Integrated genome-wide association and transcriptomic analysis to identify receptor kinase genes to stripe rust resistance in wheat germplasm from southwestern China.

Stripe rust of wheat, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most important diseases of wheat worldwide. Identification of new and elite Pst-resistance loci or genes has the potential to enhance overall resistance to this pathogen. Here, we conducted an integrated genome-wide association study (GWAS) and transcriptomic analysis to screen for loci associated with resistance to stripe rust in 335 accessions from Yunnan, including 311 landraces and 24 cultivars. Based on the environmental phenotype, we identified 113 protein kinases significantly associated with Pst resistance using mixed linear model (MLM) and generalized linear model (GLM) models. Transcriptomic analysis revealed that 52 of 113 protein kinases identified by GWAS were up and down regulated in response to Pst infection. Among these genes, a total of 15 receptor kinase genes were identified associated with Pst resistance. 11 candidate genes were newly discovered in Yunnan wheat germplasm. Our results revealed that resistance alleles to stripe rust were accumulated in Yunnan wheat germplasm, implying direct or indirect selection for improving stripe rust resistance in elite wheat breeding programs.

Pretreatment CD8+PD-1+ to CD4+PD-1+ ratio is associated with the prognosis of advanced melanoma patients treated with PD-1 inhibitors.

The aim of this study is to determine whether the pretreatment CD8+PD-1+ to CD4+PD-1+ (PERLS) ratio is an independent risk prognostic factor of advanced melanoma patients. We retrospectively analyzed the efficacy and flow cytometry data from advanced melanoma patients who received PD-1 inhibitor as monotherapy between January 1, 2018 and January 26, 2022. Fifty-nine patients were enrolled, the PERLS cutoff was 1.125. PERLS did not correlate with clinical characteristics but were significantly associated with baseline CD8+, CD4+, and CD8+PD-1+ T cells. The mean overall survival and the progression-free survival were 45.8 and 17.1 months for the low PERLS group (n = 39), compared with 29.9 (P = 0.001) and 9.7 (P = 0.003) months for the high PERLS group (n = 20), respectively. Pretreatment PERLS might contribute to selecting patients before receiving anti-PD-1 therapy.

Unveiling the activity difference cause and ring-opening reaction routes of typical radicals induced degradation of toluene.

This study employs five UV-AOPs (PMS, PDS, H2O2, NaClO and NaClO2) to produce radicals (•OH, SO4•-, ClO•, O2•- and 1O2) and further comparatively studies their activity sequence and activity difference cause in toluene degradation. The toluene mineralization efficiency as a descending order is 73 % (UV-PMS) > 71 % (UV-PDS) > 70 % (acidified-UV-NaClO) > 55 % (UV-H2O2) > 36 % (UV-NaClO) > 35 % (UV-NaClO2); that of conversion efficiency is 99 % (acidified-UV-NaClO) > 95 % (UV-PMS) > 90 % (UV-PDS) > 74 % (UV-H2O2) > 44 % (UV-NaClO) > 41 % (UV-NaClO2). Acidic pretreatment significantly boosts the reactivity of UV-NaClO. ESR combined with radical quenching tests reveals the radicals' generation and evolution, and their contribution rates to toluene conversion, i.e. ClO• > SO4•- > O2•- > 1O2 > â€¢OH. Theoretical calculations further unveil the ring-opening reaction routes and the nature of the activity difference of different radicals. The minimum energy required for ring-opening reaction is 116.77, 150.63, 168.29 and 191.92 kJ/mol with respect to ClO•, SO4•-, 1O2 and •OH, and finding that the ClO•-HO• pair is the best for toluene mineralization. The difficulty for eliminating typical VOCs by using UV-AOPs method is determined as toluene > chlorobenzene > benzene > ethyl acetate.

C-TERMINAL DOMAIN PHOSPHATASE-LIKE 3 contributes to GA-mediated growth and flowering by interaction with DELLA proteins.

