Synthesis and Biological Evaluation of Novel Furopyridone Derivatives as Potent Cytotoxic Agents against Esophageal Cancer.

Cancer continues to be a major global health issue, ranking among the top causes of death worldwide. To develop novel antitumor agents, this study focused on the synthesis of a series of 21 novel furanopyridinone derivatives through structural modifications and functional enhancements. The in vitro anti-tumor activities of these compounds were investigated through the cytotoxicity against KYSE70 and KYSE150 and led to the identification of compound 4c as the most potent compound. At a concentration of 20 µg/mL, compound 4c demonstrated a remarkable 99% inhibition of KYSE70 and KYSE150 cell growth after 48 h. IC50 was 0.655 µg/mL after 24 h. Additionally, potential anti-tumor cellular mechanisms were explored through molecular docking, which was used to predict the binding mode of 4c with METAP2 and EGFR, suggesting that the C=O part of the pyridone moiety likely played a crucial role in binding. This study provided valuable insights and guidance for the development of novel anticancer drugs with novel structural scaffolds.

A Predictive Nomogram of In-Hospital Mortality After 48 h for Atrial Fibrillation Patients in the Coronary Care Unit.

BACKGROUND: Patients with atrial fibrillation (AF) suffer a higher risk of death, and it is necessary to develop prediction tools for mortality risk in critically ill patients with AF. This study aimed to develop a novel predictive nomogram of in-hospital mortality after 48 h in the coronary care unit (CCU) for patients with AF. METHODS: We collected information on CCU patients with AF from the "Medical Information Mart for Intensive Care-III" database and developed a nomogram model for predicting the all-cause mortality risk after 48 h in the hospital. Key variables were selected by univariate logistic and least absolute shrinkage and selection operator regression. The independent predictors with p < 0.05 were screened out by multivariate logistic regression. A predictive nomogram was constructed using these independent predictors, and the model calibration and discrimination were evaluated. RESULTS: This study finally enrolled 1248 CCU patients with AF, and the in-hospital mortality was 17% (209/1248). The predictive nomogram was constructed by 13 selected independent predictors, including age, smoking status, acute kidney injury, chronic obstructive pulmonary disease, ventricular arrhythmia, shock, urea, red cell distribution width, leucocytosis, continuous renal replacement therapy, continuous positive airway pressure, anticoagulation, and heart rate. The area under the curve of the nomogram was 0.803 (95% confidence interval 0.771-0.835). The nomogram was verified to have good accuracy and calibration. CONCLUSIONS: This study developed a novel nomogram containing age, acute kidney injury, and heart rate that can be a good predictor of potential in-hospital mortality after 48 h in CCU patients with AF.

Timing and Efficacy Evaluation of 755-nm Long Pulse Alexandrite Laser and 2% Carteolol Hydrochloride Eye Drops Co-Treatment for Thicker Superficial Infantile Hemangioma.

Purpose: Superficial Infantile hemangioma (SIH) is the most common type of IH. Some studies have shown the efficacy of 755-nm long pulse alexandrite laser (LPAL) and topical 2% carteolol hydrochloride (C-HCL) eye drops for the treatment of SIH. This article retrospectively analyzes the safety and efficacy of 755-nm LPAL combined with 2% C-HCL eye drops for treating thicker SIH, and explores the optimal treatment time for SIH. Materials and Methods: This study included 2-5 mm thick SIH patients who received co-treatment of 755-nm LPAL and 2% C-HCL eye drops. The SIH patients were divided into 3 groups based on their age and IH growth curve: ≤ 1 month (≤ 1M), 1-3 months (excluding 1 month; 1-3M), and 3-12 months (excluding 3 months; 3-12M). Results: There was no difference in efficacy between the ≤ 1M and the 1-3M group, and were both better than the 3-12M group. Furthermore, there was no difference in the average number of treatments between the ≤ 1M and 1-3M groups and were both less than the 3-12M group. There was no significant difference in the incidence of adverse reactions between the groups. Compared with the ≤ 1M and 1-3M groups, the 3-12M group indicated more permanent skin lesions after the treatment. Conclusion: It was revealed that co-treatment with 755-nm LPAL and 2% C-HCL eye drops is safe and effective against thicker SIH. Compared with the 3-12M group, ≤ 3 months can achieve better efficacy, requires a shorter treatment time, less likely to leave permanent skin lesions such as scars. Moreover, patients with no proliferation can be observed to 1 month.

