Combinatory Effect of ALA-PDT and Itraconazole In the Treatment of Cutaneous protothecosis.

BACKGROUND: As a rare subcutaneous infection, protothecosis is easily misdiagnosed. Similar to other subcutaneous infection, there is no unified standard for treatment, for cases not suitable for surgery, clinicians often use antifungal drugs based on their experience, and the course of treatment varies from several months to several years. Based on the fact that there are few relevant materials and researches on photodynamic therapy (PDT), we conducted a study based on a clinical case that used oral itraconazole combined with 5-aminolevylinic acid photodynamic therapy (ALA-PDT) to treat a patient with cutaneous protothecosis caused by Prototheca wicherhamii. METHODS: Different concentrations of ALA and different light doses were used to investigate the effects of ALA-PDT on the growth inhibition of P. wickerhamii in vitro with Colony-counting Methods. And we used transmission electron microscopy (TEM) to visualize the structural changes and the effects of ALA-PDT treating on cellular structures of the P. wickerhamii. Futher, we performed the susceptibility test of P. wickerhamii to itraconazole before and after ALA-PDT in vitro. RESULTS: We have successfully treated a patient with cutaneous protothecosis caused by P. wickerhamii by using combination therapy in a total of 9-week course of treatment. In vitro, ALA-PDT can inhibit the growth of P. wickerhamii when the ALA concentration was 5mg/mL (P < 0.01), and this effect became stronger as the concentration of ALA or light dose is increased. Using TEM, we confirmed that ALA-PDT can disrupt the cell wall structure and partition structure of P. wickerhamii, which may contribute to its inhibitory effect. Further studies showed that the MIC of itraconazole for P. wickerhamii was decreased after ALA-PDT. CONCLUSIONS: ALA-PDT combined with oral itraconazole can be used to treat cutaneous protothecosis. Accordingly, ALA-PDT can destroy the cell wall and partition structure of P. wickerhamii leading to an inhibitory effect on it in vitro, and the effect is enhanced with the increase of ALA concentration and light dose. Also, the sensitivity of P. wickerhamii to itraconazole is observed increased after ALA-PDT. So our study provides a theoretical basis for the promising treatment against cutaneus protothecosis.

Retrospective clinical and microbiologic analysis of metagenomic next-generation sequencing in the microbiological diagnosis of cutaneous infectious granulomas.

BACKGROUND: Cutaneous infectious granulomas (CIG) are localized and chronic skin infection caused by a variety of pathogens such as protozoans, bacteria, worms, viruses and fungi. The diagnosis of CIG is difficult because microbiological examination shows low sensitivity and the histomorphological findings of CIG caused by different pathogens are commonly difficult to be distinguished. OBJECTIVE: The objective of this study is to explore the application of mNGS in tissue sample testing for CIG cases, and to compare mNGS with traditional microbiological methods by evaluating sensitivity and specificity. METHODS: We conducted a retrospective study at the Department of Dermatology of Sun Yat-sen Memorial Hospital, Sun Yat-sen University from January 1st, 2020, to May 31st, 2024. Specimens from CIG patients with a clinical presentation of cutaneous infection that was supported by histological examination were retrospectively enrolled. Specimens were delivered to be tested for microbiological examinations and mNGS. RESULTS: Our data show that mNGS detected Non-tuberculosis mycobacteria, Mycobacterium tuberculosis, fungi and bacteria in CIG. Compared to culture, mNGS showed a higher positive rate (80.77% vs. 57.7%) with high sensitivity rate (100%) and negative predictive value (100%). In addition, mNGS can detect more pathogens in one sample and can be used to detect variable samples including the samples of paraffin-embedded tissue with shorter detective time. Of the 21 patients who showed clinical improvement within a 30-day follow-up, eighteen had their treatments adjusted, including fifteen who continued treatment based on the results of mNGS. CONCLUSIONS: mNGS could provide a potentially rapid and effective alternative detection method for diagnosis of cutaneous infectious granulomas and mNGS results may affect the clinical prognosis resulting from enabling the patients to initiate timely treatment.

