Ultrasonic-Assisted Biphasic Aqueous Extraction of Polyphenols from Vaccinium Dunalianum Leaves: Optimization, Antioxidant, and Tyrosinase Inhibition Activities.

To optimize the ultrasonic-assisted biphasic aqueous extraction conditions for polyphenolic compounds from Vaccinium dunalianum Wight leaves and investigate their antioxidant and tyrosinase inhibition activities, single-factor experiments were conducted to investigate the effects of ethanol volume fraction (%), ammonium sulfate mass fraction (%), solid-liquid ratio (g/mL), ultrasonic temperature (°C), and ultrasonic time (min) on polyphenolic content during extraction. Based on these experiments, three key factors influencing extraction were selected for response surface methodology (RSM) optimization. The results indicated that under conditions of 26% ethanol, 20% ammonium sulfate, a solid-liquid ratio of 1:30, and extraction for 35 minutes at 50°C, the polyphenol content reached 61.62 mg/g. The relative contents of 6'-O-caffeoylarbutin, ß-arbutin, and chlorogenic acid were 34.45%, 4.56%, and 31.06%, respectively. The DPPH· and ABTS+· scavenging rates were above 95% and 96%, respectively, and the ferric reducing ability exhibited a significant dose-effect relationship. The inhibition rates of monophenolase and diphenolase activities of tyrosinase were 43.84% and 35.73%, respectively. The optimized process for ultrasonic-assisted biphasic aqueous extraction of polyphenols from Vaccinium dunalianum Wight leaves demonstrated significant antioxidant and tyrosinase inhibition activities.

In vitro cytotoxicity, pharmacokinetics and tissue distribution in rats of MXN-004, a novel conjugate of polyethylene glycol and SN38.

1. MXN-004 is a water-soluble PEGylated 7-ethyl-10-hydroxy-camptothecin (SN38). The aim of this study was to evaluate the in vitro cytotoxicity of MXN-004 and investigate pharmacokinetics and tissue distribution of MXN-004 and its active metabolite SN38 in rats. 2. In vitro cytotoxicity of MXN-004 was tested in A549, HepG2 and Caco-2 cancer cell lines by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and compared with irinotecan. The pharmacokinetics and tissue distribution of MXN-004, irinotecan and their identical active metabolite SN38 were investigated after intravenous administration of MXN-004 and irinotecan at a same dose level of 16 µmol/kg in rats. 3. In vitro cytotoxicity study showed that MXN-004 was more potent in comparison with irinotecan. In rats, MXN-004 exhibited a longer half-life (sixfold) and much greater Vss as compared with irinotecan. The AUC0-∞, T1/2 and Cmax of SN38 after intravenous administration of MXN-004 were higher than those of irinotecan (3.5-, 1.92- and 10.6-fold, respectively). In addition, the concentrations of SN38 released from MXN-004 were significantly higher in all tissues than those from irinotecan, especially in the lung. 4. These results suggested that MXN-004 might be a more potential water-soluble antitumor agent with prolonged half-life of SN38 compared to irinotecan.

Design, synthesis, and inhibitory activity of hydroquinone ester derivatives against mushroom tyrosinase.

Tyrosinase is a widely distributed copper-containing enzyme found in various organisms, playing a crucial role in the process of melanin production. Inhibiting its activity can reduce skin pigmentation. Hydroquinone is an efficient inhibitor of tyrosinase, but its safety has been a subject of debate. In this research, a scaffold hybridization strategy was employed to synthesize a series of hydroquinone-benzoyl ester analogs (3a-3g). The synthesized compounds were evaluated for their inhibitory activity against mushroom tyrosinase (mTyr). The results revealed that these hydroquinone-benzoyl ester analogs exhibited inhibitory activity against mTyr, with compounds 3a-3e displaying higher activity, with compound 3b demonstrating the highest potency (IC50 = 0.18 ± 0.06 µM). Kinetic studies demonstrated that the inhibition of mTyr by compounds 3a-3e was reversible, although their inhibition mechanisms varied. Compounds 3a and 3c exhibited non-competitive inhibition, while 3b displayed mixed inhibition, and 3d and 3e showed competitive inhibition. UV spectroscopy analysis indicated that none of these compounds chelated with copper ions in the active center of the enzyme. Molecular docking simulations and molecular dynamics studies revealed that compounds 3a-3e could access the active pocket of mTyr and interact with amino acid residues in the active site. These interactions influenced the conformational flexibility of the receptor protein, subsequently affecting substrate-enzyme binding and reducing enzyme catalytic activity, in line with experimental findings. Furthermore, in vitro melanoma cytotoxicity assay of compound 3b demonstrated its higher toxicity to A375 cells, while displaying low toxicity to HaCaT cells, with a dose-dependent effect. These results provide a theoretical foundation and practical basis for the development of novel tyrosinase inhibitors.

