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• Trx-1 overexpression inhibits the increase of METH-induced Glu and NR2B in VTA and NAc. • Trx-1 overexpression inhibits the expression of CHOP and GRP78 in VTA and NAc by METH. • Trx-1 overexpression inhibits the expression of Bcl-2/Bax in VTA and NAc by METH. • Trx-1 overexpression inhibits the decrease of procaspase12, Bcl-2, and procaspase3 in VTA and NAc by METH. • Trx-1 may block METH-induced injury through regulating ER and mitochondria mediated apoptosis. Methamphetamine (METH) has been reported to induce endoplasmic reticulum (ER) stress and neuronal apoptosis in the central nervous system (CNS) during the development of addiction. Thioredoxin-1 (Trx-1) is a redox regulating protein and plays an important role in inhibiting apoptosis and protects neurons from cytotoxicity through ER and mitochondria-mediated pathways. Our previous study has been reported that Trx-1 protects mice from METH-induced rewarding effect. However, whether Trx-1 plays the role in resisting METH injury is still unclear. Here, we aim to investigate whether Trx-1 participates in the regulation of METH-induced CNS injury via ER stress and mitochondria-mediated pathways. Our study first repeated the conditioned place preference expression induced by METH. Then we detected and found that METH increased the expression of N -methyl- d -asparate (NMDA) receptor subunit 2B (NR2B) and the level of glutamate (Glu) in the ventral tegmental area (VTA) and nucleus accumbens (NAc), while Trx-1 overexpression suppressed the increases. We further examined ER stress-related proteins and mitochondrial apoptosis pathway in the VTA and NAc, and found that METH increased the expressions of glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and Bax, as same time decreased the expressions of procaspase12, Bcl-2, and procaspase3, while Trx-1 overexpression blocked these changes. These results indicate that Trx-1 blocks METH-induced injury by suppressing ER stress and mitochondria-mediated apoptosis in the VTA and NAc via targeting glutamatergic system. [ABSTRACT FROM AUTHOR]

Surprisingly, high efficiency of 9.39% Sb 2 (S,Se) 3 solar cells has been obtained with the addition of monoatomic Al 2 O 3 layer based on the adjustment crystal orientation, tailored energy band structure and reduced density of deep-level defects. [Display omitted] • Highly (hk 1)-oriented Sb 2 (S,Se) 3 film having significantly enhanced charge separation was obtained with the buried Al 2 O 3 layer. • The buried Al 2 O 3 layer can tailor the band energy structure to improved carrier collection of the device. • With the adding of monoatomic Al 2 O 3 layer, the density of surface and deep-level defect has been decreased obviously. • A 9.39 % efficiency of the device is achieved thanks to crystal orientation modulation, band alignment optimization and deep-level defects reduction. Antimony selenosulfide (Sb 2 (S,Se) 3) reveals excellent optoelectronic characteristics, positioning it as a propitious light-absorbing substance with potential applications in photovoltaic technology. However, a multitude of deep-level defects significantly limit the efficiency of Sb 2 (S,Se) 3 solar cells. In this study, the density of the surface and deep-level defects was reduced by adding a monoatomic Al 2 O 3 layer on the surface of CdS film. Compared to the as-deposited film, highly [ hk 1]-oriented Sb 2 (S,Se) 3 film having significantly enhanced charge separation was obtained. The addition of a monoatomic Al 2 O 3 layer effectively modified the energy band structure by increasing the valence band maximum and more intrinsic Sb 2 (S,Se) 3 film between n-type CdS layers and p-type spiro. This contributed to increased carrier collection and reduced carrier recombination. Ultimately, 9.39 % efficiency of the device were obtained as a result of the optimized orientation and reduced defects. Consequently, this research demonstrates an effective method for optimizing crystallographic orientation and minimizing defect density, thereby maximizing the efficiency of Sb 2 (S,Se) 3 solar cells. [ABSTRACT FROM AUTHOR]

Aqueous zinc-ion batteries (ZIBs) have emerged as a promising alternative to traditional lithium-ion batteries due to their high safety, environmental friendliness, and cost-effectiveness, as well as their high theoretical capacity. However, developing freestanding cathodes with excellent electrochemical performance, including high specific capacity and energy density, still faces significant challenges. Herein, we present a freestanding, flexible, and interfused V 2 O 5 nanowire/reduced graphene oxide (rGO) composite fiber nonwoven fabric for the cathode of aqueous ZIBs via a novel wet-spinning and wet-fusing assembly strategy. The resulting V 2 O 5 nanowire/rGO composite fiber nonwoven fabric can be directly utilized as the cathode for aqueous ZIBs, demonstrating outstanding electrochemical performance, including high specific capacity (402.5 mAh g−1 at 0.1 A g−1), energy density (286.3 Wh kg−1 at 71.4 W kg−1), excellent rate capability, and long cycling life (4000 cycles). This study provides new insights into the development of high-performance flexible freestanding electrode materials for ZIBs [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Morphine is widely used for clinical pain management and induces the dependence. Addiction to morphine is a major public health issue. Geranylgeranylacetone (GGA) is widely used in clinic for treating ulcer. GGA induces expression of thioredoxin-1 (Trx-1) extensively. Trx-1 is a redox regulating protein and plays protecting roles in nervous system. GGA prevents mice against morphine-induced hyperlocomotion, rewarding effect, and withdrawal syndrome. However, whether GGA blocks morphine-conditioned place preference (CPP) reinstatement is still unknown. In the present study, we found that GGA administration blocked the reinstatement of morphine-CPP. The expressions of Trx-1, N -methyl d -aspartate receptor 2B subunit (NR2B), phosphorylated Ca2+/calmodulin-dependent protein kinase II (p -CaMKII), phosphorylated extracellular signaling regulated kinases (p -ERK), and phosphorylated cAMP-response element binding protein (p -CREB) were induced in nucleus accumbens (NAc) and hippocampus by morphine or GGA, whereas these proteins were not changed by morphine in GGA-treated mice. Our results indicate that GGA may prevent the reinstatement of morphine-CPP through strengthening the expression of Trx-1 and regulating NR2B/ERK pathway. Thus, we suggest that GGA may be a promising therapeutic candidate for morphine-induced relapse. Highlights • Geranylgeranylacetone (GGA) blocks the reinstatement of morphine CPP. • GGA induces expression of thioredoxin-1 (Trx-1) extensively. • GGA promotes the transduction of NR2B/ERK signal pathway. [ABSTRACT FROM AUTHOR]

