Phage-liposome nanoconjugates for orthopedic biofilm eradication.

Infection by multidrug-resistant (MDR) bacteria has become one of the biggest threats to public health worldwide. One reason for the difficulty in treatment is the lack of proper delivery strategies into MDR bacterial biofilms, where the thick extracellular polymeric substance (EPS) layer impedes the penetration of antibiotics and nanoparticles. Here, we propose a novel bioactive nanoconjugate of drug-loaded liposomes and bacteriophages for targeted eradication of the MDR biofilms in orthopedic infections. Phage Sb-1, which has the ability to degrade EPS, was conjugated with antibiotic-loaded liposomes. Upon encountering the biofilm, phage Sb-1 degrades the EPS structure, thereby increasing the sensitivity of bacteria to antibiotics and allowing the antibiotics to penetrate deeply into the biofilm. As a result, effective removal of MDR bacterial biofilm was achieved with low dose of antibiotics, which was proved in this study by both in vitro and in vivo investigations. Notably, in the rat prosthetic joint infection (PJI) model, we found that the liposome-phage nanoconjugates could effectively decrease the bacterial load in the infected area and significantly promote osteomyelitis recovery. It is therefore believed that the conjugation of bacteriophage and liposomes could open new possibilities for the treatment of orthopedic infections, possibly other infections in the deep tissues.

Visual Endoscopic Retrograde Appendicitis Therapy versus Antibiotic Therapy for Treatment of Uncomplicated Acute Appendicitis.

BACKGROUND: Visual endoscopic retrograde appendicitis therapy (V-ERAT) involves a Single-use Video Scope, allowing real-time visualization of the appendiceal lumen during the procedure to treat uncomplicated acute appendicitis (AA). This study aims to compare V-ERAT to antibiotic therapy in treating uncomplicated AA. METHODS: This multicenter, retrospective cohort study was conducted at nine hospitals in China from August 2021 to July 2023. Propensity score matching was performed to minimize selection bias. A total of 692 uncomplicated AA patients were included, with 188 undergoing V-ERAT and 504 receiving antibiotic therapy. The primary outcome was treatment success rate. The secondary outcomes included recurrent appendicitis rate, the appendectomy rate during the initial hospitalization, length of initial hospitalization, time to disease recurrence, and overall adverse events. RESULTS: The treatment success rate did not differ between the V-ERAT and antibiotic groups (93.6%; 95% confidence interval [CI] 89.1% to 96.7% vs. 90.5%; 95% CI, 87.6% to 92.9%) ( P = 0.225). However, V-ERAT demonstrated a significantly lower risk of appendicitis recurrence compared to antibiotic therapy during the follow-up (log-rank P < 0.001), with a hazard ratio of 0.14 (95% CI 0.07-0.29, P < 0.001). V-ERAT was associated with a lower appendectomy rate during the initial hospitalization (4.3%; 95% CI, 1.9% to 8.2% vs. 9.5%; 95% CI, 7.1 to 12.4%) (P = 0.027), a shorter length of initial hospitalization (3 [IQR, 3-4] vs. 4 [IQR, 4-6] days, P < 0.001), and a longer time to recurrence (269 [IQR, 210-318] vs. 70 [IQR, 21-103] days, P < 0.001). The overall adverse event rates did not differ between the two groups (log-rank P = 0.064). CONCLUSION: V-ERAT appears to be a safe and effective alternative to antibiotic therapy in treating uncomplicated AA, significantly reducing the risk of appendicitis recurrence.

Self-efficacy of ICU nurses in delirium care: an analysis of the current status and influencing factors.

OBJECTIVE: The aim of this study was to assess the current status of delirium care self-efficacy among nurses in the intensive care unit (ICU) and the level of their knowledge about delirium in the ICU, more importantly, to analyze factors influencing the delirium care self-efficacy of ICU nurses and to provide a theoretical basis for ICU nursing managers to develop strategies for effective delirium care and management. METHODS: The study was based on a sample of 283 ICU nurses from eight hospitals in Chongqing selected using a convenience sampling method between July 2023 and September 2023. The tools used included a general information questionnaire, the Chinese version of the Delirium Care Self-Efficacy of ICU Nurses Scale, and the Chinese version of the ICU Delirium Knowledge Level Questionnaire. RESULTS: The self-efficacy score (47.84 ± 9.93) of ICU nurses was positively correlated with the delirium knowledge level score (12.32 ± 3.47, r = 0.591, P < 0.001). Multivariate linear regression analysis identified the gender of the nurse, hospital level (tier), duration of ICU work experience, whether the nurse was a specialized ICU nurse, whether the nurse received delirium-related training, and the level of knowledge about delirium (all P < 0.05) as the influencing factors for the delirium care self-efficacy of ICU nurses. CONCLUSION: It is recommended that ICU nursing managers offer targeted interventions based on the influencing factors to improve the delirium care self-efficacy of ICU nurses and their delirium knowledge levels, thereby reducing the incidence of delirium and improving the quality of care provided for patients with delirium in the ICU.

