A Unique Combination of Mn2+ and Aluminum Adjuvant Acted the Synergistic Effect.

Introduction: The development of combinatorial adjuvants is a promising strategy to boost vaccination efficiency. Accumulating evidence indicates that manganese exerts strong immunocompetence and will become an enormous potential adjuvant. Here, we described a novel combination of Mn2+ plus aluminum hydroxide (AH) adjuvant that significantly exhibited the synergistic immune effect. Methodology. Initially, IsdB3 proteins as the immune-dominant fragment of IsdB proteins derived from Staphylococcus aureus (S. aureus) were prepared. IsdB3 proteins were identified by western blotting. Furthermore, we immunized C57/B6 mice with IsdB3 proteins plus Mn2+ and AH adjuvant. After the second immunization, the proliferation of lymphocytes was measured by the cell counting kit-8 (CCK-8) and the level of IFN-γ, IL-4, IL-10, and IL-17 cytokine from spleen lymphocytes in mice and generation of the antibodies against IsdB3 in serum was detected with ELISA, and the protective immune response was assessed through S. aureus challenge. Results: IsdB3 proteins plus Mn2+ and AH obviously stimulated the proliferation of spleen lymphocytes and increased the secretion of IFN-γ, IL-4, IL-10, and IL-17 cytokine in mice, markedly enhanced the generation of the antibodies against IsdB3 in serum, observably decreased bacterial load in organs, and greatly improved the survival rate of mice. Conclusion: These data showed that the combination of Mn2+ and AH significantly acted a synergistic effect, reinforced the immunogenicity of IsdB3, and offered a new strategy to increase vaccine efficiency.

Correlation of Homocysteine and Blood Pressure Variability with Left Ventricular Hypertrophy in Patients with Hypertension and Carotid Atherosclerosis.

Objective: It is of positive significance for clinical management to infer the changes of BPV and blood Hcy in the risk of cardiovascular disease progression in patients with hypertension by ambulatory blood pressure test. We aimed to explore the correlation of homocysteine and blood pressure variability with left ventricular hypertrophy in patients with hypertension and carotid atherosclerosis. Methods: A total of 333 elderly hypertensive patients admitted to Jinniu District People's Hospital in Chengdu from February 2020 to December 2021 were selected as the study subjects. They were divided into the pure hypertension group and hypertension combined with the carotid atherosclerosis group. In addition, the two groups were divided into the hypertension combined with left ventricular remodeling subgroup and the hypertension without left ventricular remodeling subgroup. Plasma Hcy levels were measured on a BECKMAN AU 680 automated biochemistry analyzer. Ambulatory blood pressure was measured by HINGMED ABP-03 monitoring system. IMT measurement was performed using a GE LOGIQ E9 ultrasound. Left ventricular diastolic function measurement was performed using a GE LOGIQ E9 ultrasound. Results: Blood Hcy, 24-h mean SBP, 24-h mean DBP, 24-h SBP coefficient of variation, and 24-h DBP coefficient of variation were significantly higher in hypertension combined with the carotid atherosclerosis group than the pure hypertension group (P < .05). Moreover, LVMI, E/A, and E/e were greater in the carotid atherosclerosis group than in the normal carotid group (P < .05). IMT, blood Hcy, 24-h mean SBP, 24-h mean DBP, 24-h SBP coefficient of variation, 24-h DBP coefficient of variation, E/A, and E/e were significantly higher in the hypertensive combined with left ventricular remodeling subgroup than in the non-left ventricular remodeling subgroup (P < .05). IMT was positively correlated with blood Hcy, 24-h SBP, 24-h DBP, 24-h SCV, 24-h DCV, LVMI, E/A, and E/e (P < .05). Conclusion: There was a position correlation of Hcy and BPV with left ventricular hypertrophy in patients with hypertension combined with carotid atherosclerosis.

LettuceDB: an integrated multi-omics database for cultivated lettuce.

