SIRT3 alleviates painful diabetic neuropathy by mediating the FoxO3a-PINK1-Parkin signaling pathway to activate mitophagy.

INTRODUCTION: Painful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays a role in the development of PDN, but its pathogenesis and mechanism have not been fully investigated. METHODS: In this study, we used high-fat diet/low-dose streptozotocin-induced rats as a model of type 2 diabetes mellitus. Behavioral testing, whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons, and complex sensory nerve conduction velocity studies were used to assess peripheral neuropathy. Mitochondrial membrane potential (MMP), ATP, tissue reactive oxygen species, and transmission electron microscopy were used to evaluate the function and morphology of mitochondria in DRG. Real-time PCR, western blot, and immunofluorescence were performed to investigate the mechanism. RESULTS: We found that damaged mitochondria were accumulated and mitophagy was inhibited in PDN rats. The expression of sirtuin 3 (SIRT3), which is an NAD+-dependent deacetylase in mitochondria, was inhibited. Overexpression of SIRT3 in DRG neurons by intrathecally administered LV-SIRT3 lentivirus ameliorated neurological and mitochondrial dysfunctions. This was evidenced by the reversal of allodynia and nociceptor hyperexcitability, as well as the restoration of MMP and ATP levels. Overexpression of SIRT3 restored the inhibited mitophagy by activating the FoxO3a-PINK1-Parkin signaling pathway. The effects of SIRT3 overexpression, including the reversal of allodynia and nociceptor hyperexcitability, the improvement of impaired mitochondria and mitophagy, and the restoration of PINK1 and Parkin expression, were counteracted when FoxO3a siRNA was intrathecally injected. CONCLUSION: These results showed that SIRT3 overexpression ameliorates PDN via activation of FoxO3a-PINK1-Parkin-mediated mitophagy, suggesting that SIRT3 may become an encouraging therapeutic strategy for PDN.

Modeling the complexity of drug-drug interactions: A physiologically-based pharmacokinetic study of Lenvatinib with Schisantherin A/Schisandrin A.

BACKGROUND: Lenvatinib's efficacy as a frontline targeted therapy for radioactive iodine-refractory thyroid carcinoma and advanced hepatocellular carcinoma owes to its inhibition of multiple tyrosine kinases. However, as a CYP3A4 substrate, lenvatinib bears susceptibility to pharmacokinetic modulation by co-administered agents. Schisantherin A (STA) and schisandrin A (SIA) - bioactive lignans abundant in the traditional Chinese medicinal Wuzhi Capsule - act as CYP3A4 inhibitors, engendering the potential for drug-drug interactions (DDIs) with lenvatinib. METHODS: To explore potential DDIs between lenvatinib and STA/SIA, we developed a physiologically-based pharmacokinetic (PBPK) model for lenvatinib and used it to construct a DDI model for lenvatinib and STA/SIA. The model was validated with clinical trial data and used to predict changes in lenvatinib exposure with combined treatment. RESULTS: Following single-dose administration, the predicted area under the plasma concentration-time curve (AUC) and maximum plasma concentrations (Cmax) of lenvatinib increased 1.00- to 1.03-fold and 1.00- to 1.01-fold, respectively, in the presence of STA/SIA. Simulations of multiple-dose regimens revealed slightly greater interactions, with lenvatinib AUC0-t and Cmax increasing up to 1.09-fold and 1.02-fold, respectively. CONCLUSION: Our study developed the first PBPK and DDI models for lenvatinib as a victim drug. STA and SIA slightly increased lenvatinib exposure in simulations, providing clinically valuable information on the safety of concurrent use. Given the minimal pharmacokinetic changes, STA/SIA are unlikely to interact with lenvatinib through pharmacokinetic alterations synergistically but rather may enhance efficacy through inherent anti-cancer efficacy of STA/ SIA.

The European livestock resistome.

