Ferulic acid restores mitochondrial dynamics and autophagy via AMPK signaling pathway in a palmitate-induced hepatocyte model of metabolic syndrome.

Mitochondrial dysfunction, characterized by elevated oxidative stress, impaired energy balance, and dysregulated mitochondrial dynamics, is a hallmark of metabolic syndrome (MetS) and its comorbidities. Ferulic acid (FA), a principal phenolic compound found in whole grains, has demonstrated potential in ameliorating oxidative stress and preserving energy homeostasis. However, the influence of FA on mitochondrial health within the context of MetS remains unexplored. Moreover, the impact of FA on autophagy, which is essential for maintaining energy homeostasis and mitochondrial integrity, is not fully understood. Here, we aimed to study the mechanisms of action of FA in regulating mitochondrial health and autophagy using palmitate-treated HepG2 hepatocytes as a MetS cell model. We found that FA improved mitochondrial health by restoring redox balance and optimizing mitochondrial dynamics, including biogenesis and the fusion/fission ratio. Additionally, FA was shown to recover autophagy and activate AMPK-related cell signaling. Our results provide new insights into the therapeutic potential of FA as a mitochondria-targeting agent for the prevention and treatment of MetS.

Novel hydroxyl-terminated hyperbranched polymer as a synergistic modifier with tannin for preparation of casein-based films with superior performance.

A hyperbranched poly (titanium oxide) (HBPTi) with hydroxyl terminal groups was synthesized via polycondensation reaction as a synergistic modifier with tannin to promote performance of casein-based composite film. The synergistic effects of HBPTis, acquiring different hyperbranched structures, with tannin on the microstructure, mechanical characteristics, barrier against water vapor, and thermal stability of casein-based film were investigated in this work. The tensile strength of the composite films increased from 7.6 MPa to 22.1 MPa, which accounts for 190.79 % increase after the addition of HBPTi compared to casein-tannin films modified with glycerol. The casein-tannin films with the help of HBPTi presented excellent water vapor permeation, thermal stability, and showed nearly 100 % UV absorption in the range 200-400 nm. Additionally, the microstructure of HBPTi modified casein-tannin films tend to be more compact due to the promoted interaction of casein-tannin composite aided by covalent bonding and/or other types of bonding between casein, tannin and HBPTi. Therefore, associative modification using such hyperbranched polymers and tannins provides extendable application value for casein-based films especially as food packaging materials and for other fields as well.

Assessment of body compositions in the prediction of metabolic syndrome in adults.

Background: The musculoskeletal system participates in the pathology of metabolic disorders. Several studies have focused on body composition changes; however, the adipose tissue between muscle bundles with different metabolic statuses has rarely been studied. This study sought to explore the association between body compositions and metabolic disorders in Asians, and identify whether these body compositions can be used to detect metabolic disorders with different waist circumferences (WCs) by computed tomography (CT). Methods: A total of 116 subjects were included in the study and categorized into the following four groups according to WC and metabolic syndrome (MS): (I) the healthy control group; (II) the normal WC with metabolic disorder group; (III) the normal WC with MS group; and (IV) the larger WC with MS group. The International Diabetes Federation (IDF) criteria based on WC, laboratory tests, body mass index (BMI), and medical history was used to diagnose MS. Body composition parameters, such as muscle attenuation, the cross-sectional area of subcutaneous adipose tissue (SAT), muscle, extramyocellular lipid (EMCL), visceral adipose tissue (VAT), and the ratios between different compositions [e.g., the SMR (SAT/muscle), EMR (EMCL/muscle), and VMR (VAT/muscle)] were calculated for the thigh and abdomen. The areas under the curve (AUCs) of the receiver operating characteristic (ROC) curves adjusted for multiple comparisons were used to discriminate among metabolic disorders. Results: The groups with metabolic disorders had more SAT (P=0.001) and EMCL (P=0.040) in the thigh, and more VAT (P=0.001) and a higher SMR (P<0.001) in the abdomen. EMCL and muscle attenuation in the thigh (AUCs =0.790 and 0.791), and the VMR and SMR in the abdomen were better able to diagnose metabolic disorders (AUCs =0.752 and 0.746) than other body composition parameters. While SAT and EMCL in the thigh (AUCs =0.768 and 0.760), and VAT and the VMR in the abdomen (AUCs =0.788 and 0.775) were better able to diagnose MS than other parameters. Conclusions: Body composition parameters for the thigh and abdomen could assist in detecting patients with an increased risk of MS.

