TSHR signaling promotes hippocampal dependent memory formation through modulating Wnt5a/ß-catenin mediated neurogenesis.

Subclinical hyperthyroidism is defined biochemically as a low or undetectable thyroid-stimulating hormone (TSH) with normal thyroid hormone levels. Low TSHR signaling is considered to associate with cognitive impairment. However, the underlying molecular mechanism by which TSHR signaling modulates memory is poorly understood. In this study, we found that Tshr-deficient in the hippocampal neurons impairs the learning and memory abilities of mice, accompanying by a decline in the number of newborn neurons. Notably, Tshr ablation in the hippocampus decreases the expression of Wnt5a, thereby inactivating the ß-catenin signaling pathway to reduce the neurogenesis. Conversely, activating of the Wnt/ß-catenin pathway by the agonist SKL2001 results in an increase in hippocampal neurogenesis, resulting in the amelioration in the deficits of memory caused by Tshr deletion. Understanding how TSHR signaling in the hippocampus regulates memory provides insights into subclinical hyperthyroidism affecting cognitive function and will suggest ways to rationally design interventions for neurocognitive disorders.

ALDOA coordinates PDE3A through the ß-catenin/ID3 axis to stimulate cancer metastasis and M2 polarization in lung cancer with EGFR mutations.

Lung cancer has a high incidence rate and requires more effective treatment strategies and drug options for clinical patients. EGFR is a common genetic alteration event in lung cancer that affects patient survival and drug strategy. Our study discovered aberrant aldolase A (ALDOA) expression and dysfunction in lung cancer patients with EGFR mutations. In addition to investigating relevant metabolic processes like glucose uptake, lactate production, and ATPase activity, we examined multi-omics profiles (transcriptomics, proteomics, and pull-down assays). It was observed that phosphodiesterase 3A (PDE3A) enzyme and ALDOA exhibit correlation, and furthermore, they impact M2 macrophage polarization through ß-catenin and downstream ID3. In addition to demonstrating the aforementioned mechanism of action, our experiments discovered that the PDE3 inhibitor trequinsin has a substantial impact on lung cancer cell lines with EGFR mutants. The trequinsin medication was found to decrease the M2 macrophage polarization status and several cancer phenotypes, in addition to transduction. These findings have potential prognostic and therapeutic applications for clinical patients with EGFR mutation and lung cancer.

Deciphering the evolution and biogeography of ant-ferns Lecanopteris s.s.

Southeast Asia is a biodiversity hotspot characterized by a complex paleogeography, and its Polypodiopsida flora is particularly diverse. While hybridization is recognized as common in ferns, further research is needed to investigate the relationship between hybridization events and fern diversity. Lecanopteris s.s., an ant-associated fern, has been subject to debate regarding species delimitations primarily due to limited DNA markers and species sampling. Our study integrates 22 newly generated plastomes, 22 transcriptomes, and flow cytometry of all native species along with two cultivated hybrids. Our objective is to elucidate the reticulate evolutionary history within Lecanopteris s.s. through the integration of phylobiogeographic reconstruction, gene flow inference, and genome size estimation. Key findings of our study include: (1) An enlarged plastome size (178-187 Kb) in Lecanopteris s.s., attributed to extreme expansion of the Inverted Repeat (IR) regions; (2) The traditional 'pumila' and 'crustacea' groups are paraphyletic; (3) Significant cytonuclear discordance attributed to gene flow; (4) Natural hybridization and introgression in the 'pumila' and 'darnaedii' groups; (5) L. luzonensis is the maternal parent of L. 'Yellow Tip', with L. pumila suggested as a possible paternal parent; (6) L. 'Tatsuta' is a hybrid between L. luzonensis and L. crustacea; (7) Lecanopteris s.s. first diverged during the Neogene and then during the middle Miocene climatic optimum in the Indochina and Sundaic regions. In conclusion, the biogeographic history and speciation of Lecanopteris have been profoundly shaped by past climate changes and geodynamics of Southeast Asia. Dispersals, hybridization and introgression between species act as pivotal factors in the evolutionary trajectory of Lecanopteris s.s.. This research provides a robust framework for further exploration and understanding of the complex dynamics driving the diversification and distribution patterns within Polypodiaceae subfamily Microsoroideae.

