Unraveling a Concerted Proton-Coupled Electron Transfer Pathway in Atomically Precise Gold Nanoclusters.

Metal nanoclusters (MNCs) represent a promising class of materials for catalytic carbon dioxide and proton reduction as well as dihydrogen oxidation. In such reactions, multiple proton-coupled electron transfer (PCET) processes are typically involved, and the current understanding of PCET mechanisms in MNCs has primarily focused on the sequential transfer mode. However, a concerted transfer pathway, i.e., concerted electron-proton transfer (CEPT), despite its potential for a higher catalytic rate and lower reaction barrier, still lacks comprehensive elucidation. Herein, we introduce an experimental paradigm to test the feasibility of the CEPT process in MNCs, by employing Au18(SR)14 (SR denotes thiolate ligand), Au22(SR)18, and Au25(SR)18- as model clusters. Detailed investigations indicate that the photoinduced PCET reactions in the designed system proceed via an CEPT pathway. Furthermore, the rate constants of gold nanoclusters (AuNCs) have been found to be correlated with both the size of the cluster and the flexibility of the Au-S framework. This newly identified PCET behavior in AuNCs is prominently different from that observed in semiconductor quantum dots and plasmonic metal nanoparticles. Our findings are of crucial importance for unveiling the catalytic mechanisms of quantum-confined metal nanomaterials and for the future rational design of more efficient catalysts.

The predictive value of the thyroid nodule benign and malignant based on the ultrasound nodule-to-muscle gray-scale ratio.

OBJECTIVE: To investigate the efficacy of the ultrasonic nodule to muscle gray scale ratio as a predictive tool for distinguishing between benign and malignant thyroid nodules. METHODS: A retrospective study was undertaken at the First People's Hospital of Hangzhou, affiliated with the Zhejiang University School of Medicine, analyzing ultrasound and pathological data of patients with thyroid nodules between May 2020 and December 2022. The study extracted ultrasound features of nodules and employed univariate and multivariate logistic regression analyses to identify independent risk factors for malignant tumors in the nodules. Subsequently, a predictive model for distinguishing benign and malignant thyroid nodules was developed. RESULTS: A total of 466 patients were included in this retrospective study, of which 275 cases were malignant tumors. Univariate and multivariate logistic regression analyses showed that the nodular-muscle gray-scale ratio, nodule diameter, margin status, aspect ratio, and calcification were closely related to thyroid malignant tumors. The area under the curve (AUC) of training group was 0.832, with a sensitivity, specificity, and accuracy of 85.5%, 67.4%, and 76.6%, respectively. The AUC of the external validation group was 0.819, with a sensitivity, specificity, and accuracy of 76.4%, 74.5%, and 75.7%, respectively. The calibration and decision curves showed that the model had good diagnostic value. CONCLUSION: The research findings indicate that ratio is significantly associated with the malignant nature of thyroid nodules. The application of a line chart model based on these parameters exhibits a high level of predictive performance.

UAV-Aided Dual-User Wireless Power Transfer: 3D Trajectory Design and Energy Optimization.

Unmanned aerial vehicles (UAVs) have been widely considered to enhance the communication coverage, as well as the wireless power transfer (WPT) of energy-constrained communication networks to prolong their lifetime. However, the trajectory design of a UAV in such a system remains a key problem, especially considering the three-dimensional (3D) feature of the UAV. To address this issue, a UAV-assisted dual-user WPT system was investigated in this paper, where a UAV-mounted energy transmitter (ET) flies in the air to broadcast wireless energy to charge the energy receivers (ERs) on the ground. By optimizing the UAV's 3D trajectory toward a balanced tradeoff between energy consumption and WPT performance, the energy harvested by all ERs during a given mission period was maximized. The above goal was achieved through the following detailed designs. On the one hand, on the basis of previous research results, there is a one-to-one correspondence between the UAV's abscissa and height, so only the relationship between the height and time was focused on in this work to obtain the UAV's optimal 3D trajectory. On the other hand, the idea of calculus was employed to calculate the total harvested energy, leading to the proposed high-efficiency trajectory design. Finally, the simulation results demonstrated that this contribution is capable of enhancing the energy supply by carefully designing the 3D trajectory of the UAV, compared to its conventional counterpart. In general, the above-mentioned contribution could be a promising way for UAV-aided WPT in the future Internet of Things (IoT) and wireless sensor networks (WSNs).