Crop genomics has advanced rapidly during the past decade, which generated a great abundance of omics data from multi-omics studies. How to utilize the accumulating data becomes a critical and urgent demand in crop science. As an attempt to integrate multi-omics data, we developed a database, LettuceDB (https://db.cngb.org/lettuce/), aiming to assemble multidimensional data for cultivated and wild lettuce germplasm. The database includes genome, variome, phenome, microbiome and spatial transcriptome. By integrating user-friendly bioinformatics tools, LettuceDB will serve as a one-stop platform for lettuce research and breeding in the future. Database URL: https://db.cngb.org/lettuce/.

Microbial bionic nano-aromatic drugs for prevention of depression induced by chronic stress.

Depression is a mood disorder mainly clinically characterized by significant and persistent low spirits. Chronic stress is the leading cause of depression. However, traditional medicine has severe side effects in treating depression, ineffective treatment, and easy recurrence. Therefore, it is of great significance to prevent depression in the environment of chronic stress. In this study, aromatherapy was used for the prevention of depression. To solve the defects of intense volatility and inconvenience in using essential oils, we designed bionic nano-aromatic drugs and adhered them to the wallpaper. Inspired by the moldy wallpaper, we successively prepared the morphology-bionic nano-aromatic drugs, the function-bionic nano-aromatic drugs, and the bionic plus nano-aromatic drugs by referring to the morphology of microorganisms and substances in bacterial biofilms. Bionic nano-aromatic drugs remarkably promoted their adhesion on wallpaper. Molecular dynamics simulation explored its molecular mechanism. The essential oils, which were slowly released from the bionic nano-aromatic drugs, showed excellent biosecurity and depression prevention. These sustainedly released essential oils could significantly increase monoamine neurotransmitters in the brain under a chronic stress environment and had excellent neuroprotection. Besides, the bionic nano-aromatic drugs with simple preparation process and low cost had excellent application potential.

Unexplained recurrent high fever observed in a depressed adolescent.

BACKGROUND: Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This case study is the first to report the relationship between unexplained recurrent high fever and depression. CASE PRESENTATION: H is a 15 year old adolescent female currently in junior year. 2 + months ago, H gradually felt depressed after a class change. Around the time, the patient suddenly developed chills with no obvious trigger and fever. H was treated with anti-infective and anti-viral treatments all of which did not show significant improvement. No significant abnormality was seen in any of the related examinations. Considering that the patient's anxiety, depression and somatic symptoms were obvious during the course of the disease, she was given venlafaxine hydrochloride extended-release capsule 75 mg/d; tandospirone citrate capsule 10 mg Bid; alprazolam tablets 0.4 mg qn to improve mood and sleep; supplemented with transcranial repetitive magnetic stimulation therapy 2 times/d; visible light therapy 1 time/d and psychological counseling once. Over the 6 days of treatment, the patient's body temperature gradually returned to the normal range and her mood improved significantly. CONCLUSION: Depression should be considered a potential cause of unexplained recurrent fevers in adolescents, even when the temperature is significantly outside the normal range.

Compound Shenma Jingfu granule alleviates cerebral ischemia via HIF-1α-mediated promotion of angiogenesis.

BACKGROUND: Shenma Jingfu Granule, a traditional Chinese medicine formula, has been used clinically for the treatment of cerebral circulation insufficiency. However, the mechanism involved in alleviating cerebral ischemia has not yet been fully elucidated. METHODS: An integrated approach involving network pharmacology and transcriptomics was utilized to clarify the potential mechanisms of SMJF Granule. Molecular docking and surface plasmon resonance (SPR) were employed to identify potential targets and ingredients of SMJF Granule. The anti-CI effect of SMJF Granule was determined on the middle cerebral artery occlusion (MCAO) model by using hematoxylin-eosin (H&E) and Nissl's staining, as well as triphenyl tetrazolium chloride (TTC) staining, and the potential targets involved in the mechanisms were validated by RT-qPCR and western blotting. RESULTS: Integrated analysis revealed the mechanism of SMJF Granule intervening in CI injury might be related to the HIF-1 signaling pathway and angiogenesis. Molecular docking and SPR assays demonstrated robust binding interactions between key compounds like salvianolic acid A and naringenin with the core target HIF-1α protein. The experiment confirmed that SMJF Granule lowered neurological scores, diminished infarct volume, and alleviated histopathological changes in vivo. The possible mechanism of SMJF Granule was due to regulating HIF-1 pathway, which contributed to up-regulating expression of VEGF and vWF in the penumbral region, showing a significant promotion of angiogenesis. CONCLUSION: SMJF Granule promoted angiogenesis through HIF-1α pathway, thereby alleviating cerebral ischemia injury. In addition, our findings provide some evidence that SMJF Granule is a candidate compound for further investigation in treating CI in the clinical.

