Both 3D organic-inorganic perovskites (Et3P(CH2)2ClCd(dca)3 (1) and Et3P(CH2)2FCd(dca)3 (2) dca = dicyanamide, N(CN)2-) display two sequentially reversible high-temperature phase transitions and ...switchable dielectric properties. Through halogen substitution, 1 shows exceptional switching behaviour of second harmonic generation effects and remarkably 2 represents the first above-room-temperature 3D ferroelastic material characterized by two ferroelastic phases.
The burden of sepsis remains high in China. The relationship between case volume and hospital mortality among patients with septic shock, the most severe complication of sepsis, is unknown in China.
...In this retrospective cohort study, we analyzed surveillance data from a national quality improvement program in intensive care units (ICUs) in China in 2020. Association between septic shock case volume and hospital mortality was analyzed using multivariate linear regression and restricted cubic splines.
We enrolled a total of 134,046 septic shock cases in ICUs from 1902 hospitals in China during 2020. In this septic shock cohort, the median septic shock volume per hospital was 33 cases (interquartile range 14-76 cases), 41.4% were female, and more than half of the patients were over 61 years old, with average hospital mortality of 21.2%. An increase in case volume was associated with improved survival among septic shock cases. In the linear regression model, the highest quartile of septic shock volume was associated with lower hospital mortality compared with the lowest quartile (β - 0.86; 95% CI - 0.98, - 0.74; p < 0.001). Similar differences were found in hospitals of respective geographic locations and hospital levels. With case volume modeled as a continuous variable in a restricted cubic spline, a lower volume threshold of 40 cases before which a substantial reduction of the hospital mortality rate was observed.
The findings suggest that hospitals with higher septic shock case volume have lower hospital mortality in China. Further research is needed to explain the mechanism of this volume-outcome relationship.
Colon cancer has attracted much attention due to its annually increasing incidence. Conventional chemotherapeutic drugs are unsatisfactory in clinical application because of their lack of targeting ...and severe toxic side effects. In the past decade, nanomedicines with multimodal therapeutic strategies have shown potential for colon cancer because of their enhanced permeability and retention, high accumulation at tumor sites, co-loading with different drugs, and comb-ination of various therapies. This review summarizes the advances in research on various nanomedicine-based therapeutic strategies including chemotherapy, radiotherapy, phototherapy (photothermal therapy and photodynamic therapy), chemodynamic therapy, gas therapy, and immunotherapy. Additionally, the therapeutic mechanisms, limitations, improvements, and future of the above therapies are discussed.
A metal-free method for the dual activation of aryl phosphinate has been developed; the P–H and P–O bonds are sequentially activated by the Tf2O/DMSO system. Without the requirement of metals and ...unstable P-reagents, this one-pot procedure provides a convenient and practical access to a variety of aryl phosphonates. A mechanism involving twice generation of electrophilic P-species and two SN-processes is proposed on the basis of the control experiments.
► Rutin inhibits Aβ42 fibrillization and attenuates Aβ42-induced cytotoxicity. ► Rutin decreases the formation of active oxygen species (ROS). ► Rutin decreases the formation of glutathione disulfide ...(GSSG) and malondialdehyde (MDA). ► Rutin decreases the production of TNF-α, and IL-1β.
Alzheimer's disease (AD) is a complex, multi-factorial neurodegenerative disease. The aggregation of soluble β-amyloid (Aβ) into fibrillar deposits is a pathological hallmark of AD. The Aβ aggregate-induced neurotoxicity, inflammatory reactions, oxidative stress, and nitric oxide (NO) generation are strongly linked to the etiology of AD. Here, we show that the common dietary flavonoid, rutin, can dose-dependently inhibit Aβ42 fibrillization and attenuate Aβ42-induced cytotoxicity in SH-SY5Y neuroblastoma cells. Moreover, rutin decreases the formation of reactive oxygen species (ROS), NO, glutathione disulfide (GSSG), and malondialdehyde (MDA), reduces inducible nitric oxide synthase (iNOS) activity, attenuates mitochondrial damage, increases the glutathione (GSH)/GSSG ratio, enhances the activities of super oxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and modulates the production of proinflammatory cytokines by decreasing TNF-α and IL-1β generation in microglia. Taken together, the actions of rutin on multiple pathogenic factors deserves further investigation for the prevention and treatment of AD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Deep learning method for extracting weak–fault–related features when the labels are insufficient.•Pseudo–label selection mechanism based on reliability assessment.•Joint learning workflow combining ...the advantages of UL, TL, and SSL.•SSL based on multiple views considering prior knowledge of signal processing.
Deep neural networks exhibit excellent performance in fault feature extraction for considerable amounts of data. However, data labeling is a difficult task in practical engineering, which may lead to problems in fault diagnosis particularly when faults are weak. To resolve the foregoing, a semi–pseudo–labeling diagnosis system is proposed in this paper. The proposed system considers the confidence and reliability of samples to cope with situations where labels are insufficient and faults are weak. By adding pseudo–labels, unlabeled data whose fault information is swamped by a large amount of noise can achieve low–density separation and entropy regularization in the sample space. Consequently, the training of deep learning models for weak–fault diagnosis is supported. Regarding the traditional pseudo–labeling problems in weak–fault–related feature extraction, a series of solutions has been proposed to solve the problems in the field of fault diagnosis. The designed model reduces pseudo–label noise and enhances the capability of weak–fault–related feature extraction. The effectiveness of this method was validated on the datasets collected by simulating faulty bearings and those sustaining actual failure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•miR-21 expression was upregulated by TGF-β1 in time- and concentration-dependent manner.•miR-21 over-expression enhanced TGF-β1-induced EMT by directly down-regulating smad7 and ...indirectly up-regulating smad3.•miR-21 inhibitor can not only inhibit EMT and fibrosis but also ameliorate renal structure and function.•Targeting miR-21 may be a better alternative to directly suppress TGF-β1-mediated fibrosis in DN.
