Changes in Physicochemical Properties and Flavor Characteristics of Rosa roxburghii Tratt. Fruit Vinegar during Fermentation

This paper investigated the compositional changes of Rosa roxburghii Tratt. fruit vinegar during fermentation. By using Rosa roxburghii Tratt. as raw material and using the whole liquid fermentation technique, fruit vinegar was prepared by fermenting alcoholic and acetic acids simultaneously. The physicochemical properties of the fermentation process were dynamically monitored. Headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and the odor activity value (OAV) were utilized to analyze volatile flavor components. As fermentation proceeded, soluble solids, pH, total sugars, and reduced sugars decreased, while total acid and VC contents increased. From the original juice to the end of acetic acid fermentation, the total acid and VC contents ranged from 1.86 g/100 mL and 956.82 mg/100 mL to 6.79 g/100 mL and 1275.88 mg/100 mL. Oxalic acid, quinic acid, pyruvic acid, ascorbic acid, lactic acid, acetic acid, and fumaric acid showed varying degrees of increasing (P<0.05). By contrast, formic acid, citric acid, maleic acid, and succinic acid exhibited little variation. A total of 92 volatile compounds were detected in the Rosa roxburghii Tratt. fruit vinegar, and with the addition of OAV analysis, ten volatile compounds were identified as key aroma compounds, which included nonanal, acetaldehyde, ethyl isobutyrate, ethyl butyrate, ethyl 2-methylbutyrate, ethanol, isoamyl alcohol, leaf alcohol, linalool, and phenyl ethanol. Among these components, ethyl butyrate and leaf alcohol contributed most to the aroma of Rosa roxburghii Tratt. fruit vinegar. Green grass and green apples were characteristic aromas of this vinegar. The results of the study would provide a theoretical basis and practical guidance for the effective control of fermentation conditions, revealing the physicochemical characteristics and flavor features of fermented Rosa roxburghii Tratt. fruit vinegar, forming a method for quality evaluation of Rosa roxburghii Tratt. fruit vinegar, and formulating quality standards

Apatinib combined with camrelizumab in the treatment of recurrent/metastatic nasopharyngeal carcinoma: a prospective multicenter phase II study

BackgroundPreclinical studies demonstrated that immune checkpoint inhibitors combined with antiangiogenic drugs have a synergistic anti-tumor effect. This present phase II trial aimed to evaluate the efficacy and safety of apatinib combined with camrelizumab in patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC).MethodsPatients with RM-NPC were administered with apatinib at 250 mg orally once every day and with camrelizumab at 200 mg via intravenous infusion every 2 weeks until the disease progressed or toxicity became unacceptable. The objective response rate (ORR) was the primary endpoint, assessed using RECIST version 1.1. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety were the key secondary endpoints. This study was registered with ClinicalTrials.gov, NCT04350190.ResultsThis study enrolled 26 patients with RM-NPC between January 14, 2021 and September 15, 2021. At data cutoff (March 31, 2023), the median duration of follow-up was 16 months (ranging from 1 to 26 months). The ORR was 38.5% (10/26), the disease control rate (DCR) was 61.5% (16/26), and the median PFS was 6 months (IQR 3.0-20.0). The median OS was 14 months (IQR 6.0-21.25). Treatment-related grade 3 or 4 adverse events occurred in seven (26.9%) patients, and comprised anemia (7.7%), stomatitis (3.8%), headache (3.8%), pneumonia (7.7%), and myocarditis (3.8%). There were no serious treatment-related adverse events or treatment-related deaths.ConclusionIn patients with RM-NPC, apatinib plus camrelizumab showed promising antitumor activity and manageable toxicities

Pitch and loudness information encoded in auditory imagery as revealed by event-related potentials