Dual Self-Assembly of Puerarin and Silk Fibroin into Supramolecular Nanofibrillar Hydrogel for Infected Wound Treatment.

The treatment of infected wounds remains a challenging biomedical problem. Some bioactive small-molecule hydrogelators with unique rigid structures can self-assemble into supramolecular hydrogels for wound healing. However, they are still suffered from low structural stability and bio-functionality. Herein, a supramolecular hydrogel antibacterial dressing with a dual nanofibrillar network structure is proposed. A nanofibrillar network created by a small-molecule hydrogelator, puerarin extracted from the traditional Chinese medicine Pueraria, is interconnected with a secondary macromolecular silk fibroin nanofibrillar network induced by Ga ions via charge-induced supramolecular self-assembly. The resulting hydrogel features adequate mechanical strength for sustainable retention at wounds. Good biocompatibility and efficient bacterial inhibition are obtained when the Ga ion concentration is 0.05%. Otherwise, the substantial release of Ga ions and puerarin endows the hydrogel with excellent hemostatic and antioxidative properties. In vivo, evaluation of a mouse-infected wound model demonstrates that its healing effect outperformed that of a commercially available silver-containing wound dressing. The experimental group successfully achieves a 100% wound closure rate on day 10. This study sheds new light on the design of nanofibrillar hydrogels based on supramolecular self-assembly of naturally derived bioactive molecules as well as their clinical use for treating chronic infected wounds.

[The dynamic monitoring of gastric residual volume by ultrasound was used to guide the early nutritional treatment of patients with severe mechanical ventilation to gradually achieve the standard].

OBJECTIVE: To explore the application value of dynamic monitoring of gastric residual volume (GRV) in achieving different target energy in severe mechanical ventilation patients. METHODS: A prospective randomized controlled study was conducted. Forty-two patients with mechanical ventilation admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from July to December 2022 were enrolled. According to the random number table method, patients were divided into GRV guided enteral nutrition by traditional gastric juice pumpback method (control group, 22 patients) and GRV guided enteral nutrition by bedside ultrasound (test group, 20 patients). General data were collected from both groups, and clinical indicators such as hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), neutrophil percentage (Neut%), procalcitonin (PCT), absolute lymphocytes (LYM), prealbumin (PA), and retinol-binding protein (RBP) were dynamically observed. Inflammation, infection, immunity, nutritional indicators, and the incidence of reflux/aspiration, ventilator-associated pneumonia (VAP) were compared between the two groups, and further compared the proportion of patients with respectively to reach the target energy 25%, 50%, and 70% on days 1, 3, and 5 of initiated enteral nutrition. RESULTS: (1) There were no significant differences in gender, age, body mass index (BMI), duration of mechanical ventilation, and acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), severe nutritional risk score (NUTRIC) at admission between the two groups, indicating comparability. (2) On day 1 of initiated enteral nutrition, there were no significant differences in infection, inflammation, immunity and nutrition indicators between the two groups. On day 3 of initiated enteral nutrition, the hs-CRP in the test group was lower than that control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 129.60±75.18 vs. 185.20±63.74, LYM: 1.00±0.84 vs. 0.60±0.41, PA (mg/L): 27.30±3.66 vs. 22.30±2.55, all P < 0.05]. On day 5 of initiated enteral nutrition, the hs-CRP, Neut%, PCT in the test group were lower than those control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 101.70±54.32 vs. 148.40±36.35, Neut%: (85.50±7.66)% vs. (92.90±6.01)%, PCT (µg/L): 0.7 (0.3, 2.7) vs. 3.6 (1.2, 7.5), LYM: 1.00±0.68 vs. 0.50±0.38, PA (mg/L): 27.10±4.57 vs. 20.80 ± 3.51, all P < 0.05]. There were no significantly differences in IL-6 and RBP between the two groups at different time points. (3) The proportion of 50% and 70% of achieved target energy in the test group on day 3, day 5 of initiated enteral nutrition were higher than those of the control group (70.0% vs. 36.4%, 70.0% vs. 36.4%, both P < 0.05). (4) The incidence of reflux/aspiration and VAP in the test group on day 5 of initiated enteral nutrition were significantly lower than those control group (incidence of reflux/aspiration: 5.0% vs. 28.6%, incidence of VAP: 10.0% vs. 36.4%, both P < 0.05). CONCLUSIONS: Dynamic monitoring of GRV by bedside ultrasound can accurately improve the proportion of 50% of achieved target energy on day 3 and 75% on day 5 in severe mechanical ventilation patients, improve the patient's inflammation, immune and nutritional status, and can prevent the occurrence of reflux/aspiration and VAP.