Relapse of drug abuse after abstinence is a major challenge to the treatment of addicts. Thioredoxin-1 (Trx-1) is an important regulator of neuroprotection, and inhibits morphine-induced hyperlocomotion, reward and withdrawal signs, as well as blocks methamphetamine (METH)-induced conditioned place preference (CPP). The nucleus accumbens (NAc) is essential for relapse like behavior in reinstatement animal models. In the present study, we aimed to investigate the role of Trx-1 in the NAc in METH-primed reinstatement by using a reinstatement procedure in mice. Adeno-associated virus vectors expressing shRNA-mTrx-1 (AAV-shRNA-mTrx-1) were bilaterally microinjected into the NAc after METH-CPP extinction. The results showed that Trx-1 downregulation in the NAc promoted the reinstatement of METH-CPP. We also examined the expression of N-methyl-D-asparate (NMDA) receptor 2B subunit (GluN2b), the levels of phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylated cAMP-response element binding protein (p-CREB) in the NAc by western blot analysis, and found that the GluN2b expression, p-ERK and p-CREB levels were increased in the NAc in response to low-dose METH in AAV-shRNA-mTrx-1 mice, but were not changed in control and AAV-vehicle mice. These data indicate that the increased GluN2b expression, and p-ERK and p-CREB levels in the NAc of AAV-shRNA-mTrx-1 mice may be responsible for the METH-primed reinstatement. Thus, we suggest that downregulation of Trx-1 in the NAc may make mice more sensitive to METH reinstatement. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), characteristic motor symptoms and cognitive impairment. Thioredoxin-1 (Trx-1) is a redox protein and protects neurons from various injuries. Our previous study has shown that Trx-1 overexpression attenuates movement disorder in PD. However, whether Trx-1 ameliorates cognitive deficits in PD is still unknown. In the present study, we investigated the effects of Trx-1 on learning and memory in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in mice. We demonstrated that deficits in learning and memory were induced by MPTP in mice through the elevated plus-maze test. We found that the retention transfer latency time was shorten, escape latency was decreased and the number of platform crossings was increased in the Morris water maze (MWM) in Trx-1 transgenic (TG) mice when compared with wild type mice. The expressions of tyrosine hydroxylase (TH) and dopamine D1 receptor (D1R) were decreased by MPTP, which were restored in Trx-1 TG mice. The expression of N-methyl-D-aspartate receptor 2B subunit (NR2B), the levels of phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cAMP-response element binding protein (CREB) in the hippocampus were decreased by MPTP, which were reversed in Trx-1 TG mice. These results suggest that Trx-1 ameliorates learning and memory deficits in MPTP-induced PD model in mice via modulating the D1R and the NMDAR-ERK1/2-CREB pathway. Trx-1 may be a therapy target for learning and memory deficits in PD. [ABSTRACT FROM AUTHOR]

Monodomain liquid crystal elastomers with excellent reversible contraction deformation under a heat stimulus have broad application prospects in artificial muscles, soft robots, and micromechanical systems. Greater control can be achieved in a flexible actuation process through the generation of Joule heat by electricity. Herein, a highly conductive liquid crystal elastomer fibre actuator (c-LCF) was continuously prepared via liquid-phase drawing, with a conductivity of up to 12.5 S/m at 30 ℃. High conductivity is realised by the semi-wrapping combination of the main-chain liquid crystal prepolymer and carbon nanotube/carbon black to achieve a high-concentration dispersion of multi-dimensional conductive carbon nanomaterials. The fabricated c-LCF had a negative temperature coefficient, which is favourable for controllability and fast electrothermal actuation. The c-LCF contracted by approximately 30 % under a load of 1 MPa with a current of 9 mA (28 V/cm, 252 mW/cm). Its output power density reached 0.94 kJ/kg, indicating a better performance than biological muscle fibres; thus, it can be used to construct high-load bio-muscles. The different structures constructed by the c-LCF and fibre bundles can realise different electric actuation modes. In addition, fast driving can be realised using an elastic instability structure. The applications of liquid-crystal elastomers will be significantly broadened by this research. [Display omitted] • A highly conductive liquid crystal elastomer fiber actuator is prepared continuously. • The high conductivity is realized by the semi-wrapping combination of CNT. • The fabricated c-LCF has a negative temperature coefficient character. • The c-LCF can contract by approximately 30 % under a load of 1 MPa. [ABSTRACT FROM AUTHOR]

Background and Objectives: Respiratory quotient (RQ) is a good marker of substrate oxidation. Low RQ is fre-quently found in patients with liver cirrhosis and is associated with poor outcome. The purpose of this study was to demonstrate the effects of eating frequency on RQ in patients with cirrhosis.Methods and Study Design: We performed a randomized controlled trial to assess the effects of eating frequency on RQ in patients with cirrhosis. Seventy patients and 30 healthy controls were enrolled, and patients were further randomized to receive either normal eating frequency (NEF) meals at 08:00, 12:00 and 18:00 h, or high eating frequency (HEF) meals at 08:00, 10:00, 12:00, 15:00, 18:00 and 20:00 h. The two groups had equivalent energy intake. Fasting RQ was measured at 07:30 h and daytime RQ was measured at 11:30 and 17:30 h. Disease severity was evaluated using the Child-Turcotte-Pugh (CTP) classification.Results: Fasting RQ and daytime RQ were significantly lower in patients with cirrhosis than in healthy controls. Patients in the HEF group had a higher RQ than patients in the NEF group at three time points. In patients with CTP-A, no significant differences in daytime RQ were observed between the two groups. However, in CTP-C patients, daytime RQ was significantly higher in the HEF group than in the NEF group. Serum free fatty acid levels were significantly decreased and albumin was significantly increased after HEF intervention.Conclusions: HEF strategy is effective in improvement of RQ and is beneficial to patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) is a highly addictive drug of abuse which induces behavioral sensitization and rewarding effects. Thioredoxin-1 (Trx-1) is a redox protein and plays roles in regulating activity of transcription factor, such as cAMP responsive element-binding protein (CREB), AP-1, p53, is emerging as an important modulator of neuronal function. It has been reported that Trx-1 is involved in morphine dependence. In this study, we examined the rewarding effect after METH administration by conditioned place preference (CPP) of mice, and detected the levels of dopamine and the activity of cAMP responsive element-binding protein (CREB), the expressions of ΔFosB and cyclin-dependent kinase 5 (CDK5) in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in mice. Our results showed that the expression of METH-CPP was occluded in Trx-1 overexpression transgenic (TG) mice. The increase of dopamine level induced by METH was not further higher in Trx-1 TG mice. METH decreased the expression of Trx-1 which was restored in TG mice. The activity of CREB and the expressions of ΔFosB and CDK5 were increased by METH in wile-type mice, which were not further increased in TG mice. These results suggest that overexpression of Trx-1 may occlude the CPP induced by METH through regulating the activity of CREB and the expression of ΔFosB. [ABSTRACT FROM AUTHOR]

Low-cost, highly stable, and high-performance non-precious metal bifunctional oxygen reduction/oxygen evolution reaction (ORR/OER) electrocatalysts ensure the large-scale commercialization of rechargeable Zn–air batteries. In this study, we obtained an efficient bifunctional electrocatalyst (FeCo-NC@Co 2 P-NC) using pyrolysis and subsequent phosphorylation of ZIF-67 after the addition of an iron source. The excellent ORR activity is primarily attributed to the FeCo-NC sites, while Co 2 P is the active site for high-performance OER. Therefore, the obtained FeCo-NC@Co 2 P-NC has high onset and half-wave potentials for the ORR and a low overpotential for the OER, indicating its excellent bifunctional activity. It exhibited a reversible oxygen overpotential that exceeded that of commercial Pt/C and RuO 2. In addition, the Zn–air battery with the FeCo-NC@Co 2 P-NC catalyst had a high peak power density and cycling stability, exhibiting better performance than the commercial 20 % Pt/C-RuO 2. Therefore, this study provides a new strategy for the rational design of efficient non-precious metal electrocatalysts for energy storage and conversion. [Display omitted] • An easily method was proposed to prepare bifunctional catalyst (FeCo-NC@Co 2 P-NC). • The FeCo-NC and Co 2 P sites are conducive to gain high ORR/OER activity. • The FeCo-NC@Co 2 P-NC were applied to Zn-Air battery with excellent performance. [ABSTRACT FROM AUTHOR]