Conjoint transcriptomics and metabolomics analyses provide insights into the toxicity of acetamiprid to Lethenteron reissneri larvae.

The neonicotinoid pesticide acetamiprid has been widely used in agricultural pest control and was frequently detected in the water environment. There have been some studies of the toxic effects of acetamiprid on fish, but studies on aquatic lower vertebrates are still very limited. As a primitive jawless vertebrate, Lethenteron reissneri has a special position in evolution and is now listed as a national second level protected animal in China. The present study aimed to investigate the toxic effect of acetamiprid on the liver of L. reissneri larvae. A conjoint analysis of the transcriptomics and metabolomics was performed to determine the responses of L. reissneri larvae liver to acetamiprid at different concentrations (L for low concentration 25 mg/L and H for high concentration 100 mg/L). Even low concentrations of acetamiprid can cause significant liver damage to L. reissneri larvae in a short period. In omics analyses, 2141 differentially expressed genes (DEGs) and 183 differentially abundant metabolites (DAMs) were identified in the H/Control group, and 229 DEGs and 144 DAMs were identified in the L/C group. Correlation analyses revealed acetamiprid affected the metabolic pathways of L. reissneri larvae liver such as the glycerophospholipid metabolism and arachidonic acid metabolism. This study not only enriches the basis for understanding the toxic effect of acetamiprid exposure to L. reissneri larvae liver and provides more information on the breeding and conservation of L. reissneri, but also further causes attention on toxicity risk from acetamiprid to aquatic lower vertebrate species.

Assessment of Water Intake among Chinese Toddlers: The Report of a Survey.

Toddlerhood (aged 13~36 months) is a period of dietary transition, with water intake being significantly influenced by parental feeding patterns, cultural traditions, and the availability of beverages and food. Nevertheless, given the lack of applicable data, it is challenging to guide and evaluate the water intake of toddlers in China. In this study, our objectives were to assess the daily total water intake (TWI), evaluate the consumption patterns of various beverages and food sources contributing to the TWI, determine the conformity of participants to the adequate intake (AI) recommendation of water released by the Chinese Nutrition Society, and analyze the various contributors to the daily total energy intake (TEI). The data for the assessment of water and dietary intake were obtained from the cross-sectional dietary intake survey of infants and young children (DSIYC, 2018-2019). A total of 1360 eligible toddlers were recruited in the analysis. The differences in related variables between two age groups were compared by Mann-Whitney U test and Chi-Square test. The potential correlation between water and energy intake was examined utilizing age-adjusted partial correlation. Toddlers consumed a median daily TWI of 1079 mL, with 670 mL (62.3%, r = 0.752) derived from beverages and 393 mL (37.7%, r = 0.716) from foods. Plain water was the primary beverage source, contributing 300 mL (52.2%, r = 0.823), followed by milk and milk derivatives (MMDs) at 291 mL (45.6%, r = 0.595). Notably, only 28.4% of toddlers managed to reach the recommended AI value. Among these, toddlers obtain more water from beverages than from foods. The median daily TEI of toddlers was 762 kcal, including 272 kcal from beverages (36.4%, r = 0.534) and 492 kcal from foods (63.6%, r = 0.894). Among these, the median daily energy intake from MMDs was 260 kcal, making up 94.6% of the energy intake from beverages (r = 0.959). As the pioneer survey on TWI of toddlers in China based on nationally representative data, attention to the quality and quantity of water intake and actions to better guide parents by both individuals and authorities are eagerly anticipated. Additionally, the revision of the reference value of TWI for Chinese toddlers is urgently required.

