Contralateral acupuncture for migraine without aura: a randomized trial protocol with multimodal MRI.

Introduction: Migraine is a common clinical disorder, ranks as the second most disabling disease worldwide, and often manifests with unilateral onset. Contralateral acupuncture (CAT), as a classical acupuncture method, has been proven to be effective in the treatment of migraine without aura (MWoA). However, its neural mechanisms have not been investigated using multimodal magnetic resonance imaging (MRI). Methods and analysis: In this multimodal neuroimaging randomized trial, a total of 96 female MWoA participants and 30 female healthy controls (HCs) will be recruited. The 96 female MWoA participants will be randomized into three groups: Group A (CAT group), Group B [ipsilateral acupuncture (IAT) group], and Group C (sham CAT group) in a 1:1:1 allocation ratio. Each group will receive 30 min of treatment every other day, three times a week, for 8 weeks, followed by an 8-week follow-up period. The primary outcome is the intensity of the migraine attack. Data will be collected at baseline (week 0), at the end of the 8-week treatment period (weeks 1-8), and during the 8-week follow-up (weeks 9-16). Adverse events will be recorded. Multimodal MRI scans will be conducted at baseline and after 8-week treatment. Discussion: This study hypothesized that CAT may treat MWoA by restoring pathological alterations in brain neural activity, particularly by restoring cross-integrated functional connectivity with periaqueductal gray (PAG) as the core pathological brain region. The findings will provide scientific evidence for CAT in the treatment of MWoA. Ethics and dissemination: The Medical Ethics Committee of the Second Affiliated Hospital of Yunnan University of Chinese Medicine has given study approval (approval no. 2022-006). This trial has been registered with the Chinese Clinical Trials Registry (registration no. ChiCTR2300069456). Peer-reviewed papers will be used to publicize the trial's findings. Clinical trial registration: https://clinicaltrials.gov/, identifier ChiCTR2300069456.

An adjustable multistage resistance switching behavior of a photoelectric artificial synaptic device with a ferroelectric diode effect for neuromorphic computing.

Neuromorphic computing, which mimics biological neural networks, is widely regarded as the optimal solution for addressing the limitations of traditional von Neumann computing architecture. In this work, an adjustable multistage resistance switching ferroelectric Bi2FeCrO6 diode artificial synaptic device was fabricated using a sol-gel method with a simple process. The device exhibits nonlinearity in its electrical characteristics, demonstrating tunable multistage resistance switching behavior and a strong ferroelectric diode effect through the manipulation of ferroelectric polarization. One of its salient advantages resides in its capacity to dynamically regulate its polarization state in response to an external electric field, thereby facilitating the fine-tuning of synaptic connection strength while maintaining synaptic stability. The device is capable of accurately simulating the fundamental properties of biological synapses, including long/short-term plasticity, paired-pulse facilitation, and spike-timing-dependent plasticity. Additionally, the device exhibits a distinctive photoelectric response and is capable of inducing synaptic plasticity by light signal activation. The utilization of a femtosecond laser for the scrutiny of carrier transport mechanisms imparts profound insights into the intricate dynamics governing the optical memory effect. Furthermore, utilizing a convolutional neural network (CNN) architecture, the recognition accuracy of the MNIST and fashion MNIST datasets was improved to 95.6% and 78%, respectively, through the implementation of improved random adaptive algorithms. These findings present a new opportunity for utilizing Bi2FeCrO6 materials in the development of artificial synapses for neuromorphic computation.

Epigallocatechin-3-gallate confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis, apoptosis, and autophagy via modulation of 14-3-3η.