The development of low-cost, high-performance, highly stable and methanol-resistant oxygen reduction (ORR) electrocatalysts is vital for zinc-air batteries (ZAB) and membraneless direct methanol fuel cells (ML-DMFC). In this study, 2D porous materials (L -Fe A @Fe-NC-1 h) were prepared by consuming self-templates to regulate the active sites of the catalysts in a simple manner. In the L-5%-Fe A @Fe-NC-1 h structure, the austenitic Fe (Fe A) particles (15 nm) were wrapped by Fe and N co-doped carbon nanosheets. The L-5%-Fe A @Fe-NC-1 h material exhibited excellent ORR performance in alkaline electrolytes. The L-5%-Fe A @Fe-NC-1 h catalyst exhibited outstanding stability and resistance to methanol. Furthermore, the ZAB with L-5%-Fe A @Fe-NC-1 h as the ORR electrocatalyst exhibited outstanding power density and long-term operational stability. The L-5%-Fe A @Fe-NC-1 h can be practically applied as a cathode catalyst of ML-DMFC with considerable power density. Therefore, this work provides a simple and reliable control scheme to obtain the optimal catalyst and provides an easy method for the preparation of ORR catalysts with low cost and high quality and stability. ● A simple easily controllable self-template method was proposed to 2D porous carbon with Fe A @Fe-N-C sites. ● The Fe-N sites combined with FeA, is conducive to gain high ORR activity, high methanol-resistant. ● The L-5%-FeA@Fe-NC-1h can be practically applied to ML-DMFC and Zn-Air battery, showing excellent performance. [ABSTRACT FROM AUTHOR]

• Present a novel classification framework by integrating the MIL method and the GAN method for glomerular with spike-like projections. • Propose a new synthetic model InsGAN, which synthesize new positive instances dataset instead of the whole glomerular images. • We give a rigorously analytical study and visualization of inference basis on the proposed framework. • Give the correlation between MN disease stages and high-probability instances proportion based on the historical case. Tiny spike-like projections on the basement membrane of glomeruli are the main pathological feature of membranous nephropathy at stage II (MN II), which is the most significant stage for the diagnosis and treatment of renal disease. Pathological technology is the gold standard in the diagnosis of spike-like and other MNs, and automatic classification of spike-like projection is a crucial step in assisting pathologists in their diagnosis. However, owing to hard-to-label spile-like projections and the scarcity of patient data, classification of glomeruli with spike-like projections based on supervised learning methods is a challenging task. To overcome the aforementioned problems, the idea of integrating weakly-supervised learning and data augmentation methods is utilized in designing the classification framework. Specifically, a multiple instance learning with instance-level data augmentation (IDA-MIL) method for the classification of glomeruli with spike-like projections is established in this paper. The proposed classification framework first trains the MIL model on a dataset with image-level labels, and the well-trained MIL model is used to extract instances that include spike-like projections in the whole glomerular image. Then, rather than using an image-level generative adversarial network (ImgGAN), an instance-level generative adversarial network (InsGAN) based on the StyleGAN2-ADA model is trained on the spike-like instances obtained by the MIL model and synthesizes new spike-like projection instances. Finally, the synthesized spike-like instances are extended to the training dataset to further improve the classification performance of MIL. The designed IDA-MIL model is verified and evaluated from two aspects based on the in-house dataset. On the one hand, the performance comparisons between InsGAN and ImgGAN on five metrics, which involve FID, KID, Precision, Recall and IS, show that InsGAN obtains a better score and can synthesize effective spike-like projections. However, the proposed IDA-MIL model achieves the best classification performance with an accuracy of 0.9405. Then, to make nephrologists believe the inference result of the proposed model, we use heatmap technology to visualize the basis of the model inferences and show the top 4 probability spike-like instances per glomerulus. Furthermore, we analyze the correlation between the disease and the proportion of spike-like instances in bags from historical cases. Compared with the ImgGAN, the InsGAN can synthesize natural and varied spike-like projections, which results in the classification performance of the MIL model achieving great improvement by adding synthesized instance samples into the training dataset. The heatmap of spike-like inferences and the proportion of spike-like instances can help nephrologists to make a preliminary reliable diagnosis in clinical practice. This work provides a valuable reference for medical image classification with limited data and small-scale lesions based on deep learning. [ABSTRACT FROM AUTHOR]

Intermedin(IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family that has anti-inflammatory, antioxidant and anti-apoptosis properties. This study aimed to evaluate the renoprotective effects of IMD on podocyte apoptotic loss and slit diaphragm protein deficiency the kidneys of rats with in streptozotocin (STZ) induced diabetes in high glucose-exposed podocytes. Our results showed that IMD significantly attenuated proteinuria, and alleviated the abnormal alterations in glomerular ultrastructure in vivo. IMD also improved the induction of slit diaphragm proteins, and restored the decreased Bcl-2 expression and suppressed Bax and caspase-3 induction in the diabetic glomeruli. In addition, IMD attenuated podocyte apoptosis and filamentous actin (F-actin) rearrangement in high glucose-exposed podocytes. Exposure to high glucose elevated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress in renal podocytes, and IMD treatment blocked such ER stress responses pertinent to podocyte apoptosis and reduced synthesis of slit diaphragm proteins in vivo and in vitro. These observations demonstrate that targeting ER stress is an underlying mechanism of IMD-mediated amelioration of diabetes-associated podocyte injury and dysfunction. • High glucose induces ERS in renal podocytes. • IMD protects against podocyte injury by inhibiting ERS-induced apoptosis. • IMD treatment decreases induction of slit diaphragm protein. [ABSTRACT FROM AUTHOR]

• A scalable fabrication of ZIF-8 nanoparticles/alginate fibers is reported. • The ZIF-8 nanoparticles are embedded on the fiber surface. • The ZIF-8/ alginate fibers show excellent antibacterial performance. • The swelling of alginate benefits for the antibacterial activity of composite fibers. Antibacterial fibers have great potential in many applications, such as medical dressings, surgical sutures and masks, etc. owing to their good growth inhibition against bacteria. However, for the fabrication of antibacterial fibers, the traditional inorganic nanoparticles coating method shows the disadvantages of high cost, low stability and binding fastness. Herein, we develop a facile, scalable and cost-effective blend spinning strategy to fabricate the highly effective antibacterial zeolitic imidazolate framework-8@alginate (ZIF-8@SA) fibers through wet spinning of the mixture of ZIF-8 and SA. The fabricated ZIF-8@SA fibers show high antibacterial efficiency, good durability and high tensile strength. The antibacterial performance of ZIF-8@SA fibers is superior to the most reported inorganic nanoparticles modified fibers. The excellent antibacterial performance of ZIF-8@SA fibers is attributed to the reactive oxygen species from the ZIF-8 and the swelling of SA. This work may shed light on the antibacterial mechanisms of metal organic frameworks and pave the way for the development of high-performance, durable and highly effective antibacterial textiles. [ABSTRACT FROM AUTHOR]