Discovery of Biphenyl Derivatives to Target Hsp70-Bim Protein-Protein Interaction in Chronic Myeloid Leukemia by Scaffold Hopping Strategy.

Hsp70-Bim protein-protein interaction (PPI) is the most recently identified specific target in chronic myeloid leukemia (CML) therapy. Herein, we developed a new class of Hsp70-Bim PPI inhibitors via scaffold hopping of S1g-10, the most potent Hsp70-Bim PPI inhibitor thus far. Through structure-activity relationship (SAR) study, we obtained a biphenyl scaffold compound JL-15 with a 5.6-fold improvement in Hsp70-Bim PPI suppression (Kd = 123 vs 688 nM) and a 4-fold improvement in water solubility (29.42 vs 7.19 µg/mL) compared to S1g-10. It maintains comparable apoptosis induction capability with S1g-10 against both TKI-sensitive and TKI-resistant CML cell lines in an Hsp70-Bim-dependent manner. Additionally, through SAR, 1H-15N TRSOY-NMR, and molecular docking, we revealed that Lys319 is a "hot spot" in the Hsp70-Bim PPI interface. Collectively, these results provide a novel chemical scaffold and structural insights for the rational design of Hsp70-Bim PPI inhibitors.

Study on the interaction between agglutinin and chondroitin sulfate and dermatan sulfate using multiple methods.

In this work, the interaction of chondroitin sulfate (CS) and dermatan sulfate (DS) with plant lectins was studied by affinity capillary electrophoresis (ACE), surface plasmon resonance (SPR) technology, molecular docking simulation, and circular dichroism spectroscopy. The ACE method was used for the first time to study the interaction of Ricinus Communis Agglutinin I (RCA I), Wisteria Floribunda Lectin (WFA), and Soybean Agglutinin (SBA) with CS and DS, and the results were in good agreement with those of the SPR method. The results of experiments indicate that RCA I has a strong binding affinity with CS, and the sulfated position does not affect the relationship, but the degree of sulfation can affect the combination of RCA I with CS to some extent. However, the binding affinity with DS is very weak. This study lays the foundation for developing more specialized analysis methods for CS and DS based on RCA I.

Dual Inhibition of Factor XIIa and Factor XIa Produces a Synergistic Anticoagulant Effect.

ABSTRACT: Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. In this study, analyses of activated partial thromboplastin time in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identifying synergistic anticoagulation effects. Both an FeCl 3 -induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.

Rational redesign of the loop dynamics of carbonyl reductase LfSDR1 to improve the stereoselectivity for asymmetric synthesis of bulky chiral alcohols.

Engineering biocatalysts with enhanced stereoselectivity is highly desirable, and active-site loop dynamics play an important role in its regulation. However, knowledge of their precise roles in catalysis and evolution is limited. Here, we used the strategy of Rosetta enzyme design combined molecular dynamic simulations (MDs) to reprogram the landscapes of the key active-site loop dynamics of the carbonyl reductase LfSDR1 to improve stereoselectivity. The key flexible loop in the active site showed the potential to regulate the catalytic properties. A library of virtual variants was produced using the Rosetta design and assessed dynamic effect of the loop with the aid of MDs. A potential candidate was obtained with significant stereoselectivity (ee > 99 %) compared to the wild-type (ee = 42 %) without loss of catalytic activity or thermostability. The molecular basis of the catalytic property enhancement was flanked by MDs, which revealed the role of the G92L mutation in regulating loop dynamics to stabilize the environment of the active site. Finally, a series of the challenge bulky substrate derivatives were assessed using the G92L variant, and all showed improved stereoselectivity ee > 99 %. This study provides novel insights for improving stereoselectivity through rational engineering of the loop dynamics of biocatalysts.

Effect of Simulated Dental Pulpal Pressure Using Fetal Bovine Serum for the Bonding Performance of Contemporary Adhesive to Dentin.