Metagenomic sequencing has proven to be a powerful tool in the monitoring of antimicrobial resistance (AMR). Here, we provide a comparative analysis of the resistome from pigs, poultry, veal calves, turkey, and rainbow trout, for a total of 538 herds across nine European countries. We calculated the effects of per-farm management practices and antimicrobial usage (AMU) on the resistome in pigs, broilers, and veal calves. We also provide an in-depth study of the associations between bacterial diversity, resistome diversity, and AMR abundances as well as co-occurrence analysis of bacterial taxa and antimicrobial resistance genes (ARGs) and the universality of the latter. The resistomes of veal calves and pigs clustered together, as did those of avian origin, while the rainbow trout resistome was different. Moreover, we identified clear core resistomes for each specific food-producing animal species. We identified positive associations between bacterial alpha diversity and both resistome alpha diversity and abundance. Network analyses revealed very few taxa-ARG associations in pigs but a large number for the avian species. Using updated reference databases and optimized bioinformatics, previously reported significant associations between AMU, biosecurity, and AMR in pig and poultry farms were validated. AMU is an important driver for AMR; however, our integrated analyses suggest that factors contributing to increased bacterial diversity might also be associated with higher AMR load. We also found that dispersal limitations of ARGs are shaping livestock resistomes, and future efforts to fight AMR should continue to emphasize biosecurity measures.IMPORTANCEUnderstanding the occurrence, diversity, and drivers for antimicrobial resistance (AMR) is important to focus future control efforts. So far, almost all attempts to limit AMR in livestock have addressed antimicrobial consumption. We here performed an integrated analysis of the resistomes of five important farmed animal populations across Europe finding that the resistome and AMR levels are also shaped by factors related to bacterial diversity, as well as dispersal limitations. Thus, future studies and interventions aimed at reducing AMR should not only address antimicrobial usage but also consider other epidemiological and ecological factors.

Research on the mechanism of government-industry-university-research collaboration for cultivating innovative talent based on game theory.

The assessment of colleges' effectiveness heavily relies on the employment status of graduates. Government-industry-university-research (GIUR) collaboration in cultivation talent is the key to improving the employment rate of college graduates. Based on the theoretical framework of the triple helix, this study develops a tripartite evolutionary game model that encompasses government, enterprises, and university research institutions. The research findings indicate (1) the evolutionary convergence of strategies among the subjects of the three-party game. (2) The attainment of a stable ideal evolution state for (1,1,1) is possible when the requisite conditions are met. This suggests that the cultivation of aligned talent in GIUR collaborations should coordinate the interests of various stakeholders. (3) Drawing inspiration from parameter-sensitive simulation, the problem of mismatch between talent cultivation and social demand can be effectively addressed through measures such as reducing the cost of cooperation, balancing the distribution of benefits, and implementing appropriate reward and punishment mechanisms. In response to these implications, we put forward some management insights and suggestions.

A wheel-shaped Zr-substituted phosphotungstate [{Zr(C2O4)2}3 (PO4)(P6W39O150)]39- with tunable proton conduction properties.

A wheel-shaped Zr-substituted phosphotungstate, [N(CH3)4]2K16Na10.5H10.5[{Zr(C2O4)2}3(PO4)(P6W39O150)]·45H2O (1), was synthesised from a hexavacant Dawson-type precursor [H2P2W12O48]12-via a conventional solution method. Compound 1 features a wheel-shaped polyanion comprising an annular [P6W39O150]36- cluster supported by a turbine-shaped [{Zr(C2O4)2}3(PO4)]3- fragment, with three oxalate groups covalently anchored to W atoms. Compound 1 was systematically characterized by IR, UV, PXRD, TGA and 31P NMR spectra. The 31P NMR spectra over time were monitored to verify the stability of 1 in aqueous solution. This compound possesses remarkable proton conductive behavior with a high conductivity of 1.18 × 10-2 S cm-1 at 368 K.

Field-free switching of perpendicular magnetization by two-dimensional PtTe2/WTe2 van der Waals heterostructures with high spin Hall conductivity.

