Epidermal secretion-purified biosensing patch with hydrogel sebum filtering membrane and unidirectional flow microfluidic channels.

The development of biosensing electronics for real-time sweat analysis has attracted increasing research interest due to their promising applications for non-invasive health monitoring. However, one of the critical challenges lies in the sebum interference that largely limits the sensing reliability in practical scenarios. Herein, we report a flexible epidermal secretion-purified biosensing patch with a hydrogel filtering membrane that can effectively eliminate the impact of sebum and sebum-soluble substances. The as-prepared sebum filtering membranes feature a dual-layer sebum-resistant structure based on the poly(hydroxyethyl methacrylate) hydrogel functionalized with nano-brush structured poly(sulfobetaine) to eliminate interferences and provide self-cleaning capability. Furthermore, the unidirectional flow microfluidic channels design based on the Tesla valve was incorporated into the biosensing patch to prevent external sebum contamination and allow effective sweat refreshing for reliable sensing. By seamlessly combining these components, the epidermal secretion-purified biosensing patch enables continuous monitoring of sweat uric acid, pH, and sodium ions with significantly improved accuracy of up to 12 %. The proposed strategy for enhanced sweat sensing reliability without sebum interference shows desirable compatibility for different types of biosensors and would inspire the advances of flexible and wearable devices for non-invasive healthcare.

Molecular switching by proton-coupled electron transport drives giant negative differential resistance.

To develop new types of dynamic molecular devices with atomic-scale control over electronic function, new types of molecular switches are needed with time-dependent switching probabilities. We report such a molecular switch based on proton-coupled electron transfer (PCET) reaction with giant hysteric negative differential resistance (NDR) with peak-to-valley ratios of 120 ± 6.6 and memory on/off ratios of (2.4 ± 0.6) × 103. The switching dynamics probabilities are modulated by bias voltage sweep rate and can also be controlled by pH and relative humidity, confirmed by kinetic isotope effect measurements. The demonstrated dynamical and environment-specific modulation of giant NDR and memory effects provide new opportunities for bioelectronics and artificial neural networks.

Synthesis of chiral α-amino acids via Pd(ii)-catalyzed enantioselective C-H arylation of α-aminoisobutyric acid.

Non-natural chiral α,α-disubstituted α-amino acids (α,α-AAs) constitute an attractive α-aminoisobutyric acid (Aib) replacement for improving bioavailability of linear peptides as therapeutics due to the ability of these amino acids to induce the peptides to form helical structures. Enantioselective ß-C(sp3)-H arylation of Aib could potentially provide a versatile one-step strategy for accessing diverse α,α-AAs, but the installation and removal of external directing groups was found in our previously reported work to reduce the efficiency of this approach. Herein we report a Pd(ii)-catalyzed enantioselective C-H arylation of N-phthalyl-protected Aib enabled by a N-2,6-difluorobenzoyl aminoethyl phenyl thioether (MPAThio) ligand, affording α,α-AAs with up to 72% yield and 98% ee. Use of this newly developed chiral catalyst has also significantly improved enantioselective C(sp3)-H arylation of cyclopropanecarboxylic acids by expanding the substrate scope to heterocyclic coupling partners and increasing enantioselectivity to 99% ee.

Oestrogen promotes the progression of adenomyosis by inhibiting CITED2 through miR-145.