Influence of boundary layer jets on the vertical distribution of ozone in Guangdong, China.

The planetary boundary layer (PBL) characteristics during ozone (O3) episodes in China have been extensively studied; however, knowledge of the impact of boundary layer jets (BLJs) on O3 vertical distribution is limited. This study conducted a field campaign from 1 to 8 December 2020 to examine the vertical structure of the O3 concentration and wind velocity within the boundary layer at two sites (Foshan: FS, Maoming: MM) in Guangdong. Utilising lidar observations and the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem), distinct spatial distribution patterns of O3 over FS and MM influenced by BLJs were identified. The BLJs at both locations exhibited pronounced diurnal variations with a nocturnal maximum exceeding 11 m/s at a height of approximately 500 m. The nocturnal enhancement of BLJs resulted from inertial oscillations coupled with diurnal thermal forcing over sloping terrain. A stronger BLJ at FS induced an evident uplift of O3 and the prevailing northeasterly wind facilitated the transport of O3 in the nocturnal residual layer from FS to MM. After sunrise, surface heating and the development of the PBL caused the air mass with elevated O3 levels in the residual layer to descend to ground level. At MM, calm surface winds, a weaker BLJ at 500 m height, and strong downdrafts collectively contributed to a significant increase in surface O3 concentration in subsequent days. These findings contribute to our understanding of the interactions between BLJs and variations in surface air pollutant concentrations, thereby providing important insights for future regional emissions control measures.

Comprehensive metabolomics profiling of seminal plasma in asthenozoospermia caused by different etiologies.

BACKGROUND: Asthenozoospermia (AZS) is a disease characterized by decreased sperm motility induced by multiple etiologies, and the pathological mechanisms of various AZS are unclear. We simultaneously analyzed the metabolic profiling of four representative AZS to provide new insights into the etiologies of AZS. METHOD: Seminal plasma samples were collected from healthy control (HC; n = 30) and four AZS induced by varicocele (VA, n = 30), obesity (OA, n = 22), reproductive system infections (RA; n = 17) and idiopathic (IA, n = 30), respectively, and were analyzed using gas chromatography-mass spectrometry. Disturbed metabolites and metabolic pathways were compared between AZS and HC, as well as IA and the other three AZS. RESULTS: A total of 40 different metabolites were identified in the seminal plasma of AZS and HC, of which lactic acid, fructose, citric acid, glutamine and pyruvic acid metabolic abnormalities associated with all the AZS groups, while each AZS group had unique metabolic changes. RA was significantly separated from the other three AZS, and metabolites such as cholesterol, octadecanoic acid and serine mainly contributed to the separation. CONCLUSION: The comprehensive metabolomic analysis and comparison of four various AZS provided evidence and clues for the mechanism mining, which will benefit future etiology, diagnosis and treatment of AZS.

Soft machining-induced surface and edge chipping damage in pre-crystalized lithium silicate glass ceramics.

Soft machining is a key procedure in fabrication of high-strength lithium-based silicate glass ceramic (LS) restorations. This paper reports on the diamond machining-induced surface and edge chipping damage in two pre-crystalized LS materials: pre-crystallized lithium metasilicate/orthophosphate glass ceramic (Pre-LS, IPS e.max CAD) and pre-crystallized zirconia-containing lithium metasilicate glass ceramic (Pre-ZLS, Vita Suprinity). Indentation techniques were used to measure the material mechanical properties. Soft machining was conducted using a robotic controlled apparatus mimicking dental CAD/CAM machining processes at different removal rates and enabling in-process force measurement. Machined surface roughness was assessed using 3D confocal optical profilometry in terms of the average and maximum surface heights. Scanning electron microscopy was used to assess diamond tool and machined surface and edge morphology. Soft machining of both materials was dominated by brittle fracture mixed with localized ductile flow. However, the higher brittleness index of Pre-ZLS than Pre-LS yielded higher degrees of machining-induced conchoidal fractures in Pre-ZLS in comparison with irregular fractures in Pre-LS. Thus, much larger surface roughness and deeper edge chipping damage were produced in Pre-ZLS than Pre-LS. Machining forces for Pre-ZLS were significantly smaller than Pre-LS, due to the lower machinability index associated with a complex relation of the mechanical properties as well as less debris adhesion for Pre-ZLS than Pre-LS. Further, increased material removal rates resulted in significantly increased machining forces, maximum surface roughness and fracture, and edge chipping damage in both Pre-ZLS and Pre-LS materials. Therefore, optimization of soft machining processes needs to be practiced to achieve accepted surface and edge quality at balanced removal rates.