Two experiments using the ERP method and a task that involved comparing an imagined-S1 (the first stimulus) with a perceived-S2 (the second stimulus) were conducted to investigate whether imagined auditory representations encode pitch and loudness information. It was found that the amplitude of the imagery-related late positive complex (LPC) decreased with pitch but increased with loudness of the imagined sound, which was consistent with amplitude modulations of the auditory perception-related N1 component, thereby providing the first neural evidence that auditory imagery encodes perceptual attributes of auditory experiences.Two experiments using the ERP method and a task that involved comparing an imagined-S1 (the first stimulus) with a perceived-S2 (the second stimulus) were conducted to investigate whether imagined auditory representations encode pitch and loudness information. It was found that the amplitude of the imagery-related late positive complex (LPC) decreased with pitch but increased with loudness of the imagined sound, which was consistent with amplitude modulations of the auditory perception-related N1 component, thereby providing the first neural evidence that auditory imagery encodes perceptual attributes of auditory experiences.NSFC (30930031, 30900442); the Ministry of Education, China (PCSIRT, IRT0710); the Project for Young Scientists Fund, IP, CAS (O9CX042004), GSCAS (2006)

Expression and significance of histone H3K27 demethylases in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>The histone H3K27 demethylases UTX and JMJD3 are important regulatory factors that modulate gene expression by altering the physical state of chromatin. Previous studies have indicated an abnormal H3K27 methylation status in carcinogenesis. We therefore investigated the expression patterns of UTX and JMJD3 in renal cell carcinoma (RCC) and their roles in cancer development.</p> <p>Methods</p> <p>The mRNA expression levels of the <it>UTX</it> and <it>JMJD3</it> genes were determined in cancer tissues and adjacent normal tissues in 36 patients with primary RCC, using quantitative real-time-polymerase chain reaction. The UTX and JMJD3 protein contents were measured by western blotting and immunohistochemical analysis.</p> <p>Results</p> <p><it>UTX</it> and <it>JMJD3</it> transcripts were significantly increased in cancer tissues compared to normal tissues (P < 0.05). mRNA levels of the inhibitor of cyclin-dependent kinases 4 and 6 <it>p16INK4a</it> were also increased in cancer tissues (P < 0.001). Western blotting indicated that levels of both demethylases were increased in cancer tissues. The level of tri-methylated H3K27 (H3K27me3) was lower in cancer tissues compared to normal tissues, but expression of the H3K27 methyltransferase EZH2 was increased (P < 0.05). These results suggest that the two H3K27 demethylases may play critical roles in the regulation of H3K27 methylation status in RCC. Immunohistochemical analysis confirmed that UTX and JMJD3 expression were upregulated in cancer tissues compared to adjacent tissues.</p> <p>Conclusions</p> <p>This study demonstrated that UTX and JMJD3 were upregulated in cancer tissues, suggesting that they may be involved in the development of primary RCC. The potential roles of H3K27 demethylases as biomarkers in the early diagnosis of RCC need to be further explored.</p

Amnestic mild cognitive impairment in Parkinson's disease: White matter structural changes and mechanisms.

Mild cognitive impairment (MCI) is a heterogeneous cognitive disorder that is often comorbid with Parkinson's diseases (PD). The amnestic subtype of PD-MCI (PD-aMCI) has a higher risk to develop dementia. However, there is a lack of studies on the white matter (WM) structural changes of PD-aMCI. We characterized the WM structural changes of PD-aMCI (n = 17) with cognitively normal PD (PD-CN, n = 19) and normal controls (n = 20), using voxel-based and tract-based spatial statistics (TBSS) analyses on fractional anisotropy (FA) axial diffusivity (AD), and radial diffusivity (RD). By excluding and then including the motor performance as a covariate in the comparison analysis between PD-aMCI and PD-CN, we attempted to discern the influences of two neuropathological mechanisms on the WM structural changes of PD-aMCI. The correlation analyses between memory and voxel-based WM measures in all PD patients were also performed (n = 36). The results showed that PD-aMCI had smaller FA values than PD-CN in the diffuse WM areas, and PD-CN had higher AD and RD values than normal controls in the right caudate. Most FA difference between PD-aMCI and PD-CN could be weakened by the motor adjustment. The FA differences between PD-aMCI and PD-CN were largely spatially overlapped with the memory-correlated FA values. Our findings demonstrated that the WM structural differences between PD-aMCI and PD-CN were mainly memory-related, and the influence of motor adjustment might indicate a common mechanism underlying both motor and memory impairment in PD-aMCI, possibly reflecting a predominant influence of dopaminergic neuropathology

