Phosphoethanolamine cytidylyltransferase ameliorates mitochondrial function and apoptosis in hepatocytes in T2DM in vitro.

Liver function indicators are often impaired in patients with type 2 diabetes mellitus (T2DM), who present higher concentrations of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase than individuals without diabetes. However, the mechanism of liver injury in patients with T2DM has not been clearly elucidated. In this study, we performed a lipidomics analysis on the liver of T2DM mice, and we found that phosphatidylethanolamine (PE) levels were low in T2DM, along with an increase in diglyceride, which may be due to a decrease in the levels of phosphoethanolamine cytidylyltransferase (Pcyt2), thus likely affecting the de novo synthesis of PE. The phosphatidylserine decarboxylase pathway did not change significantly in the T2DM model, although both pathways are critical sources of PE. Supplementation with CDP-ethanolamine (CDP-etn) to increase the production of PE from the CDP-etn pathway reversed high glucose and FFA (HG&FFA)-induced mitochondrial damage including increased apoptosis, decreased ATP synthesis, decreased mitochondrial membrane potential, and increased reactive oxygen species, whereas supplementation with lysophosphatidylethanolamine, which can increase PE production in the phosphatidylserine decarboxylase pathway, did not. Additionally, we found that overexpression of PCYT2 significantly ameliorated ATP synthesis and abnormal mitochondrial morphology induced by HG&FFA. Finally, the BAX/Bcl-2/caspase3 apoptosis pathway was activated in hepatocytes of the T2DM model, which could also be reversed by CDP-etn supplements and PCYT2 overexpression. In summary, in the liver of T2DM mice, Pcyt2 reduction may lead to a decrease in the levels of PE, whereas CDP-etn supplementation and PCYT2 overexpression ameliorate partial mitochondrial function and apoptosis in HG&FFA-stimulated L02 cells.

Magnetic Heating Amorphous NiFe Hydroxide Nanosheets Encapsulated Ni Nanoparticles@Wood Carbon to Boost Oxygen Evolution Reaction Activity.

The oxygen evolution reaction (OER) has significant effects on the water-splitting process and rechargeable metal-air batteries; however, the sluggish reaction kinetics caused by the four-electron transfer process for transition metal catalysts hinder large-scale commercialization in highly efficient electrochemical energy conversion devices. Herein, a magnetic heating-assisted enhancement design for low-cost carbonized wood with high OER activity is proposed, in which Ni nanoparticles are encapsulated in amorphous NiFe hydroxide nanosheets (a-NiFe@Ni-CW) via direct calcination and electroplating. The introduction of amorphous NiFe hydroxide nanosheets optimizes the electronic structure of a-NiFe@Ni-CW, accelerating electron transfer and reducing the energy barrier in the OER. More importantly, the Ni nanoparticles located on carbonized wood can function as magnetic heating centers under the effect of an alternating current (AC) magnetic field, further promoting the adsorption of reaction intermediates. Consequently, a-NiFe@Ni-CW demonstrated an overpotential of 268 mV at 100 mA cm-2 for the OER under an AC magnetic field, which is superior to that of most reported transition metal catalysts. Starting with sustainable and abundant wood, this work provides a reference for highly effective and low-cost electrocatalyst design with the assistance of a magnetic field.

Hyperuricemia induces liver injury by upregulating HIF-1α and inhibiting arginine biosynthesis pathway in mouse liver and human L02 hepatocytes.

The molecular mechanisms of uric acid (UA)-induced liver injury has not been clearly elucidated. In this study, we aimed to investigate the effect and action mechanisms of UA in liver injury. We analyzed the damaging effect of UA on mouse liver and L02 cells and subsequently performed metabolomics studies on L02 cells to identify abnormal metabolic pathways. Finally, we verified transcription factors that regulate related metabolic enzymes. UA directly activated the hepatic NLRP3 inflammasome and Bax apoptosis pathway invivo and invitro. Related metabolites in the arginine biosynthesis pathway (or urea cycle), l-arginine and l-argininosuccinate were decreased, and ammonia was increased in UA-stimulated L02 cells, which was mediated by carbamoyl phosphate synthase 1 (CPS1), argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) downregulation. UA upregulated hypoxia inducible factor-1alpha (HIF-1α) invivo and invitro, and HIF-1α inhibition alleviated the UA-induced ASS downregulation and hepatocyte injury. In conclusion, UA upregulates HIF-1α and inhibits urea cycle enzymes (UCEs). This leads to liver injury, with evidence of hepatocyte inflammation, apoptosis and oxidative stress.

