Curcumin and nanodelivery systems: New directions for targeted therapy and diagnosis of breast cancer.

As the global incidence of breast cancer continues to surge, the pursuit of novel, low-toxicity, and highly efficacious therapeutic strategies has emerged as a pivotal research focus. Curcumin (CUR), an active constituent of traditional Chinese medicine (TCM) renowned for its antimicrobial, anti-inflammatory, antioxidant, and antitumor properties, exhibits immense potential in breast cancer therapy. Nevertheless, CUR's poor water solubility, chemical instability, and unfavorable pharmacokinetics have impeded its clinical utilization. To address these challenges, nano-delivery systems have been extensively exploited for CUR administration, enhancing its in vivo stability and bioavailability, and facilitating precise targeting of breast cancer lesions. Therefore, we elaborate on CUR's chemical foundations, drug metabolism, and safety profile, and elucidate its potential mechanisms in breast cancer therapy, encompassing inducing apoptosis and autophagy, blocking cell cycle, inhibiting breast cancer metastasis, regulating tumor microenvironment and reversing chemotherapy resistance. The review primarily emphasizes recent advancements in CUR-based nano-delivery systems for the treatment and diagnosis of breast cancer. Liposomes, nanoparticles (encompassing polymer nanoparticles, solid lipid nanoparticles, mesoporous silica particles, metal/metal oxide nanoparticles, graphene nanomaterials, albumin nanoparticles, etc.), nanogels, and nanomicelles can serve as delivery carriers for CUR, exhibiting promising anti-breast cancer effects in both in vivo and in vitro experiments. Furthermore, nano-CUR can be integrated with fluorescence imaging, magnetic resonance imaging, computed tomography imaging, ultrasound, and other techniques to achieve precise localization and diagnosis of breast cancer masses. While this article has summarized the clinical studies of nano-curcumin, it is noteworthy that the research literature on nano-CUR applied to breast cancer diagnosis and the translation of nano-CUR clinical studies in BC patients remain limited. Therefore, future research should intensify exploration in this direction.

Development and validation of a nomogram for predicting the interstitial fibrosis and tubular atrophy in patients with lupus nephritis.

OBJECTIVE: Interstitial fibrosis and tubular atrophy (IFTA) were frequent histologic features of lupus nephritis (LN), and LN patients with IFTA have poor renal outcomes. In this study, we aimed to construct prediction models for the IFTA in LN patients. METHODS: This retrospective study included 303 patients with biopsy proven LN at the Affiliated Hospital of Qingdao University and Union Hospital of Fujian Medical University. The participants were randomly divided into development and validation cohorts. They were further divided into IFTA and non-IFTA groups. The least absolute shrinkage and selection operator (LASSO) regression model with laboratory test results collected at the time of kidney biopsy was used to optimize feature selection for the risk model. Multivariable logistic regression analysis was applied to build a predicting model incorporating the feature selected in the LASSO regression model. Discrimination, calibration, and clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and ROC curve analysis. Internal validation was assessed using the bootstrapping validation. A nomogram for individual assessment was constructed based on the preferable model. RESULTS: Predictors contained in the prediction nomogram included age, body mass index (BMI), mean arterial pressure (MAP), logANA, C3, eGFR and serum uric acid. The model displayed good discrimination with a C-index of 0.794 (95% CI 0.734-0.854) and good calibration. High C-index value of 0.857 (95% CI 0.776-0.938) could still be reached in the interval validation. A nomogram model based on the LASSO model was created for producing a probability score of IFTA in LN patients. CONCLUSION: With excellent predictive abilities, the nomogram may provide a simple and reliable tool to distinguish LN patients with IFTA and helps physicians make clinical decisions in their comprehensive assessment.

Genetic analysis of a novel FBN1 mutation in a pediatric Marfan syndrome patient.