Prevalence and Antibiotic Resistance Patterns of Methicillin-Resistant Staphylococcus aureus (MRSA) in a Hospital Setting: A Retrospective Study from 2018 to 2022.

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly infectious pathogen that poses a serious threat to human life and health. This study aimed to provide a scientific basis for the rational clinical use of antimicrobial drugs for treating MRSA infections and inform the development of preventive and control measures by analyzing the clinical distribution and resistance characteristics of MRSA in a hospital in Hebei China. To accomplish this, bacterial identification and drug sensitivity experiments were performed with 1858 Staphylococcus aureus (S. aureus) strains collected from a hospital from January 2018 to December 2022 using a phoenixTM-100 bacterial identification drug sensitivity analyzer. The experimental data were analyzed using WHONET 5.6 software, and the MRSA strains detected were analyzed for their clinical distribution and drug resistance. Of the 1858 S. aureus strains isolated, 429 were MRSA. Sputum samples had the highest MRSA detection rates (52.45%). Critical care medicine had the highest rate of MRSA (12.59%), followed by dermatology (9.79%). MRSA resistance to tetracycline increased by 13.9% over 5 years; resistance to quinupristin/dalfopristin also increased but remained low (1.9%). Resistance decreased to gentamicin, rifampicin, ciprofloxacin, and cotrimoxazole, though most significantly to erythromycin and clindamycin, exceeding 77% and 83%, respectively. No strains were resistant to vancomycin, teicoplanin, or linezolid, and drug resistance was most prevalent in patients ≥ 60 years old. This study will aid in improving the diagnosis and treatment of MRSA infections.

Association of hypophosphatemia during continuous kidney replacement therapy and clinical outcomes: a systematic review and meta-analysis.

INTRODUCTION: Hypophosphatemia is a common and potentially severe complication of continuous kidney replacement therapy (CKRT), but the evidence on the correlation between hypophosphatemia occurring during CKRT and clinical outcomes remains limited. METHODS: Electronic databases (PubMed, Embase, Web of Science, and the Cochrane database) were searched from inception to March 1, 2024. All possible studies that examined the following outcomes were included: all-cause mortality, mechanical ventilation, intensive care unit (ICU) stay, and CKRT duration. RESULTS: A total of 8,631 patients from eight cohort studies were included. There was no statistical association between hypophosphatemia during CKRT and all-cause mortality in critically ill patients (OR 0.82, 95% CI 0.57-1.18, P =0.28, I2 = 83%). However, hypophosphatemia was associated with longer duration of mechanical ventilation (WMD 80.30h, 95% CI 31.37-129.22, P =0.001, I2 = 60%). Furthermore, a longer length of ICU stay (WMD 2.76d, 95% CI 2.50-3.02, P <0.00001, I2 = 36%) and CKRT duration (WMD 51.51h, 95% CI 2.69-100.34, P =0.04, I2 = 96%) were observed in patients with hypophosphatemia. CONCLUSIONS: The association between hypophosphatemia and mortality in patients receiving CKRT was insufficient. However, hypophosphatemia during CKRT might be associated with adverse clinical outcomes for critically ill patients.

Ailanthone suppresses cell proliferation of renal cell carcinoma partially via inhibition of EZH2.

BACKGROUND: Ailanthone (Ail) extracted from medicinal plants has played an anticancer role in multiple cancers, while there is no research about Ail in renal cell carcinoma (RCC). METHODS: In the present study, we performed CCK-8 and flow cytometry to assess the effect of Ail on cell viability, apoptosis and cycle. We also performed tandem mass tags (TMT)-labeled quantitative proteomic technology and bioinformatic analysis to identify the functional pathway and proteins of Ail in RCC. RESULTS: The results showed Ail could inhibit cell viability and induce cell apoptosis. Proteomic profiling identified 1732 differentially expressed proteins in cells treated with Ail, compared to the negative control group. Gene ontology function annotation and Gene Set Enrichment Analysis (GSEA) were performed to identified the involved biological processes, molecular function and pathway. Results of GSEA proved the enrichment of Deps in EZH2 targets. The comparison between Deps and EZH2 co-expressed genes revealed 44 overlapped genes and we identified 4 hub genes (CDC20, CEP55, TOP2A, and UBE2C) associated with RCC progression. The molecular docking study revealed a moderate to tight binding potential of Ail and EZH2, and western blotting showed EZH2 was suppressed after cells treated with Ail. CONCLUSION: Altogether, we identified the anticancer role of Ail in RCC, including inhibition of cell proliferation and induction of apoptosis. The results also screened the key proteins mediate the function of Ail, which have laid a theoretical foundation for elucidating the applications of Ail in clinical research.