Evaluation of the microscopic observation drug susceptibility assay for the rapid detection of MDR-TB and XDR-TB in China: a prospective multicentre study.

OBJECTIVES: To perform a multicentre study evaluating the performance of the microscopic observation drug susceptibility (MODS) assay for the detection of MDR-TB and XDR-TB in high-burden resource-limited settings. METHODS: We performed a prospective diagnostic accuracy study of drug-resistant TB suspects from outpatient and inpatient settings in five laboratories in China. Sputum was tested by smear microscopy, liquid [mycobacterial growth indicator tube (MGIT)] culture and the MODS assay at each site. Drug susceptibility testing (DST) was by MODS and an indirect 1% proportion method. The reference standard for Mycobacterium tuberculosis detection was growth on MGIT culture; the 1% proportion method was the reference standard for rifampicin, isoniazid, ofloxacin, kanamycin and capreomycin DST. RESULTS: M. tuberculosis was identified by reference standard culture among 213/532 (40.0%) drug-resistant TB suspects. Overall MODS sensitivity for M. tuberculosis detection was 87.8%-94.3% and specificity was 96.8%-100%. For drug-resistant TB diagnosis, excellent agreement was obtained for all drugs tested at the majority of sites. The accuracy was 87.1%-96.7% for rifampicin, 87.1%-93.3% for isoniazid, 92.7%-100% for ofloxacin, 90.9%-100% for kanamycin and 90.2%-100% for capreomycin. The median time to culture positivity was significantly shorter for MODS than for the MGIT liquid culture (8 days versus 11 days, P<0.001). The contamination rate ranged between 2.1% and 5.3%. CONCLUSIONS: In the study settings, MODS provided high sensitivity and specificity for rapid diagnosis of TB and drug-resistant TB. We consider it to have a strong potential for timely detection of MDR-TB and XDR-TB in high-burden resource-limited settings.

HeadDiff: Exploring Rotation Uncertainty With Diffusion Models for Head Pose Estimation.

In this paper, we propose a probabilistic regression diffusion model for head pose estimation, dubbed HeadDiff, which typically addresses the rotation uncertainty, especially when faces are captured in wild conditions. Unlike conventional image-to-pose methods which cannot explicitly establish the rotational manifold of head poses, our HeadDiff aims to ensure the pose rotation via the diffusion process and in parallel, refine the mapping process iteratively. Specifically, we initially formulate the head pose estimation problem as a reverse diffusion process, defining a paradigm for progressive denoising on the manifold, which explores the uncertainty by decomposing the large gap into intermediate steps. Moreover, our HeadDiff is equipped with an isotropic Gaussian distribution by encoding the incoherence information in our rotation representation. Finally, we learn the facial relationship of nearest neighbors with a cycle-consistent constraint for robust pose estimation versus diverse shape variations. Experimental results on multiple datasets demonstrate that our proposed method outperforms existing state-of-the-art techniques without auxiliary data.

Self-Encapsulation of High-Entropy Alloy Nanoparticles inside Carbonized Wood for Highly Durable Electrocatalysis.

High-entropy alloy nanoparticles (HEAs) show great potential in emerging electrocatalysis due to their combination and optimization of multiple elements. However, synthesized HEAs often exhibit a weak interface with the conductive substrate, hindering their applications in long-term catalysis and energy conversion. Herein, a highly active and durable electrocatalyst composed of quinary HEAs (PtNiCoFeCu) encapsulated inside the activated carbonized wood (ACW) is reported. The self-encapsulation of HEAs is achieved during Joule heating synthesis (2060 K, 2 s) where HEAs naturally nucleate at the defect sites. In the meantime, HEAs catalyze the deposition of mobile carbon atoms to form a protective few-layer carbon shell during the rapid quenching process, thus remarkably strengthening the interface stability between HEAs and ACW. As a result, the HEAs@ACW shows not only favorable activity with an overpotential of 7 mV at 10 mA cm-2 for hydrogen evolution but also negligible attenuation during a 500 h stability test, which is superior to most reported electrocatalysts. The design of self-encapsulated HEAs inside ACW provides a critical strategy to enhance both activity and stability, which is also applicable to many other energy conversion technologies.