RESEARCH QUESTION: Is the microRNA miR-145 involved in adenomyosis, and by what mechanisms does it affect disease development and is itself regulated? DESIGN: Fluorescence in-situ hybridization was used to observe the expression pattern of miR-145 in adenomyosis ectopic endometrium (n = 13), adenomyosis eutopic endometrium (n = 15) and non-adenomyosis eutopic endometrium (n = 14). RNA sequencing was used to screen target genes as well as downstream pathways of miR-145, which were validated by reporter gene assay, quantitative polymerase chain reaction and western blot, and further analysed using cell migration assay and chromatin immunoprecipitation assay. RESULTS: The fluorescence in-situ hybridization assay revealed a noteworthy elevation in miR-145 expression in adenomyosis tissue compared with non-adenomyosis tissue. Furthermore, RNA sequencing analysis revealed that overexpression of miR-145 resulted in heightened expression of genes associated with the cytokine signalling pathway, nucleotide-binding and oligomerization domain-like pathway and adhesion pathway, including IL-1ß and IL-6. Our study has identified CITED2 as a downstream direct target gene of miR-145, which is implicated in the inhibition of stromal cell migration induced by miR-145. Moreover, chromatin immunoprecipitation was used to validate the direct effect of oestradiol on the promoter region of miR-145, mediated by oestrogen receptor α, which facilitates the upregulation of miR-145 expression. CONCLUSION: Our findings provide evidence supporting the role of oestradiol, acting through its receptor α, in modulating the discovered miR-145-CITED2 signalling axis, thereby promoting the progression of adenomyosis.

Deacetylation by SIRT6 increases the stability of GILZ to suppress NSCLC cell migration and invasion.

Glucocorticoid-induced leucine zipper (GILZ) plays a role in cancer cell proliferation in several tumor types. However, in our present study, GILZ was demonstrated to be a metastasis regulator but not a proliferation regulator in non-small cell lung cancer (NSCLC). The overexpression of GILZ had no significant effect on the proliferation of NSCLC cells but inhibited their metastasis by targeting the epithelial-mesenchymal transition pathway. The deacetylase SIRT6, a key regulator of protein stability, can enhance the stability of the GILZ protein by mediating its deacetylation, which prevents ubiquitination and degradation. This process ultimately enhances the inhibitory effect of GILZ on the migration and invasion of NSCLC cells. Thus, GILZ may be a promising new therapeutic target for tumor metastasis.

DNA aptamers for common buffer molecules: possibility of buffer interference in SELEX.

During a typical aptamer selection experiment, buffer molecules are used at the 10 to 50 mM range, whereas target molecules could be used at much lower concentrations even in low µM levels. Therefore, doubts existed regarding the potential enrichment of buffer binding aptamers, particularly for failed selections that cannot validate binding of enriched sequences. In this study, we used two common buffer molecules, Tris and HEPES, as target molecules. While we successfully isolated aptamers for Tris buffer, our attempts to generate aptamers for HEPES buffer failed. Thioflavin T (ThT) fluorescence spectroscopy showed the dissociation constant (Kd) of the Tris buffer aptamer to be 2.9 mM, while isothermal titration calorimetry showed a Kd of 43 µM. NMR spectroscopy also confirmed aptamer binding. Finally, we discussed the implications of this buffer selection work and recommended the use of certain buffers.

Transcriptome-Guided Characterization of the Environmental Toxicity of Metformin: Disruption of Energy Homeostasis and Inhibition of Embryonic Development of Zebrafish at Environmentally Relevant Concentrations.

Metformin has been widely detected in aquatic ecosystems, yet the knowledge of its impact on aquatic organisms, particularly at environmentally relevant concentrations, remains limited. In the present study, we characterized the developmental toxicity of metformin in zebrafish, utilizing a transcriptome-guided toxicological assessment framework. Transcriptomic analysis conducted at metformin concentrations within the µg/L range revealed significant disruptions in biological processes associated with nucleotide, hydrocarbon, and amino acid metabolism, suggesting a significant disturbance in energy homeostasis. This observation was corroborated by energy-targeted metabolomic analysis, wherein a considerable number of metabolites involved in purine metabolism, pyrimidine metabolism, and the citrate cycle displayed significant alterations. Notably, most intermediates in the citrate cycle such as acetyl-CoA exhibited remarkable decreases. Additionally, our study identified significant impediments in zebrafish embryonic development, including decreased yolk extension progress, spontaneous contraction and body length, and increased yolk sac area and yolk/while body lipid content ratio, at metformin concentrations as low as 0.12 µg/L. Furthermore, the disruption of energy homeostasis by metformin was observed to persist into adulthood even after a prolonged recovery period. The present findings highlighted the disruptive effects of metformin on energy homeostasis and embryonic development in teleost at environmentally relevant concentrations, thereby prompting a reevaluation of its environmental risk to nontarget aquatic organisms.