Quantitative Detection of the CP4-EPSPS Protein in Genetically Modified Soybeans Using a Novel Fluorescence Immunoassay Assay.

Protein-based detection methods, enzyme-linked immunosorbent assays (ELISAs) and lateral flow strips, have been widely used for rapid, specific, and sensitive detection of genetically modified organisms (GMOs). However, the traditional ELISA method for the quantitative detection of GMOs has certain limitations. Herein, a quantum dot (QD)-based fluorescence-linked immunosorbent assay was developed using QDs as fluorescent markers for the detection of glyphosate-resistant protein (CP4-EPSPS) in the MON89788 soybean. The end-point fluorescent detection system was carried out using QDs conjugated with a goat anti-rabbit secondary antibody. Compared with the conventional sandwich ELISA method, the newly developed fluorescence-linked immunosorbent assay was highly sensitive and accurate for detecting the CP4-EPSPS protein. The quantified linearity was achieved in the range of 0.05-5% (w/w) for the MON89788 soybean sample. The recovery of protein extracted from mixed MON89788 soybean samples ranged from 87.67% to 116.83%. The limits of detection and limits of quantification were 0.7101 and 2.152 pg/mL, respectively. All of the results indicated that the QD-based fluorescence-linked immunosorbent assay was a highly specific and sensitive method for monitoring the CP4-EPSPS protein in GMOs.

The clinical significance and anti-tumor role of PRKG1 in bladder cancer.

Introduction: cGMP-dependent protein kinase 1 (PRKG1) has shown to be associated with some tumorigenesis, while the role of PRKG1 in bladder cancer is unclear. Methods: To investigate the biological and clinical significance of PRKG1 in bladder cancer, we detected the expression of PRKG1 and explored the function of PRKG1 in bladder cancer cells. The PRKG1 transcripts data was downloaded from The Cancer Genome Atlas (TCGA) database, and immunohistochemistry staining was conducted on formalin-fixed paraffin-embedded (FFPE) sample tissues. Relationship between clinical characteristics of patients and expression of PRKG1 was analyzed in FFPE samples, TCGA database, and GSE19423 dataset. PRKG1 was over-expressed, and cell proliferation, migration, invasion, apoptosis, and spheroidizing ability were then detected. Chemosensitivity to cisplatin was detected with cell viability, and half-maximal drug inhibitory concentration (IC50) was calculated. In addition, the relation between PRKG1 expression and the infiltration level of tumor immune cells in tumor microenvironment were analyzed. Results: The results showed expression of PRKG1 was lower in bladder cancer, compared with normal tissues both at protein and transcript levels. Lower PRKG1 expression was related to higher tumor grade, T stage, and muscle invasion, also predicted worse overall survival and recurrence free survival in patients treated with Bacillus Calmette-Guerin (BCG) intravesical immunotherapy. Analysis of tumor immune cells infiltration showed lower PRKG1 was associated with non-inflamed tumor microenvironment. Conclusion: The present study firstly identified the anti-tumor role and tumor immune regulatory role of PRKG1, also found loss of PRKG1 could be used as a prognosis factor. The present study provided a potential biomarker and therapy target to bladder cancer.

Monascus red pigments alleviate high-fat and high-sugar diet-induced NAFLD in mice by modulating the gut microbiota and metabolites.