Background/aims: The occurrence and development of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is closely related to the immune pathway. We explored the heterogeneity of peripheral blood T cell subsets and the characteristics of exhausted T lymphocytes, in an attempt to identify potential therapeutic target molecules for immune dysfunction in ACLF patients., Methods: A total of 83,577 T cells from HBV-ACLF patients and healthy controls were screened for heterogeneity by single-cell RNA sequencing. In addition, exhausted T-lymphocyte subsets were screened to analyze their gene expression profiles, and their developmental trajectories were investigated. Subsequently, the expression of exhausted T cells and their capacity in secreting cytokines (interleukin 2, interferon γ, and tumor necrosis factor α) were validated by flow cytometry., Results: A total of eight stable clusters were identified, among which CD4 + TIGIT + subset and CD8 + LAG-3 + subset, with high expression of exhaust genes, were significantly higher in the HBV-ACLF patients than in normal controls. As shown by pseudotime analysis, T cells experienced a transition from naïve T cells to effector T cells and then exhausted T cells. Flow cytometry confirmed that the CD4 + TIGIT + subset and CD8 + LAG-3 + subset in the peripheral blood of the ACLF patients were significantly higher than those in the healthy controls. Moreover, in vitro cultured CD8 + LAG-3 + T cells were significantly fewer capable of secreting cytokines than CD8 + LAG-3- subset., Conclusions: Peripheral blood T cells are heterogeneous in HBV-ACLF. The exhausted T cells markedly increase during the pathogenesis of ACLF, suggesting that T-cell exhaustion is involved in the immune dysfunction of HBV-ACLF patients.

Perovskite solar cells (PSCs) have shown great potential for reducing costs and improving power conversion efficiency (PCE). One effective method to achieve the latter is to use an all-inorganic charge transport layer (ICTL). However, traditional methods for crystallizing inorganic layers often result in the formation of a powder instead of a continuous film. To address this issue, we designed a dual-layer inorganic electron transport layer (IETL). This dual-layer structure consists of a layer of SnO 2 nanocrystals (SnO 2 NCs) deposited via a solution process and a dense SnO 2 layer deposited through atomic layer deposition (ALD SnO 2 ) to fill the cracks and gaps between the SnO 2 NCs. PSCs having these dual-layer SnO 2 ETLs achieved a high efficiency of 23.0%. This efficiency surpasses the recorded performance of ICTLs deposited on the perovskite. Furthermore, the PCE is comparable to that achieved with a C60 ETL. Moreover, the high-density structure of the ALD SnO 2 layer inhibits the vertical migration of ions, resulting in improved thermal stability. After continuous heating at 85 °C in 10% humidity for 1000 h, the PCE of the dual-layer SnO 2 structure decreased by 18%, whereas that of the C60/BCP structure decreased by 36%. The integration of dual-layer SnO 2 into PSCs represents a significant advancement in achieving high-performance, commercially viable inverted monolithic PSCs or tandem solar cells.

The increasing requirements for wearable and portable electronics are driving the interests of high performance fiber supercapacitor. Layered double hydroxide (LDH) is broadly used in electrode materials, owing to the adjustability of components and the unique lamellar structure. However, limited active sites and poor electrical conductivity hinder its applications. Herein, the core-shell heterostructured Ni(OH) 2 @activation Zn-Co-Ni layered double hydroxides (Ni(OH) 2 @A-ZnCoNi-LDH) electrode was fabricated by loading pseudocapacitance material on the A-ZnCoNi-LDH to improve the electrochemical performance. Significantly, benefits from the synergistic effect of the multi-metal ions and the core-shell heterostructure, the electrodes demonstrated a capacitance of 2405 mF·cm -2 at 1 mA·cm -2 . Furthermore, Ni(OH) 2 @A-ZnCoNi-LDH was used as the core electrode and carbon nanotube (CNT) film coated with Fe 2 O 3 @reduced graphene oxide (rGO) was wrapped around the core electrode to assemble coaxial fiber asymmetric supercapacitor, which illustrated an ultrahigh energy density of 177.7 µWh·cm -2 at 0.75 mW·cm -2 . In particular, after consecutive charging and discharging 7000 cycles, the capacitance retention of the device was 95 %, indicating the excellent cycling stability. Furthermore, the device with high flexibility can be woven into textiles in different shapes. The fabricated device has an excellent development prospect as an energy source in wearable electronic devices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Accurately diagnosing chronic kidney disease requires pathologists to assess the structure of multiple tissues under different stains, a process that is timeconsuming and labor-intensive. Current AI-based methods for automatic structure assessment, like segmentation, often demand extensive manual annotation and focus on single stain domain. To address these challenges, we introduce MSMTSeg, a generative self-supervised meta-learning framework for multi-stained multi-tissue segmentation in renal biopsy whole slide images (WSIs). MSMTSeg incorporates multiple stain transform models for style translation of inter-stain domains, a self-supervision module for obtaining pre-trained models with the domain-specific feature representation, and a meta-learning strategy that leverages generated virtual data and pre-trained models to learn the domain-invariant feature representation across multiple stains, thereby enhancing segmentation performance. Experimental results demonstrate that MSMTSeg achieves superior and robust performance, with mDSC of 0.836 and mIoU of 0.718 for multiple tissues under different stains, using only one annotated training sample for each stain. Our ablation study confirms the effectiveness of each component, positioning MSMTSeg ahead of classic advanced segmentation networks, recent few-shot segmentation methods, and unsupervised domain adaptation methods. In conclusion, our proposed few-shot cross-domain technology offers a feasible and cost-effective solution for multi-stained renal histology segmentation, providing convenient assistance to pathologists in clinical practice. The source code and conditionally accessible data are available at https://github.com/SnowRain510/MSMTSeg.

Acute kidney injury (AKI) induces significant energy metabolic reprogramming in renal tubular epithelial cells (TECs), thereby altering lipid, glucose, and amino acid metabolism. The changes in lipid metabolism encompass not only the downregulation of fatty acid oxidation (FAO) but also changes in cell membrane lipids and triglycerides metabolism. Regarding glucose metabolism, AKI leads to increased glycolysis, activation of the pentose phosphate pathway (PPP), inhibition of gluconeogenesis, and upregulation of the polyol pathway. Research indicates that inhibiting glycolysis, promoting the PPP, and blocking the polyol pathway exhibit a protective effect on AKI-affected kidneys. Additionally, changes in amino acid metabolism, including branched-chain amino acids, glutamine, arginine, and tryptophan, play an important role in AKI progression. These metabolic changes are closely related to the programmed cell death of renal TECs, involving autophagy, apoptosis, necroptosis, pyroptosis, and ferroptosis. Notably, abnormal intracellular lipid accumulation can impede autophagic clearance, further exacerbating lipid accumulation and compromising autophagic function, forming a vicious cycle. Recent studies have demonstrated the potential of ameliorating AKI-induced kidney damage through calorie and dietary restriction. Consequently, modifying the energy metabolism of renal TECs and dietary patterns may be an effective strategy for AKI treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Hao, Tang, Han, Li and Zhou.)

