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BACKGROUND AND PURPOSE: Bifunctional small molecule degraders, which link the target protein with E3 ubiquitin ligase, could lead to the efficient degradation of the target protein. BGB-16673 is a Bruton's tyrosine kinase (BTK) degrader. A translational PK/PD modelling approach was used to predict the human BTK degradation of BGB-16673 from preclinical in vitro and in vivo data. EXPERIMENTAL APPROACH: A simplified mechanistic PK/PD model was used to establish the correlation between the in vitro and in vivo BTK degradation by BGB-16673 in a mouse model. Human and mouse species differences were compared using the parameters generated from in vitro human or mouse blood, and human or mouse serum spiked TMD-8 cells. Human PD was then predicted using the simplified mechanistic PK/PD model. KEY RESULTS: BGB-16673 showed potent BTK degradation in mouse whole blood, human whole blood, and TMD-8 tumour cells in vitro. Furthermore, BGB-16673 showed BTK degradation in a murine TMD-8 xenograft model in vivo. The PK/PD model predicted human PD and the observed BTK degradation in clinical studies both showed robust BTK degradation in blood and tumour at clinical dose range. CONCLUSION AND IMPLICATIONS: The presented simplified mechanistic model with reduced number of model parameters is practically easier to be applied to research projects compared with the full mechanistic model. It can be used as a tool to better understand the PK/PD behaviour for targeted protein degraders and increase the confidence when moving to the clinical stage.

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In recent decades, the escalating frequency of environmental risk events, arising from sources such as industrial accidents, chemical spills, or other anthropogenic activities, has intensified threats to the ecological environment. The targeted identification of high-risk areas, formulation of control lists for key risk sources within regions, and the implementation of differentiated management strategies remain significant challenges. This study employed an administrative region environmental risk assessment and gridded environmental risk analysis method to comprehensively evaluate the environmental risks in the city of Kunming, China. The results indicated a fourfold increase in the number of environmental risk sources from 2012 to 2022. The sources were found to be widely distributed across the entire region but exhibited localized clustering. The environmental risk receptors were primarily concentrated around a local lake, in densely populated counties, and near rivers and drinking water sources. Risk hotspot areas within the target region were identified using the gridded environmental risk analysis method. A list of 29 key control areas was proposed, including nine industrial parks and 20 streets. Measures were proposed for handling unexpected incidents. The findings provide data useful for policy formulation and environmental management in similar regions of mountainous cities.

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The design and preparation of anode materials with structural stability, fast ion transmission, and low open-circuit voltage are critical to the development of magnesium ion batteries (MIBs). The feasibility of the unique phase Haeckelite MoS2 (Hae-MoS2) monolayer with Haeckelite structure as a potential anode material for MIBs was investigated using density functional theory (DFT) calculations. The Hae-MoS2 monolayer exhibits excellent structural stability and semimetallic characteristics with a Dirac cone located at the Gamma point of band structure. Mg ion is easily adsorbed on the Hae-MoS2 monolayer surface with an adsorption energy of -2.06 eV and can diffuse rapidly with a low diffusion energy barrier (0.3 eV), indicating excellent charge and discharge rates. Most importantly, the Hae-MoS2 monolayer exhibits a suitable open-circuit voltage, which falls within the desired voltage range and ensures the safety of battery performance. These exceptional properties indicate that the Hae-MoS2 monolayer can be proposed as a candidate for anode material for MIBs.

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OBJECTIVE: Major depressive disorder (MDD) is often accompanied by psychotic symptoms. However, few studies have examined the relationship between psychotic symptoms and endocrine factors in adolescent patients with MDD. Therefore, this study aimed to investigate the prevalence and related endocrine clinical factors of psychotic symptoms in Chinese adolescent patients with MDD. METHODS: In total, 601 patients (aged 12-18) with MDD were recruited. The Patient Health Questionnaire - 9 items (PHQ - 9) was utilized for assessing depressive symptoms. Psychotic symptoms were assessed through clinical interviews. Prolactin (PRL), thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), and free thyroxine (FT4) were also measured. RESULTS: The incidence of psychotic symptoms in adolescent patients with MDD was 22.6%. The findings demonstrated that age, self-harming behavior, PHQ-9 score, FT4, and normalized PRL were independently associated with psychotic symptoms in patients with MDD (All p < 0.05). CONCLUSIONS: PRL and FT4 levels are more likely to be abnormally elevated in major depressive adolescents with psychotic symptoms. Prolactin and thyroid hormones in patients with MDD should be paid more attention.