The Association between CYP2C19 Genetic Polymorphism and Prognosis in Patients Receiving Endovascular Therapy.

Background: Potentially substantial impacts on the prognosis have been observed in individuals undergoing endovascular treatment due to cytochrome P450 2c19 (CYP2C19) polymorphism. In an attempt to improve prognosis and lower the recurrence rate, this study investigated the CYP2C19 polymorphism in acute ischemic stroke patients. Materials and Methods: A retrospective analysis was performed on 292 patients with cerebral infarction who had acute endovascular recanalization at the Department of Neurology of Chongqing Hospital of Traditional Chinese Medicine between May 2017 and 2019. The patients were categorized into rapid-, medium-, and slow-metabolism groups based on CYP2C19 gene polymorphism, and their prognosis was monitored. In addition, the prognosis of 188 patients selectively receiving carotid artery stenting at a selected time was also observed. Results: Among the 292 cerebral infarction cases receiving acute endovascular recanalization, the patients in the CYP2C19 rapid-metabolism group regularly took clopidogrel and aspirin combined with antiplatelet therapy and suffered from reoccurrence of apoplexy and cerebral hemorrhage; the 90-day good prognosis had a statistical difference (P < 0.05, prognostic assessment includes hospitalization and 6 months after discharge) and the other adverse events had no statistical difference (including mortality). The 188 patients selectively receiving carotid artery stenting had a recurrence of apoplexy, cerebral hemorrhage, and restenosis rate with a statistical difference (P < 0.05), and the other adverse events had no statistical difference. Conclusions: In conclusion, the findings of the current study indicate that irrespective of whether patients are undergoing selective carotid artery stenting or acute endovascular recanalization, those with rapid CYP2C19 metabolism have a significantly lower likelihood of experiencing adverse prognostic events compared to those with intermediate and slow metabolism. Furthermore, this group also has a more favorable prognosis than the other two groups.

Association between dietary magnesium intake and muscle mass among hypertensive population: evidence from the National Health and Nutrition Examination Survey.

BACKGROUND: Magnesium is critical for musculoskeletal health. Hypertensive patients are at high risk for magnesium deficiency and muscle loss. This study aimed to explore the association between magnesium intake and muscle mass in patients with hypertension. METHODS: In this population-based cross-sectional study, 10,279 U.S. hypertensive adults aged 20 years or older were derived from the National Health and Nutrition Examination Survey in 1999-2006 and 2011-2018. Magnesium (Mg) intake from diet and supplements was assessed using 24-hour diet recalls. Muscle mass was evaluated by appendicular skeletal muscle mass index (ASMI, total ASM in kilograms [kg] divided by square of height in meters [m2]). The association of Mg intake with ASMI was estimated using weighted multivariable-adjusted linear regression models and restricted cubic splines. RESULTS: Dose-response analyses showed a positive linear correlation between dietary Mg intake and ASMI. Every additional 100 mg/day in dietary Mg was associated with 0.04 kg/m2 (95% confidence interval [CI] 0.02-0.06 kg/m2) higher ASMI. The ASMI in participants who met the recommended dietary allowance (RDA) for dietary Mg was 0.10 kg/m2 (95% CI 0.04-0.16 kg/m2) higher than those whose dietary Mg was below estimated average requirement (EAR). However, the relationship of Mg intake from supplements with ASMI was not identified. CONCLUSION: Higher level of dietary Mg intake rather than Mg supplements was associated with more muscle mass in U.S. adults with hypertension, which highlights the importance of meeting the recommended levels for dietary Mg intake.