The aim of this study was to investigate a novel FBN1 gene mutation in a pediatric patient with Marfan syndrome (MFS) to provide a theoretical basis for genetic counseling. The subject was a 5-month-old male infant. With informed consent from the proband and his family, 2 mL of peripheral venous blood was collected from the patient, his father, mother, and sister. DNA was extracted using a DNA extraction kit with EDTA-K as an anticoagulant. The extracted DNA was subjected to minigene transcription and bioinformatics analysis. For minigene construction, wild-type and mutant minigenes were inserted into pcMINI and pcMINI-C vectors, respectively. Four recombinant vectors were transfected into the HeLa and 293T cell lines. After transfection for 48 hours, RNA was extracted from eight samples. DNA was also extracted from the family members' samples to construct a library. Target regions were captured using the SureSelect Human All Exon V6 (Agilent) kit and were sequenced with Illumina NovaSeq (sequencing read length 2×150 bp). Bioinformatic analysis identified the c.8226+5del mutation as a variant of uncertain clinical significance (VOUS). Literature and database reviews confirmed that this mutation had not been previously reported, identifying it as a novel mutation. The study identified a novel FBN1 mutation, c.8226+5del, that may be associated with clinical features such as low-set ears and distinctive facial characteristics in the proband. This mutation likely affects normal mRNA splicing, altering the structure and function of Exon 64 and potentially contributing to the development of autosomal dominant MFS.

Multi-dimensional epidemiology and informatics data on COVID-19 wave at the end of zero COVID policy in China.

Background: China exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China's pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks. Methods: Retrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny. Results: Various diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation. Conclusion: This investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19's disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.

Bibliometric analysis of global research trends between gut microbiota and breast cancer: from 2013 to 2023.

Background: Breast cancer is the most prevalent cancer globally and is associated with significant mortality. Recent research has provided crucial insights into the role of gut microbiota in the onset and progression of breast cancer, confirming its impact on the disease's management. Despite numerous studies exploring this relationship, there is a lack of comprehensive bibliometric analyses to outline the field's current state and emerging trends. This study aims to fill that gap by analyzing key research directions and identifying emerging hotspots. Method: Publications from 2013 to 2023 were retrieved from the Web of Science Core Collection database. The VOSviewer, R language and SCImago Graphica software were utilized to analyze and visualize the volume of publications, countries/regions, institutions, authors, and keywords in this field. Results: A total of 515 publications were included in this study. The journal Cancers was identified as the most prolific, contributing 21 papers. The United States and China were the leading contributors to this field. The University of Alabama at Birmingham was the most productive institution. Peter Bai published the most papers, while James J. Goedert was the most cited author. Analysis of highly cited literature and keyword clustering confirmed a close relationship between gut microbiota and breast cancer. Keywords such as "metabolomics" and "probiotics" have been prominently highlighted in the keyword analysis, indicating future research hotspots in exploring the interaction between metabolites in the breast cancer microenvironment and gut microbiota. Additionally, these keywords suggest significant interest in the therapeutic potential of probiotics for breast cancer treatment. Conclusion: Research on the relationship between gut microbiota and breast cancer is expanding. Attention should be focused on understanding the mechanisms of their interaction, particularly the metabolite-microbiota-breast cancer crosstalk. These insights have the potential to advance prevention, diagnosis, and treatment strategies for breast cancer. This bibliometric study provides a comprehensive assessment of the current state and future trends of research in this field, offering valuable perspectives for future studies on gut microbiota and breast cancer.

Green Synthesis and Antifungal Activities of Novel N-Aryl Carbamate Derivatives.

