Targeting NG2 relieves the resistance of BRAF-mutant thyroid cancer cells to BRAF inhibitors.

BRAFV600E represents a constitutively active onco-kinase and stands as the most prevalent genetic alteration in thyroid cancer. However, the clinical efficacy of small-molecule inhibitors targeting BRAFV600E is often limited by acquired resistance. Here, we find that nerve/glial antigen 2 (NG2), also known as chondroitin sulfate proteoglycan 4 (CSPG4), is up-regulated in thyroid cancers, and its expression is increased with tumor progression in a BRAFV600E-driven thyroid cancer mouse model. Functional studies show that NG2 knockout almost does not affect tumor growth, but significantly improves the response of BRAF-mutant thyroid cancer cells to BRAF inhibitor PLX4720. Mechanistically, the blockade of ERK-dependent feedback by BRAF inhibitor can activate receptor tyrosine kinase (RTK) signaling, causing the resistance to this inhibitor. NG2 knockout attenuates the PLX4720-mediated feedback activation of several RTKs, improving the sensitivity of BRAF-mutant thyroid cancer cells to this inhibitor. Based on this finding, we propose and demonstrate an alternative strategy for targeting NG2 to effectively treat BRAF-mutant thyroid cancers by combining multiple kinase inhibitor (MKI) Sorafenib or Lenvatinib with PLX4720. Thus, this study uncovers a new mechanism in which NG2 contributes to the resistance of BRAF-mutant thyroid cancer cells to BRAF inhibitor, and provides a promising therapeutic option for BRAF-mutant thyroid cancers.

Streptococcus suis Serotype 2 Type IV Secretion Effector SspA-1 Induces Proinflammatory Cytokine Production via TLR2 Endosomal and Type I Interferon Signaling.

The subtilisin-like protease-1 (SspA-1) plays an important role in the pathogenesis of a highly virulent strain of Streptococcus suis 2. However, the mechanism of SspA-1-triggered excessive inflammatory response is still unknown. In this study, we demonstrated that activation of type I IFN signaling is required for SspA-1-induced excessive proinflammatory cytokine production. Further experiments showed that the TLR2 endosomal pathway mediates SspA-1-induced type I IFN signaling and the inflammatory response. Finally, we mapped the major signaling components of the related pathway and found that the TIR adaptor proteins Mal, TRAM, and MyD88 and the downstream activation of IRF1 and IRF7 were involved in this pathway. These results explain the molecular mechanism by which SspA-1 triggers an excessive inflammatory response and reveal a novel effect of type I IFN in S. suis 2 infection, possibly providing further insights into the pathogenesis of this highly virulent S. suis 2 strain.

Novel mitophagy inducer alleviates lupus nephritis by reducing myeloid cell activation and autoantigen presentation.

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE), but its mechanism of onset remains unclear. Since impaired mitophagy has been implicated in multiple organs in SLE, we hypothesized that mitophagy dysfunction is critical in the development of LN and that pharmacologically targeting mitophagy would ameliorate this disease. Therefore, lupus-prone MRL/MpJ-Faslpr (MRL/lpr) and NZBWF1/J mice were treated with a novel mitophagy inducer, UMI-77, during their onset of LN. This treatment effectively mitigated kidney inflammation and damage as assessed by histology and flow cytometry. Furthermore, dendritic cell (DC)-T-cell coculture assay indicated that UMI-77 treatment attenuated DC function that would drive T-cell proliferation but did not directly influence the potent T-cell proliferation in lupus mice. UMI-77 also restored mitochondrial function and attenuated proinflammatory phenotypes in lupus DCs. Adoptive transfer of DCs from MRL/lpr mice augmented serum anti-dsDNA IgG, urine protein and T-cell infiltration of the kidney in MRL/MpJ mice, which could be prevented by either treating lupus donors in vivo or lupus DCs directly with UMI-77. UMI-77 also restored mitochondrial function in myeloid cells from patients with LN in vitro as evidenced by increased ATP levels. Thus, enhancing mitophagy in SLE restrains autoimmunity and limits kidney inflammation for LN development. Hence, our findings suggest targeting mitophagy as a tangible pathway to treat LN.

