular mesangial cells (GMCs) exposed to high glucose (HG). Additionally, GPS prevented the phosphorylation and degradation of IκBα, and subsequently inhibited the activation of the NF-κB signalling pathway. Further investigation found that GPS enhanced the stabilization of IκBα by promoting the interaction of ß-arrestin2 with IκBα via TGR5 activation, which contributed to the inhibition of NF-κB signalling pathway. Importantly, the depletion of TGR5 blocked the inhibition of the NF-κB signalling pathway and reversed the downregulation of FN, ICAM-1, VCAM-1 and TGF-ß1 by GPS in HG-induced GMCs. Moreover, GPS increased the TGR5 protein levels and promoted the interaction between IκBα and ß-arrestin2, thereby inhibiting the reduction of IκBα and blocked NF-κB p65 nuclear translocation in the kidneys of STZ-induced diabetic mice. Collectively, these data suggested that GPS regulates the TGR5-ß-arrestin2-NF-κB signalling pathway to prevent inflammation in the kidneys of diabetic mice, and ultimately ameliorates the pathological progression of diabetic renal fibrosis.

PAQR3 regulates phosphorylation of FoxO1 in insulin-resistant HepG2 cells via NF-κB signaling pathway.

Insulin resistance is a significant feature of type 2 diabetes mellitus and glucose and lipid metabolism disorders. Activation of NF-κB signaling pathway plays an important role in the formation of insulin resistance. FoxO1 plays a major role in regulating glucose and lipid metabolism, as well as insulin signaling pathway. Previous studies have shown that Progestin and AdipoQ Receptor 3 (PAQR3) suppresses the activity of PI3K/Akt, which is an upstream pathway of FoxO1, and additionally promotes the pathological process of diabetic renal inflammatory fibrosis via activating NF-κB pathway. On this basis, it has caused us great concern whether NF-κB is involved in PAQR3 regulation of FoxO1 under insulin resistance. In this study, we aimed to investigate whether PAQR3 regulates phosphorylation of FoxO1 via NF-κB pathway in palmitic acid (PA)-induced insulin-resistant HepG2 cells, thereby causing glucose and lipid metabolism disorders. We found that PA stimulation and PAQR3 overexpression decreased the phosphorylation of FoxO1 and the expressions of glucokinase (GCK) and low density lipoprotein receptor (LDLR), in addition, promoted the nuclear accumulation of NF-κB. Inhibition of NF-κB pathway increased the phosphorylation of FoxO1 and the expressions of GCK and LDLR which were downregulated by PA stimulation and PAQR3 overexpression. Taken together, in PA-induced insulin-resistant HepG2 cells, PAQR3 might regulate the phosphorylation of FoxO1 and the expressions of GCK and LDLR through NF-κB pathway, thereby regulating the glucose and lipid metabolism disorders induced by insulin resistance.

Polydatin attenuates renal fibrosis in diabetic mice through regulating the Cx32-Nox4 signaling pathway.

We previously found that polydatin could attenuate renal oxidative stress in diabetic mice and improve renal fibrosis. Recent evidence shows that NADPH oxidase 4 (Nox4)-derived reactive oxygen species (ROS) contribute to inflammatory and fibrotic processes in diabetic kidneys. In this study we investigated whether polydatin attenuated renal fibrosis by regulating Nox4 in vitro and in vivo. In high glucose-treated rat glomerular mesangial cells, polydatin significantly decreased the protein levels of Nox4 by promoting its K48-linked polyubiquitination, thus inhibited the production of ROS, and eventually decreasing the expression of fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1), the main factors that exacerbate diabetic renal fibrosis. Overexpression of Nox4 abolished the inhibitory effects of polydatin on FN and ICAM-1 expression. In addition, the expression of Connexin32 (Cx32) was significantly decreased, which was restored by polydatin treatment. Cx32 interacted with Nox4 and reduced its protein levels. Knockdown of Cx32 abolished the inhibitory effects of polydatin on the expression of FN and ICAM-1. In the kidneys of streptozocin-induced diabetic mice, administration of polydatin (100 mg·kg-1·d-1, ig, 6 days a week for 12 weeks) increased Cx32 expression and reduced Nox4 expression, decreased renal oxidative stress levels and the expression of fibrotic factors, eventually attenuating renal injury and fibrosis. In conclusion, polydatin promotes K48-linked polyubiquitination and degradation of Nox4 by restoring Cx32 expression, thereby decreasing renal oxidative stress levels and ultimately ameliorating the pathological progress of diabetic renal fibrosis. Thus, polydatin reduces renal oxidative stress levels and attenuates diabetic renal fibrosis through regulating the Cx32-Nox4 signaling pathway.

Introducing molecular testing of pyrazinamide susceptibility improves multidrug-resistant tuberculosis treatment outcomes: a prospective cohort study.