Diagnosis of diabetic kidney disease (DKD) mainly relies on screening the morphological variations and internal lesions of glomeruli from pathological kidney biopsy. The prominent pathological alterations of glomeruli for DKD include glomerular hypertrophy and nodular mesangial sclerosis. However, the qualitative judgment of these alterations is inaccurate and inconstant due to the intra- and inter-subject variability of pathologists. It is necessary to design artificial intelligence (AI) methods for accurate quantification of these pathological alterations and outcome prediction of DKD. In this work, we present an AI-driven framework to quantify the volume of glomeruli and degree of nodular mesangial sclerosis, respectively, based on an instance segmentation module and a novel weakly supervised Macro-Micro Aggregation (MMA) module. Subsequently, we construct classic machine learning models to predict the degree of DKD based on three selected pathological indicators via factor analysis. These corresponding modules are trained and tested on a total of 281 whole slide images (WSIs) digitized from two hospitals with different scanners. Our designed AI framework achieved inspiring results with 0.926 mIoU for glomerulus segmentation, and 0.899 F 1 score for glomerulus classification in the external testing dataset. Meantime, the visualized results of the MMA module could reflect the location of the lesions. The performance of predicting disease achieved the F 1 score of 0.917, which further proved the effectiveness of our AI-driven quantification of pathological indicators. Additionally, the interpretation of the machine learning model with the SHAP method showed similar accordance with the development of DKD in pathology. In conclusion, the proposed auxiliary diagnostic technologies have the feasibility for quantitative analysis of glomerular pathological tissues and alterations in DKD. Pathological quantitative indicators will also make it more convenient to provide doctors with assistance in clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Acute Kidney Injury (AKI), a critical clinical syndrome, has been strongly linked to mitochondrial malfunction. Mitochondria, vital cellular organelles, play a key role in regulating cellular energy metabolism and ensuring cell survival. Impaired mitochondrial function in AKI leads to decreased energy generation, elevated oxidative stress, and the initiation of inflammatory cascades, resulting in renal tissue damage and functional impairment. Therefore, mitochondria have gained significant research attention as a potential therapeutic target for AKI. Mitochondrial dynamics, which encompass the adaptive shifts of mitochondria within cellular environments, exert significant influence on mitochondrial function. Modulating these dynamics, such as promoting mitochondrial fusion and inhibiting mitochondrial division, offers opportunities to mitigate renal injury in AKI. Consequently, elucidating the mechanisms underlying mitochondrial dynamics has gained considerable importance, providing valuable insights into mitochondrial regulation and facilitating the development of innovative therapeutic approaches for AKI. This comprehensive review aims to highlight the latest advancements in mitochondrial dynamics research, provide an exhaustive analysis of existing studies investigating the relationship between mitochondrial dynamics and acute injury, and shed light on their implications for AKI. The ultimate goal is to advance the development of more effective therapeutic interventions for managing AKI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hao, Zhao, Zhao, Han and Zhou.)

Objective: Acute-on-chronic liver failure (ACLF) has a high prevalence and short-term mortality. Monocytes play an important role in the development of ACLF. However, the monocyte subpopulations with unique features and functions in ACLF and associated with disease progression remain poorly understood. We investigated the specific monocyte subpopulations associated with ACLF progression and their roles in inflammatory responses using the single-cell RNA sequencing (scRNA-seq)., Methods: We performed scRNA-seq on 17,310 circulating monocytes from healthy controls and ACLF patients and genetically defined their subpopulations to characterize specific monocyte subpopulations associated with ACLF progression., Results: Five monocyte subpopulations were obtained, including pro-inflammatory monocytes, CD16 monocytes, HLA monocytes, megakaryocyte-like monocytes, and NK-like monocytes. Comparisons of the monocytes between ACLF patients and healthy controls showed that the pro-inflammatory monocytes had the most significant gene changes, among which the expressions of genes related to inflammatory responses and cell metabolism were significantly increased while the genes related to cell cycle progression were significantly decreased. Furthermore, compared with the ACLF survival group, the ACLF death group had significantly higher expressions of pro-inflammatory cytokines (e.g., IL-6) and their receptors, chemokines (e.g., CCL4 and CCL5), and inflammation-inducing factors (e.g., HES4). Additionally, validation using scRNA-seq and flow cytometry revealed the presence of a cell type-specific transcriptional signature of pro-inflammatory monocytes THBS1, whose production might reflect the disease progression and poor prognosis., Conclusions: We present the accurate classification, molecular markers, and signaling pathways of monocytes associated with ACLF progression. Therapies targeting pro-inflammatory monocytes may be a promising approach for blocking ACLF progression., (© 2023. The Author(s).)

Introduction: PTGES3, also known as p23, is a molecule chaperone of Hsp90 that is involved in the pathogenesis of malignant tumors. Increasing studies have shown that PTGES3 plays a nonnegligible role in tumor development. However, analysis of PTGES3 in pan-cancer has not been performed yet., Methods: We explored the role of PTGES3 in 33 types of tumors and depicted the potentialimmune-related pathways among them. Using multiple databases includingTCGA, LinkedOmics, GDSC, and TIMER, we made a comprehensive analysis to explore whether there was an interaction between PTGES3 and prognosis, DNA methylation, copy number variation (CNV), tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immune microenvironment (TME)., Results: Our study revealed that PTGES3 expression level was upregulated in most cancers. PTGES3 was also associated with a positive or negative prognosis in a variety of cancers, which was mainly associated with DNA methylation, CNV, MSI, TMB, andmismatch repair-related genes. High PTGES3 expression was related to the infiltration of Th2 subsets of CD4+ T cells and immune checkpoint-related genes in most cancers, especially in hepatocellular carcinoma (HCC). Enrichment analysis demonstrated that PTGES3 was involved in cellular processes including DNA replication and spliceosome. The relationship between PTGES3 expression and HCC progression was verified at the protein level through immune histochemical analysis., Conclusions: Our research demonstrated theprognostic predictive value of PTGES3 in a wide range of cancers, which was alsoassociated with the process of tumor immune infiltration. As a result, it suggestedthat PTGES3 was a valuable prognostic biomarker in HCC treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Sun, Yao, Zhang, Zhou, Yao and He.)

Monodomain liquid crystal elastomers (m-LCEs) exhibit large reversible deformations when subjected to light and heat stimuli. Herein, we developed a new method for the large-scale continuous preparation of m-LCE fibers. These m-LCE fibers exhibit a reversible contraction ratio of 55.6%, breaking strength of 162 MPa (withstanding a load of 1 million times its weight), and maximum output power density of 1250 J/kg, surpassing those of previously reported m-LCEs. These excellent mechanical properties are mainly attributed to the formation of a homogeneous molecular network. Furthermore, the fabrication of m-LCEs with permanent plasticity using m-LCEs with impermanent instability without external intervention was realized by the synergistic effects of the self-restraint of mesogens and the prolonged relaxation process of LCEs. The designed LCE fibers, which are similar to biological muscle fibers and can be easily integrated, exhibit broad application prospects in artificial muscles, soft robots, and micromechanical systems., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Background: The heterogeneity of Type 2 Diabetes Mellitus (T2DM) complicated with renal diseases has not been fully understood in clinical practice. The purpose of the study was to propose potential predictive factors to identify diabetic kidney disease (DKD), nondiabetic kidney disease (NDKD), and DKD superimposed on NDKD (DKD + NDKD) in T2DM patients noninvasively and accurately., Methods: Two hundred forty-one eligible patients confirmed by renal biopsy were enrolled in this retrospective, analytical study. The features composed of clinical and biochemical data prior to renal biopsy were extracted from patients' electronic medical records. Machine learning algorithms were used to distinguish among different kidney diseases pairwise. Feature variables selected in the developed model were evaluated., Results: Logistic regression model achieved an accuracy of 0.8306 ± 0.0057 for DKD and NDKD classification. Hematocrit, diabetic retinopathy (DR), hematuria, platelet distribution width and history of hypertension were identified as important risk factors. Then SVM model allowed us to differentiate NDKD from DKD + NDKD with accuracy 0.8686 ± 0.052 where hematuria, diabetes duration, international normalized ratio (INR), D-Dimer, high-density lipoprotein cholesterol were the top risk factors. Finally, the logistic regression model indicated that DD-dimer, hematuria, INR, systolic pressure, DR were likely to be predictive factors to identify DKD with DKD + NDKD., Conclusion: Predictive factors were successfully identified among different renal diseases in type 2 diabetes patients via machine learning methods. More attention should be paid on the coagulation factors in the DKD + NDKD patients, which might indicate a hypercoagulable state and an increased risk of thrombosis., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: In-depth investigations of risk factors for the identification of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) are rare. We aimed to investigate the risk factors for developing DKD from multiple types of clinical data and conduct a comprehensive risk assessment for individuals with diabetes., Methods: We carried out a case-control study, enrolling 958 patients to identify the risk factors for developing DKD in T2DM patients from a database established from inpatient electronic medical records. Multivariable logistic regression was applied to develop a prediction model and the performance of the model was evaluated using the area under the curve (AUC) and calibration curve. A multifactorial risk score system was established according to the Framingham Study risk score., Results: DKD accounted for 34.03% of eligible patients in total. Twelve risk factors were selected in the final prediction model, including age, duration of diabetes, duration of hypertension, fasting blood glucose, fasting C-peptide, insulin use, systolic blood pressure, low-density lipoprotein, γ-glutamyl transpeptidase, platelet, uric acid, and thyroid stimulating hormone; and one protective factor, serum albumin. The prediction model showed an AUC of 0.862 (95% Confidence Interval (CI) 0.834-0.890) with an accuracy of 81.5% in the derivation dataset and an AUC of 0.876 (95% CI 0.825-0.928) in the validation dataset. The calibration curves were excellent and the estimated probability of DKD was more than 80% when the cumulative score for risk factors reached 17 points., Conclusion: Newly recognized risk factors were applied to assess the development of DKD in T2DM patients and the established risk score system was a reliable and feasible tool for assisting clinicians to identify patients at high risk of DKD., Competing Interests: The authors declare that they have no competing interests., (© 2023 Hui et al.)