Deep Learning-Based Sensor Array: 3D Fluorescence Spectra of Gold Nanoclusters for Qualitative and Quantitative Analysis of Vitamin B6 Derivatives.

Vitamin B6 derivatives (VB6Ds) are of great importance for all living organisms to complete their physiological processes. However, their excess in the body can cause serious problems. What is more, the qualitative and quantitative analysis of different VB6Ds may present significant challenges due to the high similarity of their chemical structures. Also, the transfer of deep learning model from one task to a similar task needs to be present more in the fluorescence-based biosensor. Therefore, to address these problems, two deep learning models based on the intrinsic fingerprint of 3D fluorescence spectra have been developed to identify five VB6Ds. The accuracy ranges of a deep neural network (DNN) and a convolutional neural network (CNN) were 94.44-97.77% and 97.77-100%, respectively. After that, the developed models were transferred for quantitative analysis of the selected VB6Ds at a broad concentration range (1-100 µM). The determination coefficient (R2) values of the test set for DNN and CNN were 93.28 and 97.01%, respectively, which also represents the outperformance of CNN over DNN. Therefore, our approach opens new avenues for qualitative and quantitative sensing of small molecules, which will enrich fields related to deep learning, analytical chemistry, and especially sensor array chemistry.

Feature Selection Assists BLSTM for the Ultrasensitive Detection of Bioflavonoids in Different Biological Matrices Based on the 3D Fluorescence Spectra of Gold Nanoclusters.

Rapid and on-site qualitative and quantitative analysis of small molecules (including bioflavonoids) in biofluids are of great importance in biomedical applications. Herein, we have developed two deep learning models based on the 3D fluorescence spectra of gold nanoclusters as a single probe for rapid qualitative and quantitative analysis of eight bioflavonoids in serum. The results proved the efficiency and stability of the random forest-bidirectional long short-term memory (RF-BLSTM) model, which was used only with the most important features after deleting the unimportant features that might hinder the performance of the model in identifying the selected bioflavonoids in serum at very low concentrations. The optimized model achieves excellent overall accuracy (98-100%) in the qualitative analysis of the selected bioflavonoids. Next, the optimized model was transferred to quantify the selected bioflavonoids in serum at nanoscale concentrations. The transferred model achieved excellent accuracy, and the overall determination coefficient (R2) value range was 99-100%. Furthermore, the optimized model achieved excellent accuracies in other applications, including multiplex detection in serum and model applicability in urine. Also, LOD in serum at nanoscale concentration was considered. Therefore, this approach opens the window for qualitative and quantitative analysis of small molecules in biofluids at nanoscale concentrations, which may help in the rapid inclusion of sensor arrays in biomedical and other applications.

Antenna effect of pyridoxal phosphate on the fluorescence of mitoxantrone-silicon nanoparticles and its application in alkaline phosphatase assay.

As a kind of sensing and imaging fluorescent probe with the merit of low toxicity, good stability, and environment-friendly, silicon nanoparticles (SiNPs) are currently attracting extensive research. In this work, we obtained mitoxantrone-SiNPs (MXT-SiNPs) with green emission by one-pot synthesis under mild temperature condition. The antenna based on pyridoxal phosphate (PLP) was designed for light-harvesting to enhance the luminescence of MXT-SiNPs and to establish a novel sensing strategy for alkaline phosphatase (ALP). PLP transfers the absorbed photon energy to MXT-SiNPs by forming Schiff base. When PLP is dephosphorized by ALP, the released free hydroxyl group reacts with aldehyde group to form internal hemiacetal, which leads to the failure of Schiff base formation. Based on the relationship between antenna formation ability and PLP hydrolysis degree, the activity of ALP can be measured. A good linear relationship was obtained from 0.2 to 3.0 U/L, with a limit of detection of 0.06 U/L. Furthermore, the sensing platform was successfully used to detect ALP in human serum with recovery of 97.6-106.2%. The rational design of antenna elements for fluorescent nanomaterials can not only provide a new pathway to manipulate the luminescence, but also provide a new direction for fluorescence sensing strategy.