Carbamate is a key structural motif in the development of fungicidal compounds, which is still promising and robust in the discovery of green pesticides. Herein, we report the synthesis and evaluation of the fungicidal activity of 35 carbamate derivatives, among which 19 compounds were synthesized in our previous report. These derivatives were synthesized from aromatic amides in a single step, which was a green oxidation process for Hofmann rearrangement using oxone, KCl and NaOH. Their chemical structures were characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry. Their antifungal activity was tested against seven plant fungal pathogens. Many of the compounds exhibited good antifungal activity in vitro (inhibitory rate > 60% at 50 µg/mL). Compound 1ag exhibited excellent broad-spectrum antifungal activities with inhibition rates close to or higher than 70% at 50 µg/mL. Notably, compound 1af demonstrated the most potent inhibition against F. graminearum, with an EC50 value of 12.50 µg/mL, while compound 1z was the most promising candidate fungicide against F. oxysporum (EC50 = 16.65 µg/mL). The structure-activity relationships are also discussed in this paper. These results suggest that the N-aryl carbamate derivatives secured by our green protocol warrant further investigation as potential lead compounds for novel antifungal agents.

Evolving immunotherapeutic solutions for triple-negative breast carcinoma.

Triple-negative breast carcinoma (TNBC) remains a formidable clinical hurdle owing to its high aggressiveness and scant therapeutic options. Nonetheless, the evolving landscape of immunotherapeutic strategies opens up promising avenues for tackling this hurdle. This review discusses the advancing immunotherapy for TNBC, accentuating personalized interventions due to tumor microenvironment (TME) diversity. Immune checkpoint inhibitors (ICIs) hold pivotal significance, both as single-agent therapies and when administered alongside cytotoxic agents. Moreover, the concurrent inhibition of multiple immune checkpoints represents a potent approach to augment the efficacy of cancer immunotherapy. Synergistic effects have been observed when ICIs are combined with targeted treatments like PARP inhibitors, anti-angiogenics, and ADCs (antibody-drug conjugates). Emerging tactics include tumor vaccines, cellular immunotherapy, and oncolytic viruses, leveraging the immune system's ability for selective malignant cell destruction. This review offers an in-depth examination of the diverse landscape of immunotherapy development for TNBC, furnishing meticulous insights into various advancements within this field. In addition, immunotherapeutic interventions offer hope for TNBC, needing further research for optimization.

Novel insights: crosstalk with non-puerperal mastitis and immunity.

The two primary types of non-puerperal mastitis (NPM) are granulomatous lobular mastitis (GLM) and plasma cell mastitis (PCM). Existing research indicates that immune inflammatory response is considered to be the core of the pathogenesis of GLM and PCM, and both innate and adaptive immune responses play an important role in the pathophysiology of PCM and GLM. However, the regulatory balance between various immune cells in these diseases is still unclear. Consequently, we present a comprehensive summary of the immune-related variables and recent advances in GLM and PCM.

The diagnostic ability of peripapillary vessel density in primary open-angle glaucoma suspects.

OBJECTIVE: To assess the diagnostic ability of peripapillary vessel density (pVD) in primary open-angle glaucoma suspect (GS) patients. METHODS: Sixteen primary open-angle GS patients (22 eyes) and 20 normal controls (22 eyes) were included. In the GS group, OCTA measurements of pVD (superior, inferior, nasal, temporal, and global), OCT measurements of retinal nerve fiber layer (RNFL) thickness, disc area, rim area and ganglion cell complex (GCC) thickness were examined. In the control group, pVD measurements were performed. The vessel density between the two groups was compared. The correlation between OCTA and OCT parameters was evaluated. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of OCTA measurements. RESULTS: The global (P < 0.001), nasal (P = 0.003), and inferior (P = 0.002) quadrant pVD in GS group was considerably lower than the control group. The global pVD was positively correlated with the inferior RNFL thickness (r = 0.492, P = 0.023) and rim area (r = 0.483, P = 0.027). The inferior pVD was positively correlated with the inferior RNFL thickness (r = 0.648, P = 0.001), the nasal RNFL thickness (r = 0.441, P = 0.045), the rim area (r = 0.439, P = 0.046) and the GCC thickness (r = 0.472, P = 0.048). The global pVD had the best diagnostic value (AUC=0.825, sensitivity 86.36 %, specificity 72.73 %, cutoff value 45 %), followed by the inferior (AUC=0.749) and nasal (AUC=0.748) quadrant pVD. CONCLUSION: In primary open-angle GS patients, the global and inferior quadrant pVD was lower than that of normal people, and it was positively correlated with the inferior RNFL thickness and rim area. The diagnostic value of pVD for discriminating GS from normal people was excellent with high sensitivity and specificity.