Exploring the dynamics of Women's field hockey performance: A comparative analysis of the impact of opponent quality between Olympic Games and Chinese National Games.

This is an observational retrospective study analyzed the performance of the Chinese women's national field hockey team during the 2020 Tokyo Olympics and 2021 National Games to assess the impact of opposition quality on performance. Game statistics were collected using notational analysis software for 76 Olympic and 40 National Games matches. Non-parametric Mann-Whitney U tests were used to compare tournaments. No significant differences existed for 35 out of 38 metrics, except Offense in 25-Yd Area (P = 0.013), Handball Style (P = 0.000) and Entry into Arc - Right Lane (P = 0.017). When exclusively considering Chinese national team's observations, superior National Games performance did emerge for Shot (P = 0.046), Goal from Short Corner (P = 0.044), Into the Arc (P = 0.046), Entry into Arc - Q3 (P = 0.009), Dribble into the Arc (P = 0.046), Handball Style into Arc (P = 0.041), Forehand Shot (P = 0.033), and Small Skill Shot (P = 0.014). The study underscores the influence of opposition quality on team performance, with a need for targeted improvements in arc penetration efficacy, conversion rates of shots to goals, and adaptation of tactical approaches against stronger defenses. The research points towards the need for strategic high-performance programs, improved domestic league quality, and a structured youth development system to elevate the overall standard of Chinese field hockey to achieve global competitiveness.

Exploring the Lower Limit of Target Concentration in Capture-SELEX Using Guanine as a Model Target.

During an aptamer selection, using a lower target concentration may result in aptamers with a higher binding affinity. Consequently, this begs the question of whether there is a lower limit for target concentration. In this work, we conducted three aptamer selections using 5 µM, 500 nM and 50 nM guanine as the targets, respectively. Successful enrichment of the same guanine aptamers was achieved at both 5 µM and 500 nM guanine, but not with 50 nM. Using 5 µM guanine, the aptamer was enriched in eight rounds of selection, compared to that for 500 nM, which was accomplished in 17 rounds. We discuss the relation of optimal target concentration to the observed Kd value of the resulting aptamers, of which the highest affinity aptamer had a measured Kd of 200 nM. Additionally, we investigated the binding of the aptamers through mutation studies, revealing a critical cytosine. Mutating this cytosine to a thymine switched the selectivity from guanine to adenine, which is reminiscent of the guanine riboswitch. This study revealed a limit in using low target concentration, and the insights described in this article will be useful for guiding the choice of target concentration during capture-SELEX.

CD36 restricts lipid-associated macrophages accumulation in white adipose tissues during atherogenesis.

Visceral white adipose tissues (WAT) regulate systemic lipid metabolism and inflammation. Dysfunctional WAT drive chronic inflammation and facilitate atherosclerosis. Adipose tissue-associated macrophages (ATM) are the predominant immune cells in WAT, but their heterogeneity and phenotypes are poorly defined during atherogenesis. The scavenger receptor CD36 mediates ATM crosstalk with other adipose tissue cells, driving chronic inflammation. Here, we combined the single-cell RNA sequencing technique with cell metabolic and functional assays on major WAT ATM subpopulations using a diet-induced atherosclerosis mouse model (Apoe-null). We also examined the role of CD36 using Apoe/Cd36 double-null mice. Based on transcriptomics data and differential gene expression analysis, we identified a previously undefined group of ATM displaying low viability and high lipid metabolism and labeled them as "unhealthy macrophages". Their phenotypes suggest a subpopulation of ATM under lipid stress. We also identified lipid-associated macrophages (LAM), which were previously described in obesity. Interestingly, LAM increased 8.4-fold in Apoe/Cd36 double-null mice on an atherogenic diet, but not in Apoe-null mice. The increase in LAM was accompanied by more ATM lipid uptake, reduced adipocyte hypertrophy, and less inflammation. In conclusion, CD36 mediates a delicate balance between lipid metabolism and inflammation in visceral adipose tissues. Under atherogenic conditions, CD36 deficiency reduces inflammation and increases lipid metabolism in WAT by promoting LAM accumulation.