The Weakened Relationship Between Prestimulus Alpha Oscillations and Response Time in Older Adults With Mild Cognitive Impairment

Background: Prestimulus alpha oscillations associated with preparatory attention have an impact on response time (RT). However, little is known about whether there is a deficit in the relationship between prestimulus alpha oscillations and RT in older adults with mild cognitive impairment (MCI). Method: We collected electroencephalography (EEG) data from 28 older adults with MCI and 28 demographically matched healthy controls (HCs) when they were performing an Eriksen flanker task. For each participant, single-trial prestimulus alpha power was calculated for combinations of congruency (congruent vs. incongruent) and response speed (fast vs. slow). Result: Statistical analysis indicated that prestimulus alpha power was significantly lower for fast trials than slow trials in HCs but not in older adults with MCI. The Fisher&#39;s z scores of the within-subject correlation coefficients between single-trial prestimulus alpha power and RT were significantly larger in HCs than in older adults with MCI. In addition, machine learning analyses indicated that prestimulus alpha power and its correlation with RT could serve as features to distinguish older adults with MCI from HCs and to predict performance on some neuropsychological tests. Conclusion: The reduced correlation between prestimulus alpha activity and RT suggests that older adults with MCI experience impaired preparatory attention.</p

MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcription

Abstract Background Dysregulated long non-coding RNAs participate in the development of diabetic cerebral ischemia. This study aimed to investigate the underlying mechanism of lncRNA MALAT1 in diabetic cerebral ischemia. Method Middle cerebral artery occlusion (MCAO) was performed to establish diabetic cerebral I/R in vivo. TTC and neurological deficits assessment were performed to assess cerebral ischemic injury. LDH was conducted to detect cytotoxicity. RT-qPCR and western blotting assays were applied to determine mRNA and protein expression. Flow cytometry was performed to detect the pyroptosis of BV2 cells. Immunofluorescence and FISH were conducted for subcellular localization of MALAT1 and STAT1. ELISA was performed to determine cytokine release. Dual luciferase reporter, RIP, and ChIP assays were used to validate the interaction between STAT1 and MALAT1/NLRP3. Diabetes aggravated cerebral injury in vivo and in vitro. Diabetic cerebral ischemia induced inflammatory response and inflammation-induced cell pyroptosis. Result MALAT1 was overexpressed in diabetic cerebral ischemia models in vivo and in vitro. However, knockdown of MALAT1 suppressed inflammatory response and the pyroptosis of BV2 cells. Moreover, MALAT1 interacted with STAT1 to transcriptionally activate NLRP3. Knockdown of STAT1 significantly reversed the effects of MALAT1. Furthermore, STAT1 promotes the MALAT1 transcription. MALAT1 interacts with STAT1 to promote the pyroptosis of microglias induced by diabetic cerebral ischemia through activating NLRP3 transcription. Conclusion Thus, knockdown of MALAT1 may be a potential promising therapy target for diabetic cerebral ischemia

Structural insights into outer membrane asymmetry maintenance in Gram-negative bacteria by MlaFEDB

The highly asymmetric outer membrane of Gram-negative bacteria functions in the defense against cytotoxic substances, such as antibiotics. The Mla pathway maintains outer membrane lipid asymmetry by transporting phospholipids between the inner and outer membranes. It comprises six Mla proteins, MlaFEDBCA, including the ABC transporter MlaFEDB, which functions via an unknown mechanism. Here we determine cryo-EM structures of Escherichia coli MlaFEDB in an apo state and bound to phospholipid, ADP or AMP-PNP to a resolution of 3.3–4.1 Å and establish a proteoliposome-based transport system that includes MlaFEDB, MlaC and MlaA–OmpF to monitor the transport direction of phospholipids. In vitro transport assays and in vivo membrane permeability assays combined with mutagenesis identify functional residues that not only recognize and transport phospholipids but also regulate the activity and structural stability of the MlaFEDB complex. Our results provide mechanistic insights into the Mla pathway, which could aid antimicrobial drug development