The current treatment for multidrug-resistant tuberculosis (MDR-TB) takes a lengthy period of 18-24 months and has a poor cure rate of 50-60%. A multicenter, prospective cohort study was conducted to assess the role of testing for molecular susceptibility to pyrazinamide (PZA) in optimising treatment for MDR-TB.We assigned 76 patients to an optimised molecular susceptibility group and 159 patients to a regular treatment group where PZA susceptibility was not determined. Of these patients, 152 were matched after propensity score matching (76 in the optimised group and 76 in the regular group). Treatment success rate was measured in the propensity-matched cohort as the primary outcome.Patients in the optimised group achieved a higher treatment success rate than those in the regular group (76.3% versus 55.3%, p=0.006). Of 51 patients with isolates that were susceptible to PZA and who were receiving a 12-month regimen, 42 (82.4%) were treated successfully. The optimised group showed faster culture conversion than the regular group (p=0.024). After exclusion of pre-extensively drug-resistant TB (pre-XDR-TB), the treatment outcome in the optimised group was still better than the regular group (83.1% versus 62.1%, p=0.009).Introducing molecular susceptibility testing for PZA improved the treatment outcomes for MDR-TB without the use of new drugs. Introducing PZA for patients with PZA-susceptible (PZA-S) MDR-TB allows the current regimen to be shortened to 12 months with comparable success rates to the World Health Organization (WHO) recommended shorter regimen.

Hybrid indoor localization scheme with image sensor-based visible light positioning and pedestrian dead reckoning.

In this paper, we propose a hybrid indoor localization scheme with image sensor-based visible light positioning and pedestrian dead reckoning. The architecture and algorithm of the proposed positioning scheme are analyzed. We build and demonstrate two different positioning prototypes with single/multiple cells, which are based on a commercial light-emitting diode lamp and off-the-shelf mobile phone equipped with an image sensor and inertial measurement unit. Experimental results show that the proposed visible light positioning scheme can achieve both cell recognition and three-dimensional positioning with a single captured image of a single light source, and the positioning error is only several centimeters. Moreover, with the proposed hybrid positioning algorithm consisting of visible light positioning and pedestrian dead reckoning, we achieved real-time decimeter-level indoor location tracking continuously and robustly with sparse light-source beacons in an actual indoor scenario.

High-Precision Indoor Visible Light Positioning Using Modified Momentum Back Propagation Neural Network with Sparse Training Point.

In this letter, we propose an indoor visible light positioning technique using a Modified Momentum Back-Propagation (MMBP) algorithm based on received signal strength (RSS) with sparse training data set. Unlike other neural network algorithms that require a large number of training data points to locate accurately, we have realized high-precision positioning for 100 test points with only 20 training points in a 1.8 m × 1.8 m × 2.1 m localization area. In order to verify the adaptability of the MMBP algorithm, we experimentally demonstrate two different training data acquisition methods adopting either even or arbitrary training sets. In addition, we also demonstrate the positioning accuracy of the traditional RSS algorithm. Experimental results show that the average localization accuracy optimized by our proposed algorithm is only 1.88 cm for the arbitrary set and 1.99 cm for the even set, while the average positioning error of the traditional RSS algorithm reaches 14.34 cm. Comparison indicates that the positioning accuracy of our proposed algorithm is 7.6 times higher. Results also show that the performance of our system is higher than some previous reports based on RSS and RSS fingerprint databases using complex machine learning algorithms trained by a large amount of training points.

Ulinastatin attenuates LPS-induced inflammation in mouse macrophage RAW264.7 cells by inhibiting the JNK/NF-κB signaling pathway and activating the PI3K/Akt/Nrf2 pathway.

Ulinastatin (UTI) is a broad-spectrum serine protease inhibitor isolated and purified from human urine with strong anti-inflammatory and cytoprotective actions, which is widely used for the treatment of various diseases, such as pancreatitis and sepsis. Although the therapeutic effects of UTI are reported to be associated with a variety of mechanisms, the signaling pathways mediating the anti-inflammatory action of UTI remain to be elucidated. In the present study we carried out a systematic study on the anti-inflammatory and anti-oxidative mechanisms of UTI and their relationships in LPS-treated RAW264.7 cells. Pretreatment with UTI (1000 and 5000 U/mL) dose-dependently decreased the mRNA levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, iNOS) and upregulated anti-inflammatory cytokines (IL-10 and TGF-ß1) in LPS-treated RAW264.7 cells. UTI pretreatment significantly inhibited the nuclear translocation of NF-κB by preventing the degradation of IκB-α. UTI pretreatment only markedly inhibited the phosphorylation of JNK at Thr183, but it did not affect the phosphorylation of JNK at Tyr185, ERK-1/2 and p38 MAPK; JNK was found to function upstream of the IκB-α/NF-κB signaling pathway. Furthermore, UTI pretreatment significantly suppressed LPS-induced ROS production by activating PI3K/Akt pathways and the nuclear translocation of Nrf2 via promotion of p62-associated Keap1 degradation. However, JNK was not involved in mediating the anti-oxidative stress effects of UTI. In summary, this study shows that UTI exerts both anti-inflammatory and anti-oxidative effects by targeting the JNK/NF-κB and PI3K/Akt/Nrf2 pathways.