Previous studies have demonstrated that the underlying mechanisms of myocardial ischemia/reperfusion injury (MIRI) are complex and involve multiple types of regulatory cell death, including ferroptosis, apoptosis, and autophagy. Thus, we aimed to identify the mechanisms underlying MIRI and validate the protective role of epigallocatechin-3-gallate (EGCG) and its related mechanisms in MIRI. An in vivo and in vitro models of MIRI were constructed. The results showed that pretreatment with EGCG could attenuate MIRI, as indicated by increased cell viability, reduced lactate dehydrogenase (LDH) activity and apoptosis, inhibited iron overload, abnormal lipid metabolism, preserved mitochondrial function, decreased infarct size, maintained cardiac function, decreased reactive oxygen species (ROS) level, and reduced TUNEL-positive cells. Additionally, EGCG pretreatment could attenuate ferroptosis, apoptosis, and autophagy induced by MIRI via upregulating 14-3-3η protein levels. Furthermore, the protective effects of EGCG could be abolished with pAd/14-3-3η-shRNA or Compound C11 (a 14-3-3η inhibitor) but not pAd/NC-shRNA. In conclusion, EGCG pretreatment attenuated ferroptosis, apoptosis, and autophagy by mediating 14-3-3η and protected cardiomyocytes against MIRI.

Performance of anterior segment OCT-based algorithms in the opportunistic screening for primary angle-closure disease.

Purpose: This study aimed to investigate the performance of deep learning algorithms in the opportunistic screening for primary angle-closure disease (PACD) using combined anterior segment parameters. Methods: This was an observational, cross-sectional hospital-based study. Patients with PACD and healthy controls who underwent comprehensive eye examinations, including gonioscopy and anterior segment optical coherence tomography (ASOCT) examinations under both light and dark conditions, were consecutively enrolled from the Department of Ophthalmology at the Beijing Tongren Hospital between November 2020 and June 2022. The anterior chamber, anterior chamber angle, iris, and lens parameters were assessed using ASOCT. To build the prediction models, backward logistic regression was utilized to select the variables to discriminate patients with PACD from normal participants, and the area under the receiver operating characteristic curve was used to evaluate the efficacy of the opportunistic screening. Results: The data from 199 patients (199 eyes) were included in the final analysis and divided into two groups: PACD (109 eyes) and controls (90 eyes). Angle opening distance at 500 µm, anterior chamber area, and iris curvature measured in the light condition were included in the final prediction models. The area under the receiver operating characteristic curve was 0.968, with a sensitivity of 91.74 % and a specificity of 91.11 %. Conclusion: ASOCT-based algorithms showed excellent diagnostic performance in the opportunistic screening for PACD. These results provide a promising basis for future research on the development of an angle-closure probability scoring system for PACD screening.

Selectivities of Stepped Cu-M (M = Pt, Ni, Pd, Zn, Ag, Au) Bimetallic Surface Environment for C1 and C2 Pathways.

Copper (Cu) emerges as a highly efficient and cheap catalytic agent for the electrochemical reduction of carbon dioxide (CO2RR), promising a sustainable route toward carbon neutrality. Despite its utility, the Cu catalyst exhibits limitations in terms of product selectivity, highlighting the need for the development of a superior catalyst design. Herein, we present a density functional theory (DFT) investigation into the selectivities of Cu-M (M = Pt, Ni, Pd, Zn, Ag, Au) bimetallic catalysts (BMCs) for the carbon dioxide reduction reaction (CO2RR). The interaction between the metals of Cu-M makes the surface electrons reconstruct so that the d-band center shifts to the Fermi level. In terms of CO2 activation, the Cu-Ni catalyst exhibits superior performance. Additionally, the Cu-Pd catalyst favors the formation of *COH along the reaction pathway, favoring the generation of CH4. Conversely, the Cu-Ni catalyst preferentially produces *CHO, thereby favoring the production of CH3OH. For the Cu-Ag catalyst, the reaction intermediates along the C2 pathway are *CO-*CHO and *COH-*CHO. The Cu-Ni catalyst follows a reaction path that proceeds via *CO-*CO → *CO-*COH → *COH-CHO. On the other hand, the Cu-Pt catalyst exhibits a reaction sequence of *CO-*CO → *CO-*CHO → *OCH-*OCH. This study provides guiding significance for the design of Cu-based bimetallic catalysts aimed at improving the selectivities and efficiency of the CO2RR process.