Programmable, Changeable, Origami Cellulose Films for Magnetically Controllable Soft Robots.

Magnetic soft robots composed of stimuli-responsive materials are promising for biomedical engineering applications; however, typical responsive materials are fabricated with nondegradable polymeric substrates. In this study, we report a flexible, biodegradable, and magnetically sensitive cellulose film (M-film) that can be utilized for magnetically controllable soft robots (M-robots) with programmable locomotion, cargo delivery, and remote wireless operation functions. The M-film with good foldability, origami, and magnetic properties is synthesized by a simple paper-making process using cellulose nanofibers, additive sodium alginate, and BaFe12O19 particles. Through the following origami-magnetization process, the M-robot with multimodal movements is designed: climbing over the obstacles in the walking environment; additionally, this process can complete various cargo transport tasks by clawing, rolling, and flipping. This approach expands the precise controllability and manipulability of environmentally friendly cellulose nanomaterials beyond the known applications and opens the prospects of their implementation in stimuli-responsive robots, wireless control electronics, and intelligent devices.

Palmitic Acid Inhibits the Growth and Metastasis of Gastric Cancer by Blocking the STAT3 Signaling Pathway.

Lipidomic analyses have suggested that palmitic acid (PA) is linked to gastric cancer. However, its effects and action mechanisms remain unclear. Therefore, we evaluated the effects of PA on cell proliferation, invasion, and apoptosis in human gastric cancer, as well as the role of p-STAT3 in mediating its effects. The results of the MTT and colony formation assays revealed that PA blocked gastric cancer cell proliferation in a concentration-dependent manner. The EdU-DNA assay indicated that 50 µM of PA could block gastric cell proliferation by 30.6-80.0%. The Transwell assay also confirmed the concentration dependence of PA-induced inhibitory effect on cell invasion. The flow cytometry analysis indicated that PA treatment for 18 h could induce gastric cancer cell apoptosis. The immunohistochemical staining revealed that p-STAT3 levels were higher in the gastric cancer tissues than in the control tissues. We demonstrated that PA treatment for 12 h decreased the expressions of p-STAT3, p-JAK2, N-cadherin, and vimentin, and inhibited the nuclear expression of p-STAT3 in gastric cancer cells. Finally, PA treatment (50 mg/kg) decreased gastric cancer growth (54.3%) in the xenograft models. Collectively, these findings demonstrate that PA inhibits cell proliferation and invasion and induces human gastric cancer cell apoptosis.

Phosphatidylserine decarboxylase downregulation in uric acid­induced hepatic mitochondrial dysfunction and apoptosis.

The molecular mechanisms underlying uric acid (UA)-induced mitochondrial dysfunction and apoptosis have not yet been elucidated. Herein, we investigated underlying mechanisms of UA in the development of mitochondrial dysfunction and apoptosis. We analyzed blood samples of individuals with normal UA levels and patients with hyperuricemia. Results showed that patients with hyperuricemia had significantly elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, which may indicate liver or mitochondrial damage in patients with hyperuricemia. Subsequently, lipidomic analysis of mouse liver tissue mitochondria and human liver L02 cell mitochondria was performed. Compared with control group levels, high UA increased mitochondrial phosphatidylserine (PS) and decreased mitochondrial phosphatidylethanolamine (PE) levels, whereas the expression of mitochondrial phosphatidylserine decarboxylase (PISD) that mediates PS and PE conversion was downregulated. High UA levels also inhibited signal transducer and activator of transcription 3 （STAT3） phosphorylation as well as mitochondrial respiration, while inducing apoptosis both in vivo and in vitro. Treatment with allopurinol, overexpression of PISD, and lyso-PE (LPE) administration significantly attenuated the three above-described effects in vitro. In conclusion, UA may induce mitochondrial dysfunction and apoptosis through mitochondrial PISD downregulation. This study provides a new perspective on liver damage caused by hyperuricemia.