Causal effect of gut microbiota on occurrence of herpes zoster and postherpetic neuralgia, and role of Tyzzerella 3.

BACKGROUND: Previous research has established connections between gut microbiota, immune modulation, and several virus-related diseases. However, no study has explored the relationships between gut microbiota and herpes zoster and postherpetic neuralgia (PHN). METHODS: A total of 205 taxa of gut microbiota were regarded as exposures. The occurrences of herpes zoster and PHN were selected as outcomes. The causal effects of gut microbiota on herpes zoster and PHN were estimated with multiple methods for two-sample Mendelian randomization, such as inverse variance weighted (IVW), MR-Egger, and weighted median. All results were subjected to FDR correction to prevent from possibility of multiple comparison. RESULTS: Among the significant findings, four taxa and one genus were identified as facilitators of herpes zoster and PHN, respectively. Conversely, six genera and eleven taxa were found to inhibit herpes zoster and PHN, respectively. The causal effect of the Tyzzerella 3 was confirmed through FDR correction, making it a key focus in this study. Specifically, it was found to causally facilitate herpes zoster primarily with IVW (OR 1.420, 95% CI 1.174-1.718, p < 0.001, q = 0.039), as there is no heterogeneity or horizontal pleiotropy found. CONCLUSIONS: With investigation of the causal association between gut microbiota, and herpes zoster/PHN, significant findings were identified in 22 different taxa. Among them, Tyzzerella 3 keeps significant after multiple comparison correction, and displays potential to facilitate the occurrence of herpes zoster.

Visualization of the Distance-Dependent Synergistic Interaction in Heterogeneous Dual-Site Catalysis.

Understanding the characteristics of interfacial hydroxyl (OH) at the solid/liquid electrochemical interface is crucial for deciphering synergistic catalysis. However, it remains challenging to elucidate the influences of spatial distance between interfacial OH and neighboring reactants on reaction kinetics at the atomic level. Herein, we visualize the distance-dependent synergistic interaction in heterogeneous dual-site catalysis by using ex-situ infrared nanospectroscopy and in situ infrared spectroscopy techniques. These spectroscopic techniques achieve direct identification of the spatial distribution of synergistic species and reveal that OH facilitates the reactant deprotonation process depending on site distances in dual-site catalysts. Via modulating Ir-Co pair distances, we find that the dynamic equilibrium between generation and consumption of OH accounts for high-efficiency synergism at the optimized distance of 7.9 Å. At farther or shorter distances, spatial inaccessibility and resistance of OH with intermediates lead to OH accumulation, thereby diminishing the synergistic effect. Hence, a volcano-shaped curve has been established between the spatial distance and mass activity using formic acid oxidation as the probe reaction. This notion could also be extended to oxophilic metals, like Ir-Ru pairs, where volcano curves and dynamic equilibrium further evidence the universal significance of spatial distances.

Discovery and Development of Caffeic Acid Analogs as Versatile Therapeutic Agents.

Caffeic acid (CA) is a polyphenolic acid compound widely distributed in plant seeds. As natural compounds with high research interest, caffeic acid and its derivatives show good activity in the treatment of tumors and inflammation and have antibacterial properties. In recent years, caffeic acid derivatives have been studied extensively, and these derivatives fall roughly into three categories: (1) caffeic acid ester derivatives, (2) caffeic acid amide derivatives, (3) caffeic acid hybrids. These caffeic acid analogues exert mainly antibacterial and antioxidant activities. Among the caffeic acid analogues summarized in this paper, compounds 1g and CAP10 have good activity against Candida albicans, and their MIC50 is 32 µg/mL and 13 µM, respectively. In a DPPH assay, compounds 3k, 5a, CS2, Phellinsin A and 8j showed strong antioxidant activity, and their IC50 values are 18.6 µM, 67.85 µM, 40.29 µM, 0.29 ± 0.004 mM, 4774.37 ± 137.20 µM, respectively. Overall, compound CAP10 had the best antibacterial activity and compound 3k had the best antioxidant activity. This paper mainly summarizes and discusses some representative caffeic acid analogs, hoping to provide better drug design strategies for the subsequent development of caffeic acid analogs.