Thermally stable Ni foam-supported inverse CeAlOx/Ni ensemble as an active structured catalyst for CO2 hydrogenation to methane.

Nickel is the most widely used inexpensive active metal center of the heterogeneous catalysts for CO2 hydrogenation to methane. However, Ni-based catalysts suffer from severe deactivation in CO2 methanation reaction due to the irreversible sintering and coke deposition caused by the inevitable localized hotspots generated during the vigorously exothermic reaction. Herein, we demonstrate the inverse CeAlOx/Ni composite constructed on the Ni-foam structure support realizes remarkable CO2 methanation catalytic activity and stability in a wide operation temperature range from 240 to 600 °C. Significantly, CeAlOx/Ni/Ni-foam catalyst maintains its initial activity after seven drastic heating-cooling cycles from RT to 240 to 600 °C. Meanwhile, the structure catalyst also shows water resistance and long-term stability under reaction condition. The promising thermal stability and water-resistance of CeAlOx/Ni/Ni-foam originate from the excellent heat and mass transport efficiency which eliminates local hotspots and the formation of Ni-foam stabilized CeAlOx/Ni inverse composites which effectively anchored the active species and prevents carbon deposition from CH4 decomposition.

Neuromorphic Computing of Optoelectronic Artificial BFCO/AZO Heterostructure Memristors Synapses.

Compared with purely electrical neuromorphic devices, those stimulated by optical signals have gained increasing attention due to their realistic sensory simulation. In this work, an optoelectronic neuromorphic device based on a photoelectric memristor with a Bi2FeCrO6/Al-doped ZnO (BFCO/AZO) heterostructure is fabricated that can respond to both electrical and optical signals and successfully simulate a variety of synaptic behaviors, such as STP, LTP, and PPF. In addition, the photomemory mechanism was identified by analyzing the energy band structures of AZO and BFCO. A convolutional neural network (CNN) architecture for pattern classification at the Mixed National Institute of Standards and Technology (MNIST) was used and improved the recognition accuracy of the MNIST and Fashion-MNIST datasets to 95.21% and 74.19%, respectively, by implementing an improved stochastic adaptive algorithm. These results provide a feasible approach for future implementation of optoelectronic synapses.

Sinomenine Hydrochloride Protects IgA Nephropathy Through Regulating Cell Growth and Apoptosis of T and B Lymphocytes.

Purpose: Sinomenine hydrochloride (SH) is used to treat chronic inflammatory diseases such as rheumatoid arthritis and may also be efficacious against Immunoglobulin A nephropathy (IgAN). However, no trial has investigated the molecular mechanism of SH on IgAN. Therefore, this study aims to investigate the effect and mechanism of SH on IgAN. Methods: The pathological changes and IgA and C3 depositions in the kidney of an IgAN rat model were detected by periodic acid-Schiff (PAS) and direct immunofluorescence staining. After extracting T and B cells using immunomagnetic beads, we assessed their purity, cell cycle phase, and apoptosis stage through flow cytometry. Furthermore, we quantified cell cycle-related and apoptosis-associated proteins by Western blotting. Results: SH reduced IgA and C3 depositions in stage 4 IgAN, thereby decreasing inflammatory cellular infiltration and mesangial injury in an IgAN model induced using heteroproteins. Furthermore, SH arrested the cell cycle of lymphocytes T and B from the spleen of IgAN rats. Regarding the mechanism, our results demonstrated that SH regulated the Cyclin D1 and Cyclin E1 protein levels for arresting the cell cycle and it also regulated Bax and Bcl-2 protein levels, thus increasing Cleaved caspase-3 protein levels in Jurkat T and Ramos B cells. Conclusion: SH exerts a dual regulation on the cell cycle and apoptosis of T and B cells by controlling cell cycle-related and apoptosis-associated proteins; it also reduces inflammatory cellular infiltration and mesangial proliferation. These are the major mechanisms of SH in IgAN.