Unlocking daidzein's healing power: Present applications and future possibilities in phytomedicine.

BACKGROUND: Cancer is one of the leading causes of death and a great threat to people around the world. Cancer treatment modalities include surgery, radiotherapy, chemotherapy, radiochemotherapy, hormone therapy, and immunotherapy. The best approach is to use a combination of several types. Among the treatment methods mentioned above, chemotherapy is frequently used, but its activity is hampered by the development of drug resistance and many side effects. In this regard, the use of medicinal plants has been discussed, and in recent decades, the use of isolated phytochemicals came into the focus of interest. By critically evaluating the available evidence and emphasizing the unique perspective offered by this review, we provide insights into the potential of daidzein as a promising therapeutic agent, as well as outline future research directions to optimize its efficacy in clinical settings. PURPOSE: To summarized the therapeutic potential of daidzein, an isoflavone phytoestrogen in the management of several human diseases with the focuses on the current status and future prospects as a therapeutic agent. METHODS: Several search engines, including PubMed, GoogleScholar, and ScienceDirect, were used, with the search terms "daidzein", "daidzein therapeutic potential", or individual effects. The study included all peer-reviewed articles. However, the most recent publications were given priority. RESULTS: Daidzein showed protective effects against malignant diseases such as breast cancer, prostate cancer but also non-malignant diseases such as diabetes, osteoporosis, and cardiovascular diseases. Daidzein activates multiple signaling pathways leading to cell cycle arrest and apoptosis as well as antioxidant and anti-metastatic effects in malignant cells. Moreover, the anticancer effects against different cancer cells were more prominent and discussed in detail. CONCLUSIONS: In short, daidzein represents a promising compound for drug development. The comprehensive potential anticancer activities of daidzein through various molecular mechanisms and its therapeutic/clinical status required further detail studies.

Effect of alterations in phospholipids and free fatty acids on aroma-active compounds in instant-boiled chuck tender, sirloin and silverside beef.

Beef flavor profiles are strongly influenced by cooking methods and lipid composition. However, the effect of instant-boiling on the aroma of different beef slices was unclear. This study investigated the lipid profiles and instant-boiling volatile profiles of chuck tender (M. Supraspinatus), sirloin (M. Longissimus dorsi) and silverside (M. Biceps femoris). Quantitative lipidomics identified 336 lipid molecular species, of which 84-112 were quantitatively different among the three beef slices. Sirloin had lower phosphatidylcholine, phosphatidylinositol, phosphatidylglycerol and free fatty acids than chuck tender and silverside. The unsaturated fatty acid acyl chains in phosphatidylethanolamine differed significantly. Solid phase microextraction-gas chromatography-olfactometry-mass spectrometry (SPME-GC-O-MS) identified hexanal, octanal, nonanal, decanal, (E)-2-octenal, (E)-2-nonenal, (E)-2-undecenal, (E,E)-2,4-nonadienal, (E,E)-2,4-decadienal, 1-octen-3-ol, 2-pentylfuran and acetoin as the aroma-active compounds of instant-boiled beef. Unsaturated free fatty acids and phosphatidylglycerols with unsaturated fatty acid residues positively correlated with the aroma-active compounds and might be crucial in flavor differences among the three beef slices. These findings provide greater understanding of the lipid and instant-boiling aroma-active compound profiles in chuck tender, sirloin and silverside, and reflect the suitability of different beef slices for instant-boiling from the aroma perspective.

Development of an electrochemical sensor modified with gold nanoparticles for detecting fumonisin B1 in packaged foods.

Fumonisin B1 (FB1) is naturally present in the environment and can easily contaminate packaged foods during processing, storage and transportation, thus posing a threat to human health. We have developed an enzyme-free FB1 detector for the detection of packaged foods, which provides rapid and sensitive detection of FB1 in food. Gold nanoparticles (AuNPs; 5-10 nm) were uniformly dispersed on screen-printed electrodes, which acted as an excellent catalytic oxidizer. The surface structure of the modified electrode was characterized using scanning electron microscope and X-ray photoelectron spectroscopy. Differential pulse voltammetry demonstrated a good linear electrochemical response towards FB1 at concentrations ranging from 1 ng L-1 to 1 mg L-1 with a detection limit of 0.08 ng L-1. We employed the AuNPs-SPE sensor to detect FB1-spiked packaged meat products achieving recovery rates ranging from 89.7% to 113.3%.