SPIN1 facilitates chemoresistance and HR repair by promoting Tip60 binding to H3K9me3.

The tandem Tudor-like domain-containing protein Spindlin1 (SPIN1) is a transcriptional coactivator with critical functions in embryonic development and emerging roles in cancer. However, the involvement of SPIN1 in DNA damage repair has remained unclear. Our study shows that SPIN1 is recruited to DNA lesions through its N-terminal disordered region that binds to Poly-ADP-ribose (PAR), and facilitates homologous recombination (HR)-mediated DNA damage repair. SPIN1 promotes H3K9me3 accumulation at DNA damage sites and enhances the interaction between H3K9me3 and Tip60, thereby promoting the activation of ATM and HR repair. We also show that SPIN1 increases chemoresistance. These findings reveal a novel role for SPIN1 in the activation of H3K9me3-dependent DNA repair pathways, and suggest that SPIN1 may contribute to cancer chemoresistance by modulating the efficiency of double-strand break (DSB) repair.

CTAC Self-Assembled Alkylated ß-Cyclodextrin Loaded onto Functionalized MWCNTs Electrochemical Sensor for NP Detection.

Nonylphenol (NP) is an important fine chemical raw material and intermediate that is widely utilized in industry and may be distributed in aquatic ecosystems. Following its entry into the food and water cycles, it can subsequently enter the human body and potentially harm the human reproductive system. For the purpose of monitoring NP in water, it is thus essential to build a straightforward, affordable, and robust electrochemical sensor. Based on a two-step chemical modification proceeding and an electrostatic self-assembly effect, a double-modified ß-cyclodextrin functionalized multiwalled carbon nanotube sensor (HE-ß-CD-CTAC/F-MWCNTs) has been successfully constructed. It incorporates the excellent host-guest interaction ability of ß-cyclodextrin and the high chemical activity of cetyltrimethylammonium chloride (CTAC), and the carbon nanotubes have an enormous particular surface area and strong electrical conductivity. The electrochemical oxidation reaction of NP with the sensor is controlled by a surface adsorption process of equal numbers of protons and electrons. In accordance with the optimized experimental parameters, the limit of detection (LOD) for the sensor is 0.13 µM, and it responds linearly to NP in the concentration range of 1-200 µM. Meanwhile, the sensor has excellent repeatability, stability, and immunity to interference. For the detection of NP in real water samples, the sensor also showed an excellent recovery rate (92.8%-98.5%) and relative standard deviation (1.16%-3.26%).

Gradual Change between Coherent and Incoherent Tunneling Regimes Induced by Polarizable Halide Substituents in Molecular Tunnel Junctions.

This paper describes a gradual transition of charge transport across molecular junctions from coherent to incoherent tunneling by increasing the number and polarizability of halide substituents of phenyl-terminated aliphatic monolayers of the form S(CH2)10OPhXn, X = F, Cl, Br, or I; n = 0, 1, 2, 3, or 5. In contrast to earlier work where incoherent tunneling was induced by introducing redox-active groups or increasing the molecular length, we show that increasing the polarizability, while keeping the organization of the monolayer structure unaltered, results in a gradual change in the mechanism of tunneling of charge carriers where the activation energy increased from 23 meV for n = 0 (associated with coherent tunneling) to 257 meV for n = 5 with X = Br (associated with incoherent tunneling). Interestingly, this increase in incoherent tunneling rate with polarizability resulted in an improved molecular diode performance. Our findings suggest an avenue to improve the electronic function of molecular devices by introducing polarizable atoms.

Severe sepsis induced by zoledronic acid: A case report.