Trend and driving factors in burden of age-related macular degeneration in older adults aged 60-89 years: a global analysis over three decades.

BACKGROUND: To explore temporal trends and determine driving factors of age-related macular degeneration (AMD) burden in older adults aged 60-89 years at global, regional and national levels from 1990 to 2019. METHODS: Prevalence and years lived with disability (YLDs) were extracted. Joinpoint regression analysis was adopted to calculate average annual percentage change and to identify the year with the most significant changes. Global trends were stratified by sex, age and sociodemographic index, and regional and national trends were explored. Decomposition analysis was conducted to determine what extent the forces of population size, age structure and epidemiologic change driving alterations of AMD burden. RESULTS: Globally, prevalence rate slightly increased whereas YLDs rate decreased. The year 2005 marked a turning point where both prevalence and YLDs started to decline. Regionally, Western Sub-Saharan Africa had the highest prevalence and YLDs rates in 2019, with East Asia experiencing the most notable rise in prevalence from 1990 to 2019. Global decomposition revealed that the increased case number was primarily driven by population growth and ageing, and epidemiological change was only detected to lessen but far from offset these impacts. CONCLUSIONS: Although there was only slight increase or even decrease in prevalence and YLDs rates of AMD in older adults, the case number still nearly doubled, which may be primarily attributed to population growth and ageing, coupled with the emerging growing pattern of prevalence rate from 2015, collectively suggesting a huge challenge in control and management of AMD.

Heterogeneous Carbonylation of Alcohols on Charge-Density-Distinct Mo-Ni Dual Sites Localized at Edge Sulfur Vacancies.

Alcohols carbonylation is of great importance in industry but remains a challenge to abandon the usage of the halide additives and noble metals. Here we report the realization of direct alcohols heterogeneous carbonylation to carbonyl-containing chemicals, especially in methanol carbonylation, with a remarkable space-time-yield (STY) of 4.74 molacetyl/kgcat./h and a durable stability as long as 100 h on Ni@MoS2 catalyst. Mechanistic analysis reveals that the Mo-Ni dual sites localized at edge sulfur vacancies of Ni@MoS2 exhibit distinct charge density, which strongly activate CH3OH to break its C-O bond and non-dissociatively activate CO. Density functional theory calculations further suggest that the low charge density in Mo-Ni, the Ni site, could significantly lower the barrier for CO migration and nucleophilic attack of methoxy species, and finally leads to the rapid formation of acetyl products. Ni@MoS2 catalyst could also effectively realize the carbonylation of ethanol, n-propanol and n-butanol to their acyl products, which may demonstrate its universal application for alcohols carbonylation.

PRELP inhibits colorectal cancer progression by suppressing epithelial-mesenchymal transition and angiogenesis via the inactivation of the FGF1/PI3K/AKT pathway.

Proline/arginine-rich end and leucine-rich protein (PRELP) is identified as a small proteoglycan in the extracellular matrix that has been tightly associated with cell adhesion. At present, the role of PRELP in colorectal cancer (CRC) remains largely unknown. PRELP expression in human CRC tissue samples was analyzed by qRT-PCR and immunochemistry. CCK-8, colony formation, transwell, and tube formation assays were utilized to determine the influences of PRELP on the malignant phenotypes of CRC cells. Mouse xenograft and tumor metastasis models were constructed to further validate the function of PRELP. Furthermore, we investigated the efficacy of PRELP combined with bevacizumab treatment in a mouse xenograft model of CRC. Additionally, RNA-seq was performed to analyze the potential signaling pathways regulated by PRELP. Immunofluorescence staining and coimmunoprecipitation were conducted to confirm the interaction between PRELP and fibroblast growth factor 1 (FGF1). In this study, we found that PRELP exerted a tumor-suppressive effect on CRC. The expression level of PRELP was significantly reduced in CRC tissues and cell lines. Both in vivo and in vitro experiments confirmed that PRELP inhibited CRC cell proliferation, promoted apoptosis, and suppressed migration and invasion via a reduction in the epithelial-mesenchymal transition and attenuated angiogenesis, thereby dampening tumor progression. In addition, PRELP markedly potentiated the efficacy of bevacizumab in a mouse xenograft model. Mechanistically, PRELP bound to FGF1 and reduced the stability of the FGF1 protein, accompanied by an increase in its degradation, which subsequently inactivated the PI3K/AKT/mTOR pathway, thereby leading to reduction in tumor angiogenesis and metastasis. Our study for the first time unveiled the tumor-suppressive role of PRELP in CRC and provided a potential effective strategy for the treatment of CRC.