Ultrasensitive analyses of zearalenone in grain samples with a catalytic oxidation platform involving gold nanomaterials.

Zearalenone (ZEN) contamination in cereals poses a serious threat to human and animal health, yet existing rapid test methods still suffer from poor stability and low sensitivity. The studied sensor reduces inspection time while enabling applications for on-site grain inspection. Specifically, a ZEN detector that can sensitively detect ZEN content in grains was developed. Ion implantation is an effective method for modifying screen-printed electrodes (SPEs). Gold nanoparticles (AuNPs; 5-10 nm) were uniformly implanted using screen-printed electrodes as a catalytic oxidation medium to generate an electrochemical sensor. The surface structure of the modified electrode was characterized using scanning electron microscopy and X-ray photoelectron spectroscopy. The results showed that differential pulse voltammetry had good linear electrochemical response to ZEN at 10 ng/kg to 10 mg/kg, with a detection limit of 1.1 ng/kg. We used AuNP-SPE sensors to detect ZEN in grain samples such as maize and oats.

Comprehensive foodomics analysis reveals key lipids affect aroma generation in beef.

Lipids are vital precursors to beef aroma compounds, but the exact lipid molecules influencing aroma generation remain unconfirmed. This study employs gas chromatography-olfactometry-mass spectrometry and absolute quantitative lipidomics to identify beef's aroma and lipid profiles and to examine lipid alterations post-thermal processing. The aim is to understand the role of lipids in aroma generation during beef's raw-to-cooked transition. Eighteen key aroma compounds were identified as significant contributors to the aroma of beef. 265 lipid molecules were quantified accurately, and we found that triglycerides containing C18:1 or C18:2 chains, such as TG(16:0_18:1_18:1), TG(16:0_18:1_18:2), TG(16:0_16:1_18:1), as well as phosphatidylcholine and phosphatidylethanolamine containing PC(16:1e_20:4), PC(16:0e_20:4), PC(18:2e_18:2), and PE(16:1e_20:4), played important roles in the generation of key aroma compounds in beef. C18:1, C18:2, C18:3, and C20:4 were key substrates for the formation of aroma compounds. In addition, lysophosphatidylcholine and lysophosphatidylethanolamine containing unsaturated fatty acid chains may serve as important aroma retainers.

Bifunctional black phosphorus quantum dots platform: Delivery and remarkable immunotherapy enhancement of STING agonist.

Cancer immunotherapy has been developed to improve therapeutic effects for patients by activating the innate immune stimulator of interferon gene (STING) pathway. However, most patients cannot benefit from this therapy, mainly due to the problems of excessively low immune responses and lack of tumor specificity. Herein, we report a solution to these two problems by developing a bifunctional platform of black phosphorus quantum dots (BPQDs) for STING agonists. Specifically, BPQDs could connect targeted functional groups and regulate surface zeta potential by coordinating metal ions to increase loading (over 5 times) while maintaining high universality (7 STING agonists). The controlled release of STING agonists enabled specific interactions with their proteins, activating the STING pathway and stimulating the secretion release of immunosuppressive factors by phosphorylating TBK1 and IFN-IRF3 and secreting high levels of immunostimulatory cytokines, including IL-6, IFN-α, and IFN-ß. Moreover, the immunotherapy was enhanced was enhanced mild photothermal therapy (PTT) of BPQDs platform, producing enough T cells to eliminate tumors and prevent tumor recurrence. This work facilitates further research on targeted delivery of small-molecule immune drugs to enhance the development of clinical immunotherapy.

Speckle-Tracking Echocardiography in Right Ventricular Function of Clinically Well Patients with Heart Transplantation.