RATIONALE: Zoledronic acid is one of the most commonly used intravenous, highly potent amino diphosphonate salts worldwide and is commonly used in patients with primary or secondary osteoporosis, most of whom are well tolerated. There are currently no reports of severe sepsis induced by zoledronic acid. Here we present the first case of severe sepsis induced by zoledronic acid. We reviewed the literature and found that there is currently a lack of reports on severe sepsis induced by zoledronic acid or other diphosphonates. PATIENT CONCERNS: A 58-year-old woman with severe osteoporosis and Behcet disease developed severe sepsis after treatment with zoledronic acid. DIAGNOSIS: Sepsis, septic shock, acute kidney injury, intestinal infection, Behcet disease. INTERVENTIONS: The patient was given intensive care immediately after admission, and massive fluid infusion to expand blood volume could not maintain normal blood pressure. Metaraminol was added to maintain circulatory stability, piperacillin-tazobactam was used to strengthen anti-infection, and glucocorticoids were used for anti-inflammatory treatment. OUTCOMES: The patient was discharged with improvement and followed up in the outpatient clinic. LESSONS: The inducing mechanism of zoledronic acid is not clear, but when the patient has immunosuppression, the use of zoledronic acid should be cautious and monitored. In conclusion, severe sepsis induced by zoledronic acid is a rare but serious complication, and physicians should be aware of this adverse event in time to avoid serious consequences.

YAP Alleviates Pulmonary Fibrosis Through Promoting Alveolar Regeneration via Modulating the Stemness of Alveolar Type 2 Cells.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no cure except transplantation. Abnormal alveolar epithelial regeneration is a key driver of IPF development. The function of Yes1 Associated Transcriptional Regulator (YAP) in alveolar regeneration and IPF pathogenesis remains elusive. Here, we first revealed the activation of YAP in alveolar epithelium 2 cells (AEC2s) from human IPF lungs and fibrotic mouse lungs. Notably, conditional deletion of YAP in mouse AEC2s exacerbated bleomycin-induced pulmonary fibrosis. Intriguingly, we showed in both conditional knockout mice and alveolar organoids that YAP deficiency impaired AEC2 proliferation and differentiation into alveolar epithelium 1 cells (AEC1s). Mechanistically, YAP regulated expression levels of genes associated with cell cycle progression and AEC1 differentiation. Furthermore, overexpression of YAP in vitro promoted cell proliferation. These results indicate the critical role of YAP in alveolar regeneration and IPF pathogenesis. Our findings provide new insights into the regulation of alveolar regeneration and IPF pathogenesis, paving the road for developing novel treatment strategies.

Nanozyme-Enabled Biomedical Diagnosis: Advances, Trends, and Challenges.

As nanoscale materials with the function of catalyzing substrates through enzymatic kinetics, nanozymes are regarded as potential alternatives to natural enzymes. Compared to protein-based enzymes, nanozymes exhibit attractive characteristics of low preparation cost, robust activity, flexible performance adjustment, and versatile functionalization. These advantages endow them with wide use from biochemical sensing and environmental remediation to medical theranostics. Especially in biomedical diagnosis, the feature of catalytic signal amplification provided by nanozymes makes them function as emerging labels for the detection of biomarkers and diseases, with rapid developments observed in recent years. To provide a comprehensive overview of recent progress made in this dynamic field, here an overview of biomedical diagnosis enabled by nanozymes is provided. This review first summarizes the synthesis of nanozyme materials and then discusses the main strategies applied to enhance their catalytic activity and specificity. Subsequently, representative utilization of nanozymes combined with biological elements in disease diagnosis is reviewed, including the detection of biomarkers related to metabolic, cardiovascular, nervous, and digestive diseases as well as cancers. Finally, some development trends in nanozyme-enabled biomedical diagnosis are highlighted, and corresponding challenges are also pointed out, aiming to inspire future efforts to further advance this promising field.

The effect of Ba Duan Jin exercise intervention on cardiovascular disease: a meta-analysis of randomized controlled trials.