Monascus red pigments (MRP) may have benefits against NAFLD with an unclear mechanism. This study aimed to explore the protective effect of MRP supplementation against NAFLD through regulation of gut microbiota and metabolites. The C57BL/6 mice animals were randomly allocated into the normal diet (NC), HFHS diet-induced NAFLD model, and MRP intervention group fed with HFHS diet. Serum lipid profiles and liver function parameters were measured. Liver and colon histopathology analysis was conducted to determine the injury in the liver and colon. 16S rRNA gene sequencing was employed to analyze gut microbial composition from fecal samples. Untargeted metabonomics was performed to analyze changes in metabolites in serum and fecal samples. MRP supplementation significantly improved the HFHS-induced alterations in body weight, lipid profiles, and liver function (p < .01). MRP supplementation decreased the abundance of Akkermansia, Candidatus saccharimonas, Dubosiella, and Oscillibacter, while increasing Lactobacillus, Lachnospiraceae NK4A136 group, and Rikenella in mice fed the HFHS diet. Furthermore, MRP supplementation improved the serum and fecal metabolic profiles induced by the HFHS diet, primarily involving the arachidonic acid metabolism, unsaturated fatty acid biosynthesis, and adipocyte lipolysis pathways. Liver function and lipid profiles were closely associated with the abundance of Lactobacillus, Streptococcus, Oscillibacter, Akkemansia, and Desulfovibrio (p < .01). These findings revealed that MRP supplementation may help restore gut microbiota composition and balance its metabolites, thereby improving NAFLD. This study presents a novel outlook on the potential benefits of MRP supplementation in ameliorating NAFLD and supports the application of MRP as a new functional food.

Novel Aminocoumarin-Based Schiff Bases: High Antifungal Activity in Agriculture.

Structural modification is an effective way to improve the antifungal activity of natural products and has been widely used in the development of novel fungicides. In this work, a series of aminocoumarin-based Schiff bases were synthesized and characterized by 1H NMR, 13C NMR and HR-MS spectra. The in vitro inhibition activity of all compounds was tested against four phytopathogenic fungi (Alternaria solani, Fusarium oxysporum, Botrytis cinerea, and Alternaria alternata) using the mycelial growth rate method. The results showed that most of the target compounds exhibited significant antifungal activities. In particular, compounds 5b, 5c, 5d, 5h, 5n, 7c, 7n, and 7p exhibited more effective antifungal activity than commercially available fungicides, chlorothalonil and azoxystrobin. The structure-activity relationship revealed that the electron-withdrawing groups with more electronegativity introduced at the C-3 position were effective in improving the inhibitory activity and that halogenated benzaldehydes would be necessary in the preparation of Schiff bases. The compound 5n against Fusarium oxysporum (EC50=8.73 µg/mL) and the compound 7p against Alternaria alternata (EC50=26.25 µg/mL) were much better than the positive controls. Therefore, compounds 5n and 7p could serve as promising lead compounds for the development of novel broad-spectrum fungicides, which could be useful for applications in the agriculture industry.

Chemotherapy affects the development of pathological scarring after general thoracic surgery in children.

Globally, a great number of children have been suffering from physical dysfunction and psychological stress due to uncontrollable scar growth and a lack of effective modalities. Despite chemotherapy's established role as a primary treatment for pathological scarring in adults, its efficacy in preventing or minimizing scar formation in paediatric patients remains underexplored. This retrospective cohort study aimed to refine the relevant clinical evidence and investigate the effect of chemotherapy on pathological scars in children. In this single-centre retrospective cohort study, the data of children aged ≤18 years who underwent thoracic surgery at the Children's Hospital of Fudan University between 1 January 2018, and 31 December 2021 were assessed. The primary outcome was pathological scarring, and the secondary outcomes were subjective symptoms accompanying pathological scarring, such as pain and itching. To mitigate indication bias, analysis was performed by inverse probability weighting (IPTW) log-binomial regression models. The cohort comprised 102 children, among whom 36 received adjuvant chemotherapy perioperatively, while 66 did not. Under the IPTW model, a statistically significant difference in pathological scarring incidence was observed between the chemotherapy and non-chemotherapy groups (16.7% vs. 29.4%, p = 0.027). And the children received chemotherapy post-operatively had a lower relative risk of pathological scarring, compared with those received chemotherapy both before and after surgery (19.8% vs. 28.8%). Adjuvant chemotherapy treatment after surgery may reduce the incidence of post-operative pathological scarring in children.

Altered regional neural activity and functional connectivity in patients with non-communicating hydrocephalus: a resting-state functional magnetic resonance imaging study.

