The kidney harbors one of the strongest circadian clocks in the body. Kidney failure has long been known to cause circadian sleep disturbances. Using an adenine-induced model of chronic kidney ...disease (CKD) in mice, we probe the possibility that such sleep disturbances originate from aberrant circadian rhythms in kidney. Under the CKD condition, mice developed unstable behavioral circadian rhythms. When observed in isolation in vitro, the pacing of the master clock, the suprachiasmatic nucleus (SCN), remained uncompromised, while the kidney clock became a less robust circadian oscillator with a longer period. We find this analogous to the silencing of a strong slave clock in the brain, the choroid plexus, which alters the pacing of the SCN. We propose that the kidney also contributes to overall circadian timekeeping at the whole-body level, through bottom-up feedback in the hierarchical structure of the mammalian circadian clocks.
Traffic emission is responsible for most small-sized particulate matter (PM) air pollution in urban areas. Several recent studies have indicated that traffic-related PM may aggravate kidney disease. ...Furthermore, exposure to particulate air pollution may be related to the risk of chronic kidney disease (CKD). However, the underlying molecular mechanisms have not been adequately addressed. In the present study, we studied the mechanisms of renal damage that might be associated with exposure to PM. In a real world of whole-body exposure to traffic-related PM model for 3–6 months, PM in urban ambient air can affect kidney function and induce autophagy, endoplasmic reticulum (ER) stress and apoptosis in kidney tissues. Exposure to traffic-related diesel particulate matter (DPM) led to a reduction in cell viability in human kidney tubular epithelial cells HK-2. DPM increased mitochondrial reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Furthermore, DPM induced ER stress and activated the unfolded protein response (UPR) pathway. Eventually, DPM exposure induced caspase pathways and triggered apoptosis. In addition, DPM induced autophagy through the inhibition of the Akt/mTOR pathway. Autophagy inhibition resulted in significantly increased cytotoxicity and apoptosis. These findings suggest that air pollution in urban areas may cause nephrotoxicity and autophagy as a protective role in PM-induced cytotoxicity.
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•PM affected kidney function in a whole-body exposure to traffic-related PM model.•DPM induced ER stress and the activation of the UPR pathway in kidney cells.•DPM caused mitochondrial damage by increasing ROS and reducing membrane potential.•DPM induced autophagy by inhibiting the Akt/mTOR pathway.
A series of compounds containing arylamine and 1,2‐diphenyl‐1H‐benzdimidazole moieties are developed as ambipolar, blue‐emitting materials with tunable blue‐emitting wavelengths, tunable ambipolar ...carrier‐transport properties and tunable triplet energy gaps. These compounds possess several novel properties: (1) they emit in the blue region with high quantum yields; (2) they have high morphological stability and thermal stability; (3) they are capable of ambipolar carrier transport; (4) they possess tunable triplet energy gaps, suitable as hosts for yellow‐orange to green phosphors. The electron and hole mobilities of these compounds lie in the range of 0.68–144 × 10−6 and 0.34–147 × 10−6 cm2 V−1 s−1, respectively. High‐performance, single‐layer, blue‐emitting, fluorescent organic light‐emitting diodes (OLEDs) are achieved with these ambipolar materials. High‐performance, single‐layer, phosphorescent OLEDs with yellow‐orange to green emission are also been demonstrated using these ambipolar materials, which have different triplet energy gaps as the host for yellow‐orange‐emitting to green‐emitting iridium complexes. When these ambipolar, blue‐emitting materials are lightly doped with a yellow‐orange‐emitting iridium complex, white organic light‐emitting diodes (WOLEDs) can be achieved, as well by the use of the incomplete energy transfer between the host and the dopant.
High‐performance, single‐layer, blue, fluorescent OLEDs based on ambipolartransport compounds containing arylamine and 1,2‐diphenyl‐1H‐benzdimidazole moieties are described. High‐performance yellow‐orange and green, single‐layer, phosphorescent OLEDs are also possible by using these materials as the host for phosphorescent dopants. White OLEDs can also be achieved.
