Engineering of Thermoelectric Composites Based on Silver Selenide in Aqueous Solution and Ambient Temperature.

The direct, solid state, and reversible conversion between heat and electricity using thermoelectric devices finds numerous potential uses, especially around room temperature. However, the relatively high material processing cost limits their real applications. Silver selenide (Ag2Se) is one of the very few n-type thermoelectric (TE) materials for room-temperature applications. Herein, we report a room temperature, fast, and aqueous-phase synthesis approach to produce Ag2Se, which can be extended to other metal chalcogenides. These materials reach TE figures of merit (zT) of up to 0.76 at 380 K. To improve these values, bismuth sulfide (Bi2S3) particles also prepared in an aqueous solution are incorporated into the Ag2Se matrix. In this way, a series of Ag2Se/Bi2S3 composites with Bi2S3 wt % of 0.5, 1.0, and 1.5 are prepared by solution blending and hot-press sintering. The presence of Bi2S3 significantly improves the Seebeck coefficient and power factor while at the same time decreasing the thermal conductivity with no apparent drop in electrical conductivity. Thus, a maximum zT value of 0.96 is achieved in the composites with 1.0 wt % Bi2S3 at 370 K. Furthermore, a high average zT value (zTave) of 0.93 in the 300-390 K range is demonstrated.

MiR-127-3p enhances macrophagic proliferation via disturbing fatty acid profiles and oxidative phosphorylation in atherosclerosis.

BACKGROUND: Atherosclerosis is a chronic pathology, leading to acute coronary heart disease or stroke. MiR-127 has been found significantly upregulated in advanced atherosclerosis. But its function in atherosclerosis remains unexplored. We explored the role of miR-127-3p in regulating atherosclerosis development and its downstream mechanisms. METHODS: The expression profile of miR-127 in carotid atherosclerotic plaques of 23 patients with severe carotid stenosis was detected by RT-qPCR and in situ hybridization. Primary bone marrow-derived macrophages (BMDM) stimulated with oxidized low-density lipoprotein were used as an in vitro model. CCK-8, EdU, RT-qPCR, and flow cytometry were used to detect the proliferative capacity and polarization of BMDM, which were infected by lentivirus-carrying plasmid to upregulate or downregulate miR-127-3p expression, respectively. RNA sequencing combined with bioinformatic analysis and targeted fatty acid metabolomics approach were used to detect the transcriptome and lipid metabolites. The association between miR-127-3p and its target was verified by dual-luciferase activity reporting and Western blotting. Oxygen consumption rate of BMDM were detected using seahorse analysis. High-cholesterol-diet-fed low density lipoprotein deficient (LDLR-/-) mice, with-or-without carotid tandem-stenosis surgery, were treated with miR-127-3p agomir or antagomir to examine its effect on plaque development and stability. RESULTS: miR-127-3p, not -5p, is elevated in human advanced carotid atheroma and its expression is positively associated with macrophage accummulation in plaques. In vitro, miR-127-3p-overexpressed macrophage exhibites increased proliferation capacity and facilitates M1 polariztion whereas the contrary trend is present in miR-127-3p-inhibited macrophage. Stearoyl-CoA desaturase-1 (SCD1) is one potential target of miR-127-3p. miR-127-3p mimics decreases the activity of 3' untranslated regions of SCD-1. Furthermore, miR-127-3p downregulates SCD1 expression, and reversing the expression of SCD1 attenuates the increased proliferation induced by miR-127-3p overexpression in macrophage. miR-127-3p overexpression could also lead to decreased content of unsaturated fatty acids(UFAs), increased content of acetyl CoA and increased level of oxidative phosphorylation. In vivo, miR-127-3p agomir significantly increases atherosclerosis progression, macrophage proliferation and decreases SCD1 expression and the content of UFAs in aortic plaques of LDLR-/- mice. Conversely, miR-127-3p antagomir attenuated atherosclerosis, macrophage proliferation in LDLR-/- mice, and enhanced carotid plaque stability in mice with vulnerable plaque induced. CONCLUSION: MiR-127-3p enhances proliferation in macrophages through downregulating SCD-1 expression and decreasing the content of unsaturated fatty acid, thereby promoting atherosclerosis development and decreasing plaque stability. miR-127-3p/SCD1/UFAs might provide potential therapeutic target for anti-inflammation and atherosclerosis.