Accelerated multi-b-value multi-shot diffusion-weighted imaging based on EPI with keyhole and a low-rank tensor constraint.

PURPOSE: Multi-Shot (MS) Echo-Planar Imaging (EPI) may improve the in-plane resolution of multi-b-value DWI, yet it also considerably increases the scan time. Here we explored the combination of EPI with Keyhole (EPIK) and a calibrationless reconstruction algorithm for acceleration of multi-b-value MS-DWI. METHODS: We firstly analyzed the impact of nonuniform phase accrual in EPIK on the reconstructed image. Based on insights gained from the analysis, we developed a calibrationless reconstruction algorithm based on a Space-Contrast-Coil Locally Low-Rank Tensor (SCC-LLRT) constraint for reconstruction of EPIK-acquired data. We compared the algorithm with a modified SPatial-Angular Locally Low-Rank (SPA-LLR) algorithm through simulations, phantoms, and in vivo study. We then compared EPIK with uniformly undersampled EPI for accelerating multi-b-value DWI in 6 healthy subjects. RESULTS: Through theoretical derivations, we found that the reconstruction of EPIK with a SENSE-encoding-based algorithm, such as SPA-LLR, may cause additional aliasing artifacts due to the frequency-dependent distortion of the coil sensitivity. Results from simulations, phantoms, and in vivo study verified the theoretical finding by showing that the calibrationless SCC-LLRT algorithm reduced aliasing artifacts compared with SPA-LLR. Finally, EPIK with SCC-LLRT substantially reduced the ghosting artifacts compared with uniform undersampled multi-b-value DWI, decreasing the fitting errors in ADC (0.05 ± 0.01 vs 0.10 ± 0.01, P < 0.001) and IVIM mapping (0.026 ± 0.004 vs 0.06 ± 0.006, P < 0.001). CONCLUSION: The SCC-LLRT algorithm reduced the aliasing artifacts of EPIK by using a calibrationless modeling of the multi-coil data. The dense sampling of k-space center offers EPIK a potential to improve image quality for acceleration of multi-b-value MS-DWI.

Platelet Concentrates Preconditioning of Mesenchymal Stem Cells and Combined Therapies: Integrating Regenerative Strategies for Enhanced Clinical Applications.

This article presents a comprehensive review of the factors influencing the efficacy of mesenchymal stem cells (MSCs) transplantation and its association with platelet concentrates (PCs). It focuses on investigating the impact of PCs' composition, the age and health status of platelet donors, application methods, and environmental factors on the outcomes of relevant treatments. In addition, it delves into the strategies and mechanisms for optimizing MSCs transplantation with PCs, encompassing preconditioning and combined therapies. Furthermore, it provides an in-depth exploration of the signaling pathways and proteomic characteristics associated with preconditioning and emphasizes the efficacy and specific effects of combined therapy. The article also introduces the latest advancements in the application of biomaterials for optimizing regenerative medical strategies, stimulating scholarly discourse on this subject. Through this comprehensive review, the primary goal is to facilitate a more profound comprehension of the factors influencing treatment outcomes, as well as the strategies and mechanisms for optimizing MSCs transplantation and the application of biomaterials in regenerative medicine, offering theoretical guidance and practical references for related research and clinical practice.

Cell-Cycle-related Protein Centromere Protein F Deficiency Inhibits Cervical Cancer Cell Growth by Inducing Ferroptosis Via Nrf2 Inactivation.