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Escherichia coli O157:H7 is a major foodborne pathogen that poses a significant threat to food safety and human health. Rapid and sensitive detection of viable Escherichia coli O157:H7 can effectively prevent food poisoning. Here, we developed a microwell-confined and propidium monoazide-assisted digital CRISPR microfluidic platform for rapid and sensitive detection of viable Escherichia coli O157:H7 in food samples. The reaction time is significantly reduced by minimizing the microwell volume, yielding qualitative results in 5 min and absolute quantitative results in 15 min. With the assistance of propidium monoazide, this platform can eliminate the interference from 99% of dead Escherichia coli O157:H7. The direct lysis method obviates the need for a complex nucleic acid extraction process, offering a limit of detection of 3.6 × 101 CFU mL-1 within 30 min. Our results demonstrated that the platform provides a powerful tool for rapid detection of Escherichia coli O157:H7 and provides reliable guidance for food safety testing.

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BACKGROUND: Cardiac hypertrophy and its associated remodeling are among the leading causes of heart failure. Lysine crotonylation is a recently discovered posttranslational modification whose role in cardiac hypertrophy remains largely unknown. NAE1 (NEDD8-activating enzyme E1 regulatory subunit) is mainly involved in the neddylation modification of protein targets. However, the function of crotonylated NAE1 has not been defined. This study aims to elucidate the effects and mechanisms of NAE1 crotonylation on cardiac hypertrophy. METHODS: Crotonylation levels were detected in both human and mouse subjects with cardiac hypertrophy through immunoprecipitation and Western blot assays. TMT-labeled quantitative lysine crotonylome analysis was performed to identify the crotonylated proteins in a mouse cardiac hypertrophic model induced by transverse aortic constriction. We generated NAE1 knock-in mice carrying a crotonylation-defective lysine to arginine K238R (lysine to arginine mutation at site 238) mutation (NAE1 K238R) and NAE1 knock-in mice expressing a crotonylation-mimicking lysine to glutamine K238Q (lysine to glutamine mutation at site 238) mutation (NAE1 K238Q) to assess the functional role of crotonylation of NAE1 at K238 in pathological cardiac hypertrophy. Furthermore, we combined coimmunoprecipitation, mass spectrometry, and dot blot analysis that was followed by multiple molecular biological methodologies to identify the target GSN (gelsolin) and corresponding molecular events contributing to the function of NAE1 K238 crotonylation. RESULTS: The crotonylation level of NAE1 was increased in mice and patients with cardiac hypertrophy. Quantitative crotonylomics analysis revealed that K238 was the main crotonylation site of NAE1. Loss of K238 crotonylation in NAE1 K238R knock-in mice attenuated cardiac hypertrophy and restored the heart function, while hypercrotonylation mimic in NAE1 K238Q knock-in mice significantly enhanced transverse aortic constriction-induced pathological hypertrophic response, leading to impaired cardiac structure and function. The recombinant adenoviral vector carrying NAE1 K238R mutant attenuated, while the K238Q mutant aggravated Ang II (angiotensin II)-induced hypertrophy. Mechanistically, we identified GSN as a direct target of NAE1. K238 crotonylation of NAE1 promoted GSN neddylation and, thus, enhanced its protein stability and expression. NAE1 crotonylation-dependent increase of GSN promoted actin-severing activity, which resulted in adverse cytoskeletal remodeling and progression of pathological hypertrophy. CONCLUSIONS: Our findings provide new insights into the previously unrecognized role of crotonylation on nonhistone proteins during cardiac hypertrophy. We found that K238 crotonylation of NAE1 plays an essential role in mediating cardiac hypertrophy through GSN neddylation, which provides potential novel therapeutic targets for pathological hypertrophy and cardiac remodeling.