The Effect and Influence of the Responsibility System Rehabilitation Nursing Model in the Nursing of Patients with Ischemic Stroke.

Objective: To explore and evaluate the effect of the accountability rehabilitation nursing model in the care of patients with ischemic stroke and the impact on nursing satisfaction, in order to improve the quality of care for patients with ischemic stroke. Design: This study selected 92 patients with ischemic stroke who met the inclusion criteria as the study objects, and divided them equally into the control group (46 cases) and the research group (46 cases) using a random number table. Data were collected by questionnaire. Interventions: The control group received standard routine rehabilitation nursing care, while the study group underwent an accountable rehabilitation care model. In the accountable rehabilitation care model, distinct nursing practices and strategies were employed to enhance clinical outcomes, limb function, neurological function, quality of life, and nursing satisfaction. Key elements of this model may include personalized care plans, increased emphasis on patient engagement, targeted therapeutic interventions, and a systematic approach to care coordination. A comparative analysis was conducted before and after the intervention to highlight the nuanced differences in outcomes between the two groups, shedding light on the specific benefits and effectiveness of the accountable rehabilitation care model as opposed to routine rehabilitation care. Results: In terms of clinical outcomes, the ESS score of the study group after intervention was significantly higher than that of the control group, indicating a positive impact on overall health (P < .05); limb function assessed by upper and lower limb muscle strength scores improved in both groups after the intervention. There was a significant enhancement, in which the score of the study group was significantly higher than that of the control group (P < .05); the NIHSS score showed that compared with the control group, the neurological function of the study group was significantly improved (P < .05); the SS-QOL score was used The assessed quality of life also improved significantly in the study group, exceeding the scores in the control group (P < .05). In addition, the nursing satisfaction of the study group was significantly higher compared with the control group, which highlighted the positive acceptance of the responsible rehabilitation nursing model by nursing staff (P < .05). Together, these findings highlight the combined benefits of the intervention in enhancing clinical, functional, and subjective outcomes. Discussion: The study underscores the promising clinical benefits of the responsibility system rehabilitation nursing model for patients with ischemic stroke. Marked enhancements in clinical outcomes, limb and nerve function, quality of life, and nursing satisfaction indicate its potential to significantly improve patient care. The personalized and accountable approach, featuring tailored care plans and heightened emphasis on patient engagement, holds promise for fostering positive health outcomes and enhancing overall patient experiences. Integrating this model into routine stroke care protocols emerges as a pivotal strategy for optimizing rehabilitation processes and adopting a patient-centered approach. Despite these advantages, acknowledging study limitations, such as non-randomized participant allocation and the absence of blinding, is crucial to recognizing potential biases. The study's sample size and single-center focus may impact generalizability. Beyond ischemic stroke, the model's broader significance aligns with contemporary healthcare trends, emphasizing accountability, personalized care plans, and enhanced care coordination. Its potential adaptation to various healthcare settings, chronic disease management, and preventive care could contribute to improved patient outcomes and healthcare quality. Future research should explore scalability and sustainability across diverse healthcare settings, investigating applicability to different patient populations and medical conditions. Assessing long-term effects, including healthcare cost-effectiveness and patient adherence, is essential for a comprehensive understanding of impact. Furthermore, delving into the perspectives of healthcare providers and patients can refine and tailor implementation strategies for optimal outcomes. Results: After the intervention, The European Stroke Scale (ESS) score of the study group was higher than that of the control group. After the intervention, the muscle strength scores of the upper and lower limbs of the study group were significantly higher than those of the control group. After intervention, the National Institutes of Health Stroke Scale (NIHSS) score of the study group was lower than that of the control group. After intervention, the stroke-specific quality of life scale (SS-QOL) score of the study group was higher than that of the control group. The nursing satisfaction of the study group was higher than that of the control group after intervention (all P < .05). Conclusion: The results of the study showed that the responsibility system rehabilitation nursing mode showed significant effects in improving the limb function, neurological function and quality of life of patients with ischemic stroke, which could promote the disease outcome of patients, and the nursing satisfaction of patients was high, which was worthy of promotion.