Identifying modifiable risk factors of peritoneal dialysis (PD)-related peritonitis is of clinical importance in patient care. Mineral bone disease (MBD) has been associated with mortality and ...morbidity in end-stage kidney disease (ESKD) patients. However, its influence on PD related peritonitis due to altered host immunity remains elusive. This study investigated whether abnormal biomarkers of MBD are associated with the development of peritonitis in patients undergoing maintenance PD. We conducted a retrospective observational cohort study, analysing data derived from a nationwide dialysis registry database in Taiwan, from 2005 to 2012. A total of 5750 ESKD patients commencing PD therapy during this period were enrolled and followed up to 60 months or by the end of the study period. The patients were stratified based on their baseline serum parathyroid hormone (PTH) levels, calcium (Ca) levels or phosphorus (P) levels, respectively or in combinations. The primary outcome was the occurrence of first episode of peritonitis, and patient outcomes such as deaths, transfer to haemodialysis or receiving renal transplantation were censored. Peritonitis-free survival and the influence of PTH, Ca, P (individual or in combination) on the peritonitis occurrence were analysed. A total of 5750 PD patients was enrolled. Of them, 1611 patients experienced their first episode of peritonitis during the study period. Patients with low PTH, high Ca or low P levels, respectively or in combination, had the lowest peritonitis-free survival. After adjusting for age, sex and serum albumin levels, we found that the combinations of low PTH levels with either high Ca levels or low/normal P levels were significant risk factors of developing peritonitis. Abnormal mineral bone metabolism in maintenance PD patients with low serum PTH levels, in combination with either high Ca levels or low/normal P levels, could be novel risk factors of PD-related peritonitis.
Background
Lung adenocarcinoma (LUAD), a subtype of non-small cell lung cancer (NSCLC), causes high mortality around the world. Previous studies have suggested that the metabolic pattern of tumor is ...associated with tumor response to immunotherapy and patient’s survival outcome. Yet, this relationship in LUAD is still unknown.
Methods
Therefore, in this study, we identified the immune landscape in different tumor subtypes classified by metabolism-related genes expression with a large-scale dataset (tumor samples,
n
= 2181; normal samples,
n
= 419). We comprehensively correlated metabolism-related phenotypes with diverse clinicopathologic characteristics, genomic features, and immunotherapeutic efficacy in LUAD patients.
Results
And we confirmed tumors with activated lipid metabolism tend to have higher immunocytes infiltration and better response to checkpoint immunotherapy. This work highlights the connection between the metabolic pattern of tumor and tumor immune infiltration in LUAD. A scoring system based on metabolism-related gene expression is not only able to predict prognosis of patient with LUAD but also applied to pan-cancer. LUAD response to checkpoint immunotherapy can also be predicted by this scoring system.