Epithelial-to-mesenchymal transition (EMT) plays an important role in renal interstitial fibrosis (RIF) with diabetic nephropathy (DN). Smad7 (a inhibitory smad), a downstream signaling molecules of TGF-β1, represses the EMT. The physiological function of miR-21 is closely linked to EMT and RIF. However, it remained unclear whether miR-21 over-expression affected TGF-β1-induced EMT by regulating smad7 in DN. In this study, real-time RT-PCR, cell transfection, luciferase reporter gene assays, western blot and confocal microscope were used, respectively. Here, we found that miR-21 expression was upregulated by TGF-β1 in time- and concentration -dependent manner. Moreover, miR-21 over-expression enhanced TGF-β1-induced EMT(upregulation of a-SMA and downregulation of E-cadherin) by directly down-regulating smad7/p-smad7 and indirectly up-regulating smad3/p-smad3, accompanied by the decrease of Ccr and the increase of col-IV, FN, the content of collagen fibers, RTBM, RTIAW and ACR. Meantime, the siRNA experiment showed that smad7 can directly regulate a-SMA and E-cadherin expression. More importantly, miR-21 inhibitor can not only inhibit EMT and fibrosis but also ameliorate renal structure and function. In conclusion, our results demonstrated that miR-21 overexpression can contribute to TGF-β1-induced EMT by inhibiting target smad7, and that targeting miR-21 may be a better alternative to directly suppress TGF-β1-mediated fibrosis in DN.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cyanide tailings(CT) are a typical hazardous waste, containing large amounts of heavy metals and highly toxic cyanide. As so far, it is difficult to solve this problem at the same time. In this ...study, a “two-step” process was proposed for the first time to treat CT, first using microorganisms to degrade cyanide and then using microbially induced carbonate precipitation (MICP) to solidify the CT. We isolated a bifunctional bacterium which exhibited cyanide degradation and high urease activity from CT, identified as Aneurinibacillus tyrosinisolvens strain (named JK-1). We used JK-1 bacteria to treat the CT in a “two-step” process. The results showed that the degradation of free cyanide (F–CN) and total cyanide (T-CN) in CT by JK-1 bacteria reached 94.54% and 88.13%. After the MICP treatment, the spindle-shaped CaCO3 solidified the CT into a block of calcite and sphalerite crystals, and the uncompressed compressive strength (UCS) reached 0.74 MPa; the morphology of heavy metals in the CT changed from the exchangeable state to the carbonate-bound state, and the mobility was significantly reduced. Compared with chemical treatment, the treatment of CT by the new process is highly efficient and green, which can realize the solidification of CT, degradation of cyanide and immobilization of heavy metals at the same time. Compared with chemical treatment, the new process is efficient and green, which can realize the solidification of CT, the degradation of cyanide and the immobilization of heavy metals at the same time; it is of great significance to the harmless treatment of CT and the sustainable development of gold smelting industry.
•A bacterium capable of cyanide-degradation and urease-production was isolated.•The new process can degrade cyanide, solidify tailings and stabilize heavy metals.•The bio-cement blocks of cyanide tailings were produced successfully.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Since cellular metabolism reprogramming is one of the crucial hallmarks of tumor, glucose metabolic pathways are emerging as an important target for modulating immunosuppressive tumor ...microenvironment (TME) in favor of anti-PD-L1 therapy. Aiming at boosting immune response by modulation immunosuppressive TME via balancing the glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) of tumor cells, we developed a dual-responsive mPEG-PLA-PHis-ss-PEI polyplexes (DRP/Res/siP) for robust co-delivery of PD-L1 siRNA and resveratrol (Res). Isothermal titration calorimetry confirmed the non-electrostatic interactions between PD-L1 siRNA and PHis block of the copolymer, which contributed to the efficient and synchronized release of siRNA with Res in response to the acidic and reductive environment by destabilizing the siRNA polyplexes. The extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) as well as some key enzymes involved in glycolysis and mitochondrial OXPHOS pathways were determined to quantify the glucose metabolism balance. Effective downregulation of glycolysis and upregulation of mitochondrial OXPHOS were observed in the tumor cells treated with DRP/Res/siP, leading to remarkably reduced lactate production and glucose consumption. In vivo anti-tumor results showed that upregulation of mitochondrial OXPHOS pathways not only significantly promoted CD8+ and CD4+ T cells infiltration, IFN-γ secretion but also significantly suppressed the Treg cells and MDSCs at the same glycolysis level, resulting in superior anti-tumor effect in combination with PD-L1 silencing. Our findings indicate that balancing glucose metabolic pathways of glycolysis and mitochondrial OXPHOS provides a more reliable immune boosting strategy to PD-L1 silencing than exclusive glycolysis inhibition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
1 For patients with severe ARDS with oxygenation indexes less than 100 mmHg, extracorporeal membrane oxygenation (ECMO) can improve oxygenation without adding average alveolar pressure. Because of ...the existence of pulmonary edema in these patients, it is necessary to accurately measure ELWI and PVPI in a timely manner during treatment, and to tailor treatment to improve outcomes. ...blood volumes and circulation patterns change during ECMO, and the reliability and prognostic value of the parameters obtained using PiCCO are controversial and lack evidence-based support. ...the aim of the present study was to comprehensively analyze the clinical value of hemodynamics obtained by PiCCO in adults with severe ARDS assisted by ECMO at our center. ...all patients in our study received various types of anti-inflammatory treatments (such as corticosteroids) that may reduce the degree of endothelial cell injury to some extent. ...there were limitations of sample size on statistical power.
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