Machine learning-based sensor array: full and reduced fluorescence data for versatile analyte detection based on gold nanocluster as a single probe.

Different acquisition data approaches have been used to fetch the fluorescence spectra. However, the comparison between them is rare. Also, the extendability of a sensor array, which can work with heavy metal ions and other types of analytes, is scarce. In this study, we used first- and second-order fluorescent data generated by 6-Aza-2-thiothymine-gold nanocluster (ATT-AuNCs) as a single probe along with machine learning to distinguish between a group of heavy metal ions. Moreover, the dimensionality reduction was carried out for the different acquisition data approaches. In our case, the accuracy of different machine learning algorithms using first-order data outperforms the second-order data before and after the dimensionality reduction. For proving the extendibility of this approach, four anions were used as an example. As expected, the same finding has been found. Furthermore, random forest (RF) showed more stable and accurate results than other models. Also, linear discriminant analysis (LDA) gave acceptable accuracy in the analysis of the high-dimensionality data. Accordingly, using LDA in high-dimensionality data (the first- and second-order data) analysis was highlighted for discrimination between the selected heavy metal ions in different concentrations and in different molar ratios, as well as in real samples. Also, the same method was applied for the anion's discrimination, and LDA gave an excellent separation ability. Moreover, LDA was able to differentiate between all the selected analytes with excellent separation ability. Additionally, the quantitative detection was considered using a wide concentration range of Cd2+, and the LOD was 60.40 nM. Therefore, we believe that our approach opens new avenues for linking analytical chemistry, especially sensor array chemistry, with machine learning.

Immunofluorescent-aggregation assay based on anti-Salmonella typhimurium IgG-AuNCs, for rapid detection of Salmonella typhimurium.

Sensitive and rapid detection of pathogenic bacteria plays an important role in avoiding food poisoning. However, the practical application value of conventional assays for detection of foodborne bacteria, are limited by major drawbacks; these include the laboriousness of pure culture preparation, complexity of DNA extraction for polymerase chain reaction, and low sensitivity of enzyme-linked immunosorbent assay. Herein, we designed a non-complex strategy for the sensitive, quantitative, and rapid detection of Salmonella typhimurium with high specificity, using an anti-Salmonella typhimurium IgG-AuNC-based immunofluorescent-aggregation assay. Salmonella typhimurium was agglutinated with fluorescent anti-Salmonella typhimurium IgG-AuNC on a glass slide, and observed using a fluorescence microscope with photoexcitation and photoemission at 560 nm and 620 nm, respectively. Under optimized reaction conditions, the AuNC-based immunofluorescent-aggregation assay had a determination range between 7.0 × 103 and 3.0 × 108 CFU/mL, a limit of detection of 1.0 × 103 CFU/mL and an assay response time of 3 min. The technique delivered good results in assessing real samples.

Sparse Space Shift Keying Modulation with Enhanced Constellation Mapping.

For reducing the switching frequency between the radio frequency (RF) chain and transmit antennas, a class of new sparse space shift keying modulation (SSSK) schemes are presented. This new class is proposed to simplify hardware implementation, through carefully designing the spatial constellation mapping pattern. Specifically, different from traditional space shift keying modulation (SSK), the proposed SSSK scheme utilizes more time slots to construct a joint design of time and spatial domain SSK modulation, while maintaining the special structure of single RF chain. Since part of the multi-dimension constellations of SSSK concentrate the energy in less time slots, the RF-switching frequency is effectively reduced due to the sparsity introduced in the time domain. Furthermore, through theoretical analysis, we obtain the closed-form expression of the bit error probability for the SSSK scheme, and demonstrate that slight performance gain can be achieved compared to traditional SSK with reduced implementation cost. Moreover, we integrate transmit antenna selection (TAS) to achieve considerable performance gain. Finally, simulation results confirm the effectiveness of the proposed SSSK scheme compared to its traditional counterpart.

