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Chemotherapy drug-induced nephrotoxicity limits clinical applications for treating cancers. Pyroptosis, a newly discovered programmed cell death, was recently reported to be associated with kidney diseases. However, the role of pyroptosis in chemotherapeutic drug-induced nephrotoxicity has not been fully clarified. Herein, we demonstrate that the chemotherapeutic drug cisplatin or doxorubicin, induces the cleavage of gasdermin E (GSDME) in cultured human renal tubular epithelial cells, in a time- and concentration-dependent manner. Morphologically, cisplatin- or doxorubicin-treated renal tubular epithelial cells exhibit large bubbles emerging from the cell membrane. Furthermore, activation of caspase 3, not caspase 9, is associated with GSDME cleavage in cisplatin- or doxorubicin-treated renal tubular epithelial cells. Meanwhile, silencing GSDME alleviates cisplatin- or doxorubicin-induced HK-2 cell pyroptosis by increasing cell viability and decreasing LDH release. In addition, treatment with Ac-DMLD-CMK, a polypeptide targeting mouse caspase 3-Gsdme signaling, inhibits caspase 3 and Gsdme activation, alleviates the deterioration of kidney function, attenuates renal tubular epithelial cell injury, and reduces inflammatory cytokine secretion in vivo. Specifically, GSDME cleavage depends on ERK and JNK signaling. NAC, a reactive oxygen species (ROS) inhibitor, reduces GSDME cleavage through JNK signaling in human renal tubular epithelial cells. Thus, we speculate that renal tubular epithelial cell pyroptosis induced by chemotherapy drugs is mediated by ROS-JNK-caspase 3-GSDME signaling, implying that therapies targeting GSDME may prove efficacious in overcoming chemotherapeutic drug-induced nephrotoxicity.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) worldwide, and the importance of tubular injury has been highlighted in recent years. However, the underlying mechanisms and effective therapeutic targets are still unclear. In this study, we investigated mtDNA, mitochondrial dynamics, function and metabolic pathways to determine if mitochondrial damage plays a critical role in the development of tubular injury in DKD patients. A cross-sectional study was carried out among healthy controls (HCs, n = 65), diabetes patients without kidney disease (DCs, n = 48) and DKD patients (n = 60). Serum, peripheral blood mononuclear cells (PBMCs) and kidney biopsy specimens were obtained from participants. Metabolomics was employed to investigate cellular metabolism. DKD patients had decreased mtDNA copy numbers and increased mtDNA damage compared to DCs. Mitochondrial fragmentation was specifically presented in tubules, but not in podocytes of DKD patients. The accumulation of damaged mtDNA and fragmented mitochondria resulted in increased reactive oxygen species (ROS) generation, activation of apoptosis and loss of mitochondrial membrane potential (ΔΨm) in tubules and PBMCs. Furthermore, glycolysis and tricarboxylic acid (TCA) cycle was perturbed, and increased dihydroxyacetone phosphate (DHAP) and decreased succinyl-CoA synthetase (SCS) respectively in these two metabolic pathways were identified as potential biomarkers for tubular injury in DKD. Our study indicates that mitochondrial damage could be the hallmark of tubular injury in DKD patients, and this would provide a novel and attractive therapeutic target to improve this disease.

Podocyte injury and the appearance of proteinuria are features of minimal-change disease (MCD). Cyclosporin A (CsA) and tacrolimus (FK506) has been reported to reduce proteinuria in patients with nephrotic syndrome, but mechanisms remain unknown. We, therefore, investigated the protective mechanisms of CsA and FK506 on proteinuria in a rat model of MCD induced by puromycin aminonucleoside (PAN) and in vitro cultured mouse podocytes. Our results showed that CsA and FK506 treatment decreased proteinuria via a mechanism associated to a reduction in the foot-process fusion and desmin, and a recovery of synaptopodin and podocin. In PAN-treated mouse podocytes, pre-incubation with CsA and FK506 restored the distribution of the actin cytoskeleton, increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the migrating activities of podocytes. Treatment with CsA and FK506 also inhibited PAN-induced podocytes apoptosis, which was associated with the induction of Bcl-xL and inhibition of Bax, cleaved caspase 3, and cleaved PARP expression. Further studies revealed that CsA and FK506 inhibited PAN-induced p38 and JNK signaling, thereby protecting podocytes from PAN-induced injury. In conclusion, CsA and FK506 inhibit proteinuria by protecting against PAN-induced podocyte injury, which may be associated with inhibition of the MAPK signaling pathway.