Application of Thermal Cycling Amplification Chip Method in the Detection of Respiratory Machine-Associated Pneumonia Pathogens.

Objective: Investigating the application effectiveness of using loop-mediated isothermal amplification (LAMP) on a microfluidic chip to detect the pathogens associated with ventilator-associated pneumonia (VAP). Methods: Eighty samples of bronchoalveolar lavage fluid from patients with ventilator-associated pneumonia (VAP) were collected at The First Hospital of Hebei Medical University from July 2022 to July 2023. The bacterial culture technique and the LAMP method were used to detect the nucleic acid of the pathogens in the patient samples. The positivity rates of bacterial culture and LAMP method in detecting VAP pathogens were analyzed. Results: A total of 80 specimens were examined, with 73 positive specimens detected using the LAMP method (positivity rate of 91.25%) and 60 positive specimens detected using bacterial culture (positivity rate of 75.00%). The LAMP method exhibited a higher number of positive detections compared to bacterial culture. Both methods showed a high level of concordance and were virtually identical in detecting methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterobacter aerogenes, Haemophilus influenzae, and Streptococcus pneumoniae. Conclusion: The LAMP method demonstrates significantly improved performance in the detection of pathogens for VAP, with a higher pathogen positivity rate compared to bacterial culture. This method holds promising prospects for clinical application.

Anti-inflammatory effect of lignans from flaxseed after fermentation by lactiplantibacillus plantarum SCB0151 in vitro.

Lignan, a beneficial constituent of Flaxseed (Linum usitatissimum L.) showed great interest in researchers because of its multiple functional properties. Nonetheless, a challenge arises due to the glycosidic structure of lignans, which the gut epithelium cannot readily absorb. Therefore, we screened 18 strains of Lactiplantibacillus plantarum, Lacticaseibacillus casei, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Pediococcus pentosaceus, Pediococcus acidilactici, and Enterococcus durans to remove glycosides from flaxseed lignan extract enzymatically. Among our findings, Lactiplantibacillus plantarum SCB0151 showed the highest activity of ß-glucosidase (8.91 ± 0.04 U/mL) and higher transformed efficiency of Secoisolariciresinol (SECO) (8.21 ± 0.13%). The conversion rate of Secoisolariciresinol diglucoside (SDG) and the generation rate of SECO was 58.30 ± 3.78% and 32.13 ± 2.78%, respectively, under the optimized conditions. According to the LC-HRMSMS analysis, SECO (68.55 ± 6.57 µM), Ferulic acid (FA) (32.12 ± 2.50 µM), and Coumaric acid (CA) (79.60 ± 6.21 µM) were identified in the biotransformation products (TP) of flaxseed lignan extract. Results revealed that the TP exhibited a more pronounced anti-inflammatory effect than the flaxseed lignan extract. SECO, FA, and CA demonstrated a more inhibitory effect on NO than that of SDG. The expression of iNOS and COX-2 was significantly suppressed by TP treatment in LPS-induced Raw264.7 cells. The secretion of IL-6, IL-2, and IL-1ß decreased by 87.09 ± 0.99%, 45.40 ± 0.87%, and 53.18 ± 0.83%, respectively, at 60 µg/mL of TP treatment. Given these data, the bioavailability of flaxseed lignan extract and its anti-inflammatory effect were significantly enhanced by Lactiplantibacillus plantarum SCB0151, which provided a novel approach to commercializing flaxseed lignan extract for functional food.

Insula→Amygdala and Insula→Thalamus Pathways Are Involved in Comorbid Chronic Pain and Depression-Like Behavior in Mice.