Introduction: Cognitive impairment is a frequent clinical symptom of non-communicating hydrocephalus (NCH) involving multiple domains, including executive function, working memory, visual-spatial function, language, and attention. Functional magnetic resonance imaging (fMRI) can be used to obtain information on functional activity in local brain areas and functional connectivity (FC) across multiple brain regions. However, studies on the associated cognitive impairment are limited; further, the pathophysiological mechanisms of NCH with cognitive impairment remain unclear. Here, we aimed to explore alterations in regional neural activity and FC, as well as the mechanisms of cognitive impairment, in patients with NCH. Methods: Overall, 16 patients with NCH and 25 demographically matched healthy controls (HCs) were assessed using the Mini-Mental State Examination (MMSE) and fMRI. Changes in regional homogeneity (ReHo), degree centrality (DC), and region of interest-based FC were analyzed in both groups. The relationship between fMRI metrics (ReHo, DC, and FC) and MMSE scores in patients with NCH was also investigated. Results and discussion: Compared with the HC group, the NCH group exhibited significantly lower ReHo values in the left precentral and postcentral gyri, and significantly higher ReHo values in the left medial prefrontal cortex (MPFC). The NCH group also showed significantly higher DC values in the bilateral MPFC compared with the HC group. Regarding seed-based FC, the MPFC showed reduced FC values in the right superior parietal and postcentral gyrus in the NCH group compared with those in the HC group. Moreover, within the NCH group, MMSE scores were significantly negatively correlated with the ReHo value in the left MPFC and the DC value in the bilateral MPFC, whereas MMSE scores were significantly positively correlated with FC values. To conclude, regional neural activity and FC are altered in patients with NCH and are correlated with cognitive impairment. These results advance our understanding of the pathophysiological mechanisms underlying the association between NCH and cognitive impairment.

Study on Oleum cinnamomi Inhibiting Cutibacterium acnes and Its Covalent Inhibition Mechanism.

Oleum cinnamomi (OCM) is a volatile component of the Cinnamomum cassia Presl in the Lauraceae family, which displays broad-spectrum antibacterial properties. It has been found that OCM has a significant inhibitory effect against Cutibacterium acnes (C. acnes), but the precise target and molecular mechanism are still not fully understood. In this study, the antibacterial activity of OCM against C. acnes and its potential effect on cell membranes were elucidated. Metabolomics methods were used to reveal metabolic pathways, and proteomics was used to explore the targets of OCM inhibiting C. acnes. The yield of the OCM was 3.3% (w/w). A total of 19 compounds were identified, representing 96.213% of the total OCM composition, with the major constituents being phenylpropanoids (36.84%), sesquiterpenoids (26.32%), and monoterpenoids (15.79%). The main component identified was trans-cinnamaldehyde (85.308%). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of OCM on C. acnes were 60 µg/mL and 180 µg/mL, respectively. The modified proteomics results indicate that cinnamaldehyde was the main bioactive ingredient within OCM, which covalently modifies the ABC transporter adenosine triphosphate (ATP)-binding protein and nicotinamide adenine dinucleotide (NADH)-quinone oxidoreductase, hindering the amino acid transport process, and disrupting the balance between NADH and nicotinamide adenine dinucleoside phosphorus (NAD+), thereby hindering energy metabolism. We have reported for the first time that OCM exerts an antibacterial effect by covalent binding of cinnamaldehyde to target proteins, providing potential and interesting targets to explore new control strategies for gram-positive anaerobic bacteria.

Photosynthetic Acclimation of Larch to the Coupled Effects of Light Intensity and Water Deficit in Regions with Changing Water Availability.

The impact of frequent water deficits on dominant tree species in boreal forests has received increased attention, particularly towards addressing the global climate change scenarios. However, the impacts of coupled light intensity and water deficit in the regeneration and growth of Larix gmelinii seedlings, a dominant species in China's boreal forests, are still unclear. We conducted a dual-factor controlled experiment with four light intensities (natural sunlight, 50% shading, 75% shading, and 90% shading) and three soil water conditions (80%, 60%, and 40% soil saturated water content). The results showed that the coupling of light and water has a significant effect on the growth and development of Larix gmelinii seedlings. In 40% of the saturated soil moisture content, net photosynthetic rate, transpiration rate, chlorophyll a, and total phenol-leaf were significantly lower than the same light conditions under 80% soil saturated water content. Under the coupling treatment of 60% soil saturated water content and 50% shading treatment, the plant height increment, net photosynthetic rate, stomatal conductance, transpiration rate, chlorophyll a, and phenolic compound content were significantly higher than those of other coupling treatments; however, more than 75% shading inhibited photosynthetic parameters, chlorophyll a, total flavonoid-leaf, and total flavonoid-branch. Our results have important implications for forest management practices; they provide a scientific reference for the early growth of Larix gmelinii seedlings under the coupling of light and water and promote the survival and growth of seedlings.

