Characterization of volatile compounds and sensory properties of spine grape (Vitis davidii Foex) brandies aged with different toasted wood chips.

Aging is an important process for improving wine and brandy quality. In this study, the chemical characterization and sensory properties of spine grape brandies were compared after aging with various species of wood chips, including French oak (FO), American oak (AO), Mongolian oak (MO), Japanese blue oak (JO), chestnut, catalpa, and cherry. The results showed that high color intensity and significant concentrations of tannins and polyphenols were observed in the brandies aged with FO, AO, and chestnut chips. The volatile compounds, such as ethyl decanoate, ethyl 2-methylbutanoate, ethyl octanoate, methyl salicylate, (Z)-2-hexenol, and furfural, contributed to the floral, fruity, and roasted/smoky attributes of the brandies aged with FO, AO, and chestnut chips. The 1-butanol, 1-propanol, phenylethanol, phenylethyl acetate, isoamyl acetate, and linalool contributed to the fruity, honey, and floral attributes of the brandies aged with JO and cherry chips. These findings are extremely useful for the production of differentiated and high-quality spine grape brandies.

Current status of nucleic acid therapy and its new progress in cancer treatment.

Nucleic acid is an essential biopolymer in all living cells, performing the functions of storing and transmitting genetic information and synthesizing protein. In recent decades, with the progress of science and biotechnology and the continuous exploration of the functions performed by nucleic acid, more and more studies have confirmed that nucleic acid therapy for living organisms has great medical therapeutic potential. Nucleic acid drugs began to become independent therapeutic agents. As a new therapeutic method, nucleic acid therapy plays an important role in the treatment of genetic diseases, viral infections and cancers. There are currently 19 nucleic acid drugs approved by the Food and Drug Administration (FDA). In the following review, we start from principles and advantages of nucleic acid therapy, and briefly describe development history of nucleic acid drugs. And then we give examples of various RNA therapeutic drugs, including antisense oligonucleotides (ASO), mRNA vaccines, small interfering RNA (siRNA) and microRNA (miRNA), aptamers, and small activating RNA (saRNA). In addition, we also focused on the current status of nucleic acid drugs used in cancer therapy and the breakthrough in recent years. Clinical trials of nucleic acid drugs for cancer treatment are under way, conventional radiotherapy and chemotherapy combined with the immunotherapies such as checkpoint inhibitors and nucleic acid drugs may be the main prospects for successful cancer treatment.

Advances in nucleic acid therapeutics: structures, delivery systems, and future perspectives in cancer treatment.

Cancer has emerged as a significant threat to human health. Nucleic acid therapeutics regulate the gene expression process by introducing exogenous nucleic acid fragments, offering new possibilities for tumor remission and even cure. Their mechanism of action and high specificity demonstrate great potential in cancer treatment. However, nucleic acid drugs face challenges such as low stability and limited ability to cross physiological barriers in vivo. To address these issues, various nucleic acid delivery vectors have been developed to enhance the stability and facilitate precise targeted delivery of nucleic acid drugs within the body. In this review article, we primarily introduce the structures and principles of nucleic acid drugs commonly used in cancer therapy, as well as their cellular uptake and intracellular transportation processes. We focus on the various vectors commonly employed in nucleic acid drug delivery, highlighting their research progress and applications in recent years. Furthermore, we propose potential trends and prospects of nucleic acid drugs and their carriers in the future.

Alveolar bone retention following treatment of dilacerated labial inversely impacted maxillary central incisors-a retrospective study.