Integrated Spatial Modulation and STBC-VBLAST Design toward Efficient MIMO Transmission.

In this contribution, the concept of spatial modulation (SM) is firstly integrated into the structure of space-time block codes (STBC)-aided vertical Bell-labs layered space-time (VBLAST) systems, in order to strike a balanced tradeoff among bit error ratio (BER), spectral efficiency and computational complexity. First of all, in order to enhance the BER performance of STBC-VBLAST, we advocate an effective transmit power allocation (TPA) scheme with negligible implementation costs, while dividing the STBC and VBLAST layers with alleviated interference, so as to facilitate combination with SM. Then, we further utilize the unique structure of SM for enhancing the spectral efficiency of original STBC-VBLAST, wherein the information is conveyed by not only the amplitude/phase modulation (APM) symbols but also the antenna indices. In addition, constellation sets of STBC symbols are specifically designed to be rotated to make full use of the degrees of freedom. Finally, the performance advantages of the above-mentioned structures over traditional STBC-VBLAST are demonstrated by the theoretical derivation of a closed-form expression for the union bound on the bit error probability for various spectral efficiencies, and they are supported by simulation results.

A Comprehensive Evolutionary Study of Chloroplast RNA Editing in Gymnosperms: A Novel Type of G-to-A RNA Editing Is Common in Gymnosperms.

Although more than 9100 plant plastomes have been sequenced, RNA editing sites of the whole plastome have been experimentally verified in only approximately 21 species, which seriously hampers the comprehensive evolutionary study of chloroplast RNA editing. We investigated the evolutionary pattern of chloroplast RNA editing sites in 19 species from all 13 families of gymnosperms based on a combination of genomic and transcriptomic data. We found that the chloroplast C-to-U RNA editing sites of gymnosperms shared many common characteristics with those of other land plants, but also exhibited many unique characteristics. In contrast to that noted in angiosperms, the density of RNA editing sites in ndh genes was not the highest in the sampled gymnosperms, and both loss and gain events at editing sites occurred frequently during the evolution of gymnosperms. In addition, GC content and plastomic size were positively correlated with the number of chloroplast RNA editing sites in gymnosperms, suggesting that the increase in GC content could provide more materials for RNA editing and facilitate the evolution of RNA editing in land plants or vice versa. Interestingly, novel G-to-A RNA editing events were commonly found in all sampled gymnosperm species, and G-to-A RNA editing exhibits many different characteristics from C-to-U RNA editing in gymnosperms. This study revealed a comprehensive evolutionary scenario for chloroplast RNA editing sites in gymnosperms, and reported that a novel type of G-to-A RNA editing is prevalent in gymnosperms.

Foxo1-induced miR-92b down-regulation promotes blood-brain barrier damage after ischaemic stroke by targeting NOX4.

The blood-brain barrier (BBB) damage is a momentous pathological process of ischaemic stroke. NADPH oxidases 4 (NOX4) boosts BBB damage after ischaemic stroke and its expression can be influenced by microRNAs. This study aimed to probe into whether miR-92b influenced the BBB damage after ischaemic stroke by regulating NOX4 expression. Here, miR-92b expression was lessened in the ischaemic brains of rats and oxygen-glucose deprivation (OGD)-induced brain microvascular endothelial cells (BMECs). In middle cerebral artery occlusion (MCAo) rats, miR-92b overexpression relieved the ameliorated neurological function and protected the BBB integrity. In vitro model, miR-92b overexpression raised the viability and lessened the permeability of OGD-induced BMECs. miR-92b targeted NOX4 and regulated the viability and permeability of OGD-induced BMECs by negatively modulating NOX4 expression. The transcription factor Foxo1 bound to the miR-92b promoter and restrained its expression. Foxo1 expression was induced by OGD-induction and its knockdown abolished the effects of OGD on miR-92b and NOX4 expressions, cell viability and permeability of BMECs. In general, our findings expounded that Foxo1-induced lessening miR-92b boosted BBB damage after ischaemic stroke by raising NOX4 expression.