Preparation and in vivo and ex vivo studies of sirolimus nano-in-situ gel ophthalmic formulation.

Sirolimus (SR) is a macrolide with antifungal and antitumor immunosuppressant properties, classified as a selective inhibitor of mammalian target of rapamycin (mTOR). In this study, an ionic in situ gel of SR (SR-SUS-ISG) was formulated using gellan gum, exhibiting stability regardless of temperature and pH variations, causing minimal irritation. Harnessing the physiological conditions of the eye, SR-SUS-ISG underwent gelation upon contact with ions, increasing drug viscosity and prolonging retention on the ocular surface. Concurrently, SR-SUS-ISG displayed favorable shear dilution properties, reducing viscosity at ambient temperature, enhancing fluidity, and facilitating convenient packaging and transport. Biocompatibility assessments on both human corneal epithelial cells and rabbit eyes demonstrated that SR-SUS-ISG could well be tolerated. Pharmacokinetic investigations in rabbit ocular aqueous humor revealed sustained release, improved corneal penetration, and enhanced bioavailability. Additionally, in a rat corneal alkali burn model, SR-SUS-ISG exhibited inhibitory effects on corneal neovascularization, associated with decreased levels of the inflammatory factors VEGF and MMPs. These findings suggested that SR-SUS-ISG held promise as an effective ocular drug delivery system.

Human umbilical cord mesenchymal stem cell exosomes deliver potent oncolytic reovirus to acute myeloid leukemia cells.

In addition to chemotherapy, oncolytic viruses are an efficient treatment for acute myeloid leukemia (AML). Like other oncolytic viruses, the anti-tumor efficacy of reovirus when administered intravenously is reduced due to the presence of neutralizing antibodies. In this study, we evaluated the role of exosomes in human umbilical cord-derived mesenchymal stem cells (UC-MSCs) to deliver reovirus to AML cells. We show that UC-MSCs loaded with reovirus can deliver reovirus to tumor cells without cellular contact. We further demonstrate that the exosome inhibitor, GW4869, inhibits the release of exosomes as well as inhibited the transfer of reovirus from UC-MSCs to tumor cells. Mechanistically, we show that exosomes derived from reovirus-infected UC-MSCs (MSCREO-EXOs) have a tumor lysis effect and transmit reovirus to tumor cells mainly through clathrin-mediated endocytosis (CME) and macropinocytosis. In addition, we demonstrate the feasibility of using MSC-derived exosomes (MSC-EXOs) as a reovirus carrier to exert an anti-tumor effect on AML cells. Collectively, our data indicate that UC-MSCs transfer reovirus to AML cells via exosome release and prompt further study of MSC-EXOs as a potential reovirus carrier to treat AML.

Abnormal hypothalamic functional connectivity associated with cognitive impairment in craniopharyngiomas.

OBJECTIVE: This study sought to characterize resting-state functional connectivity (rsFC) patterns of the hypothalamic and extrahypothalamic nuclei in craniopharyngioma (CP) patients, and to investigate potential correlations between hypothalamic and extrahypothalamic rsFC maps and neurocognitive performance. METHODS: Ninety-two CP patients and 40 demographically-matched healthy controls were included. Whole-brain seed-to-voxel analyses were used to test for between-group rsFC differences, and regression analyses were used to correlate neurocognitive performance with voxel-wise hypothalamic and extrahypothalamic rsFC maps for CP patients. Finally, spectral DCM analysis was used to explore the hypothalamus circuit associated with neurocognitive performance. RESULTS: The seed-to-voxel analyses demonstrated that the hypothalamic nuclei showed mainly significant rsFC reduction in brain areas overlayed with the cortical regions of default mode network (DMN), notably in the bilateral anterior cingulate cortices and posterior cingulate cortices. The extrahypothalamic nuclei showed significant rsFC reduction in the limbic system of bilateral caudate nuclei, corpus callosum, fornix, and thalamus. Regression analyses revealed that worse cognitive performance was correlated with abnormal hypothalamic rsFC with brain areas in DMN, and DCM analysis revealed a hypothalamus-DMN circuit responsible for functional modulation of cognitive impairment in CP patients. CONCLUSIONS: Our study demonstrated that CPs invading into hypothalamus impacted hypothalamic and extrahypothalamic rsFC with brain areas of DMN and limbic system, the severity of which was parallel with the grading system of hypothalamus involvement. In addition to the CP-induced structural damage to the hypothalamus alone, abnormal functional connectivity within the hypothalamus-DMN circuit might be a functional mechanism leading to the cognitive impairment in CP patients.