The key challenge of spin-orbit torque applications lies in exploring an excellent spin source capable of generating out-of-plane spins while exhibiting high spin Hall conductivity. Here we combine PtTe2 for high spin conductivity and WTe2 for low crystal symmetry to satisfy the above requirements. The PtTe2/WTe2 bilayers exhibit a high in-plane spin Hall conductivity σs,y ≈ 2.32 × 105 × h/2e Ω-1 m-1 and out-of-plane spin Hall conductivity σs,z ≈ 0.25 × 105 × h/2e Ω-1 m-1, where h is the reduced Planck's constant and e is the value of the elementary charge. The out-of-plane spins in PtTe2/WTe2 bilayers enable the deterministic switching of perpendicular magnetization at room temperature without magnetic fields, and the power consumption is 67 times smaller than that of the Pt control case. The high out-of-plane spin Hall conductivity is attributed to the conversion from in-plane spin to out-of-plane spin, induced by the crystal asymmetry of WTe2. Our work establishes a low-power perpendicular magnetization manipulation based on wafer-scale two-dimensional van der Waals heterostructures.

Spin-orbit coupling of electrons on separate lanthanide atoms of Pr2O2 and its singly charged cation.

Although it plays a critical role in the photophysics and catalysis of lanthanides, spin-orbit coupling of electrons on individual lanthanide atoms in small clusters is not well understood. The major objective of this work is to probe such coupling of the praseodymium (Pr) 4f and 6s electrons in Pr2O2 and Pr2O2+. The approach combines mass-analyzed threshold ionization spectroscopy and spin-orbit multiconfiguration second-order quasi-degenerate perturbation theory. The energies of six ionization transitions are precisely measured; the adiabatic ionization energy of the neutral cluster is 38 045 (5) cm-1. Most of the electronic states involved in these transitions are identified as spin-orbit coupled states consisting of two or more electron spins. The electron configurations of these states are 4f46s2 for the neutral cluster and 4f46s for the singly charged cation, both in planar rhombus-type structures. The spin-orbit splitting due to the coupling of the electrons on the separate Pr atoms is on the order of hundreds of wavenumbers.

Insight into the impacts of pyrolysis time on adsorption behavior of Pb2+ and Cd2+ by Mg modified biochar: Performance and modification mechanism.

Co-pyrolysis biomass and alkaline metals can effectively improve the adsorption performance of heavy metals (HM). Nevertheless, the researchers have ignored the relationship between the change of alkaline metal morphology and adsorption during pyrolysis. In this article, according to control the pyrolysis time (30, 60, and 180 min) synthesized Magnesium (Mg) modified biochar (MBCX) by using MgCl2·6H2O and soybean straw under 400 °C. The sorption capacities of MBC60 and MBC180 for Pb2+/Cd2+ increased by 38.65%/213.29%, 44.57%/230.36%, and the selectivity coefficient of Pb2+/Cd2+ increased by 113.28%/209.49%, 213.58%/253.62%, respectively, compared with MBC30. Additionally, the characterization results demonstrated that MgO dominated the surface phases of MBC60 and MBC180, whereas MgCl2 dominated the surface phases of MBC30. Moreover, according to the results of DFT calculation, the adsorption energy (Eads) of MgO for Pb2+ (-0.537 eV) and Cd2+ (-0.347 eV) was lower than that of MgCl2 (Pb2+: 0.37 eV, Cd2+: -0.185 eV), so that, MBC60 and MBC180 had higher sorption capacities for Pb2+ and Cd2+ than MBC30. Therefore, this work provides a new sight to clear the mechanism for modified biochar by alkali metal oxide and practical and theoretical guidance for adsorbent preparation with high adsorption ability for HMs.

Reductive N-Formylation of Nitroarenes Mediated by Rongalite.