Phosphorus Coordination in Second Shell of Single-Atom Cu Catalyst toward Acetate Production in CO Electroreduction.

It is challenging to achieve highly efficient CO-CO coupling toward C2 products in electrochemical CO and CO2 reductions on single-atom catalysts (SACs). Herein, we report a modulation strategy of phosphorus coordination in the second shell of Cu SACs with a Cu-N4 structure (Cu-N4-P4/C4) and demonstrate experimentally and theoretically the CO-CO coupling through an Eley-Rideal mechanism in electrochemical CO reduction (COR). Remarkably, the Cu SACs exhibit a selectivity of 63.9% toward acetate production in alkaline media on a gas diffusion electrode. Operando synchrotron-based X-ray absorption spectroscopy confirms the robust Cu-N4-P4/C4 structure of the Cu SACs against the harsh electrochemical reduction conditions throughout the electrochemical COR, instead of forming Cu clusters for Cu-N4 configuration, enabling an excellent COR performance toward acetate. This work not only unravels a new mechanism for CO-CO coupling toward C2 products in COR but also offers a novel strategy for SAC regulation toward multicarbon production with high activity, selectivity, and durability.

A Modified Epiglottis-Tongue Root Flap for Postoperative Laryngeal Stenosis in a Cancer Patient with a History of Radiotherapy.

Introduction: Cricohyoidoepiglottopexy (CHEP) has emerged as a promising surgical technique for treating laryngeal stenosis, offering a low rate of restenosis and a high rate of successful decannulation. However, postoperative radiation therapy can complicate open surgery for some patients due to radiation-induced cellular and tissue damage. This damage can make adequate exposure or mobilization of the larynx challenging. Case Summary: A 71-year-old male, who had undergone a partial laryngectomy 3 years prior, developed laryngeal stenosis and difficulty plugging after 35 rounds of radiotherapy. Initially, CHEP was planned, but intraoperatively, it was found that traditional CHEP would result in excessive anastomotic tension. To prevent complications, we designed an epiglottis-tongue root flap for laryngeal function reconstruction. The patient experienced no restenosis and was successfully extubated. Discussion: By separating the preepiglottal space and mobilizing the base of the tongue to construct the epiglottis-tongue root flap, modified CHEP can achieve laryngeal function reconstruction in patients postradiotherapy. It is essential to conduct a comprehensive evaluation of the patient's overall condition, degree of stenosis, tongue-to-tongue root status, and cervical tissue adhesion before surgery.

Identification of Potential Causal Genes for Neurodegenerative Diseases by Mitochondria-Related Genome-Wide Mendelian Randomization.

Current research lacks comprehensive investigations into the potential causal link between mitochondrial-related genes and the risk of neurodegenerative diseases (NDDs). We aimed to identify potential causative genes for five NDDs through an examination of mitochondrial-related gene expression levels. Through the integration of summary statistics from expression quantitative trait loci (eQTL) datasets (human blood and brain tissue), mitochondrial DNA copy number (mtDNA-CN), and genome-wide association studies (GWAS) datasets of five NDDs from European ancestry, we conducted a Mendelian randomization (MR) analysis to explore the potential causal relationship between mitochondrial-related genes and Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Lewy body dementia (LBD). Sensitivity analysis and Bayesian colocalization were employed to validate this causal relationship. Through MR analysis, we have identified potential causal relationships between 12 mitochondria-related genes and AD, PD, ALS, and FTD overlapping with motor neuron disease (FTD_MND) in human blood or brain tissue. Bayesian colocalization analysis further confirms 9 causal genes, including NDUFS2, EARS2, and MRPL41 for AD; NDUFAF2, MALSU1, and METTL8 for PD; MYO19 and MRM1 for ALS; and FASTKD1 for FTD_MND. Importantly, in both human blood and brain tissue, NDUFS2 exhibits a significant pathogenic effect on AD, while NDUFAF2 demonstrates a robust protective effect on PD. Additionally, the mtDNA-CN plays a protected role in LBD (OR = 0.62, p = 0.031). This study presents evidence establishing a causal relationship between mitochondrial dysfunction and NDDs. Furthermore, the identified candidate genes may serve as potential targets for drug development aimed at preventing NDDs.