Treatment of low-C/N nitrate wastewater using a partial denitrification-anammox granule system: Granule reconstruction, stability, and microbial structure analyses.

Industrial wastewater discharged into sewer systems is often characterized by high nitrate contents and low C/N ratios, resulting in high treatment costs when using conventional activated sludge methods. This study introduces a partial denitrification-anammox (PD/A) granular process to address this challenge. The PD/A granular process achieved an effluent TN level of 3.7 mg/L at a low C/N ratio of 2.3. Analysis of a typical cycle showed that the partial denitrification peaked within 15 min and achieved a nitrate-to-nitrite transformation ratio of 86.9%. Anammox, which was activated from 15 to 120 min, contributed 86.2% of the TN removal. The system exhibited rapid recovery from post-organic shock, which was attributed to significant increases in protein content within TB-EPS. Microbial dispersion and reassembly were observed after coexistence of the granules, with Thauera (39.12%) and Candidatus Brocadia (1.25%) identified as key functional microorganisms. This study underscores the efficacy of PD/A granular sludge technology for treating low-C/N nitrate wastewater.

Association of complete blood count parameters with the risk of incident pulmonary heart disease in pneumoconiosis: a retrospective cohort study.

BACKGROUND: Pneumoconiosis mostly combines pulmonary and cardiovascular diseases, among which pulmonary heart disease (PHD) is of major concern due to its significant impact on the survival of pneumoconiosis patients. White cell count (WCC), red cell distribution width (RDW) and platelet parameters are thought to affect inflammatory responses and may be predictors of various cardiovascular diseases. However, very few studies have focused on PHD. OBJECTIVES: To examine the relationship between baseline complete blood count parameters (WCC, RDW, platelet parameters) and the risk of incident PHD in pneumoconiosis patients. DESIGN: A retrospective cohort study. SETTING: This was a single-centre, retrospective cohort study that used data from an Occupational Disease Hospital, Chengdu, Sichuan. PARTICIPANTS: A total of 946 pneumoconiosis patients from January 2012 to November 2021 were included in the study. Female patients and patients who had PHD, coronary heart disease, hypertensive heart disease, cardiomyopathy, heart failure, oncological disease, multiple organ dysfunction, AIDS at baseline and follow-up time of less than 6 months were also excluded. OUTCOME MEASURES: We identified PHD according to the patient's discharge diagnosis. We constructed Cox proportional hazard regression models to assess the HR of incident PHD in pneumoconiosis, as well as 95% CIs. RESULTS: In the multiple Cox proportional hazard regression analysis, platelet count (PLT) and plateletcrit (PCT) above the median at baseline were associated with an increased risk of PHD in pneumoconiosis with adjusted HR of 1.52 (95% CI 1.09 to 2.12) and 1.42 (95% CI 1.02 to 1.99), respectively. CONCLUSION: Higher baseline PLT and PCT are associated with a higher risk of PHD in pneumoconiosis.

HyperGCN: an effective deep representation learning framework for the integrative analysis of spatial transcriptomics data.