Heart transplantation (HT) is the mainstream therapy for end-stage heart disease. However, the cardiac graft function can be affected by several factors. It is important to monitor HT patients for signs of graft dysfunction. Transthoracic echocardiography is a simple, first-line, and non-invasive method for the assessment of cardiac function. The emerging speckle-tracking echocardiography (STE) could quickly and easily provide additive information over traditional echocardiography. STE longitudinal deformation parameters are markers of early impairment of ventricular function. Although once called the "forgotten ventricle", right ventricular (RV) assessment has gained attention in recent years. This review highlights the potentially favorable role of STE in assessing RV systolic function in clinically well HT patients.

Embedded monitoring system and teaching of artificial intelligence online drug component recognition.

Drug testing has many test elements. It aims to prevent unqualified drugs from entering the market and ensure drug safety. The existing artificial intelligence (AI) online monitoring system identifies active ingredients in the process of use. Owing to their openness, data are easy to be lost, failing to meet user needs and inducing a specific impact on the use of the monitoring system. With the continuous development of computer and measurement technologies, various biochemical data are increasing at an unprecedented speed, and numerous databases are emerging. Extracting patterns from considerable known data and experimental facts is an essential task for a wide range of biological and chemical workers. Pattern recognition is one of the essential technologies for data mining. It is widely used in industry, agriculture, national defense, biomedicine, meteorology, astronomy, and other fields. To improve the effect of the online drug ingredient recognition system, this study used AI to design an online drug ingredient recognition-embedded monitoring system and applied AI to the teaching field to improve teaching efficiency. First, this study constructed the framework of the AI online drug ingredient recognition-embedded monitoring system and introduced the process of online drug ingredient recognition. Then, it introduced the pattern recognition method, constructed the pattern recognition system, and presented the pattern recognition algorithm and the algorithm evaluation index. Afterward, it used pattern recognition to conduct a qualitative analysis of the infrared spectrum of drug components and introduced the overall process of the qualitative analysis. In addition, this study employed AI to implement changes to the embedded system instruction in colleges and universities, summarizing the current issues. The impact of drug component recognition and the educational impact of embedded systems were investigated in the experimental portion. The experimental findings demonstrated the excellent accuracy, sensitivity, specificity, and Matthew correlation coefficient of the online drug component recognition-integrated monitoring system in this work. Compared with that of other systems, its average drug component recognition accuracy was above 0.85. Students in five majors reported high levels of satisfaction with the embedded system teaching, which is better for delivering college instruction.

A Membrane-Targeting Aggregation-Induced Emission Probe for Monitoring Lipid Droplet Dynamics in Ischemia/Reperfusion-Induced Cardiomyocyte Ferroptosis.

Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor is ischemia/reperfusion (I/R)-induced cardiomyocyte ferroptosis, marked by iron overload and lipid peroxidation. However, the impact of lipid droplet (LD) changes on I/R-induced cardiomyocyte ferroptosis is unclear. In this study, an aggregation-induced emission probe, TPABTBP is developed that is used for imaging dynamic changes in LD during myocardial I/R-induced ferroptosis. TPABTBP exhibits excellent LD-specificity, superior capability for monitoring lipophagy, and remarkable photostability. Molecular dynamics (MD) simulation and super-resolution fluorescence imaging demonstrate that the TPABTBP is specifically localized to the phospholipid monolayer membrane of LDs. Imaging LDs in cardiomyocytes and myocardial tissue in model mice with MIRI reveals that the LD accumulation level increase in the early reperfusion stage (0-9 h) but decrease in the late reperfusion stage (>24 h) via lipophagy. The inhibition of LD breakdown significantly reduces the lipid peroxidation level in cardiomyocytes. Furthermore, it is demonstrated that chloroquine (CQ), an FDA-approved autophagy modulator, can inhibit ferroptosis, thereby attenuating MIRI in mice. This study describes the dynamic changes in LD during myocardial ischemia injury and suggests a potential therapeutic target for early MIRI intervention.

Metagenomic Next-Generation Sequencing Contributes to the Early Diagnosis of Mixed Infections in Central Nervous System.