A cold front induced co-occurrence of O3 and PM2.5 pollution in a Pearl River Delta city: Temporal variation, vertical structure, and mechanism.

In this study, the spatiotemporal variabilities and characteristics of ozone (O3) and fine particulate matter (PM2.5) were reconstructed, and the interaction between meteorological conditions and the co-occurrence of O3 and PM2.5 in Zhuhai, a city in the Pearl River Delta (China), was analysed. The vertical distributions of lower tropospheric O3, aerosol extinction coefficient, and wind velocity were measured using a ground-based LiDAR system. The diurnal variations in air pollutant concentrations and meteorological conditions at ground level were examined from 28 November to December 8, 2020 considering the weather conditions in Zhuhai. Heavy pollution episodes with increased concentrations of O3 and PM2.5 were observed from 6 to 7 December after a period of cold air invasion. The maximum hourly average concentrations of O3 and PM2.5 at the ground level reached up to 190 µg/m3, 98 µg/m3, respectively. The horizontal wind speed rapidly decreased to less than 2 m/s during the heavy pollution episodes driven by O3 and PM2.5, whereas the vertical wind velocity was dominated by the downdraught. When the large-scale synoptic winds were weak, a strengthening sea breeze in the afternoon could promote the landward propagation of warm marine air masses, and a lower surface wind speed was driven by the convergence of cold air from the north and warm air from the south. In turn, this increased the residence time of air pollutants and promoted their conversion to secondary pollutants. Regarding the pollution sources, the results indicated that the Pearl River Estuary represented a 'pool' of O3 and PM2.5 pollution. In addition, the contribution of regional pollutant transport could not be ignored when considering the accumulative increase in air pollution. Overall, the relatively weak synoptic winds, low mixing height, and high generation of pollution around Zhuhai collectively resulted in high concentrations of O3 and PM2.5.

Genome-wide screen and functional analysis in Xanthomonas reveal a large number of mRNA-derived sRNAs, including the novel RsmA-sequester RsmU.

Although bacterial small noncoding RNAs (sRNAs) are known to play a critical role in various cellular processes, including pathogenesis, the identity and action of such sRNAs are still poorly understood in many organisms. Here we have performed a genome-wide screen and functional analysis of the sRNAs in Xanthomonas campestris pv. campestris (Xcc), an important phytopathogen. The 50-500-nt RNA fragments isolated from the wild-type strain grown in a virulence gene-inducing condition were sequenced and a total of 612 sRNA candidates (SRCs) were identified. The majority (82%) of the SRCs were derived from mRNA, rather than specific sRNA genes. A representative panel of 121 SRCs were analysed by northern blotting; 117 SRCs were detected, supporting the contention that the overwhelming majority of the 612 SRCs identified are indeed sRNAs. Phenotypic analysis of strains overexpressing different candidates showed that a particular sRNA, RsmU, acts as a negative regulator of virulence, the hypersensitive response, and cell motility in Xcc. In vitro electrophoretic mobility shift assay and in vivo coimmunoprecipitation analyses indicated that RsmU interacted with the global posttranscriptional regulator RsmA, although sequence analysis displayed that RsmU is not a member of the sRNAs families known to antagonize RsmA. Northern blotting analyses demonstrated that RsmU has two isoforms that are processed from the 3'-untranslated region of the mRNA of XC1332 predicted to encode ComEA, a periplasmic protein required for DNA uptake in bacteria. This work uncovers an unexpected major sRNA biogenesis strategy in bacteria and a hidden layer of sRNA-mediated virulence regulation in Xcc.

Examining the physical and chemical contributions to size spectrum evolution during the development of hazes.