The comorbidity of chronic pain and depression poses tremendous challenges for the treatment of either one because they exacerbate each other with unknown mechanisms. As the posterior insular cortex (PIC) integrates multiple somatosensory and emotional information and is implicated in either chronic pain or depression, we hypothesize that the PIC and its projections may contribute to the pathophysiology of comorbid chronic pain and depression. We show that PIC neurons were readily activated by mechanical, thermal, aversive, and stressful and appetitive stimulation in naive and neuropathic pain male mice subjected to spared nerve injury (SNI). Optogenetic activation of PIC neurons induced hyperalgesia and conditioned place aversion in naive mice, whereas inhibition of these neurons led to analgesia, conditioned place preference (CPP), and antidepressant effect in both naive and SNI mice. Combining neuronal tracing, optogenetics, and electrophysiological techniques, we found that the monosynaptic glutamatergic projections from the PIC to the basolateral amygdala (BLA) and the ventromedial nucleus (VM) of the thalamus mimicked PIC neurons in pain modulation in naive mice; in SNI mice, both projections were enhanced accompanied by hyperactivity of PIC, BLA, and VM neurons and inhibition of these projections led to analgesia, CPP, and antidepressant-like effect. The present study suggests that potentiation of the PIC→BLA and PIC→VM projections may be important pathophysiological bases for hyperalgesia and depression-like behavior in neuropathic pain and reversing the potentiation may be a promising therapeutic strategy for comorbid chronic pain and depression.

Effect of electroacupuncture on neuronal programmed necrosis by regulating RIP1/RIP3/MLKL pathway in rats with cerebral ischemia reperfusion injury. / 电针调节RIP1/RIP3/MLKLé€šè·¯å¯¹è„‘ç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ ç¥žç»å ƒç¨‹åºæ€§åæ­»çš„å½±å“.

OBJECTIVES: To investigate the neuroprotective effect of electroacupuncture (EA) at "Quchi"(LI11) and "Zusanli"(ST36) in the rats with cerebral ischemia reperfusion injury and its influence on programmed necrosis of cerebral cortical neurons. METHODS: Sixty male SD rats were randomly divided into sham-operation group, model group, EA group and inhibitor group, with 15 rats in each group. Left middle cerebral artery occlusion model was established using the modified thread embolism method. In the sham-operation group, the carotid artery was exposed and dissociated in each rat. EA was applied to "Quchi"(LI11) and "Zusanli"(ST36) on the right side for 30 min each time, once daily for 7 days in the rats of the EA group. The rats in the inhibitor group were intraperitoneally injected with norstatin-1 (0.6 mg/kg) for consecutive 7 days. The neurological deficit score of rats in each group was observed. HE staining was adopted to detect the degree of pathological damage of the cerebral cortex in the infarction area. Using TUNEL staining, the apoptosis of cortical neurons in the infarction area was determined；the contents of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and IL-6 were detected by ELISA；the mRNA and protein expression of the receptor interacting protein-1 (RIP1), the receptor interacting protein-3 (RIP3) and the substrate mixed lineage kinase like protein (MLKL) were detected by fluorescence quantitative PCR and Western blot, respectively. RESULTS: In comparison with the sham-operation group, the neurological deficit score in the model group was higher(P<0.01)；HE staining showed that there was the pathological damage in the infarction area；the neuron apoptosis rate, the contents of TNF-α, IL-1ß and IL-6, and the mRNA and protein expressions of RIP1, RIP3 and MLKL increased(P<0.01) in the model group. In the EA group, the neurological deficit score was reduced(P<0.01)；HE staining showed that the pathological damage was ameliorated in the infarction area；the neuron apoptosis rate, the contents of TNF-α, IL-1ß and IL-6, and the mRNA and protein expressions of RIP1, RIP3, MLKL decreased(P<0.05, P<0.01) when compared with those in the model group. CONCLUSIONS: EA can attenuate cerebral ischemia reperfusion injury and display its neuroprotective effect probably through inhibiting programmed necrosis of cerebral cortical neurons in the rats.

A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method for determination of phytohormones in the medicinal plant saffron.