Increasing CRISPR/Cas9-mediated gene editing efficiency in T7 phage by reducing the escape rate based on insight into the survival mechanism.

Bacteriophages have been used across various fields, and the utilization of CRISPR/Cas-based genome editing technology can accelerate the research and applications of bacteriophages. However, some bacteriophages can escape from the cleavage of Cas protein, such as Cas9, and decrease the efficiency of genome editing. This study focuses on the bacteriophage T7, which is widely utilized but whose mechanism of evading the cleavage of CRISPR/Cas9 has not been elucidated. First, we test the escape rates of T7 phage at different cleavage sites, ranging from 10 -2 to 10 -5. The sequencing results show that DNA point mutations and microhomology-mediated end joining (MMEJ) at the target sites are the main causes. Next, we indicate the existence of the hotspot DNA region of MMEJ and successfully reduce MMEJ events by designing targeted sites that bypass the hotspot DNA region. Moreover, we also knock out the ATP-dependent DNA ligase 1. 3 gene, which may be involved in the MMEJ event, and the frequency of MMEJ at 4. 3 is reduced from 83% to 18%. Finally, the genome editing efficiency in T7 Δ 1. 3 increases from 20% to 100%. This study reveals the mechanism of T7 phage evasion from the cleavage of CRISPR/Cas9 and demonstrates that the special design of editing sites or the deletion of key gene 1. 3 can reduce MMEJ events and enhance gene editing efficiency. These findings will contribute to advancing CRISPR/Cas-based tools for efficient genome editing in phages and provide a theoretical foundation for the broader application of phages.

Unraveling the Dynamic Molecular Motions of a Twin-Cavity Cage with Slow Configurational but Rapid Conformational Interconversions.

Featuring diverse structural motions/changes, dynamic molecular systems hold promise for executing complex tasks. However, their structural complexity presents formidable challenge in elucidating their kinetics, especially when multiple structural motions are intercorrelated. We herein introduce a twin-cavity cage that features interconvertible C3- and C1-configurations, with each configuration exhibiting interchangeable P- and M-conformations. This molecule is therefore composed of four interconnected chiral species (P)-C3, (M)-C3, (P)-C1, (M)-C1. We showcase an effective approach to decouple these sophisticated structural changes into two kinetically distinct pathways. Utilizing time-dependent 1H NMR spectroscopy at various temperatures, which disregards the transition between mirror-image conformations, we first determine the rate constant (kc) for the C3- to C1-configuration interconversion, while time-dependent circular dichroism spectroscopy at different temperatures quantifies the observed rate constant (kobs) of the ensemble of all the structural changes. As kobs ≫ ${{\rm { \gg }}}$ kc, it allows us to decouple the overall molecular motions into a slow configurational transformation and rapid conformational interconversions, with the latter further dissected into two independent conformational interchanges, namely (P)-C3 ← → ${ \mathbin{{\stackrel{\textstyle\rightarrow} { {\smash{\leftarrow}\vphantom{_{\vbox to.5ex{\vss}}}} } }} }$ (M)-C3 and (P)-C1 ← → ${ \mathbin{{\stackrel{\textstyle\rightarrow} { {\smash{\leftarrow}\vphantom{_{\vbox to.5ex{\vss}}}} } }} }$ (M)-C1. This work, therefore, sheds light on the comprehensive kinetic study of complex molecular dynamics, offering valuable insights for the rational design of smart dynamic materials for applications of sensing, separation, catalysis, molecular machinery, etc.

CPhaMAS: An online platform for pharmacokinetic data analysis based on optimized parameter fitting algorithm.