The root of late-dental-age labial inversely impacted maxillary central incisors (LIIMCIs) typically develops to severe dilacerated morphology. Therefore, reliable posttreatment periodontal estimates of orthodontic treatment prognosis would be critical to the treatment value of impacted incisors. This study aims to analyze further changes in dimensions of the alveolar bone following the closed-eruption treatment of late-dental-age dilacerated LIIMCIs. Cone beam computed tomography (CBCT) scanning data of 16 patients with unilateral dilacerated late-dental-age LIIMCIs were collected, including the pretreatment (T1) and at the 2.23 ± 0.78 years follow-up stage (T2) respectively. Patients underwent closed-eruption treatments to bring the impacted incisor into the dental arch. Dolphin imaging software was used to measure alveolar bone height labially, palatally, and proximally to the site at T1 and T2, as well as alveolar bone thicknesses at 0, 2, 4, 6 and 8 mm below the initial measurement plane (IMP). The alveolar bone heights on the impacted and contralateral sides increased from T1 to T2 (p < 0.05). Alveolar bone growth on both sides had no significant difference. In T2, the mean values of labial and distal alveolar heights on the contralateral sides were greater than on the impacted sides (p < 0.05). The mean values of total alveolar bone thicknesses on the impacted sides in T1 were significantly smaller than those on the contralateral sides in IMP-0, 2, 4, 6, 8 (p < 0.05). The total thicknesses on the impacted sides in T2 increased and were significantly greater than on the contralateral sides (p < 0.05), except for the thickness in IMP-0. The closed-eruption treatment of dilacerated late-dental-age LIIMCIs results in no significant changes to alveolar bone height, except on the labial and distal sides, with increased alveolar bone thickness, suggesting that this approach may be viable first choice therapy for non-extraction orthodontic cases.

L-carnitine attenuated hyperuricemia-associated left ventricular remodeling through ameliorating cardiomyocytic lipid deposition.

Hyperuricemia (HUA) is associated with left ventricular remodeling (LVR) and thereby causes the initiation and development of a large number of cardiovascular diseases. LVR is typically accompanied by cardiomyocyte energy metabolic disorder. The energy supply of cardiomyocytes is provided by glucose and fatty acid (FA) metabolism. Currently, the effect of HUA on cardiomyocytic FA metabolism is unclear. In this study, we demonstrate that UA-induced cardiomyocyte injury is associated with cytoplasmic lipid deposition, which can be ameliorated by the FA metabolism-promoting drug L-carnitine (LC). UA suppresses carnitine palmitoyl transferase 1B (CPT1B), thereby inhibiting FA transport into the mitochondrial inner matrix for elimination. LC intervention can ameliorate HUA-associated left ventricular anterior wall thickening in mice. This study showed that FA transport dysfunction plays is a critical mechanism in both cardiomyocytic injury and HUA-associated LVR and promoting cytoplasmic FA transportation through pharmacological treatment by LC is a valid strategy to attenuate HUA-associated LVR.

Assessment of the influence on left ventricle by potassium oxonate and hypoxanthine-induced chronic hyperuricemia.

Cellular cytoplasmic xanthine oxidase (XO)-mediated uric acid synthesis and extracellular excess uric acid exposure are both causes of cardiomyocytic injury under the condition of hyperuricemia (HUA). Potassium oxonate suppresses uric acid degradation to increase extracellular concentration, while hypoxanthine is the catalytic substrate of XO. We aimed to observe cardiac damage in a chronic HUA mouse model induced by potassium oxonate and hypoxanthine. The mouse model was established by the co-administration of potassium oxonate and hypoxanthine for eight weeks. Then, left ventricular parameters were examined by echocardiographic evaluation, and the heart tissues were harvested for further histopathological analysis. The results showed that plasma uric acid was persistently elevated in the model mice, which demonstrated the stable establishment of chronic HUA. The left ventricular anterior wall was significantly thickened in the model group compared with the blank control group. After the end of modeling, the left ventricular anterior wall thickness of the hyperuricemic mice increased compared with that of blank group. The histological analysis showed and myocardial structure disorganization in the model group compared with the blank control. The above cardiac impairment changes could be attenuated by allopurinol pretreatment. This study systematically assessed cardiac damage in a chronic HUA mouse model. In addition, it provides useful information for future HUA-associated heart injury mechanism investigation and therapeutic treatment evaluation.

Head Acupuncture Plus Schuell's Language Rehabilitation for Post-Stroke Aphasia: A Systematic Review and Meta-Analysis of 32 Randomized Controlled Trials.