Phylogenomic analyses of the pantropical Platycerium Desv. (Platycerioideae) reveal their complex evolution and historical biogeography.

Platycerium is a genus of pantropical epiphytic ferns consisting of ca. 18 species and are highly sought after by horticultural enthusiasts. Although the monophyly of this genus has been well supported in previous molecular studies, as an intercontinentally disjunct genus, the origin and distribution pattern of Platycerium were elusive and controversial. This is mainly due to limited taxon sampling, a plastid representing only a single coalescent history, the lack of fossil evidence, and so on. Here, by utilizing genome-skimming sequencing, transcriptome sequencing, and flow cytometry, we integrated chloroplast genomes, data of single-copy nuclear genes, ploidy levels, morphology, and geographic distribution to understand the species phylogeny and the evolutionary and biogeographic history of Platycerium. Our major results include: (1) based on both plastid and nuclear datasets, Platycerium is consistently resolved into three fully supported clades: the Afro-American (AA) clade, the Javan-Australian (JA) clade, and the Malayan-Asian (MA) clade. The AA clade and MA clade are further divided into three and two subclades, respectively; (2) a large amount of gene tree conflict, as well as cytonuclear discordance, was found and can be explained by hybridization and incomplete lineage sorting, and most of the hybridization hypotheses represented ancient hybridization events; (3) through molecular dating, the crown age of Platycerium is determined to be at approximately 32.79 Ma based on the plastid dataset or 29.08 Ma based on the nuclear dataset in the Middle Oligocene; (4) ancestral area reconstruction analysis from different datasets showed that Platycerium most likely originated from Indochina; (5) current distribution patterns are resultant from long-distance dispersals, ancient orogeny, and an ancient climate event; and (6) species diversification was driven by polyploidization, dispersal, and hybridization. This study presented here will help understand the evolution of tropical plant flora and provide a reference for the cultivation and breeding of staghorn ferns.

The causality between systemic inflammatory regulators and chronic respiratory diseases: A bidirectional Mendelian-randomization study.

INTRODUCTION: Accumulative evidence suggests the associations between systemic inflammatory regulators and chronic respiratory diseases (CRDs). However, the intrinsic causation remains implicit. Therefore, this study aimed to examine causative associations by mendelian randomization (MR) and to identify valuable active factors. METHODS: Based on data from the GWAS database, we performed MR analyses of 41 serum cytokines from 8,293 Finnish and European descent cohorts from GBMI and UKBB for five major CRDs. We mainly applied inverse variance weighted regression, supplemented by MR-Egger regression, weighted median, maximum likelihood, weighted mode, and simple mode algorithms. Moreover, sensitivity analyses were conducted using Cochrane's Q test, MR-Egger intercept, MR-PRESSO Global test and MR-Steiger filtering. Eventually, the consistency of MR results was assessed by leave-one-out. RESULTS: Our results suggest that 12 genetically predicted systemic inflammatory regulators probably participate in the progression of CRDs, including four risk factors (IL-1RA, IL-4, MIP-1A, PDGF-BB) and one protective factor (IL-6) in IPF, two protective factors (SCF, SDF-1A) in COPD, and two protective factors (SCF, SDF-1A) in asthma, two protective factors (GROA, IL-2RA) were also included in asthma, whereas only one factor (HGF) was protective against bronchiectasis. Additionally, two protective factors (FGF-BASIC, G-CSF) were identified in sarcoidosis. Sensitivity analyses showed no horizontal pleiotropy and significant heterogeneity. Finally, based on the findings of inverse MR analysis, no inverse causal association was uncovered, confirming the robustness of results. CONCLUSION: Our study unearths potential associations between systemic inflammatory modulators and common CRDs, providing new insights for inflammation-mediated CRD prevention and therapeutic approaches.

Quantum Light Generation Based on GaN Microring toward Fully On-Chip Source.