BACKGROUND AND OBJECTIVE: Clinical pharmacological modeling and statistical analysis software is an essential basic tool for drug development and personalized drug therapy. The learning curve of current basic tools is steep and unfriendly to beginners. The curve is even more challenging in cases of significant individual differences or measurement errors in data, resulting in difficulties in accurately estimating pharmacokinetic parameters by existing fitting algorithms. Hence, this study aims to explore a new optimized parameter fitting algorithm that reduces the sensitivity of the model to initial values and integrate it into the CPhaMAS platform, a user-friendly online application for pharmacokinetic data analysis. METHODS: In this study, we proposed an optimized Nelder-Mead method that reinitializes simplex vertices when trapped in local solutions and integrated it into the CPhaMAS platform. The CPhaMAS, an online platform for pharmacokinetic data analysis, includes three modules: compartment model analysis, non-compartment analysis (NCA) and bioequivalence/bioavailability (BE/BA) analysis. Our proposed CPhaMAS platform was evaluated and compared with existing WinNonlin. RESULTS: The platform was easy to learn and did not require code programming. The accuracy investigation found that the optimized Nelder-Mead method of the CPhaMAS platform showed better accuracy (smaller mean relative error and higher R2) in two-compartment and extravascular administration models when the initial value was set to true and abnormal values (10 times larger or smaller than the true value) compared with the WinNonlin. The mean relative error of the NCA calculation parameters of CPhaMAS and WinNonlin was <0.0001 %. When calculating BE for conventional, high-variability and narrow-therapeutic drugs. The main statistical parameters of the parameters Cmax, AUCt, and AUCinf in CPhaMAS have a mean relative error of <0.01% compared to WinNonLin. CONCLUSIONS: In summary, CPhaMAS is a user-friendly platform with relatively accurate algorithms. It is a powerful tool for analysing pharmacokinetic data for new drug development and precision medicine.

Locating Target Regions for Image Retrieval in an Unsupervised Manner.

Image retrieval performance can be improved by training a convolutional neural network (CNN) model with annotated data to facilitate accurate localization of target regions. However, obtaining sufficiently annotated data is expensive and impractical in real settings. It is challenging to achieve accurate localization of target regions in an unsupervised manner. To address this problem, we propose a new unsupervised image retrieval method named unsupervised target region localization (UTRL) descriptors. It can precisely locate target regions without supervisory information or learning. Our method contains three highlights: 1) we propose a novel zero-label transfer learning method to address the problem of co-localization in target regions. This enhances the potential localization ability of pretrained CNN models through a zero-label data-driven approach; 2) we propose a multiscale attention accumulation method to accurately extract distinguishable target features. It distinguishes the importance of features by using local Gaussian weights; and 3) we propose a simple yet effective method to reduce vector dimensionality, named twice-PCA-whitening (TPW), which reduces the performance degradation caused by feature compression. Notably, TPW is a robust and general method that can be widely applied to image retrieval tasks to improve retrieval performance. This work also facilitates the development of image retrieval based on short vector features. Extensive experiments on six popular benchmark datasets demonstrate that our method achieves about 7% greater mean average precision (mAP) compared to existing state-of-the-art unsupervised methods.

Efficacy of dolutegravir + lamivudine q.d. with food in people with TB/HIV using a rifampicin-based regimen: A retrospective observational case series.

OBJECTIVES: Dolutegravir + lamivudine (DTG + 3TC) is a first-line regimen for people with HIV. However, there are still concerns about its efficacy in people with tuberculosis (TB)/HIV due to the lack of available evidence and drug-drug interaction with rifampicin. METHODS: A single-centre retrospective observational case series was conducted in Guangxi Zhuang Autonomous Region, China. We included all people with TB/HIV on combined use of once-daily (q.d.) dosing DTG + 3TC and rifampicin (RIF)-containing anti-TB regimens between 2020 and 2022. HIV-RNA, CD4 cell counts were collected and analysed. RESULTS: In all, 21 people with HIV (PWH) were included in this study. All the PWH were treatment-naïve and told to take DTG + 3TC q.d. with food. The median age was 53 years, and 71.43% were male. A total of 71.43% PWH had baseline viral load (VL) > 100 000 copies/mL, and 33.33% had baseline VL greater than 500 000 copies/mL. Only one PWH had CD4 cell count greater than 200 cells/µL, and the median CD4 count was 20 cells/µL. A total of 16 PWH started DTG + 3TC after initiation of the RIF-based anti-TB regimen, and the other five PWH initiated DTG + 3TC before the treatment of TB. All the PWH had at least 24 weeks of follow-up visits and all of the TB treatments were successful. A total of 20 PWH (95.24%) achieved viral suppression (VL <50 copies/mL). All detected viral loads between weeks 24 and 48 were less than 200 copies/mL. Among the PWH who started DTG + 3TC after the initiation of RIF-based anti-TB regimen, all achieved viral suppression by week 24 except the non-suppressed PWH. CD4 counts were greatly improved after antiretroviral treatment: the median CD4 counts were raised from 20 to 171 cells/µL at week 48. No serious adverse events were reported. CONCLUSIONS: This case series preliminarily validates the efficacy of DTG + 3TC q.d. with food when combined with RIF-based anti-TB regimens in people with TB/HIV.