Background The evidence linking the triglyceride-glucose (TyG) index to osteosarcopenic adiposity (OSA) in young and middle-aged populations is limited. This study aimed to investigate the association between the TyG index and OSA, and to determine the predictive value of the TyG index for all-cause and cardiovascular disease (CVD) mortality in OSA patients. Methods This cross-sectional and cohort study enrolled 8,098 participants aged 20–59 in the National Health and Nutrition Examination Survey (1999–2006 and 2011–2018). Mortality was determined by linkage to the National Death Index through December 31, 2019. Multivariable logistic regression models and restricted cubic splines (RCS) were constructed to determine the association between the TyG index and the prevalence of OSA. Multivariable Cox proportional hazards regression and competing risk analyses were employed to evaluate the association between the TyG index and mortality among OSA patients. Results There were 4,153 participants in the 1999–2006 cycle (weighted proportion male, 50.8%; mean [SD] age, 39.53 [10.98] years), and 3,945 in the 2011–2018 cycle (weighted proportion male, 50.7%; mean [SD] age, 39.00 [11.72] years). A higher TyG index was significantly associated with a greater prevalence of OSA, with an odds ratio (OR) of 4.52 (95% confidence interval [CI]: 3.78, 5.42) for the highest quartile. A J-shaped association was identified between the TyG index and the prevalence of OSA. Additionally, during a mean follow-up period of 131.1 months, OSA patients with the TyG index ≥ 8.5 exhibited a significantly elevated risk of all-cause mortality (hazard ratio [HR] = 1.93, 95% CI: 1.37, 2.71) and CVD mortality (HR = 2.10, 95% CI: 1.13, 3.88). Furthermore, sex disparity markedly affected the association between the TyG index and the prevalence of OSA and all-cause mortality in OSA patients. Conclusions This study revealed that a higher TyG index was associated with an increased risk of OSA and predicted a higher all-cause and CVD mortality in OSA patients. The implementation of public health interventions to reduce the TyG index may prove an effective method to decrease the incidence of OSA and related mortalities.

Background/Aims: In view of the latest findings that matrix metalloproteinase-7 (MMP-7) acted as a vital marker and pathogenic mediator of renal fibrosis in a murine model, we hypothesized that serum MMP-7 level might serve as a noninvasive prognostic biomarker in IgA nephropathy (IgAN) patients. Methods: We conducted a retrospective follow-up study of 244 IgAN patients for a median of 81.9 months. Serum MMP-7 was detected at the time of diagnosis, and renal progression was assessed by Cox proportional hazards method. Results: Compared with healthy populations, the serum levels of MMP-7 were significantly elevated in IgAN patients. Besides, serum MMP-7 levels were well correlated with renal scarring lesions characterized by glomerular sclerosis and interstitial fibrosis. Follow-up analyses revealed that increased serum MMP-7 levels were linked with a greater risk of poor renal outcome with a hazard ratio of 1.898 per doubling MMP-7 concentration. By contrast with the first quartile, the risk of deterioration in renal function elevated such that the hazard ratio for the second quartile was 1.805, 3.383 for the third, and 5.173 for the fourth quartile of the MMP-7 level. Conclusions: This study showed that the higher serum MMP-7 levels were independently associated with renal fibrosis and poor prognosis in IgAN.