OBJECTIVE: To evaluate the existing randomized controlled trials (RCTs) for evidence of the efficacy and safety of head acupuncture (HA) plus Schuell's language rehabilitation (SLR) in post-stroke aphasia. METHODS: Seven databases including Embase, PubMed, Cochrane Library, Technology Periodical Database, the China National Knowledge Infrastructure, SinoMed and Wanfang Data Information Site were searched for RCTs published from database inception until November 14, 2021. RCTs that compared HA plus SLR with sham (or blank) control, acupuncture therapy alone, certain language rehabilitation therapy alone or other therapies for post-stroke aphasia were included. Data were extracted and assessed, and the quality of RCTs was evaluated. Fixed-effects model was used, with meta-inflfluence analysis, meta-regression, and regression-based sub-group analyses applied for exploration of heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. RESULTS: A total of 32 RCTs with 1,968 patients were included and 51 comparisons were conducted classified as types of strokes and aphasia. (1) For patients with aphasia after ischemic stroke, HA plus PSA showed significantly higher accumulative markedly effective rate [relative risk (RR)=1.55, 95% confidence interval (CI): 1.19-2.02, I2=0%] and accumulative effective rate (RR=1.22, 95% CI: 1.09-1.36, I2=0%). (2) For patients with comprehensive types of stroke, HA plus PSA was more effective in increasing recovery rate (RR=1.89, 95% CI: 1.39-2.56, I2=0%), accumulative markedly effective rate (RR=1.53, 95% CI: 1.36-1.72, I2=9%) and accumulative effective rate (RR=1.14, 95% CI: 1.09-1.19, I2=34%). (3) For patients with aphasia after stroke, HA plus PSA was superior to PSA alone with statistical significance in increasing recovery rate (RR=2.08, 95% CI: 1.24-3.46, I2=0%), accumulative markedly effective rate (RR=1.49, 95% CI: 1.24-1.78, I2=0%) and accumulative effective rate (RR=1.15, 95% CI: 1.06-1.24, I2=39%). (4) For patients with multiple types of aphasia, HA plus PSA also demonstrated significantly higher recovery rate (RR=1.86, 95% CI: 1.28-2.72, I2=0%), accumulative markedly effective rate (RR=1.55, 95% CI: 1.35-1.78, I2=22%), and accumulative effective rate (RR=1.17, 95% CI: 1.11-1.23, I2=41%). (5) For patients with motor aphasia after ischemic stroke, compared with PSA alone, HA plus PSA showed significantly higher accumulative markedly effective rate (RR=1.38, 95% CI: 1.06-1.79, I2=0%) and accumulative effective rate (RR=1.20, 95% CI: 1.05-1.37, I2=0%). Meta-regression analyses were performed without significant difference, and publication bias was found in some comparisons. CONCLUSION: HA plus SLR was significantly associated with better language ability and higher effective rate for patients with post-stroke aphasia, and HA should be operated cautiously especially during acupuncture at eye and neck. (Registration No. CRD42020154475).

Resveratrol, a novel inhibitor of GLUT9, ameliorates liver and kidney injuries in a D-galactose-induced ageing mouse model via the regulation of uric acid metabolism.

Accumulating evidence has shown that chronic injection of D-galactose (D-gal) can mimic natural ageing and induce liver and kidney injury. Previous studies showed that D-gal increased uric acid (UA) levels in mice. The increase in UA levels caused inflammation, accelerated oxidative stress, and aggravated liver and kidney injury. Oxidative stress and inflammation play vital roles in the ageing process. Therefore, reducing the levels of UA in ageing mice improved liver and kidney injury. Glucose transporter 9 (GLUT9) is responsible for the reabsorption of UA in the body, and its inhibition helps downregulate UA levels. The present study investigated the UA-lowering activity of the GLUT9 inhibitor resveratrol (RSV) using the patch clamping technique established in our laboratory in vitro. This research is the first study to demonstrate that RSV effectively inhibits UA uptake via GLUT9 (IC50 = 68.77 µM) in vitro. An in vivo study was also performed to investigate the possible protective effect of RSV on D-gal-induced liver and kidney injury. RSV significantly reduced serum UA levels via the downregulation of GLUT9 mRNA and protein expression and promoted the excretion of excess UA through urine. Biochemical analysis showed that RSV significantly downregulated abnormal increases in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine (CRE) caused by long-term D-gal treatment, which effectively improved pathological damage, increased superoxide dismutase (SOD) activity and decreased the content of malondialdehyde (MDA) in the liver and kidneys. RSV also downregulated the expression of the inflammatory cytokines, interleukin IL-6, IL-1ß and tumor necrosis factor (TNF)-α in the liver and kidneys of ageing mice. Our findings provide new insights into the treatment strategies for ageing-induced liver and kidney injury and reveal a new mechanism of RSV-induced reduction in UA levels in ageing individuals.