Conclusions
This work revealed the significant connection between metabolic pattern of tumor and tumor immune infiltration, regulating LUAD patients’ response to immunotherapy.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib, are effective for non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, these ...patients eventually develop resistance to EGFR-TKI. The goal of the present study was to investigate the involvement of autophagy in gefitinib resistance. We developed gefitinib-resistant cells (PC-9/gef) from PC-9 cells (containing exon 19 deletion EGFR) after long-term exposure in gefitinib. PC-9/gef cells (B4 and E3) were 200-fold more resistant to gefitinib than PC-9/wt cells. Compared with PC-9/wt cells, both PC-9/gefB4 and PC-9/gefE3 cells demonstrated higher basal LC3-II levels which were inhibited by 3-methyladenine (3-MA, an autophagy inhibitor) and potentiated by chloroquine (CQ, an inhibitor of autophagolysosomes formation), indicating elevated autophagy in PC-9/gef cells. 3-MA and CQ concentration-dependently inhibited cell survival of both PC-9wt and PC-9/gef cells, suggesting that autophagy may be pro-survival. Furthermore, gefitinib increased LC3-II levels and autolysosome formation in both PC-9/wt cells and PC-9/gef cells. In PC-9/wt cells, CQ potentiated the cytotoxicity by low gefitinib (3 nM). Moreover, CQ overcame the acquired gefitinib resistance in PC-9/gef cells by enhancing gefitinib-induced cytotoxicity, activation of caspase 3 and poly (ADP-ribose) polymerase cleavage. Using an in vivo model xenografting with PC-9/wt and PC-9/gefB4 cells, oral administration of gefitinib (50 mg/kg) completely inhibited the tumor growth of PC-9/wt but not PC-9/gefB4cells. Combination of CQ (75 mg/kg, i.p.) and gefitinib was more effective than gefitinib alone in reducing the tumor growth of PC-9/gefB4. Our data suggest that inhibition of autophagy may be a therapeutic strategy to overcome acquired resistance of gefitinib in EGFR mutation NSCLC patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectivesOver the past two decades, debates on whether the profit status of dialysis facilities influences patient prognosis have been popular in the USA. Taiwan is one of the regions with the ...highest rate per capita of kidney replacement therapy worldwide, but no similar research has been conducted to date. This is the first study to address this issue.DesignThis was a nationwide retrospective cohort study based on the Taiwan Renal Registry Data System.SettingPatients were categorised into two groups based on the profit status (for-profit, not-for-profit (NFP)) of dialysis facilities, with 31 350 patients in each group. The patients were followed up from 2005 to 2012.ParticipantsPatients with uraemia who underwent long-term haemodialysis in private dialysis facilities and public facilities were excluded.Primary and secondary outcome measuresSurvival analyses were performed to compare prognosis between the two groups. Adjustments to patients’ basic profile, and facilities’ geographical distribution, level, and length of ownership were carried out to minimise possible confounding effects.ResultsAnalysis revealed that NFP dialysis facilities had better outcomes (HR=0.91, 95% CI (0.89 to 0.93)). A favourable effect remains with the adjustment of the facilities’ level, geographical distribution (HR=0.89, 95% CI (0.86 to 0.93)) or length of ownership (HR=0.95, 95% CI (0.89 to 0.95)). Survival analysis based on the geographical distribution and level of facilities was also conducted, which showed better prognosis in medical centres in the six municipalities, whereas worse prognosis was found in local hospitals not located in these municipalities.ConclusionOur findings suggest that in contemporary settings in Taiwan, treatment at NFP dialysis facilities was associated with a better prognosis. The results should be interpreted with caution since the possibility of residual confounding effects and uncertainty of casual relations exist due to the nature of observational studies.
Mixing polyanion cathode materials are promising candidates for the development of next-generation batteries, owing to their structural robustness and low-volume changes, yet low conductivity of ...polyanion hinders their practical capacity. Herein, the anion-site regulation is proposed to elevate the electrode kinetics and properties of polyanionic cathode. Multivalent anion P2O74− is selected to substitute the PO43− in Na3V2(PO4)3 (NVP) lattice and regulate the ratio of polyanion groups to prepare Na3+xV2(PO4)3−x(P2O7)x (NVPPx, 0 ≤ x ≤ 0.15) materials. The optimal Na3.1V2(PO4)2.9(P2O7)0.1 (NVPP0.1) material can deliver remarkably elevated specific capacity (104 mAh g−1 at 0.1 C, 60 mAh g−1 at 20 C, respectively), which is higher than those of NVP. Moreover, NVPP0.1 exhibits outstanding cyclic stability (91% capacity retention after 300 cycles at 1 C). Experimental analyses reveal that the regulation of anions improves the structure stability, increases the active Na occupancy in the lattice and accelerates the Na+ migration kinetics. The strategy of anion-site regulation provides the researchers a reference for the design of new high-performance polyanionic materials.