China has experienced severe hazes with high concentrations of particulate matter in recent years. The understanding of the size spectrum evolution of submicron particulate matter is critical to making efficient remediation policies to minimize the regional and global environmental impacts from hazes. During a time period of about one month, we monitored five severe haze episodes in Xi'an and four severe haze episodes in Beijing, which were characterized by two distinct kinds of aerosol mass concentration growth processes: accumulative-rise and abrupt-rise. A new method was developed to quantitatively evaluate the physical and chemical contributions to growth processes by analysing the size spectrum evolution data. The results showed that the accumulative-rise processes are governed by primary emissions and the abrupt-rise processes are governed by secondary chemical reactions. The population balance equations (PBE) were used to describe the variation of size spectrum of fine particulate matter, and the respective contributions of the physical aggregation rate and the chemical growth rate. The PBE model is solved using the adjustable direct quadrature method of moments (ADQMOM) to simulate the abrupt-rise process of haze development and to calibrate the contribution of the physical and chemical effects on the size spectrum of aerosol particles.

A SAM-I riboswitch with the ability to sense and respond to uncharged initiator tRNA.

All known riboswitches use their aptamer to senese one metabolite signal and their expression platform to regulate gene expression. Here, we characterize a SAM-I riboswitch (SAM-IXcc) from the Xanthomonas campestris that regulates methionine synthesis via the met operon. In vitro and in vivo experiments show that SAM-IXcc controls the met operon primarily at the translational level in response to cellular S-adenosylmethionine (SAM) levels. Biochemical and genetic data demonstrate that SAM-IXcc expression platform not only can repress gene expression in response to SAM binding to SAM-IXcc aptamer but also can sense and bind uncharged initiator Met tRNA, resulting in the sequestering of the anti-Shine-Dalgarno (SD) sequence and freeing the SD for translation initiation. These findings identify a SAM-I riboswitch with a dual functioning expression platform that regulates methionine synthesis through a previously unrecognized mechanism and discover a natural tRNA-sensing RNA element. This SAM-I riboswitch appears to be highly conserved in Xanthomonas species.

[Efficacy evaluation of specific immunotherapy with standardized house dust mite allergen preparation for allergic rhinitis].

OBJECTIVE: To evaluate the efficacy of specific immunotherapy (SIT) with standardized house dust mite allergen preparation for allergic rhinitis (AR). METHOD: Fifty-five patients with allergic rhinitis caused by house dust mites were selected in this self-control study. Clinical efficacy was evaluated by symptom and sign score after two years of specific immunotherapy and compared with pre-treatment scores. RESULT: After completing the study, a clinically significant reduction in symptom and sign score in these patients was noted, compared with that of pretreatment. And the difference was statistically significant (P < 0.01). CONCLUSION: Standardized house dust mite allergen preparation is an effective treatment in patients suffering from allergic rhinitis due to house dust mites.

[The expression of oncogene AKT2 in laryngeal squamous cell carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression and clinical significance of oncogene AKT2 in laryngeal squamous cell carcinoma (LSCC). METHOD: The expression of AKT2 protein was measured with immunohistochemistry (Elivision two steps) in 60 cases of LSCC tissue, 28 cases of peri-cancer tissue and 16 cases of normal laryngeal epithelium, the relationship between AKT2 expression and clinical pathologic factors in LSCC was also analyzed. RESULT: The positive rates of AKT2 protein expression in LSCC and peri-cancer tissue were 56.7% (34/60), 14.3% (4/28) respectively. There was no expression of AKT2 in normal laryngeal epithelium. The positive rate of AKT2 protein expression in LSCC was significantly higher than that in peri-cancer tissue and normal laryngeal epithelium (P < 0.05, respectively). The positive rate of AKT2 was correlated with tumor site, lymph node metastasis and clinical stage of LSCC (P < 0.05, respectively), but wasn't correlated with patient's age, sex, and T stage (P > 0.05, respectively). CONCLUSION: AKT2 might play an important role in the tumorigenesis and development of LSCC, and it was suggested that AKT2 could be a useful marker for predicting tumorigenesis, invasion and metastasis potential of LSCC.

[Value of nasal endoscopy in the surgery of the nasal inverted papillomas].

OBJECTIVE: To evaluate the curative effect of endoscopic surgery (ESS) in the treatment of inverted papillomas in the nasal cavity and paranasal sinus. METHOD: We report on 16 clinicopathologic cases of inverted papilloma. After preoperative endoscopic examination and CT screening, endoscopic sinus surgery was performed under general anesthesia. RESULT: The follow-up period ranged between one year to two years. Recurrence was observed in 2 cases. CONCLUSION: The nasal endoscopy is a better method for treating Krouse I-II stage nasal inverted papilloma. The advantages of endoscopic surgery include clear visual field, less bleeding, limited reoccurrence, and avoidance of facial incision.