BACKGROUND: Advances of spatial transcriptomics technologies enabled simultaneously profiling gene expression and spatial locations of cells from the same tissue. Computational tools and approaches for integration of transcriptomics data and spatial context information are urgently needed to comprehensively explore the underlying structure patterns. In this manuscript, we propose HyperGCN for the integrative analysis of gene expression and spatial information profiled from the same tissue. HyperGCN enables data visualization and clustering, and facilitates downstream analysis, including domain segmentation, the characterization of marker genes for the specific domain structure and GO enrichment analysis. RESULTS: Extensive experiments are implemented on four real datasets from different tissues (including human dorsolateral prefrontal cortex, human positive breast tumors, mouse brain, mouse olfactory bulb tissue and Zabrafish melanoma) and technologies (including 10X visium, osmFISH, seqFISH+, 10X Xenium and Stereo-seq) with different spatial resolutions. The results show that HyperGCN achieves superior clustering performance and produces good domain segmentation effects while identifies biologically meaningful spatial expression patterns. This study provides a flexible framework to analyze spatial transcriptomics data with high geometric complexity. CONCLUSIONS: HyperGCN is an unsupervised method based on hypergraph induced graph convolutional network, where it assumes that there existed disjoint tissues with high geometric complexity, and models the semantic relationship of cells through hypergraph, which better tackles the high-order interactions of cells and levels of noise in spatial transcriptomics data.

Innovation for continuous aerobic granular sludge process in actual municipal sewage treatment: Self-circulating up-flow fluidized bed process.

Aerobic granular sludge (AGS) capable of nitrogen and phosphorus removal is mainly limited to the applications in sequencing batch reactors. This study introduced an innovative continuous self-circulating up-flow fluidized bed process (Zier process) using separate aeration. The process was composed of an anoxic column (Zier-A), aeration column (Zier-OO) and aerobic column (Zier-O), and was used to treat actual municipal sewage continuously for 170 days. The process achieved self-circulation of 20-32 times and an up-flow velocity within the reactor of 7-16 m/h which were accurately controlled with only separate aeration. The larger proportion of self-circulating multiple times contributed to particle formation and stability, providing hydraulic shear conditions, and screened the precipitation performance of the granular sludge (GS). Meanwhile, the dissolved oxygen (DO) of Zier-O was controlled at 0.1-0.3 mg/L, and the DO of Zier-A input water was zero. The accurate oxygen supply enhanced simultaneous nitrification and denitrification (SND) as well as short-cut nitrification and denitrification in Zier-O and improved the COD utilization rate and the nitrogen removal rate in Zier-A. The COD treatment capacity reached 2.46 kg-COD/(m³·d). With a hydraulic retention time of 10 h, the process consistently ensured that the average concentrations of ammonia nitrogen and total nitrogen in the effluent were maintained below 5 and 15 mg/L, respectively. Moreover, the process maintained the shape and stability of GS, the median diameter of GS ranged between 300-1210 µm, the percentage of mass with particle size distribution < 200 µm at a height of 150 cm within Zier-A and Zier-O accounted for as low as 0.04%-0.05%, and showed good settling performance. The suspended solids in effluent can be maintained at 50-80 mg/L. Overall, the unique structural setting and control method of the Zier process provide another approach for the application of continuous AGS treatment for municipal sewage.

Distinct functions of microtubules and actin filaments in the transportation of the male germ unit in pollen.

Flowering plants rely on the polarized growth of pollen tubes to deliver sperm cells (SCs) to the embryo sac for double fertilization. In pollen, the vegetative nucleus (VN) and two SCs form the male germ unit (MGU). However, the mechanism underlying directional transportation of MGU is not well understood. In this study, we provide the first full picture of the dynamic interplay among microtubules, actin filaments, and MGU during pollen germination and tube growth. Depolymerization of microtubules and inhibition of kinesin activity result in an increased velocity and magnified amplitude of VN's forward and backward movement. Pharmacological washout experiments further suggest that microtubules participate in coordinating the directional movement of MGU. In contrast, suppression of the actomyosin system leads to a reduced velocity of VN mobility but without a moving pattern change. Moreover, detailed observation shows that the direction and velocity of VN's movement are in close correlations with those of the actomyosin-driven cytoplasmic streaming surrounding VN. Therefore, we propose that while actomyosin-based cytoplasmic streaming influences on the oscillational movement of MGU, microtubules and kinesins avoid MGU drifting with the cytoplasmic streaming and act as the major regulator for fine-tuning the proper positioning and directional migration of MGU in pollen.