Transcatheter arterial chemoembolisation combined with lenvatinib and cabozantinib in the treatment of advanced hepatocellular carcinoma.

OBJECTIVE: The objective of this study was to evaluate the effect and prognosis of transcatheter arterial chemoembolisation (TACE) combined with lenvatinib and cabozantinib in the treatment of advanced unresectable hepatocellular carcinoma (uHCC) and identify the predictors of prognosis related to cellular inflammation and body mass index (BMI). To the best of our knowledge, this is the first study to report the efficacy and prognosis of TACE combined with lenvatinib and cabozantinib in patients with uHCC and propose the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as predictors of response and survival outcomes in this context. METHODS: The clinicopathologic data of 217 patients with advanced uHCC who underwent TACE combined with systemic therapy (lenvatinib mesylate + cabozantinib) in the Department of Hepatobiliary Surgery, Dazhou Central Hospital between October 2017 and February 2020 were collected retrospectively, and the relevant parameters were analysed and compared. RESULTS: Univariate and multivariate logistic regression analyses showed that BMI, NLR, PLR and prothrombin time were independent factors for the objective response rate (ORR) of transformed therapy for uHCC (OR = 0.812 vs 1,290.68 vs 1.067 vs 0.626, 95 % CI: 0.719-0.897 vs 108.081-11,541.137 vs 1.037-1.099 vs 0.414-0.946, respectively, p < 0.05). The results showed that BMI, NLR and PLR had certain predictive values for the ORR in patients with liver cancer undergoing translational therapy (p < 0.05); the combined predictive effect of the three was the best, and the area under the curve (AUC) of BMI + NLR + PLR for predicting the ORR in patients with liver cancer undergoing translational therapy was 0.951 (95 % CI: 0.921, 0.964). A total of 181 patients experienced adverse reactions at different grades, including 104 cases at grade 1, 50 cases at grade 2, 22 cases at grade 3 and 5 cases at grade 4. There was a significant difference in overall survival (OS) between low- and high-NLR groups, low- and high-PLR groups and low- and high-BMI groups (χ2 = 9.644, 8.313 and 10.314, respectively, p < 0.05). There was a significant difference in progression-free survival (PFS) between the low- and high-NLR groups, the low- and high-PLR groups and the low- and high-BMI groups (χ2 = 8.965, 9.783 and 6.343, respectively, p < 0.05). CONCLUSION: Transcatheter arterial chemoembolisation combined with lenvatinib and cabozantinib is safe and effective in the treatment of advanced uHCC, with controllable adverse reactions. High NLR and PLR and low BMI values before treatment were independent risk factors for the ORR. Body mass index, NLR and PLR predicted responses to triple switch therapy and survival outcomes in uHCC. Patients with pretreatment NLR ≥ 2.96 and PLR ≥ 184.41 had worse OS and PFS rates. Patients with pretreatment BMI ≥ 23 kg/m2 had improved OS and a reduced risk of death.

Stainless Steel Activation for Efficient Alkaline Oxygen Evolution in Advanced Electrolyzers.