Saffron (Crocus sativus L.) is a valuable Chinese herb with high medicinal value. Saffron pistils are used as medicine, so increasing the number of flowers can increase the yield. Plant hormones have essential roles in the growth and development of saffron, as well as the response to biotic and abiotic stresses (especially in floral initiation), which may directly affect the number of flowers. Quantitative analysis of plant hormones provides a basis for more efficient research on their synthesis, transportation, metabolism, and action. However, starch (which interferes with extraction) is present in high levels, and hormone levels are extremely low, in saffron corms, thereby hampering accurate determination of plant-hormone levels in saffron. Herein, we screened an efficient and convenient pre-treatment method for plant materials containing abundant amounts of starch. Also, we proposed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the quantification of abscisic acid (ABA) and auxin (IAA). Then, the method was applied for the detection of hormone-content differences between flowering and non-flowering top buds, as well as between lateral and top buds. Our method showed high sensitivity, reproducibility, and reliability. Specifically, good linearity in the range 2-100 ng ml-1 was achieved in the determination of ABA and IAA, and the correlation coefficient (R2) was >0.9982. The relative standard deviation was 2.956-14.51% (intraday) and 9.57-18.99% (interday), and the recovery range was 89.04-101.1% (n = 9). The matrix effect was 80.38-90.50% (n = 3). The method was thoroughly assessed employing various "green" chemistry evaluation tools: Blue Applicability Grade Index (BAGI), Complementary Green Analytical Procedure Index (Complex GAPI) and Red Green Blue 12 Algorithm (RGB12). These tools revealed the good greenness, analytical performance, applicability, and overall sustainability alignment of our method. Quantitative results showed that, compared with saffron with a flowering phenotype cultivated at 25 °C, the contents of IAA and ABA in the terminal buds of saffron cultivated at 16 °C decreased significantly. When cultivated at 25 °C, the IAA and ABA contents in the terminal buds of saffron were 1.54- and 4.84-times higher than those in the lateral buds, respectively. A simple, rapid, and accurate UPLC-MS/MS method was established to determine IAA and ABA contents. Using this method, a connection between the contents of IAA and ABA and the flowering phenotype was observed in the quantification results. Our data lay a foundation for studying the flowering mechanism of saffron.

Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5.

Immunomodulatory effects of long-chain fatty acids (LCFAs) and their activating enzyme, acyl-coenzyme A (CoA) synthetase long-chain family (ACSL), in the tumor microenvironment remain largely unknown. Here, we find that ACSL5 functions as an immune-dependent tumor suppressor. ACSL5 expression sensitizes tumors to PD-1 blockade therapy in vivo and the cytotoxicity mediated by CD8+ T cells in vitro via regulation of major histocompatibility complex class I (MHC-I)-mediated antigen presentation. Through screening potential substrates for ACSL5, we further identify that elaidic acid (EA), a trans LCFA that has long been considered harmful to human health, phenocopies to enhance MHC-I expression. EA supplementation can suppress tumor growth and sensitize PD-1 blockade therapy. Clinically, ACSL5 expression is positively associated with improved survival in patients with lung cancer, and plasma EA level is also predictive for immunotherapy efficiency. Our findings provide a foundation for enhancing immunotherapy through either targeting ACSL5 or metabolic reprogramming of antigen presentation via dietary EA supplementation.

Traditional Chinese medicine polysaccharide in nano-drug delivery systems: Current progress and future perspectives.

Traditional Chinese medicine polysaccharides (TCMPs) have gained increasing attention in the field of nanomedicine due to their diverse biological activities and favorable characteristics as drug carriers, including biocompatibility, biodegradability, safety, and ease of modification. TCMPs-based nano-drug delivery systems (NDDSs) offer several advantages, such as evasion of reticuloendothelial system (RES) phagocytosis, protection against biomolecule degradation, enhanced drug bioavailability, and potent therapeutic effects. Therefore, a comprehensive review of the latest developments in TCMPs-based NDDSs and their applications in disease therapy is of great significance. This review provides an overview of the structural characteristics and biological activities of TCMPs relevant to carrier design, the strategies employed for constructing TCMPs-based NDDSs, and the versatile role of TCMPs in these systems. Additionally, current challenges and future prospects of TCMPs in NDDSs are discussed, aiming to provide valuable insights for future research and clinical translation.

Research progress on the structure, derivatives, pharmacological activity, and drug carrier capacity of Chinese yam polysaccharides: A review.