The clinical significance of inflammatory mediators in predicting obesity and progression-free survival in patients with adult-onset Craniopharyngioma.

BACKGROUND: Craniopharyngioma (CP) is a rare malformational tumor characterized by high rates of recurrence and morbid obesity. However, the role of inflammatory mediators in obesity and the prognosis of patients with CP remains unknown. Therefore, the present study aimed to analyze associations of inflammatory mediators with weight-related outcomes and the prognosis of patients with CP. METHODS: A total of 130 consecutive patients with CP were included in this study. The expression levels of seven inflammatory mediators and the plasma leptin concentration were investigated. Clinical parameters, weight changes, new-onset obesity, and progression-free survival (PFS) were recorded. The relationships between inflammatory mediators, clinicopathologic parameters, weight-related outcomes, and PFS were explored. RESULTS: Compared with those in normal pituitary tissue, the expressions of inflammatory mediators in tumor tissue were higher. Higher expression levels of CXCL1 and CXCL8 were identified as independent risk factors for significant weight gain, and CXCL1 and TNF were identified as independent risk factors for new-onset postoperative obesity. Poor PFS was associated with higher expression levels of CXCL1, CXCL8, IL1A, IL6, and TNF. CONCLUSION: The present study revealed that inflammatory mediators are associated with morbid obesity in patients with CP. Inflammatory mediators may be the critical bridge between elevated leptin and weight-related outcomes. Additionally, PFS was associated with the expression of inflammatory mediators. Further research is needed to elucidate the underlying mechanisms of inflammatory mediators and their potential as targets for novel therapies for CP.

Moringa oleifera leaf extracts improve exercise performance in young male adults: A pilot study.

BACKGROUND: Moringa oleifera leaves are rich in bioactive substances. PURPOSE: The purpose of this study was to evaluate the effects of Moringa oleifera leaf aqueous extract supplements on energy metabolism and antioxidant function in young male adults. METHODS: Forty-four young male adults (26.3 ± 3.5 years) were randomly assigned to two groups: a supplement group (n = 23) receiving aqueous extract of Moringa oleifera leaves and a placebo group (n = 21). The supplementation period lasted for 30 days. Baseline measurements were taken at the beginning of the study, and further measurements were taken at the end of the supplementation period. Changes in upper- and lower-body strength, treadmill endurance, and certain blood biochemical parameters were evaluated. RESULTS: After 30 days of supplementation, participants in the supplement group exhibited enhanced performance in push-ups and treadmill exhaustion tests compared to the placebo group. Levels of glucose, urea, malondialdehyde, and glutathione peroxidase activity in serum were also improved in the supplement group. CONCLUSION: The findings suggest that Moringa oleifera leaf aqueous extracts have the potential to improve post-exercise energy metabolism and antioxidant function in young male adults.

Research on the Mechanism and Application of Acupuncture Therapy for Asthma: A Review.

Asthma is a high-risk disease based on airway hyperresponsiveness (AHR). In this review, we found that there are many studies on clinical therapy for asthma that focus on the efficacy of acupuncture therapy and its mechanisms, including the functional connectivity of different brain regions, with the aid of functional magnetic resonance imaging (fMRI), immune responses/cell recognition (innate lymphoid cells and balance of Th1/Th2 and Treg/Th17), intracellular mechanism (autophagy, endoplasmic reticulum stress, and epigenetic alteration), and ligand-receptor/chemical signaling pathway (neurotransmitter, hormone, and small molecules). In this review, we summarized the clinical and experimental evidence for the mechanisms of acupuncture therapy in asthma to offer insights into drug discovery and clinical therapy. Given the paucity of clinical studies on the mechanisms of acupuncture in the treatment of asthma, this review notably included studies based on animal models to investigate the mechanisms of acupuncture in the treatment of asthma.