Rare-Earth Eu3+/Gold Nanocluster Ensemble-Based Fluorescent Photoinduced Electron Transfer Sensor for Biomarker Dipicolinic Acid Detection.

The use of metal ions to bridge the fluorescent materials to target analytes has been demonstrated to be a promising way to sensor design. Herein, the effect of rare-earth ions on the fluorescence of l-methionine-stabilized gold nanoclusters (Met-AuNCs) was investigated. It was found that europium (Eu3+) can significantly suppress the emission of Met-AuNCs, while other rare-earth ions showed a negligible impact. The mechanism on the observed fluorescence quenching of Met-AuNCs triggered by Eu3+ was systematically explored, with results revealing the dominant role of photoinduced electron transfer (PET). Eu3+ can bind to the surface of Met-AuNCs by the coordination effect and accepts the electron from the excited Met-AuNCs, which results in Met-AuNC fluorescence suppression. After introducing dipicolinic acid (DPA), an excellent biomarker for spore-forming pathogens, Eu3+ was removed from the surface of Met-AuNCs owing to the higher binding affinity between Eu3+ and DPA. Consequently, an immediate fluorescence recovery occurred when DPA was present in the system. Based on the Met-AuNC/Eu3+ ensemble, we then established a simple and sensitive fluorescence strategy for turn-on determination of biomarker DPA, with a linear range of 0.2-4 µM and a low limit of detection of 110 nM. The feasibility of the proposed method was further validated by the quantitative detection of DPA in the soil samples. We believe that this study would significantly facilitate the construction of metal-ion-mediated PET sensors for the measurement of various interested analytes by applying fluorescent AuNCs as detection probes.

Identification and Characterization of the Masculinizing Function of the Helicoverpa armigera Masc Gene.

The Masculinizer (Masc) gene has been known to control sex development and dosage compensation in lepidopterans. However, it remains unclear whether its ortholog exists and plays the same roles in distantly related lepidopterans such as Helicoverpa armigera. To address this question, we cloned Masc from H. armigera (HaMasc), which contains all essential functional domains of BmMasc, albeit with less than 30% amino acid sequence identity with BmMasc. Genomic PCR and qPCR analyses showed that HaMasc is a Z chromosome-linked gene since its genomic content in males (ZZ) was two times greater than that in females (ZW). RT-PCR and RT-qPCR analyses revealed that HaMasc expression was sex- and stage-biased, with significantly more transcripts in males and eggs than in females and other stages. Transfection of a mixture of three siRNAs of HaMasc into a male embryonic cell line of H. armigera led to the appearance of female-specific mRNA splicing isoforms of H. armigeradoublesex (Hadsx), a downstream target gene of HaMasc in the H. armigera sex determination pathway. The knockdown of HaMasc, starting from the third instar larvae resulted in a shift of Hadsx splicing from male to female isoforms, smaller male pupa and testes, fewer but larger/longer spermatocytes and sperm bundles, delayed pupation and internal fusion of the testes and follicles. These data demonstrate that HaMasc functions as a masculinizing gene in the H. armigera sex-determination cascade.

Rational Design of High-Performance Donor-Linker-Acceptor Hybrids Using a Schiff Base for Enabling Photoinduced Electron Transfer.