Herein, we disclose a straightforward approach to access transition-metal-free reductive N-formylation of nitroarenes. This reaction integrates the dual role of rongalite, which acts as a reductant and a C1 building block concurrently. This provides an alternative method for the synthesis of N-aryl formamides from nitroarenes, including the construction of a C-N bond. The utility of this protocol was demonstrated by scale-up synthesis and late-stage functionalizations of complex molecules.

The immunogenicity of Alum+CpG adjuvant SARS-CoV-2 inactivated vaccine in mice.

The ongoing evolution and emergence of SARS-CoV-2 variants have raised concerns regarding the efficacy of existing vaccines and therapeutic agents. This study aimed to investigate the immunogenicity of an aluminum hydroxide (Alum) and CpG adjuvanted inactivated vaccine (IAV) candidate against SARS-CoV-2 in mice. A comparison was made between the immune response of mice vaccinated with the Alum+CpG adjuvant IAV and those vaccinated with the Alum adjuvant IAV. Mice immunized with Alum+CpG adjuvant IAV demonstrated high antibody titers and a durable humoral immune response, as well as a Th1-type cellular immune response. Notably, compared to Alum alone vaccine, the Alum+CpG adjuvant IAV induced significantly higher proportions of GC B cells in the splenocytes of immunized mice. Importantly, the changes in inflammatory cytokine levels in the sera of mice vaccinated with the Alum+CpG adjuvant IAV followed a similar trend to that of the Alum adjuvant IAV, which had been proven safe in clinical trials. Overall, our results demonstrate that Alum+CpG adjuvant has the potential to serve as a novel adjuvant, thereby providing valuable insights into the development of vaccine formulations.

Development and evaluation of a Chinese herbal gel for analgesic and anti-inflammatory effects.

This study aimed to develop a film-forming gel containing three Chinese herbal extracts, an extracted mixture of Corydalis yanhusuo, Cynanchum paniculatum and Armadillidium vulgare (Latreille) (MCCA) and evaluate its analgesic and anti-inflammatory activities. Using the Box Behnken Design, the optimal prescription for the MCCA gel was determined. The analgesic effects were tested through acid writhing and formalin pain models. while the rheumatoid arthritis model assessed the pain and anti-inflammatory effects. For the evaluation of the effect of MCCA gels on pro-inflammatory cytokines, as well, Elisa was used. Results showed that the MCCA Gel with 2% mint oil had the highest transdermal volume of 32.57±0.92µg/cm2. High doses of MCCA gel were effective in suppressing pain, with a pain inhibition rate of 54.37% during the acetic acid peristaltic test that showed pronounced inhibition in the second phase of the formalin-induced analgesia test. In the rheumatoid arthritis model, the MCCA gel reduced inflammation scores in rat feet and decreased the expressions of four inflammatory factors in serum. Generally, The MCCA gel exhibits noticeable pain-relieving and anti-inflammatory properties with high penetration with the skin.

Synthesis of co-pyrolyzed biochar using red mud and peanut shell for removing phosphate from pickling wastewater: Performance and mechanism.

Iron (Fe)/iron oxide-modified biochar has practicable adsorption capability for phosphorus (P), but it is expensive. In this study, we synthesized novel low-cost and eco-friendly adsorbents co-pyrolyzed biochars using Fe-rich red mud (RM) and peanut shell (PS) wastes via a one-step pyrolysis process for removing P from pickling wastewater. The preparation conditions (heating rate, pyrolysis temperature, and feedstock ratio) and P adsorption behaviors were systematically investigated. In addition, a series of characterization and approximate site energy distribution (ASED) analyses were conducted to understand the P adsorption mechanisms. The magnetic biochar (BR7P3) with m (RM):m (PS) of 7:3 prepared at 900°C and 10 °C/min had a high surface area (164.43 m2/g) and different abundant ions (including Fe3+, and Al3+). In addition, BR7P3 exhibited the best P removal capability (142.6 mg/g). The Fe2O3 from RM was successfully reduced to Fe0, which was easily oxidized as Fe3+ to precipitate with H2PO4-. The electrostatic effect, Fe-O-P bonding, and surface precipitation were the main mechanisms of P removal. ASED analyses revealed that high distribution frequency and solution temperature led to a high P adsorption rate of the adsorbent. Therefore, this study provides new insight into the waste-to-wealth strategy by transforming PS and RM into mineral-biomass biochar with excellent P adsorption capability and environmental adaptability.