Designing robust and cost-effective electrocatalysts for efficient alkaline oxygen evolution reaction (OER) is of great significance in the field of water electrolysis. In this study, an electrochemical strategy to activate stainless steel (SS) electrodes for efficient OER is introduced. By cycling the SS electrode within a potential window that encompasses the Fe(II)↔Fe(III) process, its OER activity can be enhanced to a great extent compared to using a potential window that excludes this redox reaction, decreasing the overpotential at current density of 100 mA cm-2 by 40 mV. Electrochemical characterization, Inductively Coupled Plasma - Optical Emission Spectroscopy, and operando Raman measurements demonstrate that the Fe leaching at the SS surface can be accelerated through a Fe → γ-Fe2O3 → Fe3O4 or FeO → Fe2+ (aq.) conversion process, leading to the sustained exposure of Cr and Ni species. While Cr leaching occurs during its oxidation process, Ni species display higher resistance to leaching and gradually accumulate on the SS surface in the form of OER-active Fe-incorporated NiOOH species. Furthermore, a potential-pulse strategy is also introduced to regenerate the OER-activity of 316-type SS for stable OER, both in the three-electrode configuration (without performance decay after 300 h at 350 mA cm-2) and in an alkaline water electrolyzer (≈30 mV cell voltage increase after accelerated stress test-AST). The AST-stabilized cell can still reach 1000 and 4000 mA cm-2 at cell voltages of 1.69 and 2.1 V, which makes it competitive with state-of-the-art electrolyzers based on ion-exchange membrane using Ir-based anodes.

Sevoflurane causes cognitive impairment by inducing iron deficiency and inhibiting the proliferation of neural precursor cells in infant mice.

AIMS: Numerous studies on animals have shown that exposure to general anesthetics in infant stage may cause neurocognitive impairment. However, the exact mechanism is not clear. The dysfunction of iron metabolism can cause neurodevelopmental disorders. Therefore, we investigated the effect of iron metabolism disorder induced by sevoflurane (Sev) on cognitive function and the proliferation of neural precursor cells (NPCs) and neural stem cells (NSCs) in infant mice. METHODS: C57BL/6 mice of postnatal day 14 and neural stem cells NE4C were treated with 2% Sev for 6 h. We used the Morris water maze (MWM) to test the cognitive function of infant mice. The proliferation of NPCs was measured using bromodeoxyuridine (BrdU) label and their markers Ki67 and Pax6 in infant brain tissues 12 h after anesthesia. Meanwhile, we used immunohistochemical stain, immunofluorescence assay, western blot, and flow cytometer to evaluate the myelinogenesis, iron levels, and cell proliferation in cortex and hippocampus or in NE4C cells. RESULTS: The results showed that Sev significantly caused cognitive deficiency in infant mice. Further, we found that Sev inhibited oligodendrocytes proliferation and myelinogenesis by decreasing MBP and CC-1 expression and iron levels. Meanwhile, Sev also induced the iron deficiency in neurons and NSCs by downregulating FtH and FtL expression and upregulating the TfR1 expression in the cortex and hippocampus, which dramatically suppressed the proliferation of NSCs and NPCs as indicated by decreasing the colocalization of Pax6+ and BrdU+ cells, and caused the decrease in the number of neurons. Interestingly, iron supplementation before anesthesia significantly improved iron deficiency in cortex and hippocampus and cognitive deficiency induced by Sev in infant mice. Iron therapy inhibited the decrease of MBP expression, iron levels in neurons and oligodendrocytes, and DNA synthesis of Pax6+ cells in hippocampus induced by Sev. Meanwhile, the number of neurons was partially recovered in hippocampus. CONCLUSION: The results from the present study demonstrated that Sev-induced iron deficiency might be a new mechanism of cognitive impairment caused by inhaled anesthetics in infant mice. Iron supplementation before anesthesia is an effective strategy to prevent cognitive impairment caused by Sev in infants.

Dynamic modulation of transthylakoid electric potential by chloroplast ATP synthases.