Donor-linker-acceptor (D-L-A)-based photoinduced electron transfer (PET) has been frequently used for the construction of versatile fluorescent chemo/biosensors. However, sophisticated and tedious processes are generally required for the synthesis of these probes, which leads to poor design flexibility. In this work, by exploiting a Schiff base as a linker unit, a covalently bound D-L-A system was established and subsequently utilized for the development of a PET sensor. Cysteamine (Cys) and N-acetyl-l-cysteine (NAC) costabilized gold nanoclusters (Cys/NAC-AuNCs) were synthesized and adopted as an electron acceptor, and pyridoxal phosphate (PLP) was selected as an electron donor. PLP can form a Schiff base (an aldimine) with the primary amino group of Cys/NAC-AuNC through its aldehyde group and thereby suppresses the fluorescence of Cys/NAC-AuNC. The Rehm-Weller formula results and a HOMO-LUMO orbital study revealed that a reductive PET mechanism is responsible for the observed fluorescence quenching. Since the pyridoxal (PL) produced by the acid phosphatase (ACP)-catalyzed cleavage of PLP has a weak interaction with Cys/NAC-AuNC, a novel turn-on fluorescent method for selective detection of ACP was successfully realized. To the best of our knowledge, this is the first example of the development of a covalently bound D-L-A system for fluorescent PET sensing of enzyme activity based on AuNC nanoprobes using a Schiff base.

miR-877-5p alleviates chondrocyte dysfunction in osteoarthritis models via repressing FOXM1.

BACKGROUND: The present study aimed to investigate whether forkhead box M1 (FOXM1), as a putative target of miR-877-5p, participated in interleukin (IL)-1ß-induced cartilage degeneration in experimental osteoarthritis (OA) models in vitro and in vivo. METHODS: In vitro and in vivo models of OA were established using IL-1ß treated primary mouse chondrocytes and anterior cruciate ligament transection (ACLT) operation in mice. miR-877-5p mimics or agomir-miR-877-5p were used as therapeutic agents in both in vitro and in vivo models of OA. Cell viability and apoptosis were evaluated using cell counting kit-8 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining, respectively. A quantitative reverse transcriptase-polymerase chain reaction and western blotting were used to measure gene and protein expression, respectively. RESULTS: FOXM1 was up-regulated in IL-1ß-stimulated chondrocytes and the proximal tibia of ACLT-operated mice. Bioinformatics algorithms deduced a highly conserved sequence in the 3'-UTR of FOXM1 that could be bound with miR-877-5p. A luciferase assay indicated that miR-877-5p directly targeted the 3'-UTR of FOXM1. Overexpression of miR-877-5p could reduce protein expression of FOXM1 in chondrocytes. Concurrently, IL-1ß-evoked up-regulation of FOXM1 protein expression was neutralized in chondrocytes following transfection with miR-877-5p mimics. miR-877-5p mimics or agomir-miR-887-5p could inhibit IL-1ß-induced inflammation in both in vitro and in vivo models of OA. miR-877-5p might have beneficial effects on the synthesis of cartilage matrix via the promotion of SRY-box transcription factor 9 and type II collagen expression and inhibition of matrix metalloproteinase 9 expression. CONCLUSIONS: miR-877-5p can improve chondrocyte function in both in vivo and in vitro models of OA, based on post-transcriptional repression of FOXM1 as a postulated molecular mechanism.

Dual Enhancement of Gold Nanocluster Electrochemiluminescence: Electrocatalytic Excitation and Aggregation-Induced Emission.

Ligand-protected gold nanoclusters (AuNCs) have emerged as a new class of electrochemiluminescence (ECL) luminophores for their interesting catalytic and emission properties, although their quantum yield (ΦECL ) in aqueous medium is low with a poor mechanistic understanding of the ECL process. Now it is shown that drying AuNCs on electrodes enabled both enhanced electrochemical excitation by an electrocatalytic effect, and enhanced emission by aggregation-induced ECL (AIECL) for 6-aza-2-thiothymine (ATT) protected AuNCs with triethylamine (TEA) as a coreactant. The dried ATT-AuNCs/TEA system resulted in highly stable visual ECL with a ΦECL of 78 %, and a similar enhancement was also achieved with methionine-capped AuNCs. The drying enabled dual-enhancement mechanism has solved a challenging mechanistic problem for AuNC ECL probes, and can guide further rational design of ECL emitters.