Introduction: Chronic kidney disease (CKD) is a progressive disease with high incidence but early imperceptible symptoms. Since China's rural areas are subject to inadequate medical check-ups and single disease screening programme, it could easily translate into end-stage renal failure. This study aimed to construct an early warning model for CKD tailored to impoverished areas by employing machine learning (ML) algorithms with easily accessible parameters from ten rural areas in Shanxi Province, thereby, promoting a forward shift of treatment time and improving patients' quality of life., Methods: From April to November 2019, CKD opportunistic screening was carried out in 10 rural areas in Shanxi Province. First, general information, physical examination data, blood and urine specimens were collected from 13,550 subjects. Afterward, feature selection of explanatory variables was performed using LASSO regression, and target datasets were balanced using the SMOTE (synthetic minority over-sampling technique) algorithm, i.e., albuminuria-to-creatinine ratio (ACR) and α1-microglobulin-to-creatinine ratio (MCR). Next, Bagging, Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) were employed for classification of ACR outcomes and MCR outcomes, respectively., Results: 12,330 rural residents were included in this study, with 20 explanatory variables. The cases with increased ACR and increased MCR represented 1,587 (12.8%) and 1,456 (11.8%), respectively. After conducting LASSO, 14 and 15 explanatory variables remained in these two datasets, respectively. Bagging, RF, and XGBoost performed well in classification, with the AUC reaching 0.74, 0.87, 0.87, 0.89 for ACR outcomes and 0.75, 0.88, 0.89, 0.90 for MCR outcomes. The five variables contributing most to the classification of ACR outcomes and MCR outcomes constituted SBP, TG, TC, and Hcy, DBP and age, TG, SBP, Hcy and FPG, respectively. Overall, the machine learning algorithms could emerge as a warning model for CKD., Conclusion: ML algorithms in conjunction with rural accessible indexes boast good performance in classification, which allows for an early warning model for CKD. This model could help achieve large-scale population screening for CKD in poverty-stricken areas and should be promoted to improve the quality of life and reduce the mortality rate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Song, Liu, Qiu, Qing, Li, Zhao, Li, Li and Zhou.)

Background: Established prognostic models of idiopathic membranous nephropathy (IMN) were limited to traditional modeling methods and did not comprehensively consider clinical and pathological patient data. Based on the electronic medical record (EMR) system, machine learning (ML) was used to construct a risk prediction model for the prognosis of IMN., Methods: Data from 418 patients with IMN were diagnosed by renal biopsy at the Fifth Clinical Medical College of Shanxi Medical University. Fifty-nine medical features of the patients could be obtained from EMR, and prediction models were established based on five ML algorithms. The area under the curve, recall rate, accuracy, and F1 were used to evaluate and compare the performances of the models. Shapley additive explanation (SHAP) was used to explain the results of the best-performing model., Results: One hundred and seventeen patients (28.0%) with IMN experienced adverse events, 28 of them had compound outcomes (ESRD or double serum creatinine (SCr)), and 89 had relapsed. The gradient boosting machine (LightGBM) model had the best performance, with the highest AUC (0.892 ± 0.052, 95% CI 0.840-0.945), accuracy (0.909 ± 0.016), recall (0.741 ± 0.092), precision (0.906 ± 0.027), and F1 (0.905 ± 0.020). Recursive feature elimination with random forest and SHAP plots based on LightGBM showed that anti-phospholipase A2 receptor (anti-PLA2R), immunohistochemical immunoglobulin G4 (IHC IgG4), D-dimer (D-DIMER), triglyceride (TG), serum albumin (ALB), aspartate transaminase (AST), β2-microglobulin (BMG), SCr, and fasting plasma glucose (FPG) were important risk factors for the prognosis of IMN. Increased risk of adverse events in IMN patients was correlated with high anti-PLA2R and low IHC IgG4., Conclusions: This study established a risk prediction model for the prognosis of IMN using ML based on clinical and pathological patient data. The LightGBM model may become a tool for personalized management of IMN patients.

Opioids and their receptors are involved in cancer progression. However, the roles of the nociceptin receptor (NOP) and its antagonist (JTC801) in hepatocellular carcinoma (HCC) are poorly understood. The prognostic value of NOP expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HCC cohort. The biological role and mechanism of NOP in HCC tumor growth were determined in vitro and in vivo. We found that NOP was associated with the clinicopathological features and survival outcomes of HCC patients. NOP overexpression promoted HCC growth in vitro and in vivo. Mechanistically, NOP activated NF-kB signaling to promote autophagy, which inhibited apoptosis, in HCC cells. An inhibitor of autophagy, 3-MA, and an inhibitor of NF-kB, JSH-23, attenuated the function of NOP in HCC. E2F1 was identified as a transcription factor of NOP. The oncogenic role of NOP was positively regulated by E2F1. Furthermore, JTC801, a selective antagonist of NOP, abolished the function of NOP by inhibiting NF-kB signaling and autophagy. Our study demonstrates that NOP is an oncogene in HCC. We provide a potential therapeutic candidate and prognostic predictor for HCC. JTC801 could become a potential drug for HCC therapy., (© 2022. The Author(s).)