This study evaluated the effect of simulated pulpal pressure (SPP) conditions and storage time on contemporary adhesive systems' microtensile bond strength (µTBS) to dentin. Extracted human molars were prepared and randomly divided into four groups according to the adhesives: Clearfil Megabond 2 (CSE), Beautibond Xtreme Universal (BXU), G2-Bond (G2B), and Scotchbond Universal Plus (SBP). Each adhesive group was further divided following the SPP conditions: control with no simulation (SPP-CTR), SPP with distilled water (SPP-DTW), and SPP with fetal bovine serum (SPP-FBS). Resin composite build-ups were prepared, and teeth were stored in water (37 °C) for 24 h (24 h) and 3 months (3 m). Then, teeth were sectioned to obtain resin-dentin bonded beams and tested to determine the µTBS. Data were analyzed using three-way ANOVA, Tukey post hoc tests (=0.05), and Weibull failure analysis. Failure mode was observed using scanning electron microscopy. The µTBS response was affected by adhesive systems, simulated pulpal pressure conditions, and storage time. SPP-CTR groups presented a higher overall bond strength than SPP-DTW and SPP-FBS, which were not significantly different from each other. Only for SBP, the SPP-FBS group showed higher µTBS than the SPP-DTW group. The Weibull analysis showed that the bonding reliability and durability under SPP-DTW and SPP-FBS were inferior to SPP-CTR, and the 24 h bonding quality of adhesives to dentin was superior to that of 3 m. SPP drastically reduced the µTBS of all adhesives to dentin regardless of solution (distilled water or fetal bovine serum). Storage after 3 m also decreased µTBS despite the SPP condition.

A53T α-synuclein mutation increases susceptibility to postoperative delayed neurocognitive recovery via hippocampal Ang-(1-7)/MasR axis.

Delayed neurocognitive recovery (dNCR) is a common complication in geriatric surgical patients. The impact of anesthesia and surgery on patients with neurodegenerative diseases, such as Parkinson's disease (PD) or prion disease, has not yet been reported. In this study, we aimed to determine the association between a pre-existing A53T genetic background, which involves a PD-related point mutation, and the development of postoperative dNCR. We observed that partial hepatectomy induced hippocampus-dependent cognitive deficits in 5-month-old A53T transgenic mice, a model of early-stage PD without cognitive deficits, unlike in age-matched wild-type (WT) mice. We respectively examined molecular changes at 6 h, 1 day, and 2 days after partial hepatectomy and observed that cognitive changes were accompanied by weakened angiotensin-(1-7)/Mas receptor [Ang-(1-7)/MasR] axis, increased alpha-synuclein (α-syn) expression and phosphorylation, decreased methylated protein phosphatase-2A (Me-PP2A), and prompted microglia M1 polarization and neuronal apoptosis in the hippocampus at 1 day after surgery. Nevertheless, no changes in blood-brain barrier (BBB) integrity or plasma α-syn levels in either A53T or WT mice. Furthermore, intranasal administration of selective MasR agonist AVE 0991, reversed the mentioned cognitive deficits in A53T mice, enhanced MasR expression, reduced α-syn accumulation and phosphorylation, and attenuated microglia activation and apoptotic response. Our findings suggest that individuals with the A53T genetic background may be more susceptible to developing postoperative dNCR. This susceptibility could be linked to central α-syn accumulation mediated by the weakened Ang-(1-7)/MasR/methyl-PP2A signaling pathway in the hippocampus following surgery, independent of plasma α-syn level and BBB.

Pin1-Catalyzed Conformation Changes Regulate Protein Ubiquitination and Degradation.