Direct Hydrodefluorination of CF3-Alkenes via a Mild SN2' Process Using Rongalite as a Masked Proton Reagent.

A concise and efficient hydrodefluorination process was developed for the synthesis of gem-difluoroalkenes. This reaction employs rongalite as a masked proton source and does not require any additional catalysts or reductants. Notably, trifluoromethyl alkenes having both terminal and internal double bonds are compatible with this process, allowing for a wider range of substrates. The successful late-stage functionalizations of pharmaceuticals and gram-scale syntheses were used to demonstrate the viability of this method.

Self-Powered Wireless Flexible Ionogel Wearable Devices.

Ionogels are promising soft materials for flexible wearable devices because of their unique features such as ionic conductivity and thermal stability. Ionogels reported to date show excellent sensing sensitivity; however, they suffer from a complicated external power supply. Herein, we report a self-powered wearable device based on an ionogel incorporating poly(vinylidene fluoride) (PVDF). The three-dimensional (3D) printed PVDF-ionogel exhibits amazing stretchability (1500%), high conductivity (0.36 S/m at 105 Hz), and an extremely low glass transition temperature (-84 °C). Moreover, the flexible wearable devices assembled from the PVDF-ionogel can precisely detect physiological signals (e.g., wrist, gesture, running, etc.) with a self-powered supply. Most significantly, a self-powered wireless flexible wearable device based on our PVDF-ionogel achieves monitoring healthcare of a human by transmitting obtained signals with a Bluetooth module timely and accurately. This work provides a facile and efficient method for fabricating cost-effective wireless wearable devices with a self-powered supply, enabling their potential applications for healthcare, motion detection, human-machine interfaces, etc.

Selective removal behavior of lead and cadmium from calcium-rich solution by MgO loaded soybean straw biochars and mechanism analysis.

Modified biochars has great potential for removing heavy metals from aquatic environments, but the removal of heavy metals by biochars is usually significantly affected by the co-presence of the macro amount of metal ions, such as Ca. Enhancing the ion exchange capacity of biochar by increasing its alkali metal content is a very prospective method to improve its selectivity. In this paper, MgO loaded biochar (MBC) was synthesized by co-pyrolysis of soybean straw and MgCl2·6H2O for selective remove Pb and Cd from calcium-rich wastewater. MBC exhibited excellent selective adsorption performance for Pb and Cd in calcium-rich wastewater due to the successful loading of MgO. The adsorption capacities of MBC for Pb and Cd were 582.57 and 167.40 mg/g, and the removal efficiency of Ca below 2.5% with an initial concentration of 800 mg/L. The ion exchange capacities of Pb and Cd enhanced almost 27 and 23 times than BC. By analyzing the results of BET, XRD, SEM-EDS, XPS and FTIR, the adsorption mechanisms of MBC were mainly including ion exchange, precipitation with minerals, and interaction with oxygen-containing functional groups. The easy preparation method and high selective adsorption capacity makes MBC an ideal alternative for efficiently selective removal Pb and Cd from calcium-rich wastewater.

Enhanced adsorption of phosphate from pickling wastewater by Fe-N co-pyrolysis biochar: Performance, mechanism and reusability.