Anion-site regulation by substituting P2O74− to PO43− is achieved to prepare Na3+xV2(PO4)3-x (P2O7)x cathode materials, which improved working voltage and electrochemical properties. In addition, the theoretical and experimental analyses reveal the anionic manipulation mechanism of the P2O74−. Display omitted
In recent years, the technology of artificial intelligence (AI) and robots is rapidly spreading to countries around the world. More and more scholars and industry experts have proposed AI deep ...learning models and methods to solve human life problems and improve work efficiency. Modern people's lives are very busy, which led us to investigate whether the demand for Bento buffet cafeterias has gradually increased in Taiwan. However, when eating at a buffet in a cafeteria, people often encounter two problems. The first problem is that customers need to queue up to check out after they have selected and filled their dishes from the buffet. However, it always takes too much time waiting, especially at lunch or dinner time. The second problem is sometimes customers question the charges calculated by cafeteria staff, claiming they are too expensive at the checkout counter. Therefore, it is necessary to develop an AI-enabled checkout system. The AI-enabled self-checkout system will help the Bento buffet cafeterias reduce long lineups without the need to add additional workers. In this paper, we used computer vision and deep-learning technology to design and implement an AI-enabled checkout system for Bento buffet cafeterias. The prototype contains an angle steel shelf, a Kinect camera, a light source, and a desktop computer. Six baseline convolutional neural networks were applied for comparison on food recognition. In our experiments, there were 22 different food categories in a Bento buffet cafeteria employed. Experimental results show that the inception_v4 model can achieve the highest average validation accuracy of 99.11% on food recognition, but it requires the most training and recognition time. AlexNet model achieves a 94.5% accuracy and requires the least training time and recognition time. We propose a hierarchical approach with two stages to achieve good performance in both the recognition accuracy rate and the required training and recognition time. The approach is designed to perform the first step of identification and the second step of recognizing similar food images, respectively. Experimental results show that the proposed approach can achieve a 96.3% accuracy rate on our test dataset and required very little recognition time for input images. In addition, food volumes could be estimated using the depth images captured by the Kinect camera, and a framework of visual checkout system was successfully built.
Abstract
The escape of bladder cancer from immunosurveillance causes monotherapy to exhibit poor efficacy; therefore, designing a multifunctional nanoparticle that boosts programmed cell death and ...immunoactivation has potential as a treatment strategy. Herein, we developed a facile one-pot coprecipitation reaction to fabricate cluster-structured nanoparticles (CNPs) assembled from Fe
3
O
4
and iron chlorophyll (Chl/Fe) photosensitizers. This nanoassembled CNP, as a multifunctional theranostic agent, could perform red-NIR fluorescence and change the redox balance by the photoinduction of reactive oxygen species (ROS) and attenuate iron-mediated lipid peroxidation by the induction of a Fenton-like reaction. The intravesical instillation of Fe
3
O
4
@Chl/Fe CNPs modified with 4-carboxyphenylboronic acid (CPBA) may target the BC wall through glycoproteins in the BC cavity, allowing local killing of cancer cells by photodynamic therapy (PDT)-induced singlet oxygen and causing chemodynamic therapy (CDT)-mediated ferroptosis. An interesting possibility is reprogramming of the tumor microenvironment from immunosuppressive to immunostimulatory after PDT-CDT treatment, which was demonstrated by the reduction of PD-L1 (lower “off” signal to the effector immune cells), IDO-1, TGF-β, and M2-like macrophages and the induction of CD8
+
T cells on BC sections. Moreover, the intravesical instillation of Fe
3
O
4
@Chl/Fe CNPs may enhance the large-area distribution on the BC wall, improving antitumor efficacy and increasing survival rates from 0 to 91.7%. Our theranostic CNPs not only demonstrated combined PDT-CDT-induced cytotoxicity, ROS production, and ferroptosis to facilitate treatment efficacy but also opened up new horizons for eliminating the immunosuppressive effect by simultaneous PDT-CDT.
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