The unique prolyl isomerase Pin1 binds to and catalyzes cis-trans conformational changes of specific Ser/Thr-Pro motifs after phosphorylation, thereby playing a pivotal role in regulating the structure and function of its protein substrates. In particular, Pin1 activity regulates the affinity of a substrate for E3 ubiquitin ligases, thereby modulating the turnover of a subset of proteins and coordinating their activities after phosphorylation in both physiological and disease states. In this review, we highlight recent advancements in Pin1-regulated ubiquitination in the context of cancer and neurodegenerative disease. Specifically, Pin1 promotes cancer progression by increasing the stabilities of numerous oncoproteins and decreasing the stabilities of many tumor suppressors. Meanwhile, Pin1 plays a critical role in different neurodegenerative disorders via the regulation of protein turnover. Finally, we propose a novel therapeutic approach wherein the ubiquitin-proteasome system can be leveraged for therapy by targeting pathogenic intracellular targets for TRIM21-dependent degradation using stereospecific antibodies.

Differential fluorescence features and recovery speeds of different scorpion exoskeleton parts during the molting process.

Scorpion fluorescence under ultraviolet light is a well-known phenomenon, but its features under excitation in the UVA, UVB and UVC bands have not been characterized. Systematic fluorescence characterization revealed indistinguishable fluorescence spectra with a peak wavelength of 475 nm for whole exuviae from second-, third- and fifth-instar scorpions under different ultraviolet light ranges. In-depth investigations of the chelae, mesosoma, metasoma and telson of adult scorpions further indicated heterogeneity in the typical fluorescence spectrum within the visible light range and in the newly reported fluorescence spectrum with a peak wavelength of 320 nm within the ultraviolet light range, which both showed excitation wavelength-independent features. Dynamic fluorescence changes during the molting process of third-instar scorpions revealed the fluorescence heterogeneity-dependent recovery speed of scorpion exoskeletons. The typical fluorescence spectra of the molted chelae and telson rapidly recovered approximately 6 h after ecdysis under UVA light and approximately 36 h after ecdysis under UVB and UVC light. However, it took approximately 12 h and 24 h to obtain the typical fluorescence spectra of the molted metasoma and mesosoma, respectively, under UVA irradiation and 72 h to obtain the typical fluorescence spectra under UVB and UVC irradiation. The fluorescence heterogeneity-dependent fluorescence recovery of the scorpion exoskeleton was further confirmed by tissue section analysis of different segments from molting third-instar scorpions. These findings reveal novel scorpion fluorescence features and provide potential clues on the biological function of scorpion fluorescence.

A Compact Millimeter-Wave Multilayer Patch Antenna Array Based on a Mixed CPW-Slot-Couple Feeding Network.

A compact Ka-band antenna array has been proposed to realize broadband and high gain for millimeter-wave applications. The antenna array is divided into a multilayer composed of a driven slot patch layer and a parasitic patch array layer, which is excited by a mixed CPW-Slot-Couple feeding network layer. According to characteristic mode analysis, a pair of narrow coupling slots are introduced in the driven patch to move the resonant frequency of characteristic mode 3 to the resonant frequency of characteristic mode 2 for enhanced bandwidth. In this article, a 1to4 CPW-Slot-Couple feeding network for a 2 × 2 driven slot patch array is implemented, and then each driven slot patch excites a 2 × 2 parasitic patch array. Finally, a proposed 4 × 4 × 3 (row × column × layer) Ka-band antenna array is fabricated to verify the design concepts. The measured results show that the frequency bandwidth of the antenna array is 25 GHz to 32 GHz, and the relative bandwidth is 24.5%. The peak gain is 20.1 dBi. Due to its attractive properties of miniaturization, broadband, and high gain, the proposed antenna array could be applied to millimeter-wave wireless communication systems.

Synthesis and Structural Revision of the Cyclic Hexapeptide Dimers Antatollamides A and B.

The synthesis and structural revision of the dimerized cyclic hexapeptides antatollamides A (1) and B (2) are reported. These are unique peptides with two proline residues and bicyclic peptides combined by a disulfide bond. Cyclization and disulfide bond formation of the linear peptide led to antatollamide A (1). However, the 1H and 13C NMR spectra of synthetic antatollamide A (1) were not consistent with those of isolated antatollamide A (1). Meanwhile, the NMR spectra of the monomeric cyclic hexapeptide cyclo(Pro-Pro-Phe-dCys-Ile-Val) (3) and the isolated antatollamide A (1) were identified completely. In addition, we found that isolated antatollamide B (2) is cyclo(Pro-Pro-dPhe-dCys-Ile-Val) (4).