Ecofriendly Protocol for ipso-Bromination of Arylboronic Acids.

We report a novel and environmentally friendly method for the ipso-bromination of arylboronic acids by exploiting the oxone/KBr system. We discovered that CuBr can catalyze the reaction and increase the yield from 63 to 97%. We believe that CuBr might catalyze the in situ generation of HOBr from oxone/KBr. The mild reaction condition permits tolerance of a diverse array of functional groups with exclusive regio- and chemoselectivity and allows low-cost large-scale reaction without explosion risk.

Relationship of postprandial fibroblast growth factor 21 with lipids, inflammation and metabolic dysfunction-associated fatty liver disease during oral fat tolerance test.

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is closely associated with serum fibroblast growth factor (FGF) 21; however, previous studies have typically focused on the static fasting state, and the relationships between postprandial FGF21 levels, postprandial metabolic status, and MAFLD remain unclear. Therefore, we measured postprandial lipids, inflammatory factors, and FGF21 levels in MAFLD and further analyzed their relationship using an oral fat tolerance test (OFTT). Patients and methods: In total, 103 non-diabetic adult volunteers, including 46 patients with MAFLD, were included in this study. All participants underwent the OFTT. Venous blood samples were collected at 0, 2, 4, and 6 h. Circulating total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), hypersensitive-C reactive protein(hs-CRP) and FGF21 were assessed. Results: Serum FGF21 significantly increased in the fasting state (P < 0.05) and showed a biphasic change of first decreasing and then increasing in MAFLD during the OFTT. The postprandial levels of TG, TC, LDL-C, FFA, IL-6, TNF-α and hs-CRP were significantly increased in MAFLD (P < 0.05). After adjusting for multiple factors, the FGF21 incremental area under the curve (iAUC) was linearly correlated with the FFA iAUC, TG iAUC, and IL-6 iAUC (P < 0.05) and was an independent factor for MAFLD (P < 0.05, OR=1.403). Conclusion: Dyslipidemia and excessive inflammation in MAFLD are associated to FGF21 levels in the postprandial period. An abnormal postprandial FGF21 response may be an important mechanism of MAFLD.

Targeted Quantification of Glutathione/Arginine Redox Metabolism Based on a Novel Paired Mass Spectrometry Probe Approach for the Functional Assessment of Redox Status.

Glutathione (GSH) redox control and arginine metabolism are critical in regulating the physiological response to injury and oxidative stress. Quantification assessment of the GSH/arginine redox metabolism supports monitoring metabolic pathway shifts during pathological processes and their linkages to redox regulation. However, assessing the redox status of organisms with complex matrices is challenging, and single redox molecule analysis may not be accurate for interrogating the redox status in cells and in vivo. Herein, guided by a paired derivatization strategy, we present a new ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based approach for the functional assessment of biological redox status. Two structurally analogous probes, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and newly synthesized 2-methyl-6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (MeAQC), were set for paired derivatization. The developed approach was successfully applied to LPS-stimulated RAW 264.7 cells and HDM-induced asthma mice to obtain quantitative information on GSH/arginine redox metabolism. The results suggest that the redox status was remarkably altered upon LPS and HDM stimulation. We expect that this approach will be of good use in a clinical biomarker assay and potential drug screening associated with redox metabolism, oxidative damage, and redox signaling.

The regulatory mechanism of rapid lignification for timely anther dehiscence.

Anther dehiscence is a crucial event in plant reproduction, tightly regulated and dependent on the lignification of the anther endothecium. In this study, we investigated the rapid lignification process that ensures timely anther dehiscence in Arabidopsis. Our findings reveal that endothecium lignification can be divided into two distinct phases. During Phase I, lignin precursors are synthesized without polymerization, while Phase II involves simultaneous synthesis of lignin precursors and polymerization. The transcription factors MYB26, NST1/2, and ARF17 specifically regulate the pathway responsible for the synthesis and polymerization of lignin monomers in Phase II. MYB26-NST1/2 is the key regulatory pathway responsible for endothecium lignification, while ARF17 facilitates this process by interacting with MYB26. Interestingly, our results demonstrate that the lignification of the endothecium, which occurs within approximately 26 h, is much faster than that of the vascular tissue. These findings provide valuable insights into the regulation mechanism of rapid lignification in the endothecium, which enables timely anther dehiscence and successful pollen release during plant reproduction.