Cervical cancer (CC) is one of the severe cancers that pose a threat to women's health and result in death. CENPF, the centromere protein F, plays a crucial role in mitosis by regulating numerous cellular processes, such as chromosome segregation during mitosis. According to bioinformatics research, CENPF serves as a master regulator that is upregulated and activated in cervical cancer. Nevertheless, the precise biological mechanism that CENPF operates in CC remains unclear. The aim of this study was to analyze the function of CENPF on cervical cancer and its mechanism. We conducted immunohistochemistry and western blot analysis to examine the expression levels of CENPF in both cervical cancer tissues and cells. To explore the hidden biological function of CENPF in cell lines derived from CC, we applied lentivirus transfection to reduce CENPF manifestation. CENPF's main role is to regulate ferroptosis which was assessed by analyzing Reactive Oxygen Species (ROS), malonaldehyde (MDA), etc. The vitro findings were further validated through a subcutaneous tumorigenic nude mouse model. Our research finding indicates that there is an apparent upregulation of CENPF in not merely tumor tissues but also cell lines in the carcinomas of the cervix. In vitro and vivo experimental investigations have demonstrated that the suppression of CENPF can impede cellular multiplication, migration, and invasion while inducing ferroptosis. The ferroptosis induced by CENPF inhibition in cervical cancer cell lines is likely mediated through the Nrf2/HO-1 pathway. The data herein come up with the opinion that CENPF may have a crucial role in influencing anti-cervical cancer effects by inducing ferroptosis via the triggering of the Nrf2/HO-1 signaling pathway.

Minor ergosteroids and a 19-nor labdane-type diterpenoid with anti-inflammatory effects from Ganoderma lucidum.

A chemical investigation on the fruiting bodies of Ganoderma lucidum led to the isolation and identification of five undescribed ergosteroids including two des-D-steroids (3 and 4) and one rare 6/6/7/5-fused carbon skeletal ergosterol (5) along with one 19-nor labdane-type diterpenoid (6). Their structures including their absolute configurations, were assigned by spectroscopic methods, ECD calculations, and X-ray diffraction analysis. In addition, the anti-inflammatory activities of all the isolates were evaluated. The results indicated that compound 1 can significantly down-regulate the protein expression of iNOS and COX-2 at 20 µM in LPS- stimulated RAW264.7 cells.

The Effect of the Solution Flow and Electrical Field on the Homogeneity of Large-Scale Electrodeposited ZnO Nanorods.

In this paper, we demonstrate the significant impact of the solution flow and electrical field on the homogeneity of large-scale ZnO nanorod electrodeposition from an aqueous solution containing zinc nitrate and ammonium nitrate, primarily based on the X-ray fluorescence results. The homogeneity can be enhanced by adjusting the counter electrode size and solution flow rate. We have successfully produced relatively uniform nanorod arrays on an 8 × 10 cm2 i-ZnO-coated fluorine-doped tin oxide (FTO) substrate using a compact counter electrode and a vertical stirring setup. The as-grown nanorods exhibit similar surface morphologies and dominant, intense, almost uniform near-band-edge emissions in different regions of the sample. Additionally, the surface reflectance is significantly reduced after depositing the ZnO nanorods, achieving a moth-eye effect through subwavelength structuring. This effect of the nanorod array structure indicates that it can improve the utilization efficiency of light reception or emission in various optoelectronic devices and products. The large-scale preparation of ZnO nanorods is more practical to apply and has an extremely broad application value. Based on the research results, it is feasible to prepare large-scale ZnO nanorods suitable for antireflective coatings and commercial applications by optimizing the electrodeposition conditions.

Glsirt1-mediated deacetylation of GlCAT regulates intracellular ROS levels, affecting ganoderic acid biosynthesis in Ganoderma lucidum.