A one-step method of preparation using a novel nitrogen (N)-doped Fe-rich biochar (N5-CB) resulted in a maximum adsorption capacity (314.52 mg/g) compared with Fe-rich biochar (CB, 104.044 mg/g). It can be used to adsorb phosphate (P) efficiently. Additionally, the adsorption kinetics, isotherms, and thermodynamics indicated that the adsorption of P onto N5-CB was mainly mediated via multilayer coverage, endothermic, spontaneous, and physical mechanisms. The main adsorption mechanisms include Fe-P precipitation, FeOP bonding, and electronic effect. Further, the highly active Fe-Nx sites and graphitic N induced by N doping were the dominant driving force underlying enhanced P adsorption. Active Fe-Nx sites resulted in a positively-charged carbon structure and P absorption via electrostatic effect. Based on the simple method of pyrolysis, N5-CB can be used in P removal from pickling wastewater with excellent adsorption capacity and remarkable recyclability.

dl-Alanine Covalently Bonded Giant Arsenotungstate with Rapid Photochromic and Decent Proton Conduction Properties.

A dl-alanine covalently bonded giant arsenotungstate, namely, Na3Ba11H16[(AsW9O33)6{W2O5(H2O)(dl-Ala)}2{W3O6(H2O)(dl-Ala)}2{W2O5(dl-Ala)}] (1; dl-Ala = dl-alanine), has been synthesized and is composed of six [AsW9O33]9- fragments fused together via two [W2O5(H2O)(dl-Ala)]+ segments, two [W3O6(H2O)(dl-Ala)]5+ segments, and a [W2O5(dl-Ala)]+ segment. This complex represents the first carboxylate-based hybrid polyoxotungstate without the introduction of lanthanide ions. Besides, compound 1 demonstrates not only fast photochromic properties but also interesting proton conductivity properties, with an achieved conductivity of 2.830 × 10-4 S·cm-1 (65 °C, 75% relative humidity).

Optical three-dimensional shape measurement based on structured light and a binocular vision system.

Three-dimensional shape measurement based on structured light is affected by two factors: the number of fringe patterns and the phase unwrapping process. Although one-shot technology can get the wrapped phase, it is not suitable for measuring complex surface. Moreover, phase unwrapping also affects measurement speed and accuracy. To overcome these problems, a two-dimensional wavelet transform with binocular vision system is proposed. Wavelet transform is used to get the wrapped phase based on the Morlet wavelet. In order to get a three-dimensional shape without phase unwrapping, a binocular vision system is used. The increase matching accuracy, the preliminary disparity, and the sub-pixel optimization are calculated, respectively. Based on the calibration parameters, three-dimensional information can be obtained directly from the wrapped phase. In addition, the average phase is calculated based on ambient pixels to confirm wrapped phase boundary. Experimental results demonstrate the feasibility and advantage of the proposed method. Compared with traditional methods, both measurement accuracy and measurement speed can be increased.

A membrane-based seawater electrolyser for hydrogen generation.

Electrochemical saline water electrolysis using renewable energy as input is a highly desirable and sustainable method for the mass production of green hydrogen1-7; however, its practical viability is seriously challenged by insufficient durability because of the electrode side reactions and corrosion issues arising from the complex components of seawater. Although catalyst engineering using polyanion coatings to suppress corrosion by chloride ions or creating highly selective electrocatalysts has been extensively exploited with modest success, it is still far from satisfactory for practical applications8-14. Indirect seawater splitting by using a pre-desalination process can avoid side-reaction and corrosion problems15-21, but it requires additional energy input, making it economically less attractive. In addition, the independent bulky desalination system makes seawater electrolysis systems less flexible in terms of size. Here we propose a direct seawater electrolysis method for hydrogen production that radically addresses the side-reaction and corrosion problems. A demonstration system was stably operated at a current density of 250 milliamperes per square centimetre for over 3,200 hours under practical application conditions without failure. This strategy realizes efficient, size-flexible and scalable direct seawater electrolysis in a way similar to freshwater splitting without a notable increase in operation cost, and has high potential for practical application. Importantly, this configuration and mechanism promises further applications in simultaneous water-based effluent treatment and resource recovery and hydrogen generation in one step.