Amiodarone (AM) is one of the most effective antiarrhythmic drugs and normally administrated by intravenous infusion which is liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. Intermedin (IMD), a member of calcitonin family, has a broad spectrum of biological effects including anti-inflammatory effects, antioxidant activities, and antiapoptosis. But now, the protective effects of IMD against amiodarone-induced phlebitis and the underlying molecular mechanism are not well understood. In this study, the aim was to investigate the protective efficiency and potential mechanisms of IMD in amiodarone-induced phlebitis. The results of this study revealed that treatment with IMD obviously attenuated apoptosis and exfoliation of vascular endothelial cells and infiltration of inflammatory cells in the rabbit model of phlebitis induced by intravenous infusion of amiodarone compared with control. Further tests in vitro demonstrated that IMD lessened amiodarone-induced endothelial cell apoptosis, improved amiodarone-induced oxidative stress injury, reduced inflammatory reaction, and activated the Wnt/ β -catenin signal pathway which was inhibited by amiodarone. And these effects could be reversed by Wnt/ β -catenin inhibitor IWR-1-endo, and si-RNA knocked down the gene of Wnt pathway. These results suggested that IMD exerted the protective effects against amiodarone-induced endothelial injury via activating the Wnt/ β -catenin pathway. Thus, IMD could be used as a potential agent for the treatment of phlebitis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Yanhong Wang et al.)

Background and Aims: Programmed cell death-1 (PD-1) plays an important role in downregulating T lymphocytes but the mechanisms are still poorly understood. This study aimed to explore the role of PD-1 in CD8 + T lymphocyte dysfunction in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF)., Methods: Thirty patients with HBV-ACLF and 30 healthy controls (HCs) were recruited. The differences in the numbers and functions of CD8 + T lymphocytes, PD-1 and glucose transporter-1 (Glut1) expression from the peripheral blood of patients with HBV-ACLF and HCs were analyzed. In vitro , the CD8 + T lymphocytes from HCs were cultured (HC group) and the CD8 + T lymphocytes from ACLF patients were cultured with PD-L1-IgG (ACLF+PD-1 group) or IgG (ACLF group). The numbers and functions of CD8 + T lymphocytes, PD-1 expression, glycogen uptake capacity, and Glut1, hexokinase-2 (HK2), and pyruvate kinase (PKM2) expression were analyzed among the HC group, ACLF group and ACLF+ PD-1group., Results: The absolute numbers of CD8 + T lymphocytes in the peripheral blood from patients with HBV-ACLF were lower than in the HCs ( p <0.001). The expression of PD-1 in peripheral blood CD8 + T lymphocytes was lower in HCs than in patients with HBV-ACLF ( p =0.021). Compared with HCs, PD-1 expression was increased ( p =0.021) and Glut1 expression was decreased ( p =0.016) in CD8 + T lymphocytes from the HBV-ACLF group. In vitro , glycogen uptake and functions of ACLF CD8 + T lymphocytes were significantly lower than that in HCs ( p =0.017; all p <0.001). When PD-1/PD-L1 was activated, the glycogen uptake rate and expression levels of Glut1, HK2, and PKM2 showed a decreasing trend (ACLF+PD-1 group compared to ACLF group , all p <0.05). The functions of CD8 + T lymphocytes in the ACLF+PD-1 group [using biomarkers of Ki67, CD69, IL-2, interferon-gamma, and tumor necrosis factor-alpha- were lower than in the ACLF group (all p <0.05)., Conclusions: CD8 + T lymphocyte dysfunction is observed in patients with HBV-ACLF. PD-1-induced T lymphocyte dysfunction might involve glycolysis inhibition., Competing Interests: The authors have no conflict of interests related to this publication., (© 2021 Authors.)

Objectives: The intestinal microbiota plays an important role in the nutritional status and energy metabolism of the host. Liver cirrhosis is accompanied by muscle wasting or sarcopenia. The aim of this study was to to explore the changes in intestinal microbiota in patients with liver cirrhosis and muscle wasting by using metagenomics., Methods: This was a cross-sectional study of patients with (n = 30) and without (n = 30) muscle wasting and age- and sex-matched healthy controls (n = 30) to evaluate changes in intestinal microbiota by metagenomic gene sequencing. Muscle wasting was determined by the third lumbar vertebrae skeletal muscle index (L3 SMI)., Results: The Shannon index, which represents species diversity, of patients in the muscle-wasting group (2.11 ± 0.88) was lower than in the non-muscle-wasting group (2.64 ± 0.68; P = 0.039), which was significantly lower than in the healthy control group (2.70 ± 0.53; P = 0.023). There were 17 microbial species with significant differences in relative abundance between the two groups (linear discriminant analysis score >2; P < 0.05). The relative abundance of Escherichia coli, Peptostreptococcus stomatis, and Bacteroides uniformis showed the most significant association with L3 SMI., Conclusions: There were compositional alterations in intestinal microbiota in patients with liver cirrhosis and muscle wasting. L3 SMI is closely related to E. coli, P. stomatis, and B. uniformis in liver cirrhosis. Further interventional studies are needed to confirm whether improving intestinal microbiota can improve the nutritional status of patients with liver cirrhosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Sarcopenia is an independent predictor of mortality in patients with liver cirrhosis. However, evidence has emerged that skeletal muscles mediate their protective effect against sarcopenia by secreting myokines. Therefore, we investigated whether irisin was associated with sarcopenia in patients with liver cirrhosis. This was an observational cross-sectional study of data collected from 187 cirrhotic patients. Sarcopenia was defined by computed tomography (CT) scans using specific cutoffs of the 3rd lumbar vertebra skeletal muscle index (L 3 SMI). Morning irisin levels were obtained in all patients. Of the 187 patients, sarcopenia was noted in 73 (39%). Irisin concentrations were lower in sarcopenic patients (32.40 pg/ml [interquartile range (IQR): 18.70, 121.26], p < 0.001) than in nonsarcopenic patients. There was a weak correlation between L 3 SMI and irisin levels (r = 0.516, p < 0.001). Multivariable regression analysis including L 3 SMI, body mass index (BMI), very-low-density lipoprotein (VLDL)-cholesterol, aspartate aminotransferase (AST), adiponectin, and irisin levels showed that L 3 SMI (odds ratio [OR] = 0.915, p = 0.023), adiponectin levels (OR = 1.074, p = 0.014), irisin levels (OR = 0.993, p < 0.001) and BMI (OR = 0.456, p = 0.004) were independently associated with sarcopenia. Irisin levels are associated with sarcopenia in patients with liver cirrhosis. This paper addresses a gap in the literature and facilitates the future transition into clinical treatment.

Background & Aims: The objective nutritional assessment indicators, body mass index (BMI), upper arm muscle circumference (MAMC), and triceps skinfold thickness (TSF), are often limited due to ascites. This study investigated the prognostic value of the third lumbar vertebrae skeletal muscle mass index (L3 SMI) in addition to the objective nutritional evaluation indicators (BMI, MAMC and TSF) in patients with liver cirrhosis and ascites., Methods: In this retrospective analysis, a total of 147 patients with liver cirrhosis and ascites were included. The L3 SMI, BMI, MAMC and TSF were detected in all patients. The severity of liver disease was assessed by the Model End-Stage Liver Disease (MELD) score and Child-Turcotte-Pugh (CTP) classification. These variables were compared between non-surviving and surviving patients who were classified according to 5-year mortality., Results: Of the 147 patients, 62 (42.2%) died and 85 (57.8%) survived within 5 years. The L3 SMI of patients was significantly lower than that of the normal control group (39.58 ± 7.18 cm 2 /m 2 vs. 53.73 ± 7.92 cm 2 /m, 2 p < 0.001). The L3 SMI (OR 4.02; 95% CI 2.17-9.63; p < 0.001), MELD score (OR 2.11; 95% CI 1.12-4.13; p < 0.001) and CTP class (OR 2.69; 95% CI 1.09-5.06; p < 0.001) were independent predictive indicators of 5-year mortality. Furthermore, the performance of the two variables (L3 SMI and MELD) together (AUROC: 0.812) was significantly better than that of MELD alone (AUROC: 0.787) for prediction of 5-year mortality (p < 0.001)., Conclusion: Compared with MAMC, TSF and BMI, L3 SMI is an independent risk factor for 5-year mortality in patients with liver cirrhosis and ascites. Further nutritional intervention studies are needed to confirm the impact of the L3 SMI index on clinical outcomes., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