Gibberellic acid (GA) plays a central role in many plant developmental processes and is crucial for crop improvement. DELLA proteins, the core suppressors in the GA signaling pathway, are degraded by GA via the 26S proteasomal pathway to release the GA response. However, little is known about the phosphorylation-mediated regulation of DELLA proteins. In this study, we combined GA response assays with protein-protein interaction analysis to infer the connection between Arabidopsis thaliana DELLAs and the C-TERMINAL DOMAIN PHOSPHATASE-LIKE 3 (CPL3), a phosphatase involved in the dephosphorylation of RNA polymerase II. We show that CPL3 directly interacts with DELLA proteins and promotes DELLA protein stability by inhibiting its degradation by the 26S proteasome. Consequently, CPL3 negatively modulates multiple GA-mediated processes of plant development, including hypocotyl elongation, flowering time, and anthocyanin accumulation. Taken together, our findings demonstrate that CPL3 serves as a novel regulator that could improve DELLA stability and thereby participate in GA signaling transduction.

WTI, Brent or implied volatility index: Perspective of volatility spillover from oil market to Chinese stock market.

This study investigates the impact of oil market uncertainty on the volatility of Chinese sector indexes. We utilize commonly used realized volatility of WTI and Brent oil price along with the CBOE crude oil volatility index (OVX) to embody the oil market uncertainty. Based on the sample span from Mar 16, 2011 to Dec 31, 2019, this study utilizes vector autoregression (VAR) model to derive the impacts of the three different uncertainty indicators on Chinese stock volatilities. The empirical results show, for all sectors, the impact of OVX on sectors volatilities are more economically and statistically significant than that of realized volatility of both WTI and Brent oil prices, especially after the Chinese refined oil pricing reform of March 27, 2013. That implies OVX is more informative than traditional WTI and Brent oil prices with respect to volatility spillover from oil market to Chinese stock market. This study could provide some important implications for the participants in Chinese stock market.

Memristor-based circuit design of episodic memory neural network and its application in hurricane category prediction.

Episodic memory, as a type of long-term memory (LTM), is used to learn and store the unique personal experience. Based on the episodic memory biological mechanism, this paper proposes a bionic episodic memory memristive neural network circuit. The proposed memristive neural network circuit includes a neocortical module, a parahippocampal module and a hippocampus module. The neocortical module with the two paths structure is used to receive the sensory signal, and is also used to separate and transmit the spatial information and the non-spatial information involved in the sensory signal. The parahippocampal module is composed of the parahippocampal cortex-MEA and the perirhinal cortex-LEA, which receives the two types of information from the neocortical module respectively. As the last module, the hippocampus module receives and integrates the output information of the parahippocampal module as well as generates the corresponding episodic memory. Meanwhile, the specific scenario information with the certain temporal signal from the generated episodic memory is also extracted by the hippocampus module. The simulation results in PSPICE show that the proposed memristive neural network circuit can generate the various episodic memories and extract the specific scenario information successfully. By configuring the memristor parameters, the proposed bionic episodic memory memristive neural network circuit can be applied to the hurricane category prediction, which verifies the feasibility of this work.

Sensitivity improvement of subharmonic-based pressure measurement using phospholipid-coated monodisperse microbubbles.