Streptococcus suis Serotype 2 Type IV Secretion Effector SspA-1 Induces Proinflammatory Cytokine Production via TLR2 Endosomal and Type I Interferon Signaling.

The subtilisin-like protease-1 (SspA-1) plays an important role in the pathogenesis of a highly virulent strain of Streptococcus suis 2. However, the mechanism of SspA-1-triggered excessive inflammatory response is still unknown. In this study, we demonstrated that activation of type I IFN signaling is required for SspA-1-induced excessive proinflammatory cytokine production. Further experiments showed that the TLR2 endosomal pathway mediates SspA-1-induced type I IFN signaling and the inflammatory response. Finally, we mapped the major signaling components of the related pathway and found that the TIR adaptor proteins Mal, TRAM, and MyD88 and the downstream activation of IRF1 and IRF7 were involved in this pathway. These results explain the molecular mechanism by which SspA-1 triggers an excessive inflammatory response and reveal a novel effect of type I IFN in S. suis 2 infection, possibly providing further insights into the pathogenesis of this highly virulent S. suis 2 strain.

Changes in m6A RNA methylation are associated with male sterility in wolfberry.

BACKGROUND: N6-methyladenosine (m6A) modification is the most abundant type of RNA modification in eukaryotic cells, playing pivotal roles in multiple plant growth and development processes. Yet the potential role of m6A in conferring the trait of male sterility in plants remains unknown. RESULTS: In this study, we performed RNA-sequencing (RNA-Seq) and m6A-sequencing (m6A-Seq) of RNAs obtained from the anther tissue of two wolfberry lines: 'Ningqi No.1' (LB1) and its natural male sterile mutant 'Ningqi No.5' (LB5). Based on the newly assembled transcriptome, we established transcriptome-wide m6A maps for LB1 and LB5 at the single nucleus pollen stage. We found that the gene XLOC_021201, a homolog of m6A eraser-related gene ALKBH10 in Arabidopsis thaliana, was significantly differentially expressed between LB1 and LB5. We also identified 1642 and 563 m6A-modified genes with hypermethylated and hypomethylated patterns, respectively, in LB1 compared with LB5. We found the hypermethylated genes significantly enriched in biological processes related to energy metabolism and lipid metabolism, while hypomethylation genes were mainly linked to cell cycle process, gametophyte development, and reproductive process. Among these 2205 differentially m6A methylated genes, 13.74% (303 of 2205) were differentially expressed in LB1 vis-à-vis LB5. CONCLUSIONS: This study constructs the first m6A transcriptome map of wolfberry and establishes an association between m6A and the trait of male sterility in wolfberry.

Therapeutic role of curcumin in adult neurogenesis for management of psychiatric and neurological disorders: a scientometric study to an in-depth review.

Aberrant neurogenesis is a major factor in psychiatric and neurological disorders that have significantly attracted the attention of neuroscientists. Curcumin is a primary constituent of curcuminoid that exerts several positive pharmacological effects on aberrant neurogenesis. First, it is important to understand the different processes of neurogenesis, and whether their dysfunction promotes etiology as well as the development of many psychiatric and neurological disorders; then investigate mechanisms by which curcumin affects neurogenesis as an active participant in pathophysiological events. Based on scientometric studies and additional extensive research, we explore the mechanisms by which curcumin regulates adult neurogenesis and in turn affects psychiatric diseases, i.e., depression and neurological disorders among them traumatic brain injury (TBI), stroke, Alzheimer's disease (AD), Gulf War Illness (GWI) and Fragile X syndrome (FXS). This review aims to elucidate the therapeutic effects and mechanisms of curcumin on adult neurogenesis in various psychiatric and neurological disorders. Specifically, we discuss the regulatory role of curcumin in different activities of neural stem cells (NSCs), including proliferation, differentiation, and migration of NSCs. This is geared toward providing novel application prospects of curcumin in treating psychiatric and neurological disorders by regulating adult neurogenesis.

A genome-wide association study identifies a novel association between SDC3 and apparent treatment-resistant hypertension.