With the increasing prevalence of obesity in adults worldwide, the incidence of obesity-related glomerulopathy (ORG) has increased yearly, becoming one of the leading causes of end-stage renal disease. Studies have demonstrated significant correlations between hyperlipidemia and impaired renal function in patients with ORG, indicating that hyperlipidemia causes damage in kidney cells. In podocytes, the endocytosis of lipids triggers an intracellular oxidative stress response that disrupts cellular integrity, resulting in proteinuria and glomerular sclerosis. However, the specific molecular mechanisms through which podocytes endocytose lipids remain unclear. Here, we demonstrated the enhanced endocytosis of lipids by podocytes from patients with ORG. This response was associated with decreased expression of phosphatase and tensin homolog (PTEN). In vitro silencing of PTEN promoted the endocytosis of low-density lipoprotein in mouse podocytes. Conversely, overexpression of PTEN inhibited the endocytosis of lipoproteins in podocytes. PTEN directly dephosphorylates and activates the actin-depolymerizing factor cofilin-1, leading to depolymerization of filamentous actin (F-actin), which is necessary for endocytosis. Notably, inhibition of PTEN resulted in the phosphorylation and inactivation of cofilin-1, leading to F-actin formation that enhanced the endocytosis of lipoproteins in podocytes. When hyperlipidemia was induced in mice with podocyte-specific deletion of PTEN, these mice recapitulated the major pathophysiological features of ORG. Thus, PTEN downregulation in podocytes may contribute to the pathogenesis of ORG.

Prophylactic use of levosimendan in cardiac surgery remains controversial and no meta-analysis has been done exclusively about that in patients undergoing coronary artery bypass graft (CABG) surgery. We conducted this systematic review and meta-analysis of levosimendan in CABG using PubMed, Embase, Scopus, and Cochrane Library (till April 20, 2018). Two-hundred and forty manuscripts were identified and 21 randomized trials (1727 patients in total) investigating the effect of levosimendan on the patients undergoing CABG surgery were finally included in this analysis. We found that levosimendan was an effective, well-tolerated inotropic agent in CABG, which was associated with a significantly reduced mortality rate [odds ratio (OR) 0.43, 95% confidence interval (CI) (0.26, 0.71), p = 0.001, I 2  = 0%] and postoperative atrial fibrillation [OR 0.50, 95% CI (0.26, 0.97), p = 0.04, I 2  = 76%], but a higher incidence of hypotension [OR 2.26, 95% CI (1.05, 4.85), p = 0.04, I 2  = 79%]. Subgroup analyses revealed that such a benefit was mainly observed in the isolated CABG, the preoperative administration, with-bolus and on-pump subgroups. More high-quality and well-designed prospective studies are needed to confirm or disprove our findings in future.

Linear stretchable supercapacitors have attracted much attention because they are well suited to applications in the rapidly expanding field of wearable electronics. However, poor conductivity of the electrode material, which limits the transfer of electrons in the axial direction of the linear supercapacitors, leads to a serious loss of capacity at high rates. To solve this problem, we use gold nanoparticles to decorate aligned multiwall carbon nanotube to fabricate stretchable linear electrodes. Furthermore, we have developed fine stretchable linear supercapacitors, which exhibited an extremely high elasticity up to 400% strain with a high capacitance of about 8.7 F g -1 at the discharge current of 1 A g -1 .

Copper is a vital cofactor in various enzymes, plays a pivotal role in maintaining cell homeostasis. When copper metabolism is disordered and mitochondrial dysfunction is impaired, programmed cell death such as apoptosis, paraptosis, pyroptosis, ferroptosis, cuproptosis, autophagy and necroptosis can be induced. In this review, we focus on the metabolic mechanisms of copper. In addition, we discuss the mechanism by which copper induces various programmed cell deaths. Finally, this review examines copper's involvement in prevalent kidney diseases such as acute kidney injury and chronic kidney disease. The findings indicate that the use of copper chelators or plant extracts can mitigate kidney damage by reducing copper accumulation, offering novel insights into the pathogenesis and treatment strategies for kidney diseases.

IgA nephropathy is the most frequent type of glomerulonephritis worldwide. The role of cell cycle regulation in the pathogenesis of IgA nephropathy has been studied. The present study was designed to explore whether rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms. After establishing an IgA nephropathy model, rats were randomly divided into four groups. Coomassie Brilliant Blue was used to measure the 24-h urinary protein levels. Renal function was determined using an autoanalyzer. Proliferation was assayed via Proliferating Cell Nuclear Antigen (PCNA) immunohistochemistry. Rat mesangial cells were cultured and divided into the six groups. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and flow cytometry were used to detect cell proliferation and the cell cycle phase. Western blotting was performed to determine cyclin E, cyclin-dependent kinase 2, p27(Kip1), p70S6K/p-p70S6K, and extracellular signal-regulated kinase 1/2/p- extracellular signal-regulated kinase 1/2 protein expression. A low dose of the mammalian target of rapamycin (mTOR) inhibitor rapamycin prevented an additional increase in proteinuria, protected kidney function, and reduced IgA deposition in a model of IgA nephropathy. Rapamycin inhibited mesangial cell proliferation and arrested the cell cycle in the G1 phase. Rapamycin did not affect the expression of cyclin E and cyclin-dependent kinase 2. However, rapamycin upregulated p27(Kip1) at least in part via AKT (also known as protein kinase B)/mTOR. In conclusion, rapamycin can affect cell cycle regulation to inhibit mesangial cell proliferation, thereby reduce IgA deposition, and slow the progression of IgAN., (© 2014 by the Society for Experimental Biology and Medicine.)

The present study investigated the effects of immunosuppressive agents [tacrolimus (Tac), cyclosporine A (CsA), mycophenolic acid (MMF) and methylprednisone (MP)] on the proliferation, cell cycle progression and apoptotic rate of human mesangial cells. Cultured human mesangial cells were treated with several concentrations of the immunosuppressive agents for 24, 48 or 72 h. Cell cycle progression, proliferation and apoptosis were analyzed using an MTT assay and flow cytometry. Tac and CsA significantly inhibited the proliferation of human mesangial cells in a dose- and time-dependent manner. Cell cycle analysis revealed that Tac and CsA arrested mesangial cells in the G0/G1 phase, preventing them from entering S phase. Similarly, MP inhibited human mesangial cell growth by causing cell cycle arrest in G0/G1 phase. MMF also inhibited mesangial cell proliferation, but accomplished this by preventing progression from S phase to the G2/M phase. The combination of MP and MMF synergistically inhibited mesangial cell proliferation. Tac, CsA, MP and MMF inhibited proliferation of human mesangial cells by blocking progression of the cell cycle. In conclusion, these agents, sequentially or in combination, may be used to effectively treat mesangial proliferative glomerular disease.