Preparation of strongly fluorescent water-soluble dithiothreitol modified gold nanoclusters coated with carboxychitosan, and their application to fluorometric determination of the immunosuppressive 6-mercaptopurine.

Water-soluble and non-aggregating gold nanoclusters (AuNCs) were obtained by modification of the AuNCs with dithiothreitol (DTT) and then coating them with carboxylated chitosan. This process remarkably enhances the dispersibility of DTT-coated AuNCs in water. The resulting AuNCs, on photoexcitation at 285 nm, display strong red emission with a maximum at 650 nm and a 23% quantum yield. Fluorescence is strongly and selectively suppressed in the presence of 6-mercaptopurine (6-MP). Photoluminescence drops linearly in the 0.1-100 µM 6-MP concentration range, and the detection limit of this assay is 0.1 µM. Other features of the modified AuNCs include a decay time of 8.56 µs, a 365 nm Stokes shift, good colloidal stability, ease of chemical modification, and low toxicity. Conceivably, these NCs may find a range of applications in biological imaging and optical sensing. Graphical abstract Highly fluorescent and water-soluble gold nanoclusters (AuNCs) were obtained by modification of the AuNCs with dithiothreitol (DTT) and then coating them with carboxylated chitosan (CC). The resulting CC/DTT-AuNCs were used for sensitive and selective detection of 6-mercaptopurine.

Buyang Huanwu Decoction attenuates H2O2-induced apoptosis by inhibiting reactive oxygen species-mediated mitochondrial dysfunction pathway in human umbilical vein endothelial cells.

BACKGROUND: Apoptosis of endothelial cells caused by reactive oxygen species plays an important role in ischemia/reperfusion injury after cerebral infarction. Buyang Huanwu Decoction (BYHWD) has been used to treat stroke and stroke-induced disability, however, the mechanism for this treatment remains unknown. In this study, we investigated whether BYHWD can protect human umbilical vein endothelial cells (HUVECs) from H2O2-induced apoptosis and explored the underlying mechanisms. METHODS: To investigate the effect of BYHWD on the apoptosis of HUVECs, we established a H2O2-induced oxidative stress model and detected apoptosis by Hoechst 33342 and propidium iodide staining. JC-1 and DCFH-DA assays,western blotting and electron microscopy were used to examine the mechanism of BYHWD on apoptosis. RESULTS: Pretreatment with BYHWD significantly inhibited H2O2-induced apoptosis and protein caspase-3 expression in a concentration-dependent manner. In addition, BYHWD reduced reactive oxygen species production and promoted endogenous antioxidant defenses. Furthermore, loss of mitochondrial membrane potential and structural disruption of mitochondria were both rescued by BYHWD. CONCLUSIONS: BYHWD protects HUVECs from H2O2-induced apoptosis by inhibiting oxidative stress damage and mitochondrial dysfunction. These findings indicate that BYHWD is a promising treatment for cerebral ischemia diseases.

Reciprocal expression of MADS-box genes and DNA methylation reconfiguration initiate bisexual cones in spruce.

The naturally occurring bisexual cone of gymnosperms has long been considered a possible intermediate stage in the origin of flowers, but the mechanisms governing bisexual cone formation remain largely elusive. Here, we employed transcriptomic and DNA methylomic analyses, together with hormone measurement, to investigate the molecular mechanisms underlying bisexual cone development in the conifer Picea crassifolia. Our study reveals a "bisexual" expression profile in bisexual cones, especially in expression patterns of B-class, C-class and LEAFY genes, supporting the out of male model. GGM7 could be essential for initiating bisexual cones. DNA methylation reconfiguration in bisexual cones affects the expression of key genes in cone development, including PcDAL12, PcDAL10, PcNEEDLY, and PcHDG5. Auxin likely plays an important role in the development of female structures of bisexual cones. This study unveils the potential mechanisms responsible for bisexual cone formation in conifers and may shed light on the evolution of bisexuality.