The use of the subharmonic signal from microbubbles exposed to ultrasound is a promising safe and cost-effective approach for the non-invasive measurement of blood pressure. Achieving a high sensitivity of the subharmonic amplitude to the ambient overpressure is crucial for clinical applications. However, currently used microbubbles have a wide size distribution and diverse shell properties. This causes uncertainty in the response of the subharmonic amplitude to changes in ambient pressure, which limits the sensitivity. The aim of this study was to use monodisperse microbubbles to improve the sensitivity of subharmonic-based pressure measurements. With the same shell materials and gas core, we used a flow-focusing microfluidic chip and a mechanical agitation method to fabricate monodisperse (∼2.45-µm mean radius and 4.7 % polydisperse index) and polydisperse microbubbles (∼1.51-µm mean radius and 48.4 % polydisperse index), respectively. We varied the ultrasound parameters (i.e., the frequency, peak negative pressure (PNP) and pulse length), and found that there was an optimal excitation frequency (2.8 MHz) for achieving maximal subharmonic emission for monodisperse microbubbles, but not for polydisperse microbubbles. Three distinct regimes (occurrence, growth, and saturation) were identified in the response of the subharmonic amplitude to increasing PNP for both monodisperse and polydisperse microbubbles. For the polydisperse microbubbles, the subharmonic amplitude decreased either monotonically or non-monotonically with ambient overpressure, depending on the PNP. By contrast, for the monodisperse microbubbles, there was only a monotonic decrease at all PNPs. The maximum sensitivity (1.18 dB/kPa, R2 = 0.97) of the subharmonic amplitude to ambient overpressure for the monodisperse microbubbles was ∼6.5 times higher than that for the polydisperse microbubbles (0.18 dB/kPa, R2 = 0.88). These results show that monodisperse microbubbles can achieve a more consistent response of the subharmonic signal to changes in ambient overpressure and greatly improve the measurement sensitivity.

Identification of adult resistant genes to stripe rust in wheat from southwestern China based on GWAS and WGCNA analysis.

KEY MESSAGE: In this study, genome-wide association studies combined with transcriptome data analysis were utilized to reveal potential candidate genes for stripe rust resistance in wheat, providing a basis for screening wheat varieties for stripe rust resistance. Wheat stripe rust, which is caused by the wheat stripe rust fungus (Puccinia striiformis f. sp. tritici, Pst) is one of the world's most devastating diseases of wheat. Genetic resistance is the most effective strategy for controlling diseases. Although wheat stripe rust resistance genes have been identified to date, only a few of them confer strong and broad-spectrum resistance. Here, the resistance of 335 wheat germplasm resources (mainly wheat landraces) from southwestern China to wheat stripe rust was evaluated at the adult stage. Combined genome-wide association study (GWAS) and weighted gene co-expression network analysis (WGCNA) based on RNA sequencing from stripe rust resistant accession Y0337 and susceptible accession Y0402, five candidate resistance genes to wheat stripe rust (TraesCS1B02G170200, TraesCS2D02G181000, TraesCS4B02G117200, TraesCS6A02G189300, and TraesCS3A02G122300) were identified. The transcription level analyses showed that these five genes were significantly differentially expressed between resistant and susceptible accessions post inoculation with Pst at different times. These candidate genes could be experimentally transformed to validate and manipulate fungal resistance, which is beneficial for the development of the wheat cultivars resistant to stripe rust.

Integration of transcriptome and metabolome reveals the accumulation of related metabolites and gene regulation networks during quinoa seed development.

Quinoa seeds are gluten- and cholesterol-free, contain all amino acids required by the human body, have a high protein content, provide endocrine regulation, protein supplementation, and cardiovascular protection effects. However, metabolite accumulation and transcriptional regulatory networks in quinoa seed development are not well understood. Four key stages of seed development in Dianli-3260 and Dianli-557 were thus analyzed and 849 metabolites were identified, among which sugars, amino acids, and lipids were key for developmental processes, and their accumulation showed a gradual decrease. Transcriptome analysis identified 40,345 genes, of which 20,917 were differential between the M and F phases, including 8279 and 12,638 up- and down-regulated genes, respectively. Grain development processes were mainly enriched in galactose metabolism, pentose and glucuronate interconversions, the biosynthesis of amino acids, and carbon metabolism pathways, in which raffinose, phosphoenolpyruvate, series and other metabolites are significantly enriched, gene-LOC110689372, Gene-LOC110710556 and gene-LOC110714584 are significantly expressed, and these metabolites and genes play an important role in carbohydrate metabolism, lipid and Amino acid synthesis of quinoa. This study provides a theoretical basis to expand our understanding of the molecular and metabolic development of quinoa grains.

Integrative metabolome and transcriptome profiling provide insights into elucidation of the synthetic mechanisms of phenolic compounds in Yunnan hulled wheat (Triticum aestivum ssp. yunnanense King).