The conventional reverse time migration utilizes regularly sampled computational grids to simulate wave propagation. Selecting the appropriate grid sampling is important for computational accuracy and efficiency. In general, the uniform-size grid cannot represent the complexity of the geology well. The grid may appear sparse in the low-velocity zone, especially in shallow depths where dispersion may occur. Conversely, it may appear excessively dense in the high-velocity zone, such as at greater depths or within a salt body, which results in higher computational memory and time consumption. To overcome these issues, we developed an efficient and accurate adaptive variable grid discretization method that automatically selects the vertical grid size based on the velocity, depth, and dominant frequency of the wavelet in elastic medium. Then we reformulated the elastic equations based on the adaptive variable grid by introducing a mapping relationship. To test the effectiveness, accuracy, and efficiency of the equation, we implemented it to both the forward propagation and migration of elastic wavefield. Synthetic numerical examples demonstrate that our proposed method can achieve elastic wavefield separation and no significant dispersion phenomenon. The multi-component imaging accuracy of reverse time migration is nearly equivalent to the traditional method, while significantly improving computational efficiency and saving storage space.

This paper proposes a system that applies electroencephalogram (EEG) technology to achieve music intervention therapy. The system can identify emotions of autistic children in real-time and play music considering their emotions as a musical treatment to assist the treatment of music therapists and the principle of playing homogenous music is to finally calm people down. The proposed method firstly collects EEG of autistic children using a 14-channel EMOTIV EPOC + and preprocesses signals through bandpass filtering, wavelet decomposition and reconstruction, then extracts frequency band-power characteristics of reconstructed EEG signals. Later, the data are classified as one of the three types of emotions (positive, middle and negative) using a support vector machine (SVM). The system also displays the recognized emotion type on a user interface and gives real-time emotional state feedback on emotional changes, which helps music therapists to evaluate the treatment and results more conveniently and effectively. Real EEG data are used to conduct the verification of system feasibility which reaches a classification accuracy of 88%. As the Internet of Things develops, the combination of edge computing with Wise Information Technology of 120 (WIT120) becomes a new trend. In this work, we propose a system to combine edge computing devices with cloud computing resources to form the music regulation system for autistic children to meet processing requirements for EEG signals in terms of timeliness and computational performance. In the designed system, preprocessing EEG signals is done in edge nodes then the preprocessed signals are sent to the cloud where frequency band-power characteristics can be extracted as features to be used in SVM. At last, the results are sent to a mobile app or computer software for therapists to evaluate.

To investigate the effect of Apatinib (an inhibitor targeting VEGFR‐2) enhances chemosensitivity of ABT‐199 on diffuse large B‐cell lymphoma (DLBCL). Viability assay and flow cytometric assay for determining apoptosis, cell cycle, mitochondrial membrane potential, reactive oxygen species and immunoblotting were used to explore the combination effect in DLBCL cell lines, DLBCL patient samples, and DLBCL mouse models. RNA sequencing assay helped identify mechanisms of ABT‐199 plus Apatinib. The results show that ABT‐199 combined with Apatinib inhibited cell proliferation, reduced colony‐forming capacity, and induced apoptosis and cell cycle arrest in DLBCL cells. Mechanistically, the combination therapy inhibited tumour cell growth and promoted tumour cell death by regulating EDN1 and MAPK‐related pathways and activating the intrinsic apoptotic pathway. The effect of the combination therapy was also validated in primary DLBCL blasts and xenograft mouse models. Our findings indicate that Apatinib enhances the chemosensitivity of ABT‐199 and might serve as a promising therapeutic strategy for DLBCL. Apatinib enhances the chemosensitivity of ABT‐199. Combined treatment inhibits tumour cell growth and promotes tumour cell death by regulating EDN1 and MAPK‐related pathways, and by activating the intrinsic apoptotic pathway.