BACKGROUND: Compared with patients who require fewer antihypertensive agents, those with apparent treatment-resistant hypertension (aTRH) are at increased risk for cardiovascular and all-cause mortality, independent of blood pressure control. However, the etiopathogenesis of aTRH is still poorly elucidated. METHODS: We performed a genome-wide association study (GWAS) in first cohort including 586 aTRHs and 871 healthy controls. Next, expression quantitative trait locus (eQTL) analysis was used to identify genes that are regulated by single nucleotide polymorphisms (SNPs) derived from the GWAS. Then, we verified the genes obtained from the eQTL analysis in the validation cohort including 65 aTRHs, 96 hypertensives, and 100 healthy controls through gene expression profiling analysis and real-time quantitative polymerase chain reaction (RT-qPCR) assay. RESULTS: The GWAS in first cohort revealed four suggestive loci (1p35, 4q13.2-21.1, 5q22-23.2, and 15q11.1-q12) represented by 23 SNPs. The 23 significant SNPs were in or near LAPTM5, SDC3, UGT2A1, FTMT, and NIPA1. eQTL analysis uncovered 14 SNPs in 1p35 locus all had same regulation directions for SDC3 and LAPTM5. The disease susceptible alleles of SNPs in 1p35 locus were associated with lower gene expression for SDC3 and higher gene expression for LAPTM5. The disease susceptible alleles of SNPs in 4q13.2-21.1 were associated with higher gene expression for UGT2B4. GTEx database did not show any statistically significant eQTLs between the SNPs in 5q22-23.2 and 15q11.1-q12 loci and their influenced genes. Then, gene expression profiling analysis in the validation cohort confirmed lower expression of SDC3 in aTRH but no significant differences on LAPTM5 and UGT2B4, when compared with controls and hypertensives, respectively. RT-qPCR assay further verified the lower expression of SDC3 in aTRH. CONCLUSIONS: Our study identified a novel association of SDC3 with aTRH, which contributes to the elucidation of its etiopathogenesis and provides a promising therapeutic target.

Screening 5-lipoxygenase inhibitors from selected traditional Chinese medicines and isolation of the active compounds from Polygoni Cuspidati Rhizoma by an on-line bioactivity evaluation system.

To identify natural products as new prototypes for 5-lipoxygenase (5-LOX), 12 traditional Chinese medicines (TCMs) were selected for screening their 5-LOX inhibition activities. The results showed that the methanol extracts of all selected TCMs (n = 12) possessed inhibitory activities against 5-LOX at 200 µg/mL, of which six extracts of the TCMs showed significant inhibitory effects with IC50 values in the range from 33.2 ± 1.4 µg/mL to 153.5 ± 1.7 µg/mL, and the extract of Polygoni Cuspidati Rhizoma (RPC) was the most active sample. An on-line ultra-performance liquid chromatography-photodiode array-MSn -5-LOX-fluorescence detector (UPLC-PDA-MSn -5-LOX-FLD) method was applied to further identify the potential 5-LOX inhibitory constituents in RPC extracts, which resulted in the identification of seven components with 5-LOX-binding activities. Finally, four compounds (polydatin, resveratrol, emodin-8-O-glucoside, and emodin) were successfully purified from RPC extracts. The 5-LOX inhibition action was assayed in vitro, and the results showed that these compounds possessed potent inhibitory effects against 5-LOX with IC50 values of 15.3 ± 2.1, 4.5 ± 1.2, 23.8 ± 0.4, and 11.8 ± 1.5 µg/mL, respectively. This was the first study to reveal the 5-LOX inhibitory constituents of RPC, and the present investigation might provide a valuable approach for the rapid discovery of natural inhibitors from TCMs.

Enzymatic Cycle-Inspired Dynamic Biosensors Affording No False-Positive Identification.