Background: There is a growing interest in the use of complementary therapies for the prevention of disease and the maintenance of health. Furthermore, complementary therapies that incorporate exercise are becoming increasingly prevalent among the older adult, and thus may represent a crucial strategy for the primary and secondary prevention of cardiovascular disease (CVD). Exercise therapy, as a means to prevent and treat cardiovascular diseases, has been gradually applied in clinical practice. It has the advantages of reducing mortality, improving clinical symptoms, restoring physical function and improving quality of life. In recent years, traditional Chinese sports such as Ba Duan Jin and Qigong have developed rapidly. Therefore, a comprehensive systematic review is required to examine interventions involving Ba Duan Jin exercise in healthy adults or those at increased risk of CVD in order to determine the effectiveness of Ba Duan Jin exercise for the primary prevention of CVD. Objective: To investigate the effect of Ba Duan Jin exercise intervention for the primary prevention of cardiovascular diseases. Methods: Eight databases were systematically searched from inception to July, 2024 for randomized controlled trials (RCTs) to evaluated the impact of Ba Duan Jin exercise intervention on cardiovascular diseases. The search terms were "Cardiovascular diseases" "Ba Duan Jin" and "Randomized controlled." The Cochrane risk assessment tool was used to evaluate the study quality, and the meta-analysis was performed using Rev. Man 5.4 software. Results: Seventeen completed trials were conducted with 1,755 participants who were randomly assigned and met the inclusion criteria. All 17 studies were conducted in China. The meta-analysis indicates that Ba Duan Jin exercise therapy can provide long-term benefits (20-30 years) by reducing all-cause mortality (RR = 0.55, 95% CI: 0.44-0.68, p < 0.01) and stroke mortality (RR = 0.49, 95% CI: 0.36-0.66, p < 0.01) in hypertensive patients. Subgroup analyses reveal that Ba Duan Jin exercise therapy decreases SBP (MD = -4.05, 95% CI = -6.84 to -1.26, p < 0.01) and DBP (MD = -3.21, 95% CI = -5.22 to -1.20, p < 0.01) levels in patients with essential hypertension, significantly reduces serum TC (MD = -0.78, 95% CI = -1.06 to -0.50, p < 0.01), TG (MD = -0.78, 95% CI = -0.93 to -0.62, p < 0.01), and LDL-C (MD = -0.76, 95% CI = -0.92 to -0.60, p < 0.01) levels in patients with hyperlipidemia, increases HDL-C (MD = 0.32, 95% CI = 0.14-0.51, p < 0.01) levels, and produces beneficial effects on cardiovascular function. Additionally, it can alleviate anxiety (MD = -3.37, 95% CI = -3.84 to -2.89, p < 0.01) and improve sleep quality (MD = -2.68, 95% CI = -3.63to -1.73, p < 0.01). Conclusion: Ba Duan Jin exercise therapy can improve the physical and mental condition and quality of life of patients with cardiovascular diseases, and it is worthy of further promotion and application in clinical practice. Systematic review registration: PROSPERO, identifier: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024496934.

CMOS-compatible reconstructive spectrometers with self-referencing integrated Fabry-Perot resonators.

Miniaturized reconstructive spectrometers play a pivotal role in on-chip and portable devices, offering high-resolution spectral measurement through precalibrated spectral responses and AI-driven reconstruction. However, two key challenges persist for practical applications: artificial intervention in algorithm parameters and compatibility with complementary metal-oxide-semiconductor (CMOS) manufacturing. We present a cutting-edge miniaturized reconstructive spectrometer that incorporates a self-adaptive algorithm referenced with Fabry-Perot resonators, delivering precise spectral tests across the visible range. The spectrometers are fabricated with CMOS technology at the wafer scale, achieving a resolution of ~2.5 nm, an average wavelength deviation of ~0.27 nm, and a resolution-to-bandwidth ratio of ~0.46%. Our approach provides a path toward versatile and robust reconstructive miniaturized spectrometers and facilitates their commercialization.