As a lignocellulose-based substrate for anaerobic digestion, rice straw is characterized by low density, high water absorbability, and poor fluidity. Its mixing performances in digestion are completely different from traditional substrates such as animal manures. Computational fluid dynamics (CFD) simulation was employed to investigate mixing performances and determine suitable stirring parameters for efficient biogas production from rice straw. The results from CFD simulation were applied in the anaerobic digestion tests to further investigate their reliability. The results indicated that the mixing performances could be improved by triple impellers with pitched blade, and complete mixing was easily achieved at the stirring rate of 80 rpm, as compared to 20–60 rpm. However, mixing could not be significantly improved when the stirring rate was further increased from 80 to 160 rpm. The simulation results agreed well with the experimental results. The determined mixing parameters could achieve the highest biogas yield of 370 mL (g TS) −1 (729 mL (g TS digested ) −1 ) and 431 mL (g TS) −1 (632 mL (g TS digested ) −1 ) with the shortest technical digestion time ( T 80 ) of 46 days. The results obtained in this work could provide useful guides for the design and operation of biogas plants using rice straw as substrates.

Objectives In order to explore the impact of pegylated liposomal doxorubicin (PLD) dose intensity on survival outcomes of newly diagnosed elderly patients with diffuse large B‐cell lymphoma (DLBCL), we performed a retrospective study to compare the efficacy and adverse effects of RCEOP (70 mg/m2), RCdOP (20–30 mg/m2) and RCDOP (30–45 mg/m2). The optimal PLD dose of patients with different clinical characteristics of subgroups was explored to provide a clue for the selection of clinical PLD dose. Methods A total of 335 DLBCL patients (60–85 years old) who were newly diagnosed and completed at least four cycles of RCE(D)OP were selected. The patients were mainly divided into RCEOP (126 cases) (epirubicin 70 mg/m2), RCdOP (151 cases) (PLD 20–30 mg/m2) and RCdOP (58 cases) (PLD 30–45 mg/m2). The effects of different doses of PLD on clinical efficacy, cardiotoxicity and prognosis of patients were retrospectively analyzed. Subgroup analysis was performed to compare the clinical characteristics of different subgroups. Results Our study showed that PLD and epirubicin had similar efficacy (overall survival (OS) p = 0.776; progression‐free survival (PFS) p = 0.959). RCDOP (30–45 mg/m2 PLD) group had a higher complete remission (CR) rate of 75.9% compared with RCdOP (20–30 mg/m2 PLD) group (P D vs. d = 0.018). In the overall population, there was no significant difference in survival between RCDOP and RCdOP groups (OS P D vs. d = 0.661; PFS P D vs. d = 0.212). In patients with underlying cardiovascular diseases, the PFS of the RCDOP group was significantly better than the RCdOP group (p = 0.043). Meanwhile, patients in the RCDOP group tended to have a better prognosis than those in the RCEOP group (OS: RCDOP vs. RCEOP p = 0.054, PFS: RCDOP vs. RCEOP p = 0.053). There was no significant difference in the incidence of cardiotoxicity and other adverse events among the three groups. For the low‐risk (age‐adjusted‐International Prognostic Index = 0/1) old patients without cardiovascular disease, RCdOP was considered a better strategy in OS (p = 0.020). Conclusion In the general population, the CR rate in the RCDOP group was significantly higher than that in the RCdOP group (p = 0.018). For elderly DLBCL patients with cardiovascular disease, the effect benefit brought by the PLD dose was more obvious, and the PFS of the RCDOP group was significantly better than that of the RCdOP group (p = 0.043). Full dose of PLD is an efficient alternative in the treatment of patients with preexisting cardiovascular diseases. Generally, the complete remission rate of the RCDOP group was significantly higher than that of the RCdOP group. For elderly diffuse large B‐cell lymphoma patients with cardiovascular disease, the effect benefit brought by pegylated liposomal doxorubicin dose was more obvious, and the progression‐free survival of the RCDOP group was significantly longer than that of the RCdOP group (p = 0.043).