There is an urgent need for reliable biosensors to detect nucleic acid of interest in clinical samples. We propose that the accuracy of the present nucleic acid-sensing method can be advanced by avoiding false-positive identifications derived from nonspecific interactions (e.g., nonspecific binding, probe degradation). The challenge is to exploit biosensors that can distinguish false-positive from true-positive samples in nucleic acid screening. In the present study, by learning from the enzymatic cycle in nature, we raise an allostery tool displaying invertible positive/negative cooperativity for reversible or cyclic activity control of the biosensing probe. We demonstrate that the silencing and regeneration of a positive (or negative) allosteric effector can be carried out through toehold displacement or an enzymatic reaction. We, thus, have developed several dynamic biosensors that can repeatedly measure a single nucleic acid sample. The ability to distinguish a false-positive from a true-positive signal is ascribed to the nonspecific interaction presenting equivalent signal variations, while the specific target binding exhibits diverse signal variations according to repeated measurements. Given its precise identification, such consequent dynamic biosensors offer exciting opportunities in physiological and pathological diagnosis.

Tunable Dual-Effector Allostery System for Nucleic Acid Analysis with Enhanced Sensitivity and an Extended Dynamic Range.

In the last few years, studies have demonstrated the existence of dual-effector allosteric cooperativity in nature and the mechanism underlying enhanced activation/inhibition performance. In this work, we design an artificial dual-effector allostery system for the construction of a dynamic biosensor that can achieve nucleic acid detection with superior sensitivity and across an extraordinary broad detection range. Our dual-effector allostery-regulated biosensor is based on the multibranched hybridization chain reaction (mHCR) involving three hairpins (H1, H2, and H3). In the presence of the target nucleic acid, the mHCR is initiated via cascading strand displacement events. The products of mHCR are then captured on the electrode surface based on the mechanism of the multivalent proximity ligation assay (mPLA) and the multivalent binding assay (mBA). The subsequent conjugation of streptavidin-modified horseradish peroxidase (SA-HRP) can lead to an increase in the electrochemical signal. Importantly, two distinct allosteric activation sites and two distinct allosteric inhibition sites in H1 are designed to fine-tune the nucleic acid detection sensitivity and the dynamic range. Using this new dual-effector allostery tool, we report the detection of nucleic acid at a dynamic range spanning 10-1012 aM, 11 orders of magnitude showing the broadest dynamic range reported to date with an allosteric regulation biosensor construct.

Capsaicin on stem cell proliferation and fate determination - a novel perspective.

Capsaicin (CAP), a member of the vanilloid family, is the main active component of chili peppers, which has been widely explored for its various pharmacological effects and influence on cell physiology, such as axonal growth and apoptosis of tumor cells. In particular, CAP plays a crucial role in determining the proliferation and fate specification of stem cells by modulating a variety of signaling pathways, such as PPARγ, C/EBPα and Notch signaling. Since CAP-mediated processes are complex and multifactorial, we hope to achieve a better understanding of these processes and their implications in clinical applications. This review aims to shed light on the influences and mechanisms of CAP on the actions of various stem cells in adults and discusses the role of CAP in the different process of stem cell behaviors, including proliferation and differentiation. Our purpose is to provide certain prospects for the application of CAP and stem cell therapy in treating diseases.

PtNPs-GNPs-MWCNTs-ß-CD nanocomposite modified glassy carbon electrode for sensitive electrochemical detection of folic acid.

A novel electrochemical sensor, platinum nanoparticles/graphene nanoplatelets/multi-walled carbon nanotubes/ß-cyclodextrin composite (PtNPs-GNPs-MWCNTs-ß-CD) modified carbon glass electrode (GCE), was fabricated and used for the sensitive detection of folic acid (FA). The PtNPs-GNPs-MWCNTs-ß-CD nanocomposite was easily prepared with an ultrasound-assisted assembly method, and it was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The electrochemical behavior of FA at PtNPs-GNPs-MWCNTs-ß-CD/GCE was investigated in detail. Some key experimental parameters such as pH, amount of PtNPs-GNPs-MWCNTs-ß-CD composite, and scan rate were optimized. A good linear relationship (R2 = 0.9942) between peak current of cyclic voltammetry (CV) and FA concentration in the range 0.02-0.50 mmol L-1 was observed at PtNPs-GNPs-MWCNTs-ß-CD/GCE. The detection limit was 0.48 µmol L-1 (signal-to-noise ratio = 3). A recovery of 97.55-102.96% was obtained for the determination of FA in FA pills (containing 0.4 mg FA per pill) at PtNPs-GNPs-MWCNTs-ß-CD/GCE, indicating that the modified electrode possessed relatively high sensitivity and stability for the determination of FA in real samples.