Trends in the Prevalence of Common Retinal and Optic Nerve Diseases in China: An Artificial Intelligence Based National Screening.

Purpose: Retinal and optic nerve diseases have become the primary cause of irreversible vision loss and blindness. However, there is still a lack of thorough evaluation regarding their prevalence in China. Methods: This artificial intelligence-based national screening study applied a previously developed deep learning algorithm, named the Retinal Artificial Intelligence Diagnosis System (RAIDS). De-identified personal medical records from January 2019 to December 2021 were extracted from 65 examination centers in 19 provinces of China. Crude prevalence and age-sex-adjusted prevalence were calculated by mapping to the standard population in the seventh national census. Results: In 2021, adjusted referral possible glaucoma (63.29, 95% confidence interval [CI] = 57.12-68.90 cases per 1000), epiretinal macular membrane (21.84, 95% CI = 15.64-29.22), age-related macular degeneration (13.93, 95% CI = 11.09-17.17), and diabetic retinopathy (11.33, 95% CI = 8.89-13.77) ranked the highest among 10 diseases. Female participants had significantly higher adjusted prevalence of pathologic myopia, yet a lower adjusted prevalence of diabetic retinopathy, referral possible glaucoma, and hypertensive retinopathy than male participants. From 2019 to 2021, the adjusted prevalence of retinal vein occlusion (0.99, 95% CI = 0.73-1.26 to 1.88, 95% CI = 1.42-2.44), macular hole (0.59, 95% CI = 0.41-0.82 to 1.12, 95% CI = 0.76-1.51), and hypertensive retinopathy (0.53, 95% CI = 0.40-0.67 to 0.77, 95% CI = 0.60-0.95) significantly increased. The prevalence of diabetic retinopathy in participants under 50 years old significant increased. Conclusions: Retinal and optic nerve diseases are an important public health concern in China. Further well-conceived epidemiological studies are required to validate the observed increased prevalence of diabetic retinopathy, hypertensive retinopathy, retinal vein occlusion, and macular hole nationwide. Translational Relevance: This artificial intelligence system can be a potential tool to monitor the prevalence of major retinal and optic nerve diseases over a wide geographic area.

Applications of Data Characteristic AI-Assisted Raman Spectroscopy in Pathological Classification.

Raman spectroscopy has been widely used for label-free biomolecular analysis of cells and tissues for pathological diagnosis in vitro and in vivo. AI technology facilitates disease diagnosis based on Raman spectroscopy, including machine learning (PCA and SVM), manifold learning (UMAP), and deep learning (ResNet and AlexNet). However, it is not clear how to optimize the appropriate AI classification model for different types of Raman spectral data. Here, we selected five representative Raman spectral data sets, including endometrial carcinoma, hepatoma extracellular vesicles, bacteria, melanoma cell, diabetic skin, with different characteristics regarding sample size, spectral data size, Raman shift range, tissue sites, Kullback-Leibler (KL) divergence, and significant Raman shifts (i.e., wavenumbers with significant differences between groups), to explore the performance of different AI models (e.g., PCA-SVM, SVM, UMAP-SVM, ResNet or AlexNet). For data set of large spectral data size, Resnet performed better than PCA-SVM and UMAP. By building data characteristic-assisted AI classification model, we optimized the network parameters (e.g., principal components, activation function, and loss function) of AI model based on data size and KL divergence etc. The accuracy improved from 85.1 to 94.6% for endometrial carcinoma grading, from 77.1 to 90.7% for hepatoma extracellular vesicles detection, from 89.3 to 99.7% for melanoma cell detection, from 88.1 to 97.9% for bacterial identification, from 53.7 to 85.5% for diabetic skin screening, and mean time expense of 5 s.