An integrated quantum light source is increasingly desirable in large-scale quantum information processing. Despite recent remarkable advances, a new material platform is constantly being explored for the fully on-chip integration of quantum light generation, active and passive manipulation, and detection. Here, for the first time, we demonstrate a gallium nitride (GaN) microring based quantum light generation in the telecom C-band, which has potential toward the monolithic integration of quantum light source. In our demonstration, the GaN microring has a free spectral range of 330 GHz and a near-zero anomalous dispersion region of over 100 nm. The generation of energy-time entangled photon pair is demonstrated with a typical raw two-photon interference visibility of 95.5±6.5%, which is further configured to generate a heralded single photon with a typical heralded second-order autocorrelation g_{H}^{(2)}(0) of 0.045±0.001. Our results pave the way for developing a chip-scale quantum photonic circuit.

Spiroannulations of ß-Ketothioamides with Bromoenals via Selective C-Michael Addition and S-Michael Addition-Triggered Cascade Reactions.

A spiroannulation reaction of ß-ketothioamides with aromatic ß-bromoenals and aromatic α-bromoenals via selective C-Michael addition and S-Michael addition-triggered cascade reactions has been developed. This protocol provides a novel and rapid approach for the synthesis of substituted spirothiopyran and spirothiophene derivatives under mild conditions with moderate to good yields and a broad substrate scope.

Exploring the causal relationship between immune cells and idiopathic pulmonary fibrosis: a bi-directional Mendelian randomization study.

BACKGROUND: The potential pathogenic mechanism of idiopathic pulmonary fibrosis is widely recognized to involve immune dysregulation. However, the current pool of studies has yet to establish a unanimous agreement regarding the correlation between various types of immune cells and IPF. METHODS: By conducting a two-sample Mendelian randomization analysis using publicly available genetic data, the study examined the causal relationship between IPF and 731 immune cells. To ensure the reliability of the results, combined sensitivity analyses and inverse Mendelian analyses were conducted. Moreover, within subgroups, multivariate Mendelian randomization analyses were utilized to investigate the autonomous causal connection between immune cell characteristics and IPF. RESULTS: After adjusting for false discovery rate, it was discovered that 20 immunophenotypes exhibited a significant association with IPF. After subgrouping for multivariate Mendelian randomization analysis, there were six immunophenotypes that remained significantly associated with IPF. These included CD33 + HLA DR + CD14dim (OR = 0.96, 95% CI 0.93-0.99, P = 0.033), HLA DR + NK (OR = 0.92, 95% CI 0.85-0.98, P = 0.017), CD39 + CD8 + T cell %T cell (OR = 0.93, 95% CI 0.88-0.99, P = 0.024), CD3 on activated & secreting Treg (OR = 0.91, 95% CI 0.84-0.98, P = 0.026), PDL-1 on CD14- CD16 + monocyte (OR = 0.89, 95% CI 0.84-0.95, P = 8 × 10-4), and CD45 on CD33 + HLA DR + CD14- (OR = 1.08, 95% CI 1.01-1.15, P = 0.011). CONCLUSION: Our study reveals a noteworthy association between IPF and various immune cells, providing valuable insights for clinical research and aiding the advancement of immunologically-based therapeutic strategies.

Assessment of vibration modulated regional cerebral blood flow with MRI.

Human brain experiences vibration of certain magnitude and frequency during various physical activities such as vehicle transportation and machine operation, which may cause traumatic brain injury or other brain diseases. However, the mechanisms of brain pathogenesis due to vibration are not fully elucidated due to the lack of techniques to study brain functions while applying vibration to the brain at a specific magnitude and frequency. Here, this study reported a custom-built head-worn electromagnetic actuator that applied vibration to the brain in vivo at an accurate frequency inside a magnetic resonance imaging scanner while cerebral blood flow (CBF) was acquired. Using this technique, CBF values from 45 healthy volunteers were quantitatively measured immediately following vibration at 20, 30, 40 Hz, respectively. Results showed increasingly reduced CBF with increasing frequency at multiple regions of the brain, while the size of the regions expanded. Importantly, the vibration-induced CBF reduction regions largely fell inside the brain's default mode network (DMN), with about 58 or 46% overlap at 30 or 40 Hz, respectively. These findings demonstrate that vibration as a mechanical stimulus can change strain conditions, which may induce CBF reduction in the brain with regional differences in a frequency-dependent manner. Furthermore, the overlap between vibration-induced CBF reduction regions and DMN suggested a potential relationship between external mechanical stimuli and cognitive functions.