The light-induced transthylakoid membrane potential (ΔΨm) can function as a driving force to help catalyzing the formation of ATP molecules, proving a tight connection between ΔΨm and the ATP synthase. Naturally, a question can be raised on the effects of altered functioning of ATP synthases on regulating ΔΨm, which is attractive in the area of photosynthetic research. Lots of findings, when making efforts of solving this difficulty, can offer an in-depth understanding into the mechanism behind. However, the functional network on modulating ΔΨm is highly interdependent. It is difficult to comprehend the consequences of altered activity of ATP synthases on adjusting ΔΨm because parameters that have influences on ΔΨm would themselves be affected by ΔΨm. In this work, a computer model was applied to check the kinetic changes in polarization/depolarization across the thylakoid membrane (TM) regulated by the modified action of ATP synthases. The computing data revealed that under the extreme condition by numerically "switching off" the action of the ATP synthase, the complete inactivation of ATP synthase would markedly impede proton translocation at the cytb6f complex. Concurrently, the KEA3 (CLCe) porter, actively pumping protons into the stroma, further contributes to achieving a sustained low level of ΔΨm. Besides, the quantitative consequences on every particular component of ΔΨm adjusted by the modified functioning of ATP synthases were also explored. By employing the model, we bring evidence from the theoretical perspective that the ATP synthase is a key factor in forming a transmembrane proton loop thereby maintaining a propriate steady-state ΔΨm to meet variable environmental conditions.

Transmembrane serine protease 6, a novel target for inhibition of neuronal tumor growth.

Transmembrane serine protease 6 (Tmprss6) has been correlated with the occurrence and progression of tumors, but any specific molecular mechanism linking the enzyme to oncogenesis has remained elusive thus far. In the present study, we found that Tmprss6 markedly inhibited mouse neuroblastoma N2a (neuro-2a) cell proliferation and tumor growth in nude mice. Tmprss6 inhibits Smad1/5/8 phosphorylation by cleaving the bone morphogenetic protein (BMP) co-receptor, hemojuvelin (HJV). Ordinarily, phosphorylated Smad1/5/8 binds to Smad4 for nuclear translocation, which stimulates the expression of hepcidin, ultimately decreasing the export of iron through ferroportin 1 (FPN1). The decrease in cellular iron levels in neuro-2a cells with elevated Tmprss6 expression limited the availability of the metal forribo nucleotide reductase activity, thereby arresting the cell cycle prior to S phase. Interestingly, Smad4 promoted nuclear translocation of activating transcription factor 3 (ATF3) to activate the p38 mitogen-activated protein kinases signaling pathway by binding to ATF3, inducing apoptosis of neuro-2a cells and inhibiting tumor growth. Disruption of ATF3 expression significantly decreased apoptosis in Tmprss6 overexpressed neuro-2a cells. Our study describes a mechanism whereby Tmprss6 regulates the cell cycle and apoptosis. Thus, we propose Tmprss6 as a candidate target for inhibiting neuronal tumor growth.

Efficient and accurate registration with BWPH descriptor for low-quality point clouds.

Point cloud registration based on local descriptors plays a crucial role in 3D computer vision applications. However, existing methods often suffer from limitations such as low accuracy, a large memory footprint, and slow speed, particularly when dealing with 3D point clouds from low-cost sensors. To overcome these challenges, we propose an efficient local descriptor called Binary Weighted Projection-point Height (BWPH) for point cloud registration. The core idea behind the BWPH descriptor is the integration of Gaussian kernel density estimation with weighted height characteristics and binarization components to encode distinctive information for the local surface. Through extensive experiments and rigorous comparisons with state-of-the-art methods, we demonstrate that the BWPH descriptor achieves high matching accuracy, strong compactness, and feasibility across contexts. Moreover, the proposed BWPH-based point cloud registration successfully registers real datasets acquired by low-cost sensors with small errors, enabling accurate initial alignment positions.

Structural design of an improved SPIDER optical system based on a multimode interference coupler.

The Segmented Planar Imaging Detector for Electro-Optical Reconnaissance (SPIDER) is a small volume, lightweight, low energy consumption, and high-resolution system expected to replace traditional large aperture telescopes for long-distance detection. In this paper, an improved SPIDER system is proposed, which uses a multimode interference (MMI) coupler instead of an orthogonal detector, and successfully doubles the space spectrum coverage. We present a three-point configuring method to configure lenslets, calculate spatial spectrum values from the output currents obtained by MMI. By comparing the performance of the MMI-SPIDER and SPIDER systems through simulations, we demonstrate that the former has more complete spatial spectrum coverage, resulting in better image restoration quality.