High expression of SULF1 is associated with adverse prognosis in breast cancer brain metastasis.

BACKGROUND: Breast cancer is the most common cancer in women, and in advanced stages, it often metastasizes to the brain. However, research on the biological mechanisms of breast cancer brain metastasis and potential therapeutic targets are limited. METHODS: Differential gene expression analysis (DEGs) for the datasets GSE43837 and GSE125989 from the GEO database was performed using online analysis tools such as GEO2R and Sangerbox. Further investigation related to SULF1 was conducted using online databases such as Kaplan-Meier Plotter and cBioPortal. Thus, expression levels, variations, associations with HER2, biological processes, and pathways involving SULF1 could be analyzed using UALCAN, cBioPortal, GEPIA2, and LinkedOmics databases. Moreover, the sensitivity of SULF1 to existing drugs was explored using drug databases such as RNAactDrug and CADSP. RESULTS: High expression of SULF1 was associated with poor prognosis in advanced breast cancer brain metastasis and was positively correlated with the expression of HER2. In the metastatic breast cancer population, SULF1 ranked top among the 16 DEGs with the highest mutation rate, reaching 11%, primarily due to amplification. KEGG and GSEA analyses revealed that the genes co-expressed with SULF1 were positively enriched in the 'ECM-receptor interaction' gene set and negatively enriched in the 'Ribosome' gene set. Currently, docetaxel and vinorelbine can act as treatment options if the expression of SULF1 is high. CONCLUSIONS: This study, through bioinformatics analysis, unveiled SULF1 as a potential target for treating breast cancer brain metastasis (BM).

2D Ferromagnetic M3GeTe2 (M = Ni/Fe) for Boosting Intermediates Adsorption toward Faster Water Oxidation.

In this work, 2D ferromagnetic M3GeTe2 (MGT, M = Ni/Fe) nanosheets with rich atomic Te vacancies (2D-MGTv) are demonstrated as efficient OER electrocatalyst via a general mechanical exfoliation strategy. X-ray absorption spectra (XAS) and scanning transmission electron microscope (STEM) results validate the dominant presence of metal-O moieties and rich Te vacancies, respectively. The formed Te vacancies are active for the adsorption of OH* and O* species while the metal-O moieties promote the O* and OOH* adsorption, contributing synergistically to the faster oxygen evolution kinetics. Consequently, 2D-Ni3GeTe2v exhibits superior OER activity with only 370 mV overpotential to reach the current density of 100 mA cm-2 and turnover frequency (TOF) value of 101.6 s-1 at the overpotential of 200 mV in alkaline media. Furthermore, a 2D-Ni3GeTe2v-based anion-exchange membrane (AEM) water electrolysis cell (1 cm2) delivers a current density of 1.02 and 1.32 A cm-2 at the voltage of 3 V feeding with 0.1 and 1 m KOH solution, respectively. The demonstrated metal-O coordination with abundant atomic vacancies for ferromagnetic M3GeTe2 and the easily extended preparation strategy would enlighten the rational design and fabrication of other ferromagnetic materials for wider electrocatalytic applications.

Novel insights into macrophage immunometabolism in nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH), an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis, and has been becoming the leading cause of liver-related morbidity and mortality worldwide. Unfortunately, the pathogenesis of NASH has not been completely clarified, and there are no approved therapeutic drugs. Recent accumulated evidences have revealed the involvement of macrophage in the regulation of host liver steatosis, inflammation and fibrosis, and different phenotypes of macrophages have different metabolic characteristics. Therefore, targeted regulation of macrophage immunometabolism may contribute to the treatment and prognosis of NASH. In this review, we summarized the current evidences of the role of macrophage immunometabolism in NASH, especially focused on the related function conversion, as well as the strategies to promote its polarization balance in the liver, and hold promise for macrophage immunometabolism-targeted therapies in the treatment of NASH.