BACKGROUND: Yunnan hulled wheat grains (YHWs) have abundant phenolic compounds (PCs). However, a systematic elucidation of the phenolic characteristics and molecular basis in YHWs is currently lacking. The aim of the study, for the first time, was to conduct metabolomic and transcriptomic analyses of YHWs at different developmental stages. RESULTS: A total of five phenolic metabolite classes (phenolic acids, flavonoids, quinones, lignans and coumarins, and tannins) and 361 PCs were identified, with flavonoids and phenolic acids being the most abundant components. The relative abundance of the identified PCs showed a dynamic decreasing pattern with grain development, and the most significant differences in accumulation were between the enlargement and mature stage, which is consistent with the gene regulation patterns of the corresponding phenolic biosynthesis pathway. Through co-expression and co-network analysis, PAL, HCT, CCR, F3H, CHS, CHI and bZIP were identified and predicted as candidate key enzymes and transcription factors. CONCLUSION: The results broaden our understanding of PC accumulation in wheat whole grains, especially the differential transfer between immature and mature grains. The identified PCs and potential regulatory factors provide important information for future in-depth research on the biosynthesis of PCs and the improvement of wheat nutritional quality. © 2024 Society of Chemical Industry.

Effects of meteorological factors on influenza transmissibility by virus type/subtype.

BACKGROUND: Quantitative evidence on the impact of meteorological factors on influenza transmissibility across different virus types/subtypes is scarce, and no previous studies have reported the effect of hourly temperature variability (HTV) on influenza transmissibility. Herein, we explored the associations between meteorological factors and influenza transmissibility according to the influenza type and subtype in Guangzhou, a subtropical city in China. METHODS: We collected influenza surveillance and meteorological data of Guangzhou between October 2010 and December 2019. Influenza transmissibility was measured using the instantaneous effective reproductive number (Rt). A gamma regression with a log link combined with a distributed lag non-linear model was used to assess the associations of daily meteorological factors with Rt by influenza types/subtypes. RESULTS: The exposure-response relationship between ambient temperature and Rt was non-linear, with elevated transmissibility at low and high temperatures. Influenza transmissibility increased as HTV increased when HTV < around 4.5 °C. A non-linear association was observed between absolute humidity and Rt, with increased transmissibility at low absolute humidity and at around 19 g/m3. Relative humidity had a U-shaped association with influenza transmissibility. The associations between meteorological factors and influenza transmissibility varied according to the influenza type and subtype: elevated transmissibility was observed at high ambient temperatures for influenza A(H3N2), but not for influenza A(H1N1)pdm09; transmissibility of influenza A(H1N1)pdm09 increased as HTV increased when HTV < around 4.5 °C, but the transmissibility decreased with HTV when HTV < 2.5 °C and 3.0 °C for influenza A(H3N2) and B, respectively; positive association of Rt with absolute humidity was witnessed for influenza A(H3N2) even when absolute humidity was larger than 19 g/m3, which was different from that for influenza A(H1N1)pdm09 and influenza B. CONCLUSIONS: Temperature variability has an impact on influenza transmissibility. Ambient temperature, temperature variability, and humidity influence the transmissibility of different influenza types/subtypes discrepantly. Our findings have important implications for improving preparedness for influenza epidemics, especially under climate change conditions.

Exploration of quality variation and stability of hybrid rice under multi-environments.

Improving quality is an essential goal of rice breeding and production. However, rice quality is not solely determined by genotype, but is also influenced by the environment. Phenotype plasticity refers to the ability of a given genotype to produce different phenotypes under different environmental conditions, which can be a representation of the stability of traits. Seven quality traits of 141 hybrid combinations, deriving from the test-crossing of 7 thermosensitive genic male sterile (TGMS) and 25 restorer lines, were evaluated at 5 trial sites with intermittent sowing of three to five in Southern China. In the Yangtze River Basin, it was observed that delaying the sowing time of hybrid rice combinations leads to an improvement in their overall quality. Twelve parents were identified to have lower plasticity general combing ability (GCA) values with increased ability to produce hybrids with a more stable quality. The parents with superior quality tend to exhibit lower GCA values for plasticity. The genome-wide association study (GWAS) identified 13 and 15 quantitative trait loci (QTLs) associated with phenotype plasticity and BLUP measurement, respectively. Notably, seven QTLs simultaneously affected both phenotype plasticity and BLUP measurement. Two cloned rice quality genes, ALK and GL7, may be involved in controlling the plasticity of quality traits in hybrid rice. The direction of the genetic effect of the QTL6 (ALK) on alkali spreading value (ASV) plasticity varies in different cropping environments. This study provides novel insights into the dynamic genetic basis of quality traits in response to different cropping regions, cultivation practices, and changing climates. These findings establish a foundation for precise breeding and production of stable and high-quality rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01442-3.