Ru-Cu Nanoheterostructures for Efficient Hydrogen Evolution Reaction in Alkaline Water Electrolyzers.

Combining multiple species working in tandem for different hydrogen evolution reaction (HER) steps is an effective strategy to design HER electrocatalysts. Here, we engineered a hierarchical electrode for the HER composed of amorphous-TiO2/Cu nanorods (NRs) decorated with cost-effective Ru-Cu nanoheterostructures (Ru mass loading = 52 µg/cm2). Such an electrode exhibits a stable, over 250 h, low overpotential of 74 mV at -200 mA/cm2 for the HER in 1 M NaOH. The high activity of the electrode is attributed, by structural analysis, operando X-ray absorption spectroscopy, and first-principles simulations, to synergistic functionalities: (1) mechanically robust, vertically aligned Cu NRs with high electrical conductivity and porosity provide fast charge and gas transfer channels; (2) the Ru electronic structure, regulated by the size of Cu clusters at the surface, facilitates the water dissociation (Volmer step); (3) the Cu clusters grown atop Ru exhibit a close-to-zero Gibbs free energy of the hydrogen adsorption, promoting fast Heyrovsky/Tafel steps. An alkaline electrolyzer (AEL) coupling the proposed cathode and a stainless-steel anode can stably operate in both continuous (1 A/cm2 for over 200 h) and intermittent modes (accelerated stress tests). A techno-economic analysis predicts the minimal overall hydrogen production cost of US$2.12/kg in a 1 MW AEL plant of 30 year lifetime based on our AEL single cell, hitting the worldwide targets (US$2-2.5/kgH2).

High-performance alkaline water electrolyzers based on Ru-perturbed Cu nanoplatelets cathode.

Alkaline electrolyzers generally produce hydrogen at current densities below 0.5 A/cm2. Here, we design a cost-effective and robust cathode, consisting of electrodeposited Ru nanoparticles (mass loading ~ 53 µg/cm2) on vertically oriented Cu nanoplatelet arrays grown on metallic meshes. Such cathode is coupled with an anode based on stacked stainless steel meshes, which outperform NiFe hydroxide catalysts. Our electrolyzers exhibit current densities as high as 1 A/cm2 at 1.69 V and 3.6 A/cm2 at 2 V, reaching the performances of proton-exchange membrane electrolyzers. Also, our electrolyzers stably operate in continuous (1 A/cm2 for over 300 h) and intermittent modes. A total production cost of US$2.09/kgH2 is foreseen for a 1 MW plant (30-year lifetime) based on the proposed electrode technology, meeting the worldwide targets (US$2-2.5/kgH2). Hence, the use of a small amount of Ru in cathodes (~0.04 gRu per kW) is a promising strategy to solve the dichotomy between the capital and operational expenditures of conventional alkaline electrolyzers for high-throughput operation, while facing the scarcity issues of Pt-group metals.

AMPK activation coupling SENP1-Sirt3 axis protects against acute kidney injury.

Acute kidney injury (AKI) is a critical clinical condition that causes kidney fibrosis, and it currently lacks specific treatment options. In this research, we investigate the role of the SENP1-Sirt3 signaling pathway and its correlation with mitochondrial dysfunction in proximal tubular epithelial cells (PTECs) using folic acid (FA) and ischemia-reperfusion-induced (IRI) AKI models. Our findings reveal that Sirt3 SUMOylation site mutation (Sirt3 KR) or pharmacological stimulation (metformin) protected mice against AKI and subsequent kidney inflammation and fibrosis by decreasing the acetylation level of mitochondrial SOD2, reducing mitochondrial reactive oxygen species (mtROS), and subsequently restoring mitochondrial ATP level, reversing mitochondrial morphology and alleviating cell apoptosis. In addition, AKI in mice was similarly alleviated by reducing mtROS levels using N-acetyl-L-cysteine (NAC) or MitoQ. Metabolomics analysis further demonstrated an increase in antioxidants and metabolic shifts in Sirt3 KR mice during AKI, compared with Sirt3 wild-type (WT) mice. Activation of the AMPK pathway using metformin promoted the SENP1-Sirt3 axis and protected PTECs from apoptosis. Hence, the augmented deSUMOylation of Sirt3 in mitochondria, activated through the metabolism-related AMPK pathway, protects against AKI and subsequently mitigated renal inflammation and fibrosis through Sirt3-SOD2-mtROS, which represents a potential therapeutic target for AKI.