DpCoA tagSeq: Barcoding dpCoA-Capped RNA for Direct Nanopore Sequencing via Maleimide-Thiol Reaction.

Recent discoveries of noncanonical RNA caps, such as nicotinamide adenine dinucleotide (NAD+) and 3'-dephospho-coenzyme A (dpCoA), have expanded our knowledge of RNA caps. Although dpCoA has been known to cap RNAs in various species, the identities of its capped RNAs (dpCoA-RNAs) remained unknown. To fill this gap, we developed a method called dpCoA tagSeq, which utilized a thiol-reactive maleimide group to label dpCoA cap with a tag RNA serving as the 5' barcode. The barcoded RNAs were isolated using a complementary DNA strand of the tag RNA prior to direct sequencing by nanopore technology. Our validation experiments with model RNAs showed that dpCoA-RNA was efficiently tagged and captured using this protocol. To confirm that the tagged RNAs are capped by dpCoA and no other thiol-containing molecules, we used a pyrophosphatase NudC to degrade the dpCoA cap to adenosine monophosphate (AMP) moiety before performing the tagSeq protocol. We identified 44 genes that transcribe dpCoA-RNAs in mouse liver, demonstrating the method's effectiveness in identifying and characterizing the capped RNAs. This strategy provides a viable approach to identifying dpCoA-RNAs that allows for further functional investigations of the cap.

Battery-Operated and Self-Heating Solid-Phase Microextraction Device for Field Detection and Long-Term Preservation of Mercury in Soil.

The application of headspace solid-phase microextraction (HS-SPME) for mercury preservation and detection still has several shortcomings, including the use of high-temperature desorption chamber, the consumption of expensive reagent (NaBEt4 or NaBPr4), and analyte loss during sample storage. Herein, a self-heating HS-SPME device using a gold-coated tungsten (Au@W) fiber was developed for the field detection of mercury in soil by miniature point discharge optical emission spectrometry (µPD-OES). Hg2+ was reduced to Hg0 with NaBH4 solution and then preconcentrated with the Au@W fiber. The adsorbed Hg0 could be rapidly desorbed by directly heating the fiber with a mini lithium battery and subsequently detected by µPD-OES. A limit of detection (LOD) of 0.008 mg kg-1 was obtained with a relative standard deviation (RSD) of 2.4%. The accuracy of the self-heating HS-SPME was evaluated by analyzing a soil certified reference material (CRM) and nine soil samples with satisfactory recoveries (86-111%). Compared to the conventional external heating method, the proposed method reduces desorption time and power consumption from 80 s and 60 W to 20 s and 2.5 W, respectively. Moreover, the self-heating device enables the µPD-OES system to remove the high-temperature desorption chamber, making it more compact and suitable for field analytical chemistry. Interestingly, the Au@W SPME fiber can be also used for the long-term preservation of mercury with a sample loss rate <5% after 30 days of storage at room temperature.

Au@Ag Nanopencil with Au Tip and Au@Ag Rod: Multimodality Plasmonic Nanoprobe based on Asymmetric Etching for the Detection of SCN- and ClO.