Directed evolution of Baeyer-Villiger monooxygenase for highly secretory expressed in Pichia pastoris and efficient preparation of chiral pyrazole sulfoxide.

The methylotrophic yeast Pichia pastoris (Komagataella phaffii) is a highly distinguished expression platform for the excellent synthesis of various heterologous proteins in recent years. With the advantages of high-density fermentation, P. pastoris can produce gram amounts of recombinant proteins. While not every protein of interest can be expressed to such high titers, such as Baeyer-Villiger monooxygenase (BVMO) (AcPSMO) which is responsible for pyrazole sulfide asymmetric oxidation. In this work, an excellent yeast expression system was established to facilitate efficient AcPSMO expression, which exhibited 9.5-fold enhanced secretion. Subsequently, an ultrahigh throughput screening method based on fluorescence-activated cell sorting by fusing super folder green fluorescent protein (sfGFP) in the C-terminal of AcPSMO was developed, and directed evolution was performed. The protein expression level of the superior mutant AcPSMOP1 (S58T/T252P/E336N/H456D) reached 84.6 mg/L at 100 mL shaking flask, which was 4.7 times higher than the levels obtained with the wild-type. Finally, the optimized chassis cells were used for high-density fermentation on a 5-L scale, and AcPSMOP1 protein yield of 3.4 g/L was achieved, representing approximately 85% of the total protein secreted. By directly employing the pH-adjusted supernatant as a biocatalyst, 20 g/L pyrmetazole sulfide was completely transformed into the corresponding (S)-sulfoxide, with a 78.8% isolated yield. This work confers dramatic benefits for efficient secretion of other BVMOs in P. pastoris.

SKI-349, a Sphingosine Kinases 1/2 Inhibitor, Suppresses Cell Viability, Invasion, and AKT/mTOR Signaling Pathway, and Shows Synergistic Cytotoxic Effects with Sorafenib in Hepatocellular Carcinoma.

SKI-349 is a novel sphingosine kinases (SPHK) inhibitor with anti-tumor effects. This study aimed to assess the effect of SKI-349 on cell biological behaviors, downstream pathways, and its synergistic effect with sorafenib in hepatocellular carcinoma (HCC). HCC cell lines (Huh7 and Hep3B) were treated with SKI-349 at concentrations of 1, 2, 4, or 8 µM. Then, SPHK1/2 activity, cell viability, proliferation, apoptosis, invasion, and protein expressions of phosphorylated-protein kinase B (p-AKT), AKT, phosphorylated-mammalian target of rapamycin (p-mTOR) and mTOR were detected. Combination index values of SKI-349 (0, 1, 2, 4, or 8 µM) and sorafenib (0, 2.5, 5, 10, or 20 µM) were calculated. SKI-349 decreased the relative SPHK1 and SPHK2 activity compared with blank control in a dose-dependent manner in the Huh7 and Hep3B cell lines. Meanwhile, SKI-349 reduced cell viability, 5-ethynyl-2'-deoxyuridine (EdU) positive cells, and invasive cells, while it increased apoptotic cells compared to blank control in a dose-dependent manner in Huh7 and Hep3B cell lines. Based on the western blot assay, SKI-349 decreased the ratio of p-AKT to AKT and that of p-mTOR to mTOR compared with blank control in a dose-dependent manner in the Huh7 and Hep3B cell lines. Additionally, SKI-349 combined with sorafenib declined cell viability with concentration gradient effects compared to SKI-349 sole treatment, and they had synergistic cytotoxic effects in Huh7 and Hep3B cell lines. SKI-349 suppresses SPHK1 and SPHK2 activity, cell viability, invasion, and AKT/mTOR signaling pathway, as well as exhibits a synergistic cytotoxic effect with sorafenib in HCC.