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Ferroptosis is a novel form of programmed cell death caused by damage to lipid membranes due to the accumulation of lipid peroxides in response to various stimuli, such as high levels of iron, oxidative stress, metabolic disturbance, etc. Sugar, lipid, amino acid, and iron metabolism are crucial in regulating ferroptosis. The solute carrier transporters (SLCs) family, known as the "metabolic gating" of cells, is responsible for transporting intracellular nutrients and metabolites. Recent studies have highlighted the significant role of SLCs family members in ferroptosis by controlling the transport of various nutrients. Here, we summarized the function and mechanism of SLCs in ferroptosis regulated by ion, metabolic control of nutrients, and multiple signaling pathways, with a focus on SLC-related transporters that primarily transport five significant components: glucose, amino acid, lipid, trace metal ion, and other ion. Furthermore, the potential clinical applications of targeting SLCs with ferroptosis inducers for various diseases, including tumors, are discussed. Overall, this paper delves into the novel roles of the SLCs family in ferroptosis, aiming to enhance our understanding of the regulatory mechanisms of ferroptosis and identify new therapeutic targets for clinical applications.

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BACKGROUND: Myocardial fibrosis is a common feature in various cardiac diseases. It causes adverse cardiac remodeling and is associated with poor clinical outcomes. Late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) are the standard MRI techniques for detecting focal and diffuse myocardial fibrosis. However, these contrast-enhanced techniques require the administration of gadolinium contrast agents, which is not applicable to patients with gadolinium contraindications. To eliminate the need of contrast agents, we develop and apply an endogenous free-breathing T1ρ dispersion imaging technique (FB-MultiMap) for diagnosing diffuse myocardial fibrosis in a cohort with suspected cardiomyopathies. METHODS: The proposed FB-MultiMap technique, enabling T2, T1ρ and their difference (myocardial fibrosis index, mFI) quantification in a single scan was developed in phantoms and 15 healthy subjects. In the clinical study, 55 patients with suspected cardiomyopathies were imaged using FB-MultiMap, conventional native T1 mapping, LGE, and ECV imaging. The accuracy of the endogenous parameters for predicting increased ECV was evaluated using receiver operating characteristic (ROC) curve analysis. In addition, the correlation of native T1, T1ρ, and mFI with ECV was respectively assessed using Pearson correlation coefficients. RESULTS: FB-MultiMap showed a good agreement with conventional separate breath-hold mapping techniques in phantoms and healthy subjects. Considering all the patients, T1ρ was more accurate than mFI and native T1 for predicting increased ECV, with area under the curve (AUC) values of 0.91, 0.79 and 0.75, respectively, and showed stronger correlation with ECV (correlation coefficient r: 0.72 vs. 0.52 vs. 0.40). In the subset of 47 patients with normal T2 values, the diagnostic performance of mFI was significantly strengthened (AUC=0.90, r=0.83), outperforming T1ρ and native T1. CONCLUSION: The proposed free-breathing T1ρ dispersion imaging technique enabling simultaneous quantification of T2, T1ρ and mFI in a single scan has shown great potential for diagnosing diffuse myocardial fibrosis in patients with complex cardiomyopathies without contrast agents.

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Soil nitrogen (N) significantly influences the interaction between plants and pathogens, yet its impact on host defenses and pathogen strategies via alterations in plant metabolism remains unclear. Through metabolic and genetic studies, this research demonstrates that high-N-input exacerbates tomato bacterial wilt by altering γ-aminobutyric acid (GABA) metabolism of host plants. Under high-N conditions, the nitrate sensor NIN-like protein 7 (SlNLP7) promotes the glutamate decarboxylase 2/4 (SlGAD2/4) transcription and GABA synthesis by directly binding to the promoters of SlGAD2/4. The tomato plants with enhanced GABA levels showed stronger immune responses but remained susceptible to Ralstonia solanacearum. This led to the discovery that GABA produced by the host actually heightens the pathogen's virulence. We identified the R. solanacearum LysR-type transcriptional regulator OxyR protein, which senses host-derived GABA and, upon interaction, triggers a response involving protein dimerization that enhances the pathogen's oxidative stress tolerance by activating the expression of catalase (katE/katGa). These findings reveal GABA's dual role in activating host immunity and enhancing pathogen tolerance to oxidative stress, highlighting the complex relationship between tomato plants and R. solanacearum, influenced by soil N status.