Asymmetric catalytic concise synthesis of 3-(3-indolomethyl)-oxindoles for the construction of trigolute analogs.

Asymmetric synthesis of 3-(3-indolomethyl)oxindoles through the addition of indole-substituted enolized ketoesters to 3-bromo-3-substituted oxindoles has been achieved using a N,N'-dioxide/Ho(III) complex. A number of 3-(3-indolomethyl)oxindoles, which may possess biological activity, were obtained in good yields with high diastereo- and enantioselectivities (up to 97% yield, >19 : 1 dr, 98% ee). Furthermore, time-dependent reversal of diastereoselectivity enabled access to optically active diastereomers. The product followed by facile transformations gave a new route into trigolute analogs.

Clinical Outcomes of Tirzepatide or GLP-1 Receptor Agonists in Individuals With Type 2 Diabetes.

Importance: Despite its demonstrated benefits in improving cardiovascular risk profiles, the association of tirzepatide with mortality and cardiovascular and kidney outcomes compared with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) remains unknown. Objective: To investigate the association of tirzepatide with mortality and adverse cardiovascular and kidney outcomes compared with GLP-1 RAs in patients with type 2 diabetes. Design, Setting, and Participants: This retrospective cohort study used US Collaborative Network of TriNetX data collected on individuals with type 2 diabetes aged 18 years or older initiating tirzepatide or GLP-1 RA between June 1, 2022, and June 30, 2023; without stage 5 chronic kidney disease or kidney failure at baseline; and without myocardial infarction or ischemic or hemorrhagic stroke within 60 days of drug initiation. Exposures: Treatment with tirzepatide compared with GLP-1 RA. Main Outcomes and Measures: The primary outcome was all-cause mortality, and secondary outcomes included major adverse cardiovascular events (MACEs), the composite of MACEs and all-cause mortality, kidney events, acute kidney injury, and major adverse kidney events. All outcomes were analyzed using Cox proportional hazards regression models. Results: There were 14 834 patients treated with tirzepatide (mean [SD] age, 55.4 [11.8] years; 8444 [56.9%] female) and 125 474 treated with GLP-1 RA (mean [SD] age, 58.1 [13.3] years; 67 474 [53.8%] female). After a median (IQR) follow-up of 10.5 (5.2-15.7) months, 95 patients (0.6%) in the tirzepatide group and 166 (1.1%) in the GLP-1 RA group died. Tirzepatide treatment was associated with lower hazards of all-cause mortality (adjusted hazard ratio [AHR], 0.58; 95% CI, 0.45-0.75), MACEs (AHR, 0.80; 95% CI, 0.71-0.91), the composite of MACEs and all-cause mortality (AHR, 0.76; 95% CI, 0.68-0.84), kidney events (AHR, 0.52; 95% CI, 0.37-0.73), acute kidney injury (AHR, 0.78; 95% CI, 0.70-0.88), and major adverse kidney events (AHR, 0.54; 95% CI, 0.44-0.67). Treatment with tirzepatide was associated with greater decreases in glycated hemoglobin (treatment difference, -0.34 percentage points; 95% CI, -0.44 to -0.24 percentage points) and body weight (treatment difference, -2.9 kg, 95% CI, -4.8 to -1.1 kg) compared with GLP-1 RA. An interaction test for subgroup analysis revealed consistent results stratified by estimated glomerular filtration rate, glycated hemoglobin level, body mass index, comedications, and comorbidities. Conclusions and Relevance: In this study, treatment with tirzepatide was associated with lower hazards of all-cause mortality, adverse cardiovascular events, acute kidney injury, and adverse kidney events compared with GLP-1 RA in patients with type 2 diabetes. These findings support the integration of tirzepatide into therapeutic strategies for this population.

Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1ß pathway.

BACKGROUND: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored. PURPOSE: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL. METHODS: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments. RESULTS: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1ß pathway and increased proinflammatory IL1ß in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1ß pathway. CONCLUSIONS: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1ß pathway, specifically by targeting AKK and tryptophan metabolites.

Characteristics of Bacteria in Urine and Stones from Patients Treated with Percutaneous Nephrolithotomy and Association with Postoperative Infection.