Hydroxyl and amino dual-functionalized core-shell molecular sieves featuring hydrogen bond donor groups for efficient CO2 cycloaddition.

In CO2 cycloaddition reactions, hydrogen bond donor (HBD) groups are considered environmentally friendly substitutes for metals to promote epoxide ring-opening through interactions with nucleophilic anions. A core-shell structured ILs-based catalyst (mSiO2@MCM-NH2-OH) with dual hydrogen bond donors (-OH and -NH2) was synthesized by copolymerization strategy. Through in-depth characterization, it has been demonstrated that the catalyst (mSiO2@MCM-NH2-OH) possesses multiple catalytic active sites including -OH, -NH2, Br- groups, and the synergistic effect of double HBD groups (-OH and -NH2) and Lewis base (Br-) significantly improved the catalytic activity. Meanwhile, the core-shell structure of the catalyst effectively prevents the loss of active components, which makes the yield remain at about 94 % after 10 cycles. Based on Density Functional Theory (DFT) calculations, a synergistic catalytic mechanism, which involves dual hydrogen-bond donors (-OH and -NH2) and Lewis bases (Br-) was proposed. The cooperative interaction between -OH/-NH2 and Br- reduced the ring-opening barrier of epoxide from 58.6 to 32.0 kcal mol-1 significantly, and thereby facilitated the CO2 cycloaddition reaction.

The inter-link of ageing, cancer and immunity: findings from real-world retrospective study.

BACKGROUND: Although the concept of declined immune function associated with cancer has been accepted extensively, real-world clinical studies focusing on analysis of the peripheral blood immune changes underlying ageing, immunity and cancer are scarce. METHODS: In this case-control study, we retrospectively analysed 1375 cancer patients and enrolled 275 age and gender matched healthy individuals. Flow cytometry was conducted to assess the immune changes. Further analysis was examined by SPSS 17.0 and GraphPad Prism 9 software. RESULTS: Cancer patients showed obviously decreased CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B, CD16+CD56+ NK cell counts and lower percentage of PD-1 (programmed cell death protein-1, PD-1) positive cells than healthy control (P < 0.0001). For cancer patients, the reference range of circulating percentage of PD-1+CD45+ cells, PD-1+CD3+ T cells, PD-1+CD3+CD4+ Th cells and PD-1+CD3+CD8+ CTL (Cytotoxic T Lymphocyte, CTL) were 11.2% (95% CI 10.8%-11.6%), 15.5% (95% CI 14.7%-16.0%), 15.4% (95% CI 14.9%-16.0%) and 14.5% (95% CI 14.0%-15.5%), respectively. Moreover, the reduction of CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B cell counts accompanied with age and stage advancing (P < 0.05). CD16+CD56+ NK cells decreased with stage, but elevated in aged and male cancer patients (P < 0.05). Additionally, the percentage of PD-1 positive cells varied across cancer types, raised with age and stage. Head and neck, pancreatic, gynaecological and lung demonstrated a higher level of the percentage of PD-1 positive cells than melanoma, prostate, and breast cancer (P < 0.05). CONCLUSIONS: This study provides the reference range of the percentage of PD-1 positive cells on peripheral blood, confirms the decreased immune cells and a series of immune changes accompanying with cancer, expands our real world evidence to better understand the interactions of ageing, cancer and immunity. Moreover, the circulating percentage of PD-1 positive cells shows similar tumor type distribution with tumor mutational burden (TMB), supports that it maybe a potential predictive biomarker for immune checkpoint inhibitor therapy.

Ursolic acid: biological functions and application in animal husbandry.