MInet: A Novel Network Model for Point Cloud Processing by Integrating Multi-Modal Information.

Three-dimensional LiDAR systems that capture point cloud data enable the simultaneous acquisition of spatial geometry and multi-wavelength intensity information, thereby paving the way for three-dimensional point cloud recognition and processing. However, due to the irregular distribution, low resolution of point clouds, and limited spatial recognition accuracy in complex environments, inherent errors occur in classifying and segmenting the acquired target information. Conversely, two-dimensional visible light images provide real-color information, enabling the distinction of object contours and fine details, thus yielding clear, high-resolution images when desired. The integration of two-dimensional information with point clouds offers complementary advantages. In this paper, we present the incorporation of two-dimensional information to form a multi-modal representation. From this, we extract local features to establish three-dimensional geometric relationships and two-dimensional color relationships. We introduce a novel network model, termed MInet (Multi-Information net), which effectively captures features relating to both two-dimensional color and three-dimensional pose information. This enhanced network model improves feature saliency, thereby facilitating superior segmentation and recognition tasks. We evaluate our MInet architecture using the ShapeNet and ThreeDMatch datasets for point cloud segmentation, and the Stanford dataset for object recognition. The robust results, coupled with quantitative and qualitative experiments, demonstrate the superior performance of our proposed method in point cloud segmentation and object recognition tasks.

Sevoflurane inhibited reproductive function in male mice by reducing oxidative phosphorylation through inducing iron deficiency.

Sevoflurane (Sev) is one of the commonly used inhalation anesthetic chemicals in clinics. It has great impact on spermatogenesis and fertilization in male animals. The underlying mechanism remains largely unexplored. Based on our previous research, we hypothesized that Sev induced iron metabolism disturbance in the testis and epididymis and inhibited the spermatogenesis. In this study, two-month-old C57BL/6 male mice were treated with 3% Sev for 6 h, and their fertility (including sperm concentration, sperm mobility, and the number of offspring) was evaluated. Mice testis, epididymis, and sperm were harvested and subjected to Western blot analysis and immunofluorescence analysis. Iron levels were reflected by the gene expression of iron metabolism-related proteins (including ferritin, TfR1, and FpN1) and ICP-MS and Perl's iron staining. Electron transport and oxidative phosphorylation levels were measured by Oxygraph-2k and ATP contents. The activity of ribonucleotide reductase was evaluated by assay kit. DNA synthesis status in testis and/or epididymis was marked with BrdU. Cell proliferation was evaluated by double immunofluorescence staining of specific protein marker expression. Our results revealed that the mice exposed to Sev showed damaged testicular and epididymis structure and significantly reduced the sperm concentration, sperm motility, and fertility. Sev decreases the iron levels through down-regulating the expression of H-ferritin, L-ferritin, and FpN1, and up-regulating the expression of TfR1 in the testis and epididymis. Iron levels also significantly reduced in germ cells which decrease the number of germ cells, including sperm, Sertoli cells, and primary spermatocyte. Iron deficiency not only decreases electron transport, oxidative phosphorylation level, and ATP production but also suppresses the activity of ribonucleotide reductase and the expression of Ki67, DDX4, GATA1, and SCP3, indicating that Sev affects the spermatogenesis and development. Meanwhile, Sev impaired the blood-testis barrier by decreasing the ZO1 expression in the testis and epididymis. The damage effect induced by Sev can be significantly ameliorated by iron supplementation. In conclusion, our study illustrates a new mechanism by which Sev inhibits spermatogenesis and fertility through an oxidative phosphorylation pathway due to iron deficiency of epididymis and testis or sperm. Furthermore, the damaging effects could be ameliorated by iron supplementation.