Lysine acetylation is a reversible, dynamic protein modification regulated by lysine acetyltransferases and deacetylases. However, in Basidiomycetes, the extent of lysine acetylation of nonhistone proteins remains largely unknown. Recently, we identified the deacetylase Glsirt1 as a key regulator of the biosynthesis of ganoderic acid (GA), a key secondary metabolite of Ganoderma lucidum. To gain insight into the characteristics, extent, and biological function of Glsirt1-mediated lysine acetylation in G. lucidum, we aimed to identify additional Glsirt1 substrates via comparison of acetylomes between wild-type (WT) and Glsirt1-silenced mutants. A large amount of Glsirt1-dependent lysine acetylation occurs in G. lucidum according to the results of this omics analysis, involving energy metabolism, protein synthesis, the stress response and other pathways. Our results suggest that GlCAT is a direct target of Glsirt1 and that the deacetylation of GlCAT by Glsirt1 reduces catalase activity, thereby leading to the accumulation of intracellular reactive oxygen species (ROS) and positively regulating the biosynthesis of GA. Our findings provide evidence for the involvement of nonhistone lysine acetylation in the biological processes of G. lucidum and help elucidate the involvement of important ROS signaling molecules in regulating physiological and biochemical processes in this organism. In conclusion, this proteomic analysis reveals a striking breadth of cellular processes affected by lysine acetylation and provides new nodes of intervention in the biosynthesis of secondary metabolites in G. lucidum.

Emerging ferroelectric materials ScAlN: applications and prospects in memristors.

The research found that after doping with rare earth elements, a large number of electrons and holes will be produced on the surface of AlN, which makes the material have the characteristics of spontaneous polarization. A new type of ferroelectric material has made a new breakthrough in the application of nitride-materials in the field of integrated devices. In this paper, the application prospects and development trends of ferroelectric material ScAlN in memristors are reviewed. Firstly, various fabrication processes and structures of the current ScAlN thin films are described in detail to explore the implementation of their applications in synaptic devices. Secondly, a series of electrical properties of ScAlN films, such as the current switching ratio and long-term cycle durability, were tested to explore whether their electrical properties could meet the basic needs of memristor device materials. Finally, a series of summaries on the current research studies of ScAlN thin films in the synaptic simulation are made, and the working state of ScAlN thin films as a synaptic device is observed. The results show that the ScAlN ferroelectric material has high residual polarization, no wake-up function, excellent stability and obvious STDP behavior, which indicates that the modified material has wide application prospects in the research and development of memristors.

Dyslipidemia may impact initial recovery following arthroscopic rotator cuff repair: a retrospective study.

BACKGROUND: The current literature shows that dyslipidemia can lead to a higher incidence of rotator cuff tears (RCTs) and an increased retear rate after repair. We aimed to evaluate the influence of preoperative dyslipidemia on postoperative pain, patient-reported outcomes (PROs), active range of motion (ROM), and structural integrity. METHODS: A cohort of 111 patients who underwent arthroscopic RCT repair between January 2021 and July 2022, and whose complete preoperative serum lipid data were available within one week prior to surgery was retrospectively reviewed. Dyslipidemia was defined as the presence of an increase or decrease in at least one blood lipid profile (triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, or non-high-density lipoprotein). There were 43 patients in the dyslipidemia group and 68 in the ortholiposis group. Patient evaluations, including pain score, PROs, and ROMs, were conducted preoperatively; at 3 and 6 months postoperatively; and at the last follow-up. Structural integrity was assessed by magnetic resonance imaging (MRI) 6 months after surgery if possible, and Sugaya type 4 or 5 was considered a retear. Propensity score matching (PSM) was used to reduce bias. RESULTS: The RCT size, surgical technique, preoperative pain status, PROs, and active ROM were comparable between patients with dyslipidemia and those with ortholiposis. Three months after surgery, patients in the dyslipidemia group had worse average PROs (Constant score: P = 0.001; ASES score: P = 0.012; UCLA score: P = 0.015), forward flexion (P = 0.012), and internal rotation (P = 0.001) than patients in the ortholiposis group did. The difference between the two groups persisted after PSM but disappeared at the sixth month after surgery. No significant differences in pain score, PROs, or active ROMs were detected between the dyslipidemia and ortholiposis groups after a mean follow-up of 24 months. Of the 72 patients who underwent MRI, 4 retears (5.6%) were found, and all were in the ortholiposis group. There was no difference in the rate of retears between the two groups (P = 0.291) or with (P = 0.495) PSM. CONCLUSIONS: In conclusion, we found that perioperative dyslipidemia may impact initial recovery within the first 3 months following arthroscopic rotator cuff repair but may have no effect on pain, PROs, or active ROMs at a mean 2-year follow-up or rotator cuff integrity at 6 months postoperatively. Trail registration Retrospectively registered.