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BACKGROUND: Heart failure (HF) with improved ejection fraction (EF, HFimpEF) is a distinct HF subtype, characterized by left ventricular (LV) reverse remodeling and myocardial functional recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear. METHODS: A total of 203 hospitalized HF patients with reduced EF (HFrEF, LVEF ≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute LVEF improvement ≥ 10% and (2) a second LVEF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans. RESULTS: During a median follow-up of 8.6 (4.9 ~ 13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (115.36 [IQR 87.08 ~ 154.78] mL vs. 169.67 [IQR 137.22 ~ 218.89] mL, P < 0.001) and higher EAT density (-74.92 ± 6.84 HU vs. -78.76 ± 6.28 HU, P < 0.001). Multivariate analysis showed lower EAT volume (OR: 0.885 [95%CI 0.822 ~ 0.947]) and higher density (OR: 1.845 [95%CI 1.023 ~ 3.437]) were both independently associated with the incidence of HFimpEF. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology. CONCLUSIONS: This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.

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Testicular choriocarcinoma is a relatively rare malignancy with a highly aggressive nature. Timely diagnosis and treatment can help prolong the survival of patients and even cure them. This case reports a 29-year-old male who presented to the clinic for a month with epigastric pain. On examination, a massive mass of approximately 9*10 cm could be palpated in the upper abdomen. When asked about his previous history, the patient only described a history of a right inguinal hernia that had been repaired 12 years earlier. The admission diagnosis was considered the retroperitoneal tumor, which was found to have metastasized to the liver and lungs after the completion of relevant tests. We then performed a CT-guided lune puncture biopsy on day 8 of admission. The biopsy pathology suggested metastatic cancer was considered. As the symptoms of tumor compression gradually worsened, we performed surgical treatment (retroperitoneal tumor resection + partial duodenal resection + enteroanastomosis) on day 13 of admission. The postoperative pathology was choriocarcinoma. We subsequently conducted a detailed inquiry with the patient's family about his medical history and found a history of inguinal testicle. Through testicular ultrasound examination, it was preliminarily determined to be testicular choriocarcinoma (not yet pathologically confirmed). We wanted to start salvage chemotherapy as soon as possible after surgery. However, the patient's postoperative condition was poor, with rapid progression of hepatopulmonary metastases and gradually increased thyrotoxicosis, and we started salvage chemotherapy (EP regimen: etoposide and cisplatin) on postoperative day 12. However, the patient was forced to stop due to a severe chemotherapy reaction and died of respiratory and cardiac arrest in the hospital. For male patients with retroperitoneal mass, the possibility of germ-cell neoplasm should first be excluded. By inquiring in detail about a history of cryptorchidism and in the initial days of hospitalization, testicular exploration, ultrasounds, and serum tumor markers (AFP, ß-HCG) tests can be conducted to rule out the possibility of germ-cell neoplasm, thereby preventing misdiagnosis and treatment delays. If the clinical diagnosis is metastatic germ-cell tumor with severe symptoms of metastatic disease, surgery should never be used as the initial treatment.

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Adding an appropriate amount and the stable precipitation of surfactant on the inner surface of agricultural plastic greenhouse films can prevent the formation of water droplets on the inner surface of the film to reduce its harmful effects in the process of plant cultivation and production. In this work, for the stable precipitation of the surfactant glycerol monostearate, diatomite minerals from three origins in China were compared through structural analysis and adsorption performance. The effects of acid treatments and alkali treatments on the mineral structure were studied, and the adsorption mechanism of glycerol monostearate was further investigated. The results show that the structural characteristics of Jilin diatomite are more suitable as adsorbents for glyceryl monostearate adsorption. Because diatomite is resistant to acids but not alkalis, when diatomite is treated with an alkali, impurities on its surface can be removed and the hydroxyl group and specific surface area can be greatly increased. The adsorption capacity of glycerol stearate was increased to 218.4 mg/g, or 32.08%, over its pretreatment level. The results show that this is mainly the result of physical adsorption caused by van der Waals force imbalance and chemisorption caused by a small number of hydrogen bonds. In addition, the dripping performance of this composite dripping film with mineral diatomite was better than that of the commercial dripping film, which provided a theoretical basis for efficient mineral slow-release drip irrigation composite film.