Chinese yam is a traditional Chinese medicine that has a long history of medicinal and edible usage in China and is widely utilised in food, medicine, animal husbandry, and other industries. Chinese yam polysaccharides (CYPs) are among the main active components of Chinese yam. In recent decades, CYPs have received considerable attention because of their remarkable biological activities, such as immunomodulatory, antitumour, hypoglycaemic, hypolipidaemic, antioxidative, anti-inflammatory, and bacteriostatic effects. The structure and chemical alterations of polysaccharides are the main factors affecting their biological activities. CYPs are potential drug carriers owing to their excellent biodegradability and biocompatibility. There is a considerable amount of research on CYPs; however, a systematic summary is lacking. This review summarises the structural characteristics, derivative synthesis, biological activities, and their usage as drug carriers, providing a basis for future research, development, and application of CYPs.

[Effect and mechanism of Jiedu Huoxue Decoction in regulating YAP/ACSL4 pathway to inhibit ferroptosis in treatment of acute kidney injury].

Jiedu Huoxue Decoction(JDHX), first recorded in the Correction on Errors in Medical Works by WANG Qing-ren, is an effective formula screened out from ancient formulas by the traditional Chinese medicine(TCM) master ZHANG Qi to treat acute kidney injury(AKI) caused by heat, toxicity, stasis, and stagnation. This paper elucidated the therapeutic effect of JDHX on AKI and probed into the potential mechanism from ferroptosis. Thirty-two male C57BL/6 mice were randomized into four groups(n=8): normal, model, and low-and high-dose JDHX. Since the clinical treatment of AKI depends on supportive or alternative therapies and there is no specific drug, this study did not include a positive drug group. The low dose of JDHX corresponded to half of clinically equivalent dose, while the high dose corresponded to the clinically equivalent dose. Mice were administrated with JDHX by gavage daily for 7 consecutive days, while those in the normal group and the model group were administered with the corresponding volume of distilled water. On day 5 of drug administration, mice in other groups except the normal group were injected intraperitoneally with cisplatin solution at a dose of 20 mg·kg~(-1) to induce AKI, and the normal group was injected with saline. All of the mice were sacrificed 72 h after modeling, blood and kidney samples were collected for subsequent analysis. The levels of serum creatine(Scr) and blood urea nitrogen(BUN) were measured by the commercial kits. The expression level of kidney injury molecule 1(KIM-1) in the serum was measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin(HE) staining, periodic acid-Schiff(PAS) staining, and Prussian blue staining were employed to observe the pathological changes, glycogen deposition, and iron deposition, respectively, in the renal tissue. In addition, the levels of glutathione(GSH), superoxide dismutase(SOD), and catalase(CAT) in the renal tissue were examined by biochemical colorimetry. Western blot was performed to determine the protein levels of acyl-CoA synthetase long chain family member 4(ACSL4), lysophosphatidylcholine acyltransferase 3(LPCAT3), and Yes-associated protein(YAP, a key molecule in the Hippo pathway) in the renal tissue. Immunohistochemistry was then employed to detect the location and expression of YAP in the renal tissue. Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR) was performed to measure the mRNA levels of ACSL4 and glutathione peroxidase 4(GPX4). Compared with the normal group, the model group showed elevated serum levels of Scr, BUN, and KIM-1. In the AKI model group, the tubular epithelial cells underwent atrophy and necrotic detachment, disappearance of brush border, and some tubules became protein tubules or experienced vacuole-like degeneration. In addition, this group presented widening of the interstitium or even edema, increased renal tubule injury score, and obvious glycogen and iron deposition in parts of the renal tissue. Moreover, the model group had lower GSH, SOD, and CAT levels, higher ASCL4 and LPCAT3 levels, and lower GPX4 expression and higher YAP expression than the normal group. Compared with the model group, high dose of JDHX effectively protected renal function, lowered the levels of Scr, BUN and KIM-1, alleviated renal pathological injury, reduced glycogen and iron deposition, and elevated the GSH, SOD, and CAT levels in the renal tissue. Furthermore, JDHX down-regulated the protein levels of ACSL4, LPCAT3, and YAP and up-regulated the level of GPX4, compared with the model group. In conclusion, JDHX can protect mice from cisplatin-induced AKI by inhibiting ferroptosis via regulating the YAP/ACSL4 signaling pathway.