In this paper, Au@Ag nanopencil is designed as a multimodality plasmonic nanoprobe based on asymmetric etching for the detection of SCN- and ClO- . Au@Ag nanopencil with Au tip and Au@Ag rod is prepared by asymmetric tailoring of uniformly grown silver-covered gold nanopyramids under the combined effect of partial galvanic replacement and redox reaction. By asymmetric etching in different systems, Au@Ag nanopencil exhibits diversified changes in the plasmonic absorption band: O2 •- facilitated by SCN- etches Au@Ag rod from the end to the tip, causing a blue shift of the localized surface plasmon resonance (LSPR) peak as the aspect ratio decreases; while the ClO- can retain Au@Ag shell and etch Ag within rod from the tip to the end, causing a redshift of the LSPR peak as the coupling resonance weakens. Based on peak shifts in different directions, a multimodality detection of SCN- and ClO- has been established. The results demonstrate the detection limits of SCN- and ClO- are 160 and 6.7 nm, and the linear ranges are 1-600 µm and 0.05-13 µm, respectively. The finely designed Au@Ag nanopencil not only broadens the horizon of designing heterogeneous structures, but also enriches the strategy of constructing multimodality sensing platform.

Oxidative (3+3) Cycloaddition/Ring-Opening Reactions of Simple Urea Derivatives and N,N'-Cyclic Azomethine Imines to Construct 1,2,3,5-Tetrazine-4(1H)-one Derivatives.

A novel oxidative (3 + 3) cycloaddition/ring-opening reaction of N,N'-cyclic azomethine imines with the in situ generated diaza-oxylallyl cations from simple urea derivatives in the presence of base and PhI(OAc)2 has been developed. This transformation performs well over a broad substrate scope, which provides facile and rapid access to 1,2,3,5-tetrazine-4(1H)-one derivatives in good yields.

Base-Mediated Tandem [3 + 2] Cycloaddition/Ring Openning Reaction of Arylhydrazonoyl Chlorides with Arylnitroso Compounds for Synthesis of Substituted Diazene Oxides.

A base-mediated tandem [3 + 2] cycloaddition/ring opening reaction of nitrilimines generated from arylhydrazonoyl chlorides with arylnitroso compounds has been developed. This protocol provides a novel and rapid approach for the synthesis of substituted azoxy compounds under mild conditions with moderate to good yields and a broad substrate scope.

MicroRNA: Crucial modulator in purinergic signalling involved diseases.

Both microRNAs (miRNAs) and purinergic signalling are widely and respectively expressed in various tissues of different organisms and play vital roles in a variety of physiological and pathological processes. Here, we reviewed the current publications contributed to the relationship of miRNAs and purinergic signalling in cardiovascular diseases, gastrointestinal diseases, neurological diseases, and ophthalmic diseases. We tried to decode the miRNAs-purinergic signalling network of purinergic signalling involved diseases. The evidence indicated that more than 30 miRNAs (miR-22, miR-30, miR-146, miR-150, miR-155, miR-187, etc.) directly or indirectly modulate P1 receptors (A1, A2A, A2B, A3), P2 receptors (P2X1, P2X3, P2X4, P2X7, P2Y2, P2Y6, P2Y12), and ecto-enzymes (CD39, CD73, ADA2); P2X7 and CD73 could be modulated by multiple miRNAs (P2X7: miR-21, miR-22, miR-30, miR-135a, miR-150, miR-186, miR-187, miR-216b; CD73: miR-141, miR-101, miR-193b, miR-340, miR-187, miR-30, miR-422a); miR-187 would be the common miRNA to modulate P2X7 and CD73.

Targeting Mitochondrial Oxidative Stress: Potential Neuroprotective Therapy for Spinal Cord Injury.

Spinal cord injury (SCI) is a serious central nervous system (CNS) injury disease related to hypoxia-ischemia and inflammation. It is characterized by excessive reactive oxygen species (ROS) production, oxidative damage to nerve cells, and mitochondrial dysfunction. Mitochondria serve as the primary cellular origin of ROS, wherein the electron transfer chain complexes within oxidative phosphorylation frequently encounter electron leakage. These leaked electrons react with molecular oxygen, engendering the production of ROS, which culminates in the occurrence of oxidative stress. Oxidative stress is one of the common forms of secondary injury after SCI. Mitochondrial oxidative stress can lead to impaired mitochondrial function and disrupt cellular signal transduction pathways. Hence, restoring mitochondrial electron transport chain (ETC), reducing ROS production and enhancing mitochondrial function may be potential strategies for the treatment of SCI. This article focuses on the pathophysiological role of mitochondrial oxidative stress in SCI and evaluates in detail the neuroprotective effects of various mitochondrial-targeted antioxidant therapies in SCI, including both drug and non-drug therapy. The objective is to provide valuable insights and serve as a valuable reference for future research in the field of SCI.