A haplotype-resolved gap-free genome assembly provides novel insight into monoterpenoid diversification in Mentha suaveolens 'Variegata'.

Mentha is a commonly used spice worldwide, which possesses medicinal properties and fragrance. These characteristics are conferred, at least partially, by essential oils such as menthol. In this study, a gap-free assembly with a genome size of 414.3 Mb and 31,251 coding genes was obtained for Mentha suaveolens 'Variegata'. Based on its high heterozygosity (1.5%), two complete haplotypic assemblies were resolved, with genome sizes of 401.9 and 405.7 Mb, respectively. The telomeres and centromeres of each haplotype were almost fully annotated. In addition, we detected a total of 41,135 structural variations. Enrichment analysis demonstrated that genes involved in terpenoid biosynthesis were affected by these structural variations. Analysis of volatile metabolites showed that M. suaveolens mainly produces piperitenone oxide rather than menthol. We identified three genes in the M. suaveolens genome which encode isopiperitenone reductase (ISPR), a key rate-limiting enzyme in menthol biosynthesis. However, the transcription levels of ISPR were low. Given that other terpenoid biosynthesis genes were expressed, M. suaveolens ISPRs may account for the accumulation of piperitenone oxide in this species. The findings of this study may provide a valuable resource for improving the detection rate and accuracy of genetic variants, thereby enhancing our understanding of their impact on gene function and expression. Moreover, our haplotype-resolved gap-free genome assembly offers novel insights into molecular marker-assisted breeding of Mentha.

Ganoderma lucidum-Derived Meroterpenoids Show Anti-Inflammatory Activity In Vitro.

Ganoderma lucidum, known as the "herb of spiritual potency", is used for the treatment and prevention of various diseases, but the responsible constituents for its therapeutic effects are largely unknown. For the purpose of obtaining insight into the chemical and biological profiling of meroterpenoids in G. lucidum, various chromatographic approaches were utilized for the title fungus. As a result, six undescribed meroterpenoids, chizhienes A-F (1-6), containing two pairs of enantiomers (4 and 5), were isolated. Their structures were identified using spectroscopic and computational methods. In addition, the anti-inflammatory activities of all the isolates were evaluated by Western blot analysis in LPS-induced macrophage cells (RAW264.7), showing that 1 and 3 could dose dependently inhibit iNOS but not COX-2 expression. Further, 1 and 3 were found to inhibit nitric oxide (NO) production using the Greiss reagent test. The current study will aid in enriching the structural and biological diversity of Ganoderma-derived meroterpenoids.

Transcriptional regulation of SARS-CoV-2 receptor ACE2 by SP1.

Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The induction of ACE2 expression may serve as a strategy by SARS-CoV-2 to facilitate its propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. Using 45 different luciferase reporters, the transcription factors SP1 and HNF4α were found to positively and negatively regulate ACE2 expression, respectively, at the transcriptional level in human lung epithelial cells (HPAEpiCs). SARS-CoV-2 infection increased the transcriptional activity of SP1 while inhibiting that of HNF4α. The PI3K/AKT signaling pathway, activated by SARS-CoV-2 infection, served as a crucial regulatory node, inducing ACE2 expression by enhancing SP1 phosphorylation-a marker of its activity-and reducing the nuclear localization of HNF4α. However, colchicine treatment inhibited the PI3K/AKT signaling pathway, thereby suppressing ACE2 expression. In Syrian hamsters (Mesocricetus auratus) infected with SARS-CoV-2, inhibition of SP1 by either mithramycin A or colchicine resulted in reduced viral replication and tissue injury. In summary, our study uncovers a novel function of SP1 in the regulation of ACE2 expression and identifies SP1 as a potential target to reduce SARS-CoV-2 infection.