Ursolic acid (UA) is a plant-derived pentacyclic triterpenoid with 30 carbon atoms. UA has anti-inflammatory, antioxidative, antimicrobial, hepato-protective, anticancer, and other biological activities. Most studies on the biological functions of UA have been performed in mammalian cell (in vitro) and rodent (in vivo) models. UA is used in animal husbandry as an anti-inflammatory and antiviral agent, as well as for enhancing the integrity of the intestinal barrier. Although UA has been shown to have significant in vitro bacteriostatic effects, it is rarely used in animal nutrition. The use of UA as a substitute for oral antibiotics or as a novel feed additive in animal husbandry should be considered. This review summarizes the available data on the biological functions of UA and its applications in animal husbandry.

Research on atrial fibrillation mechanisms and prediction of therapeutic prospects: focus on the autonomic nervous system upstream pathways.

Atrial fibrillation (AF) is the most common clinical arrhythmia disorder. It can easily lead to complications such as thromboembolism, palpitations, dizziness, angina, heart failure, and stroke. The disability and mortality rates associated with AF are extremely high, significantly affecting the quality of life and work of patients. With the deepening of research into the brain-heart connection, the link between AF and stroke has become increasingly evident. AF is now categorized as either Known Atrial Fibrillation (KAF) or Atrial Fibrillation Detected After Stroke (AFDAS), with stroke as the baseline. This article, through a literature review, briefly summarizes the current pathogenesis of KAF and AFDAS, as well as the status of their clinical pharmacological and non-pharmacological treatments. It has been found that the existing treatments for KAF and AFDAS have limited efficacy and are often associated with significant adverse reactions and a risk of recurrence. Moreover, most drugs and treatment methods tend to focus on a single mechanism pathway. For example, drugs targeting ion channels primarily modulate ion channels and have relatively limited impact on other pathways. This limitation underscores the need to break away from the "one disease, one target, one drug/measurement" dogma for the development of innovative treatments, promoting both drug and non-drug therapies and significantly improving the quality of clinical treatment. With the increasing refinement of the overall mechanisms of KAF and AFDAS, a deeper exploration of physiological pathology, and comprehensive research on the brain-heart relationship, it is imperative to shift from long-term symptom management to more precise and optimized treatment methods that are effective for almost all patients. We anticipate that drugs or non-drug therapies targeting the central nervous system and upstream pathways can guide the simultaneous treatment of multiple downstream pathways in AF, thereby becoming a new breakthrough in AF treatment research.

TMT and PRM Based Quantitative Proteomics to Explore the Protective Role and Mechanism of Iristectorin B in Stroke.

Stroke is a serious disease caused by the rupture or blockage of the cerebrovascular system. Its pathogenesis is complex and involves multiple mechanisms. Iristectorin B is a natural isoflavone that has certain anti stroke effects. In this study, an in vitro stroke injury model of glyoxylate deprivation was established using PC12 cells, which was used to evaluate the anti-stroke activity of Iristectorin B in ejecta stem. The results showed that Iristectorin B, a natural isoflavone derived from Dried Shoot, significantly reduced the damage to PC12 cells caused by oxygen glucose deprivation/reoxygenation, decreased apoptosis, enhanced cell survival and reduced Ca2+, LDH and ROS levels. The results showed that Iristectorin B had a significant protective effect on Na2S2O4-injured PC12 cells, and the mechanism may be related to the protective effect of neurons in the brain. After protein extraction and various analyses were performed, a series of cutting-edge technologies were organically combined to study the quantitative proteome of each group. Differential proteins were then analyzed. According to the protein screening principle, ferroptosis-related proteins were most closely associated with stroke. The differential proteins associated with ferroptosis screened were SLC3A2, TFR1 and HMOX1, with HMOX1 being the most significantly elevated and reduced via dosing. Iristectorin B may act as a protective agent against stroke by regulating ferroptosis, and SLC3A2, TFR1 and HMOX1 may serve as potential diagnostic biomarkers for stroke, providing additional evidence to support the importance of ferroptosis in stroke.