Highly sensitive and selective determination of p-nitrophenol at an interpenetrating networks structure of self-assembled rod-like lanthanum hydroxide-oxidized multi-walled carbon nanotubes nanocomposite.

In this study, a novel electrochemical sensor based on self-assembled rod-like lanthanum hydroxide-oxidized multi-walled carbon nanotubes (La(OH)3-OxMWCNTs) nanocomposite was developed for sensitive determination of p-nitrophenol (p-NP). The La(OH)3-OxMWCNTs nanocomposite with an interpenetrating networks structure was characterized by field emission electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, Raman spectra and X-ray photoelectron spectroscopy (XPS). The cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) measurements were performed to study the electrochemical behaviors of La(OH)3-OxMWCNTs modified glassy carbon electrode (La(OH)3-OxMWCNTs/GCE). The La(OH)3-OxMWCNTs/GCE was used for sensitive determination of p-NP by CV and linear sweep voltammetry (LSV). Under the optimum conditions, the peak currents of LSV versus the concentrations of p-NP in the range 1.0-30.0 µmol L-1 showed a good linear relationship (R2=0.9971), and the limit of detection (LOD) was calculated to be 0.27 µmol L-1 (signal-to-noise ratio of 3, S/N=3). The recoveries of p-NP in real samples of industrial wastewater and Xiangjiang water at La(OH)3-OxMWCNTs/GCE were in the range of 95.62-110.75% with relative standard deviation (RSD) in the range of 1.65-3.85%. The intra-day and inter-day precisions were estimated to be less than 2.76% (n= 5), indicating that La(OH)3-OxMWCNTs/GCE possessed highly stability. In addition, La(OH)3-OxMWCNTs/GCE sensor showed good anti-interference ability for determination of p-NP in aqueous mixtures containing high concentrations of inorganic and organic interferents, and a decrease of oxidation peak currents by less than 3.57% relative to the initial levels indicated it possessed excellent selectivity. Therefore, La(OH)3-OxMWCNTs/GCE could be used as a fast, selective and sensitive electrochemical sensor platform for the selective determination and quantification of aqueous p-NP.

A novel electrochemical sensor based on self-assembled platinum nanochains - Multi-walled carbon nanotubes-graphene nanoparticles composite for simultaneous determination of dopamine and ascorbic acid.

In this study, platinum nanochains (PtNCs), multi-walled carbon nanotubes (MWCNTs) and graphene nanoparticles (GNPs) were assembled together to form a novel nanocomposite by a facile ultrasonic-assisted blending process. The PtNCs-MWCNTs-GNPs nanocomposite was characterized by high resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM) and X-ray diffraction (XRD). The nanocomposite was used for the modification of glass carbon electrode (GCE) and simultaneous determination of dopamine (DA) and ascorbic acid (AA) by differential pulse voltammetry (DPV) and cycle voltammetry (CV). Under the optimum conditions, the calibration curves obtained are linear for the currents versus DA and AA concentrations over the range 2.00-50.0 µM and 100-1200 µM, respectively. And the detection limits for DA and AA are 0.500 µM and 10.0 µM, respectively. The detection and quantitative analysis of DA and AA in human serum and vitamin C tablets on PtNCs-MWCNTs-GNPs/GCE gave the recoveries of 104-110% and 101-108% with relative standard deviations (RSD) of 4.36-7.48% and 0.620-2.90%, respectively. The proposed PtNCs-MWCNTs-GNPs composite could provide a new platform for the routine analysis of DA and AA in terms of its good anti-interference ability, excellent reproducibility and repeatability, and feasibility of use.

Novel FBN1 mutations are responsible for cardiovascular manifestations of Marfan syndrome.