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This review explores the intricate roles of metal ions-iron, copper, zinc, and selenium-in glioma pathogenesis and immune evasion. Dysregulated metal ion metabolism significantly contributes to glioma progression by inducing oxidative stress, promoting angiogenesis, and modulating immune cell functions. Iron accumulation enhances oxidative DNA damage, copper activates hypoxia-inducible factors to stimulate angiogenesis, zinc influences cell proliferation and apoptosis, and selenium modulates the tumor microenvironment through its antioxidant properties. These metal ions also facilitate immune escape by upregulating immune checkpoints and secreting immunosuppressive cytokines. Targeting metal ion pathways with therapeutic strategies such as chelating agents and metalloproteinase inhibitors, particularly in combination with conventional treatments like chemotherapy and immunotherapy, shows promise in improving treatment efficacy and overcoming resistance. Future research should leverage advanced bioinformatics and integrative methodologies to deepen the understanding of metal ion-immune interactions, ultimately identifying novel biomarkers and therapeutic targets to enhance glioma management and patient outcomes.

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Objectives: Anti-signal recognition particle (SRP) antibodies, markers of immune-mediated necrotising myopathy, are reportedly related to cardiac involvement; however, whether they are pathogenic to the myocardium remains unclear. We aimed, therefore, to explore the pathogenicity of anti-SRP antibodies against the myocardium through in vivo and in vitro studies. Methods: Total immunoglobulin G (IgG), purified from patients with positive anti-SRP antibodies, was passively transferred into C57BL/6 mice. Cardiac function was evaluated via echocardiography and the ventricular pressure-volume loop; cardiac histological changes were analysed using haematoxylin-eosin staining, picrosirius red staining, immunofluorescence and immunohistochemistry. Additionally, reactive oxygen species (ROS) formation was evaluated by dihydroethidium (DHE) staining; mitochondrial morphology and function were evaluated using transmission electron microscopy and seahorse mitochondrial respiration assay, respectively. The myositis cohort at our centre was subsequently reviewed in terms of cardiac assessments. Results: After the passive transfer of total IgG from patients with positive anti-SRP antibodies, C57BL/6 mice developed significant left ventricular diastolic dysfunction (LVDD). Transcriptomic analysis and corresponding experiments revealed increased oxidative stress and mitochondrial damage in the hearts of the experimental mice. Cardiomyocytes exposed to anti-SRP-specific IgG, however, recovered normal mitochondrial metabolism after treatment with N-acetylcysteine, an ROS scavenger. Moreover, patients positive for anti-SRP antibodies manifested worse diastolic but equivalent systolic function compared to their counterparts after propensity score matching. Conclusion: Anti-SRP antibodies may play a pathogenic role in the development of LVDD by promoting ROS production and subsequent myocardial mitochondrial impairment. The inhibition of oxidative stress was effective in reversing anti-SRP antibody-induced LVDD.

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The effects of typical organic compounds including easily degradable organic matters sodium acetate, yeast and methanol, and refractory organic matter (ROM) humic acid on anaerobic ammonium oxidation (anammox) systems in short-term and medium-term exposure time were studied. During short-term experiments, nitrogen removal activity (NRA) was inhibited at sodium acetate level of 150 mg L-1 total organic carbon (TOC) and methanol level of 30-150 mg L-1 TOC, but humic acid and yeast (≤150 mg L-1 TOC) enhanced nitrogen removal in anammox systems. The greatest NRA of 30.10 mg TN g-1 VSS h-1 was recorded at yeast level of 90 mg L-1 TOC. In medium-term experiments, organics significantly inhibited the nitrogen removal ability. As a ROM, humic acid enhanced sludge aggregation and biological diversity, but decreased the bioactivity and extracellular polymeric substances levels. Due to the endogenous denitrification, the relative abundance of anammox bacteria (AnAOB) was decreased. Candidatus Kuenenia is still dominant in sludge with methanol and humid acid, but AnAOB are not dominant due to the addition of sodium acetate and yeast. This research would be beneficial for the full-scale application of the anammox process in treating real wastewater with organics and ammonia.