Serum Gamma Glutamyltransferase: A Biomarker for Identifying Postprandial Hypertriglyceridemia.

Purpose: Elevated serum gamma-glutamyltranspeptidase (GGT) is an independent marker of the activation of systemic inflammation, while conditions associated with elevated triglyceride (TG) levels, such as type 2 diabetes, non-alcoholic fatty liver disease, obesity, and metabolic syndrome, are associated with an increased inflammatory burden. Moreover, serum liver enzymes (GGT, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]) are associated with metabolic syndrome and its components, including hypertriglyceridemia. However, the relationship between liver enzymes and postprandial hypertriglyceridemia (PHTG) remains unclear. Therefore, in this study we conducted oral fat tolerance tests (OFTTs) to understand the differences in serum liver enzyme levels among individuals with different lipid tolerance levels and their correlation with PHTG. Patients and Methods:  For the OFTT, we enrolled 202 non-diabetic volunteers whose fasting triglyceride (TG) levels were less than 1.7 mmol/L in this case-control study. The participants were categorized into two groups according to the TG levels at the 0- and 4-h OFTT: a postprandial normal TG (PNTG) group and a PHTG group. Routine fasting serum biochemical indices, liver enzyme (GGT, ALT, AST, and ALP) levels, and 0- and 4-h OFTT lipid levels were assessed. Results: The PHTG group had significantly higher serum GGT and ALT levels and a lower AST/ALT ratio than those in the PNTG group. However, no significant difference was observed in AST and ALP levels compared with the PNTG group. After adjusting for major confounders, logistic regression analysis indicated a significant correlation between serum GGT and PHTG (odds ratio = 1.168, P < 0.001), but not with ALT level, AST level, AST/ALT ratio, and ALP level. The receiver operating characteristic curve analysis demonstrated that the serum GGT level was an effective predictor of PHTG. Conclusion: Serum GGT levels are significantly associated with PHTG risk and serve as an effective biomarker for early identification.

Enzyme-Driven LC-HRMS Approach for Specific Recognition of 12α-Hydroxy Bile Acids.

The synthesis of 12α-hydroxylated bile acids (12HBAs) and non-12α-hydroxylated bile acids (non-12HBAs) occurs via classical and alternative pathways, respectively. The composition of these BAs is a crucial index for pathophysiologic assessment. However, accurately differentiating 12HBAs and non-12HBAs is highly challenging due to the limited standard substances. Here, we innovatively introduce 12α-hydroxysteroid dehydrogenase (12α-HSDH) as an enzymatic probe synthesized by heterologous expression in Escherichia coli, which can specifically and efficiently convert 12HBAs in vitro under mild conditions. Coupled to the conversion rate determined by liquid chromatography-high resolution mass spectrometry (LC-HRMS), this enzymatic probe allows for the straightforward distinguishing of 210 12HBAs and 312 non-12HBAs from complex biological matrices, resulting in a BAs profile with a well-defined hydroxyl feature at the C12 site. Notably, this enzyme-driven LC-HRMS approach can be extended to any molecule with explicit knowledge of enzymatic transformation. We demonstrate the practicality of this BAs profile in terms of both revealing cross-species BAs heterogeneity and monitoring the alterations of 12HBAs and non-12HBAs under asthma disease. We envisage that this work will provide a novel pattern to recognize the shift of BA metabolism from classical to alternative synthesis pathways in different pathophysiological states, thereby offering valuable insights into the management of related diseases.