The fibrillin-1 (FBN1) gene mutations result in Marfan syndrome (MFS) and have a variety of phenotypic variations. This disease is involved in the skeletal, ocular and cardiovascular system. Here we analyzed genotype-phenotype correlation in two Chinese families with MFS. Two patients with thoracic aortic aneurysms and dissections were diagnosed as MFS according to the revised Ghent criteria. Peripheral blood samples were collected and genomic DNAs were isolated from available cases, namely, patient-1 and his daughter and son, and patient-2 and his parents. According to the next-generation sequencing results, the mutations in FBN1 were confirmed by direct sequencing. A heterozygous frameshift mutation in exon 12 of FBN1 was found in the proband-1 and his daughter. They showed cardiovascular phenotype thoracic aortic aneurysms and dissections, a life-threatening vascular disease, and atrial septal defect respectively. One de novo missense mutation in exon 50 of FBN1 was identified only in the patient-2, showing aortic root aneurysm and aortic root dilatation. Intriguingly, two novel mutations mainly caused the cardiovascular complications in affected family members. No meaningful mutations were found in these two patients by screening all exons of 428 genes related with cardiovascular disease. The high incidence of cardiovascular manifestations might be associated with the two novel mutations in exon 12 and 50 of FBN1.

Neuroprotective effects of (E)-3,4-diacetoxystyryl sulfone and sulfoxide derivatives in vitro models of Parkinson's disease.

(E)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides have been reported as novel multifunctional neuroprotective agents in previous studies, which as phenolic compounds display antioxidative and antineuroinflammatory properties. To further enhance the neuroprotective effects and study structure-activity relationship of the derivatives, we synthesized their acetylated derivatives, (E)-3,4-diacetoxystyryl sulfones and sulfoxides, and examined their neuroprotective effects in vitro models of Parkinson's disease. The results indicate that (E)-3,4-diacetoxystyryl sulfones and sulfoxides can significantly inhibit kinds of neuron cell injury induced by toxicities, including 6-OHDA, NO, and H2O2. More important, they show higher antineuroinflammatory properties and similar antioxidative properties to corresponding un-acetylated compounds. Thus, we suggest that (E)-3,4-diacetoxystyryl sulfones and sulfoxides may have potential for the treatment of neurodegenerative disorders, especially Parkinson's disease.

Does All Social Support Work? Examining the Mechanisms of Patient-Reported Symptom Interference after Esophagectomy Affecting Life Satisfaction.

Purpose: We intended to explore the chain mediation role of resilience and different sources of social support on the relationship between symptom interference and life satisfaction from the patient-reported perspective. Patients and Methods: Two hundred and twenty-six patients after esophagectomy were investigated using four validated scales to estimate the symptom interference, resilience, different sources of social support, and life satisfaction. The chain mediation analysis was conducted using SPSS PROCESS Macro Model 6. Results: Mediation analysis showed that symptom interference indirectly influenced life satisfaction through two significant mediating pathways: (i) resilience (B = -0.138, 95% CI: -0.194 to -0.091); (ii) the chain mediators involving in resilience and family support (B = -0.049, 95% CI: -0.073 to -0.026). Surprisingly, the mediating pathway of family support was not significant. Conclusion: Interventions for resilience and family support could mitigate the adverse effects of symptom interference in patients after esophagectomy, improving life satisfaction. Of these, resilience may be more critical in terms of the utilization of social resources than family support.

Roles of sulfur-containing compounds in fermented beverages with 2-furfurylthiol as a case example.

Aroma is a critical component of the flavor and quality of beverages. Among the volatile chemicals responsible for fragrance perception, sulfur compounds are unique odorants due to their extremely low odor threshold. Although trace amounts of sulfur compounds can enhance the flavor profile of beverages, they can lead to off-odors. Sulfur compounds can be formed via Maillard reaction and microbial metabolism, imparting coffee aroma and altering the flavor of beverages. In order to increase the understanding of sulfur compounds in the field of food flavor, 2-furfurylthiol (FFT) was chosen as a representative to discuss the current status of their generation, sensory impact, enrichment, analytical methods, formation mechanisms, aroma deterioration, and aroma regulation. FFT is comprehensively reviewed, and the main beverages of interest are typically baijiu, beer, wine, and coffee. Challenges and recommendations for FFT are also discussed, including analytical methods and mechanisms of formation, interactions between FFT and other compounds, and the development of specific materials to extend the duration of aroma after release.