Central nervous system (CNS) infections represent a challenge due to the complexities associated with their diagnosis and treatment, resulting in a high incidence rate and mortality. Here, we presented a case of CNS mixed infection involving Candida and human cytomegalovirus (HCMV), successfully diagnosed through macrogenomic next-generation sequencing (mNGS) in China. A comprehensive review and discussion of previously reported cases were also provided. Our study emphasizes the critical role of early pathogen identification facilitated by mNGS, underscoring its significance. Notably, the integration of mNGS with traditional methods significantly enhances the diagnostic accuracy of CNS infections. This integrated approach has the potential to provide valuable insights for clinical practice, facilitating early diagnosis, allowing for treatment adjustments, and ultimately, improving the prognosis for patients with CNS infections.

18Beta-Glycyrrhetinic Acid Attenuates H2O2-Induced Oxidative Damage and Apoptosis in Intestinal Epithelial Cells via Activating the PI3K/Akt Signaling Pathway.

Oxidative stress causes gut dysfunction and is a contributing factor in several intestinal disorders. Intestinal epithelial cell survival is essential for maintaining human and animal health under oxidative stress. 18beta-Glycyrrhetinic acid (GA) is known to have multiple beneficial effects, including antioxidant activity; however, the underlying molecular mechanisms have not been well established. Thus, the present study evaluated the therapeutic effects of GA on H2O2-induced oxidative stress in intestinal porcine epithelial cells. The results showed that pretreatment with GA (100 nM for 16 h) significantly increased the levels of several antioxidant enzymes and reduced corresponding intracellular levels of reactive oxidative species and malondialdehyde. GA inhibited cell apoptosis via activating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, as confirmed by RNA sequencing. Further analyses demonstrated that GA upregulated the phosphorylation levels of PI3K and Akt and the protein level of B cell lymphoma 2, whereas it downregulated Cytochrome c and tumor suppressor protein p53 levels. Moreover, molecular docking analysis predicted the binding of GA to Vasoactive intestinal peptide receptor 1, a primary membrane receptor, to activate the PI3K/Akt signaling pathway. Collectively, these results revealed that GA protected against H2O2-induced oxidative damage and cell apoptosis via activating the PI3K/Akt signaling pathway, suggesting the potential therapeutic use of GA to alleviate oxidative stress in humans/animals.

Role of Dectin-1 in immune response of macrophages induced by Fonsecaea monophora wild strain and melanin-deficient mutant strain.

Chromoblastomycosis is a chronic granulomatous subcutaneous fungal disease caused mainly by Fonsecaea monophora in southern China. Melanin is an important virulence factor in wild strain (Mel+), and the strains lack of the polyketide synthase gene is a melanin-deficient mutant strain (Mel-). We investigated the effect of melanin in F. monophora on Dectin-1 receptor-mediated immune responses in macrophages. Conidia and tiny hyphae of Mel+ and Mel- were co-cultured with THP-1 macrophages expressing normal or low levels of Dectin-1. Compare the killing rate, phagocytosis rate, and expression levels of the inflammatory cytokines tumour necrosis factor-α, interleukin-1ß, interleukin-6, and nitric oxide in each group. The results showed that the killing rate, phagocytosis rate, and pro-inflammatory factor levels of Mel+ infected macrophages with normal expression of Dectin-1 were lower than those of Mel-. And the knockdown of Dectin-1 inhibited the phagocytic rate, killing rate, and proinflammatory factor expression in macrophages infected with Mel+ and Mel-. And there was no significant difference in the above indexes between Mel+ and Mel- groups in Dectin-1 knockdown macrophages. In summary, the study reveals that melanin of F. monophora inhibits the immune response effect of the host by hindering its binding to Dectin-1 on the surface of macrophage, which may lead to persistent fungal infections.

Selenium maintains intestinal epithelial cells to activate M2 macrophages against deoxynivalenol injury.