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The severely low influent chemical oxygen demand (COD) concentration at wastewater treatment plants (WWTPs) has become a critical issue. A key factor is the excessive biodegradation of organic matter by microbial communities within sewer systems. Intense disinfection commonly adopted for medical wastewater leads to abundant residual chlorine entering sewers, likely causing significant changes in microbial communities and sewage quality in sewers, yet our understanding is limited. Through long-term sewer simulation batch tests, this study revealed the response mechanism of microbial communities to residual chlorine and its impact on organic matter concentration in sewage. Under residual chlorine stress, microbial community structure rapidly changed, and more complex microbial interactions were observed. Besides, pathways related to stress response such as two-component system were significantly enriched; pathways related to energy metabolism (such as carbon fixation in prokaryotes and citrate cycle) in microbial communities were inhibited, and carbon metabolism shifted from the Embden-Meyerhof pathway to the pentose phosphate pathway to enhance cellular reducing power, reduce oxidative stress, and consequently decrease organic matter degradation. Therefore, compared to sewers with normal disinfection, concentrations of COD and dissolved organic carbon in sewage under chlorine stress increased by 12.6 % and 7.4 %, respectively. Besides, the decay and transformation of residual chlorine in sewers were explored. These findings suggest a new approach to medical wastewater discharge management: placing the medical wastewater outlet at the upstream in sewer systems, which ensures that residual chlorine consumption reaches maximum during long-distance transportation, mitigating its harmful effects on WWTPs, and increases the influent organic matter concentration, thereby reducing the need for additional carbon sources.

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BACKGROUND: Traumatic brain injury (TBI) could induce multiple forms of cell death, ferroptosis, a novel form of cell death distinct from apoptosis and autophagy, plays an important role in disease progression in TBI. Therapies targeting ferroptosis are beneficial for recovery from TBI. Paeoniflorin (Pae) is a water-soluble monoterpene glycoside and the active ingredient of Paeonia lactiflora pall. It has been shown to exert anti-inflammatory and antioxidant effects. However The effects and mechanisms of paeoniflorin on secondary injury after TBI are unknown. PURPOSE: To investigate the mechanism by which Pae regulates ferroptosis after TBI. METHODS: The TBI mouse model and cortical primary neurons were utilized to study the protective effect of paeoniflorin on the brain tissue after TBI. The neuronal cell ferroptosis model was established by treating cortical primary neurons with erastin. Liproxstatin-1(Lip-1) was used as a positive control drug. Immunofluorescence staining, Nissl staining, biochemical analyses, pharmacological analyses, and western blot were used to evaluate the effects of paeoniflorin on TBI. RESULTS: Pae significantly ameliorated neuronal damage after TBI, inhibited mitochondrial damage, increased glutathione peroxidase 4 (GPX4) activity, decreased malondialdehyde (MDA) production, restored neurological function and inhibited cerebral edema. Pae promotes the degradation of P53 in the form of proteasome, promotes its ubiquitination, and reduces the stability of P53 by inhibiting its acetylation, thus alleviating the P53-mediated inhibition of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) by P53. CONCLUSION: Pae inhibits ferroptosis by promoting P53 ubiquitination out of the nucleus, inhibiting P53 acetylation, and modulating the SLC7A11-GPX4 pathway.

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Colorectal cancer (CRC) is a common malignant tumor and is one of the three most common cancers worldwide. Traditional surgical treatment, supplemented by chemotherapy and radiotherapy, has obvious side effects on patients. Immunotherapy may lead to some unpredictable complications. Low introduction rate and high cost are some of the problems of gene therapy, so finding a safe, reliable and least toxic treatment method became the main research direction for this study. Lactic acid bacteria and their metabolites are widely used in functional foods or as adjuvant therapies for various diseases because they are safe to eat and have no adverse reactions. Research has shown that lactic acid bacteria and their metabolites play an auxiliary therapeutic role in colorectal cancer mainly by improving the intestinal flora composition, inhibiting the growth of pathogenic bacteria and inhibiting the proliferation of cancer cells. It is now widely believed that the substances that probiotics such as lactic acid bacteria exert anti-cancer effects are mainly secondary metabolites such as butyric acid. Lb. plantarum AY01 isolated from fermented food has good anti-cancer ability, and its main anti-cancer substance is 2'-deoxyinosine. Through flow cytometry detection, it was found that Lb. plantarum AY01 can block cell proliferation in the S phase. In addition, Lb. plantarum AY01 culture reduces the sensitivity of mice to colitis-associated CRC induced by azoxymethane (AOM)/dextran sulfate sodium salt (DSS) and exhibits the occurrence and promotion of tumors. According to transcriptome analysis, Lb. plantarum AY01 may induce apoptosis of colorectal cancer cells by activating the p38 MAPK pathway. This experiment provided possibilities for the treatment of CRC.