Magnetically Driven 3D Cellulose Film for Improved Energy Efficiency in Solar Evaporation.

The architecture of cellulose nanomaterials is definitized by random deposition and cannot change in response to shifting application requirements. Herein, we present a magnetic field-controlled cellulose film derived from wood that exhibits great magnetic properties and reliable tunability enabled by incorporated Fe3O4 nanoparticles and cellulose nanofibers (CNF) with a large length-diameter ratio. Fe3O4 nanoparticles are dispersed in suspensions of CNF so as to enhance the magnetic response. The plane magnetic CNF can be processed to form a three-dimensional (3D) flower-like structure along the magnetic induction line after applying an external magnet. Inspired by the fluidic transport in natural flowers, a bilayer structure was created using the 3D flower-like film as the solar energy receiver and natural wood as the water pathway in a solar-derived evaporation system. Compared with a planar cellulose film decorated with Fe3O4, the 3D structure design can greatly improve the evaporation rate from 1.19 to 1.39 kg m-2 h-1 and the efficiency from 76.9 to 90.6% under 1 sun. Finite element molding further reveals that the 3D structural top layer is beneficial for the formation of a gradient temperature profile and the improvement of the energy efficiency through the reduction of thermal radiation. The magnetically controlled fabrication represents a promising strategy for designing cellulose nanomaterials with a complicated structure and controllable topography, which has a wide spectrum of applications in energy storage devices and water treatment.

Ultra-high rate capability of nanoporous carbon network@V2O5 sub-micron brick composite as a novel cathode material for asymmetric supercapacitors.

A green biomass-derived nanoporous carbon network (NCN) has been prepared and integrated with V2O5 sub-micron bricks (SMBs). The large surface area and high pore volume of the NCN can not only provide abundant sites for electrochemical reactions but also stabilize the structure of the V2O5 SMBs. The NCN@V2O5 SMB composite, acting as a novel cathode material, delivers a high areal capacitance of 786 mF cm-2 at 0.2 mA cm-2 and superior cycling stability with 89.5% capacitance retention after 5000 cycles. Besides, the electrode achieves an ultra-high rate capability (82% capacitance retention as the current density increases from 0.2 to 5 mA cm-2) since the contribution from the non-diffusion-controlled process is estimated to be as high as 95.5%-98.5% according to the kinetic analysis. Furthermore, the micropores are more favorable than the mesopores at lower current densities (0.2-2 mA cm-2), while the contribution of the external surface area becomes more significant for current densities higher than 2 mA cm-2. Moreover, an asymmetric supercapacitor assembled using this cathode and the NCN anode shows superior electrochemical properties, such as wide operating voltage, long cycle life and large energy density (72.2 µW h cm-2). Their excellent electrochemical features and good eco-friendliness confirm the potential of the NCN@V2O5 SMBs for use as supercapacitors.

Multicentre laboratory validation of the nitrate reductase assay using liquid medium for the rapid detection of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis.

To perform a multicentre study evaluating the performance of the nitrate reductase assay (NRA) using liquid medium for the detection of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis and to establish the MICs and critical concentrations of rifampicin, isoniazid, ofloxacin, amikacin, kanamycin and capreomycin. The study was carried out in three phases. Phase I determined the MIC of each drug. Phase II established the critical concentration of each drug. Phase III validated critical concentrations for the six drugs tested by the NRA using liquid medium compared with the agar proportion method or MGIT 960 system at each site. The critical concentrations for the six drugs used in the NRA are as follows: rifampicin, 1 mg/L; isoniazid, 0.2 mg/L; ofloxacin, 2 mg/L; amikacin, 2 mg/L; kanamycin, 5 mg/L; capreomycin, 2.5 mg/L. Phase III: Excellent agreement was obtained for all drugs tested at the majority of sites. The accuracy was 97%-100% for rifampicin, 96.8%-99.2% for isoniazid, 98%-100% for ofloxacin, 96.8%-98.5% for amikacin, 96.4%-99.5% for kanamycin and 96.8%-100% for capreomycin. Results for NRA using liquid medium were obtained in a median time of 7 days. NRA performed in liquid medium offers a rapid, economical and feasible method for detection of M. tuberculosis resistance to first- and second-line drugs in resource-limited settings.