Effect of accessory hepatic artery reconstruction on prognosis in orthotopic liver transplantation: a single center experience.

BACKGROUND: In orthotopic liver transplantation (OLT), preserving an aberrant hepatic artery (AHA) can increase the number of arterial anastomoses and may lead to arterial-related complications. AHA includes accessory hepatic artery and replaced hepatic artery. Herein, the purpose of our research is to evaluate the requirement for accessory anastomosis in OLT. METHODS: We retrospectively reviewed a total of 95 patients who underwent OLT in our hospital between April 2020 and December 2022. We found seven cases of donor livers with accessory HA. The method of arterial anastomosis and details of the diagnosis and treatment of complications were collated. RESULTS: Among 95 consecutive patients with OLT, complications occurred in two of seven patients-patient 2 had an accessory right hepatic artery, while patient 5 had an accessory left hepatic artery. Patient 2 showed bile leakage leading to rupture and bleeding of the accessory HA anastomosis after OLT, and was treated with interventional coil embolization. In patient 5, hepatic artery thrombosis and accessory HA occlusion were treated with embolization and thrombolysis of the splenic artery and left gastric artery. During the intervention, we also found that the internal hepatic artery and accessory HA had communicating branches. After treatment, both patients remain healthy with no complications such as liver necrosis or liver abscess. CONCLUSION: An AHA can be ligated when assessed as an accessory artery. This can reduce the incidence of arterial complications, contribute to the perioperative management of liver transplantation (LT) patients, and improve the prognosis of LT.

Plastome structure, evolution, and phylogeny of Selaginella.

As one of the earliest land plant lineages, Selaginella is important for studying land plant evolution. It is the largest genus of lycophytes containing 700-800 species. Some unique characters of Selaginella plastomes have been reported, but based only on 20 species. There have been no plastome phylogenies of Selaginella based on a relatively large sampling, and no efforts have been made to resolve the phylogeny of the enigmatic Sinensis group whose relationships have been unclear based on small datasets. Here we investigated the structures of 59 plastomes representing 51 species covering all six subgenera and 18 sections of Selaginella except two sections and including the intriguing Sinensis group for the first time. Our major results include: (1) the plastome size of Selaginella ranges tremendously from 78,492 bp to 187,632 bp; (2) there are numerous gene losses in Selaginella comparing with other lycophytes, Isoëtaceae and Lycopodiaceae; (3) the gene contents and plastome structures in Selaginella vary lineage-specifically and all infrageneric taxa are well supported in the plastome phylogeny; (4) the ndh gene family tends to lose or pseudogenize in those species with DR structure and without other short or medium repeats; (5) the short and medium repeat regions in SC mediate many conformations causing diverse and complex plastome structures, and six new conformations are discovered; (6) forty-eight species sampled have high GC content (>50%) but three species in the Sinensis group have âˆ¼ 30% GC content in plastomes, similar to most vascular plants; (7) the Sinensis group is monophyletic, includes at least two subgroups, and has the smallest plastomes in land plants except some parasitic plants, and their plastomes do not contain any tRNAs; (8) the younger lineages in Selaginella tend to have higher GC content, whereas the older lineages tend to have lower GC content; and (9) because of incomplete genomic data and abnormal structures or some unknown reasons, even the concatenated plastomes could not well resolve the phylogenetic relationships in Selaginella with confidence, highlighting the difficulty in resolving the phylogeny and evolution of this particularly important land plant lineage.

Alkali-Induced In Situ Formation of Amorphous NixFe1-x(OH)2 from a Linear [M3(COO)6]-Based MOF Template for Overall Electrochemical Water Splitting.