Selenium (Se) is indispensable in alleviating various types of intestinal injuries. Here, we thoroughly investigated the protective effect of Se on the regulation of the epithelial cell-M2 macrophages pathway in deoxynivalenol (DON)-induced intestinal damage. In the present study, Se has positive impacts on gut health by improving gut barrier function and reducing the levels of serum DON in vivo. Furthermore, our study revealed that Se supplementation increased the abundances of GPX4, p-PI3K, and AKT, decreased the levels of 4-HNE and inhibited ferroptosis. Moreover, when mice were treated with DON and Fer-1(ferroptosis inhibitor), ferroptosis was suppressed and PI3K/AKT pathway was activated. These results indicated that GPX4-PI3K/AKT-ferroptosis was a predominant pathway in DON-induced intestinal inflammation. Interestingly, we discovered that both the number of M2 anti-inflammatory macrophages and the levels of CSF-1 decreased while the pro-inflammatory cytokine IL-6 increased in the intestine and MODE-K cells supernatant. Therefore, Se supplementation activated the CSF-1-M2 macrophages axis, resulting in a decrease in IL-6 expression and an enhancement of the intestinal anti-inflammatory capacity. This study provides novel insights into how intestinal epithelial cells regulate the CSF-1-M2 macrophage pathway, which is essential in maintaining intestinal homeostasis confer to environmental hazardous stimuli.

Deposition and enrichment of carotenoids in livestock products: An overview.

A wide range of research has illustrated that carotenoids play a key role in human health through their versatile beneficial biological functions. Traditionally, the majority dietary sources of carotenoids for humans are obtained from vegetables and fruits, however, the contribution of animal-derived foods has attracted more interest in recent years. Livestock products such as eggs, meat, and milk have been considered as the appropriate and unique carriers for the deposition of carotenoids. In addition, with the enrichment of carotenoids, the nutritional quality of these animal-origin foods would be improved as well as the economic value. Here, we offer an overview covering aspects including the physicochemical properties of carotenoids, the situation of carotenoids fortified in livestock products, and the pathways that lead to the deposition of carotenoids in livestock products. The summary of these important nutrients in livestock products will provide references for animal husbandry and human health.

A novel nucleic acid linker for multi-gene expression enhances plant and animal synthetic biology.

The production of compact vectors for gene stacking is hindered by a lack of effective linkers. Here, we report that a 26-nt nucleic acid linker, NAL1, from the fungus Glarea lozoyensis and its truncated derivatives could connect two genes as a bicistron, enabling independent translation in a maize protoplast transient expression system and human 293 T cells. The optimized 9-nt NAL10 linker was then used to connect four genes driven by a bidirectional promoter; this combination was successfully used to reconstruct the astaxanthin biosynthesis pathway in transgenic maize. The short and efficient nucleic acid linker NAL10 can be widely used in multi-gene expression and synthetic biology in animals and plants.

Identification of Characteristic Bioactive Compounds in Silkie Chickens, Their Effects on Meat Quality, and Their Gene Regulatory Network.

Silkie chicken, an important chicken breed with high medicinal and nutritional value, has a long history of being used as a dietary supplement in China. However, the compounds with health-promoting effects in Silkie chickens remain unclear. In the present study, we conducted a comprehensive analysis of metabolic and lipidomic profiles to identify the characteristic bioactive compounds in Silkie chickens, using a common chicken breed as control. The results showed that the levels of 13 metabolites including estradiol, four lipid subclasses including cardiolipin (CL), eight lipid molecules, and three fatty acids including docosahexaenoic acid (C22:6) were significantly increased in Silkie chickens, which have physiological activities such as resisting chronic diseases and improving cognition. These characteristic bioactive compounds have effects on meat quality characteristics, including improving its water-holding capacity and umami taste and increasing the content of aromatic compounds and phenols. The differentially expressed genes (DEGs) between the two chicken breeds revealed the regulatory network for these characteristic bioactive compounds. Fifteen DEGs, including HSD17B1, are involved in the synthesis of characteristic metabolites. Eleven DEGs, including ELOVL2, were involved in the synthesis and transport of characteristic lipids and fatty acids. In summary, we identified characteristic bioactive compounds in Silkie chickens, and analyzed their effects on meat quality characteristics. This study provided important insight into Silkie chicken meat as a functional food.