Apigenin ameliorates hyperuricemic nephropathy by inhibiting URAT1 and GLUT9 and relieving renal fibrosis via the Wnt/ß-catenin pathway.

BACKGROUND: Hyperuricemia (HUA) is characterized by abnormal serum uric acid (UA) levels and demonstrated to be involved in renal injury leading to hyperuricemic nephropathy (HN). Apigenin (API), a flavonoid naturally present in tea, berries, fruits, and vegetables, exhibits various biological functions, such as antioxidant and anti-inflammatory activity. PURPOSE: To investigate the effect of API treatment in HN and to reveal its underlying mechanisms. METHODS: The mice with HN were induced by potassium oxonate intraperitoneally and orally administered for two weeks. The effects of API on renal function, inflammation, fibrosis, and uric acid (UA) metabolism in mice with HN were evaluated. The effects of API on urate transporters were further examined in vitro. RESULTS: The mice with HN exhibited abnormal renal urate excretion and renal dysfunction accompanied by increased renal inflammation and fibrosis. In contrast, API reduced the levels of serum UA, serum creatinine (CRE), blood urea nitrogen (BUN) and renal inflammatory factors in mice with HN. Besides, API ameliorated the renal fibrosis via Wnt/ß-catenin pathway suppression. Furthermore, API potently promoted urinary UA excretion and inhibited renal urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in mice with HN. In vitro, API competitively inhibited URAT1 and GLUT9 in a dose-dependent manner, with IC50 values of 0.64 ± 0.14 µM and 2.63 ± 0.69 µM, respectively. CONCLUSIONS: API could effectively attenuate HN through co-inhibiting UA reabsorption and Wnt/ß-catenin pathway, and thus it might be a potential therapy to HN.

Association between palatally displaced maxillary central incisors and lateral incisors: A retrospective cone-beam computed tomographic study.

INTRODUCTION: The objective of this study was to investigate the location, orientation and root development of maxillary lateral incisors in patients with palatally impacted central incisors. Comparison was made between the lateral incisor on the affected side and that on the normally erupted side. METHODS: Cone-beam computed tomographic images from 20 patients (10 boys, 10 girls, mean age (9.01 ± 1.52 years old) with unilateral palatally impacted maxillary central incisors were imported into Dolphin imaging software 11.8 for 3-dimensional reconstruction and reorientation. Software measurement tools were used to measure the root length, crown distance, angle to palatal plane, distance to midline, and angle to midsagittal plane of the maxillary lateral incisors on both the impacted and unaffected sides. RESULTS: The Wilcoxon signed rank test indicated that lateral incisors on the impacted side were more proclined, at a mean angle difference of 29.47° in the sagittal plane (P < 0.001). The mean length of the roots of the lateral incisors was 1.21 mm shorter (P < 0.05) on the affected side compared with the normal side, and the lateral incisor crowns on the impacted side were located at an average of 4.57 mm closer to the palatal plane than on the normally erupted side (P < 0.001). The angle of long axis of the lateral incisors on the affected side had a greater angulation to the midsagittal plane compared with the unaffected side, with a mean difference of 30.27° (P < 0.001). CONCLUSIONS: Maxillary lateral incisors adjacent to palatally impacted maxillary central incisors side had abnormal root development and demonstrated angulation and position change compared with those adjacent to normally erupted central incisors.