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Acting as the most abundant and widely distributed volatile secondary metabolites in plants, terpenoids play crucial roles in diverse physiological regulations and metabolic processes. Terpene synthases play a decisive role in determining the composition and diversity of terpenoids. Though the regulation of terpene synthases has been extensively investigated across various plant species, limited studies have focused on the upstream transcriptional regulation of terpene synthases. In this study, we have identified linalool as the predominant volatile compound that is released gradually from Freesia hybrida flowers throughout flower blooming. In the context of the transcriptome, a typical MYB transcription factor, FhMYB108, was screened based on homologous gene comparison. FhMYB108 is capable of regulating the expression of FhTPS1, and both their expression levels showed gradual increase during flower opening. Moreover, FhMYB108 exerts a stimulatory effect on the transcription of Arabidopsis thaliana AtTPS14, while no significant increase in AtTPS14 expression is observed upon the stabilization of FhMYB108 in A. thaliana. The highly expressed AtMYC2 in A. thaliana could interact with FhMYB108 to suppress the activation of AtTPS14 by FhMYB108. The present study not only elucidates the regulatory mechanism underlying linalool synthesis but also discovers the synergistic effect of MYB and bHLH transcription factors in governing the biosynthesis of volatile terpenoids.

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BACKGROUND: Cardiac T1 mapping is valuable for evaluating myocardial fibrosis, yet its resolution and acquisition efficiency are limited, potentially obscuring visualization of small pathologies. PURPOSE: To develop a technique for high-resolution cardiac T1 mapping with a less-than-100-millisecond acquisition window based on radial MOdified Look-Locker Inversion recovery (MOLLI) and a calibrationless space-contrast-coil locally low-rank tensor (SCC-LLRT) constrained reconstruction. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: Sixteen healthy subjects (age 25 ± 3 years, 44% females) and 12 patients with suspected cardiomyopathy (age 57 ± 15 years, 42% females), NiCl2-agar phantom. FIELD STRENGTH/SEQUENCE: 3-T, standard MOLLI, radial MOLLI, inversion-recovery spin-echo, late gadolinium enhancement. ASSESSMENT: SCC-LLRT was compared to a conventional locally low-rank (LLR) method through simulations using Normalized Root-Mean-Square Error (NRMSE) and Structural Similarity Index Measure (SSIM). Radial MOLLI was compared to standard MOLLI across phantom, healthy subjects, and patients. Three independent readers subjectively evaluated the quality of T1 maps using a 5-point scale (5 = best). STATISTICAL TESTS: Paired t-test, Wilcoxon signed-rank test, intraclass correlation coefficient analysis, linear regression, Bland-Altman analysis. P < 0.05 was considered statistically significant. RESULTS: In simulations, SCC-LLRT demonstrated a significant improvement in NRMSE and SSIM compared to LLR. In phantom, both radial MOLLI and standard MOLLI provided consistent T1 estimates across different heart rates. In healthy subjects, radial MOLLI exhibited a significantly lower mean T1 (1115 ± 39 msec vs. 1155 ± 36 msec), similar T1 SD (74 ± 14 msec vs. 67 ± 23 msec, P = 0.20), and similar T1 reproducibility (28 ± 18 msec vs. 22 ± 15 msec, P = 0.34) compared to standard MOLLI. In patients, the proposed method significantly improved the sharpness of myocardial boundaries (4.50 ± 0.65 vs. 3.25 ± 0.43), the conspicuity of papillary muscles and fine structures (4.33 ± 0.74 vs. 3.33 ± 0.47), and artifacts (4.75 ± 0.43 vs. 3.83 ± 0.55). The reconstruction time for a single slice was 5.2 hours. DATA CONCLUSION: The proposed method enables high-resolution cardiac T1 mapping with a short acquisition window and improved image quality. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.