Background: The purpose of this study was to identify bacterial differences between urine cultures (UC) and stone cultures (SC) in patients with complex kidney stones and to determine any correlation with post-percutaneous nephrolithotomy Systemic Inflammatory Response Syndrome (SIRS). Methods: Perioperative data of 1055 patients with complex kidney stones treated with first-stage Percutaneous Nephrolithotomy (PCNL) from September 2016 until September 2021 were included. Preoperative mid-stream urine samples and surgically obtained stone material were subjected to bacterial culture and antibiotic sensitivity tests. Preoperatively, antibiotic usage was determined by the UC or local bacterial resistance patterns. After PCNL treatment, antibiotic selection was guided by stone bacterial culture result and clinical symptoms. The effect of different preoperative antibiotic regimens based on urine cultures and postoperative antibiotic treatment based on stone cultures were assessed. Results: Positive stone cultures (SC+) were significantly more common than positive urine cultures (UC+) (31.9% vs 20.9%, p < 0.05). Escherichia coli (E. coli) was the most common uropathogen in both urine (54.3%) and stones (43.9%). The difference was statistically significant (p < 0.05). Moreover, UC+SC-, UC-SC+, UC+SC+, and preoperative serum creatinine were independent risk factors of postoperative SIRS. The incidence of SIRS in the UC+SC+ patients with different bacteria in stones and urine (51.6%) was higher than that in other culture groups. The antibiotic resistance of E. coli inside the stone was increased when prolonged preoperative antibiotics were administered to UC+ patients. Conclusion: The bacterial spectrum and positive outcome of culture in urine and stones were significantly different. The incidence of postoperative SIRS was highest in patients with UC+SC+ but with different bacteria strains. Prolonged pre-surgical antibiotic treatment apparently induced higher drug resistance for bacteria inside the stone.

Hydrogen therapy: recent advances and emerging materials.

Hydrogen therapy, leveraging its selective attenuation of hydroxyl radicals (˙OH) and ONOO-, has emerged as a pivotal pathophysiological modulator with antioxidant, anti-inflammatory, and antiapoptotic attributes. Hydrogen therapy has been extensively studied both preclinically and clinically, especially in diseases with an inflammatory nature. Despite the substantial progress, challenges persist in achieving high hydrogen concentrations in target lesions, especially in cancer treatment. A notable breakthrough lies in water/acid reactive materials, offering enhanced hydrogen generation and sustained release potential. However, limitations include hydrogen termination upon material depletion and reduced bioavailability at targeted lesions. To overcome these challenges, catalytic materials like photocatalytic and sonocatalytic materials have surfaced as promising solutions. With enhanced permeability and retention effects, these materials exhibit targeted delivery and sustained stimuli-reactive hydrogen release. The future of hydrogen therapy hinges on continuous exploration and modification of catalytic materials. Researchers are urged to prioritize improved catalytic efficiency, enhanced lesion targeting effects, and heightened biosafety and biocompatibility in future development.

Comprehensive evaluation and screening of phytochemical compounds and their hypolipidemic activities of lotus leaf based on HPLC-Q-TOF-MS and spectral-effect analysis.

This study aimed to identify and quantify the primary components in lotus leaf and to explore the hypolipidemic components through spectral-effect relationships and chemometric methods. Utilizing a data-dependent acquisition-diagnostic fragment ion/characteristic neutral loss screening strategy (DFI-NLS), a reliable HPLC-Q-TOF-MS analysis was conducted, identifying 77 compounds, including 36 flavonoids, 21 alkaloids, 3 terpenoids, 11 organic acids, 4 phenols, 1 lignin and 1 unsaturated hydrocarbon. A straightforward HPLC-DAD method was developed for the simultaneous determination of seven major components in lotus leaf, and quercetin-3-O-glucuronide (Q3GA) was identified as the most abundant component. The HPLC fingerprints of 36 lotus leaf sample batches were assessed using chemometric approaches such as principal component analysis and hierarchical cluster analysis. The hypolipidemic effect of these samples was analyzed by measuring total cholesterol (TC) and total triglycerides (TG) levels in palmitic acid (PA) and oleic acid (OA)-induced lipid modeling in HepG-2 cells, employing partial least squares regression and grey relation analysis to investigate the spectral-effect relationship of the lotus leaf. The in vivo hypolipidemic effect of these compounds was assessed using an egg yolk powder-induced high-fat zebrafish model. The findings indicated that peak No.11 (Q3GA) in the chemical fingerprint was significantly associated with hypolipidemic activity, suggesting it as a potential hypolipidemic compound in lotus leaf. In summary, this study facilitates the exploration of the phytochemical compounds and their bioactive properties in the lotus leaf.