Amorphous and bifunctional electrocatalysts based on 3d transition metals tend to exhibit better performance than their crystalline counterparts and are a promising choice for efficient overall water splitting yet far from being well explored. A 3,6-net metal-organic framework (MOF) of [Ni3(bpt)2(DMF)2(H2O)2]·1.5DMF (Ni-MOF), based on linear [Ni3(COO)6] as a node and [1,1'-biphenyl]-3,4',5-tricarboxylic acid (H3bpt) as a linker, was conveniently prepared via a hydrothermal reaction. Benefitting from the wide compatibility of the octahedral coordination geometry in Ni-MOF for different 3d metal ions, the molecular level and controllable metal doping facilitates the production of the desired Ni/Fe bimetallic MOF. A high-concentration alkali solution of 1 M KOH induced the in situ transformation of the MOF as a precursor to new amorphous electrocatalysts of [Ni(OH)2(H2O)0.6]·H2O [a-Ni(OH)2] and its metal-doped derivatives of a-Ni0.77Fe0.23(OH)2 and a-Ni0.65Fe0.35(OH)2. In particular, the costly organic ligand H3bpt was fully dissolved in the alkaline solution and can be recovered for cyclic utilization by subsequent acidification. The obtained amorphous hydroxide was deduced to be loose and defective layers containing both coordinated and lattice water based on combined characterizations of TG, IR, Raman, XPS, and sorption analysis. As opposed to the crystalline counterpart of Ni(OH)2 with stacked packing layers and an absent lattice water, the abundant catalytic active sites of the amorphous electrocatalyst endow good performance in both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). The bifunctional a-Ni0.65Fe0.35(OH)2 coated on nickel foam realizes small overpotentials of 247 and 99 mV for OER and HER, respectively, under a current density of 10 mA cm-2, which can work with a cell voltage of merely 1.60 V for overall water splitting. This study provides an efficient strategy for widely screening and preparing new functional amorphous materials for electrocatalytic application.

Sulforaphane ameliorates non-alcoholic fatty liver disease in mice by promoting FGF21/FGFR1 signaling pathway.

Most studies regarding the beneficial effect of sulforaphane (SFN) on non-alcoholic fatty liver disease (NAFLD) have focused on nuclear factor E2-related factor 2 (Nrf2). But the molecular mechanisms underlying the beneficial effect of SFN in the treatment of NAFLD remain controversial. Fibroblast growth factor (FGF) 21 is a member of the FGF family expressed mainly in liver but also in adipose tissue, muscle and pancreas, which functions as an endocrine factor and has been considered as a promising therapeutic candidate for the treatment of NAFLD. In the present study we investigated whether FGF21 was involved in the therapeutic effect of SFN against NAFLD. C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to generate NAFLD and continued on the HFD for additional 6 weeks with or without SFN treatment. We showed that administration of SFN (0.56 g/kg) significantly ameliorated hepatic steatosis and inflammation in NAFLD mice, along with the improved glucose tolerance and insulin sensitivity, through suppressing the expression of proteins responsible for hepatic lipogenesis, while enhancing proteins for hepatic lipolysis and fatty acids oxidation. SFN administration significantly increased hepatic expression of FGFR1 and fibroblast growth factor 21 (FGF21) in NAFLD mice, along with decreased phosphorylation of p38 MAPK (the downstream of FGF21). HepG2 cells were treated in vitro with FFAs (palmitic acid and oleic acid) followed by different concentrations of SFN. We showed that the effects of SFN on FGF21 and FGFR1 protein expression were replicated in FFAs-treated HepG2 cells. Moreover, the increased FGFR1 protein occurred earlier than increased FGF21 protein. Interestingly, the rapid effect of SFN on FGFR1 protein was not regulated by the FGFR1 gene transcription. Knockdown of FGFR1 and p38 genes weakened SFN-reduced lipid deposition in FFAs-treated HepG2 cells. SFN administration in combination with rmFGF21 (1.5 mg/kg, i.p., every other day) for 3 weeks further suppressed hepatic steatosis in NAFLD mice. In conclusion, SFN ameliorates lipid metabolism disorders in NAFLD mice by upregulating FGF21/FGFR1 pathway. Our results verify that SFN may become a promising intervention to treat or relieve NAFLD.