[Effect of 2-phenylethyl-beta-glucopyranoside isolated from Huaizhong No. 1 Rehmannia glutinosa on hypoxic pulmonary hypertension by regulating PI3K/Akt/m TOR/HIF-1α pathway].

The study investigated the protective effect and mechanism of 2-phenylethyl-beta-glucopyranoside(Phe) from Huaizhong No.1 Rehmannia glutinosa on hypoxic pulmonary hypertension(PH), aiming to provide a theoretical basis for clinical treatment of PAH. Male C57BL/6N mice were randomly divided into normal group, model group, positive drug(bosentan, 100 mg·kg~(-1)) group, and low-and high-dose Phe groups(20 and 40 mg·kg~(-1)). Except for the normal group, all other groups were continuously subjected to model induction in a 10% hypoxic environment for 5 weeks, with oral administration for 14 days starting from the 3rd week. The cardiopulmonary function, right ventricular pressure, cough and asthma index, lung injury, cell apoptosis, oxidative stress-related indicators, immune cells, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxic inducible factor 1α(HIF-1α) pathway-related proteins or mRNA levels were examined. Furthermore, hypoxia-induced pulmonary arterial smooth muscle cell(PASMC) were used to further explore the mechanism of Phe intervention in PH combined with PI3K ago-nist(740Y-P). The results showed that Phe significantly improved the cardiopulmonary function of mice with PH, decreased right ventricular pressure, cough and asthma index, and lung injury, reduced cell apoptosis, oxidative stress-related indicators, and nuclear levels of phosphorylated Akt(p-Akt) and phosphorylated mTOR(p-mTOR), inhibited the expression levels of HIF-1α and PI3K mRNA and proteins, and maintained the immune cell homeostasis in mice. Further mechanistic studies revealed that Phe significantly reduced the viability and migration ability of hypoxia-induced PASMC, decreased the expression of HIF-1α and PI3K proteins and nuc-lear levels of p-Akt and p-mTOR, and this effect was blocked by 740Y-P. Therefore, it is inferred that Phe may exert anti-PH effects by alleviating the imbalance of oxidative stress and apoptosis in lung tissues and regulating immune levels, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR/HIF-1α pathway. This study is expected to provide drug references and research ideas for the treatment of PH.

Characterization of linoleate dioxygenases in basidiomycetes and the functional role of CcLdo1 in regulating fruiting body development in Coprinopsis cinerea.

Coprinopsis cinerea, a model fungus, is utilized for investigating the developmental mechanisms of basidiomycetes. The development of basidiomycetes is a highly organized process that requires coordination among genetic, environmental, and physiological factors. Oxylipins, a class of widely distributed signaling molecules, play crucial roles in fungal biology. Among oxylipins, the sexual pheromone-inducing factors (psi factors) have been identified as key regulators of the balance between asexual and sexual spore development in Ascomycetes. Linoleate dioxygenases are enzymes involved in the biosynthesis of psi factors, yet their specific physiological functions in basidiomycete development remain unclear. In this study, linoleate dioxygenases in basidiomycetes were identified and characterized. Phylogenetic analysis revealed that linoleate dioxygenases from Basidiomycota formed a distinct clade, with linoleate dioxygenases from Agaricomycetes segregating into three groups and those from Ustilaginomycetes forming a separate group. Both basidiomycete and ascomycete linoleate dioxygenases shared two characteristic domains: the N-terminal of linoleate dioxygenase domain and the C-terminal of cytochrome P450 domain. While the linoleate dioxygenase domains exhibited similarity between basidiomycetes and ascomycetes, the cytochrome P450 domains displayed high diversity in key sites. Furthermore, the gene encoding the linoleate dioxygenase Ccldo1 in C. cinerea was knocked out, resulting in a significant increase in fruiting body formation without affecting asexual conidia production. This observation suggests that secondary metabolites synthesized by CcLdo1 negatively regulate the sexual reproduction process in C. cinerea while not influencing the asexual reproductive process. This study represents the first identification of a gene involved in secondary metabolite synthesis that regulates basidiocarp development in a basidiomycete.