Acyl-quinic acids from the root bark of Acanthopanax gracilistylus and their inhibitory effects on neutrophil elastase and cyclooxygenase-2 in vitro.

Eleven new acyl-quinic acids (AQAs) 1a-9, and 18 known AQAs 10-27 were isolated from the root bark of Acanthopanax gracilistylus W. W. Smith (Acanthopanacis Cortex). The planar structures of 1a-9 were determined based on their HR-ESIMS, IR, and NMR data. The absolute configurations of 1a-6 were identified by comparing the experimental and the calculated electronic circular dichroism (ECD) spectra. This is the first report of the isolation of AQAs from Acanthopanacis Cortex. Notably, 1a-6 were determined as unusual oxyneolignan-(-)-quinic acids heterodimers, representing a new class of natural products. The inhibitory activities of 1a-27 on neutrophil elastase (NE) and cyclooxygenase-2 (COX-2) were studied in vitro, and the results indicated they possessed significant inhibitory activities on COX-2. Among them, the IC50 values of 1a-9 were 0.63±0.014, 0.75±0.028, 0.15±0.023, 0.63±0.016, 0.30±0.013, 35.63±4.600, 8.70±1.241, 16.51±0.480, 0.69±0.049, 0.39±0.017, and 0.26±0.080 µM, respectively. This study represents the inaugural disclosure of the anti-COX-2 constituents found in Acanthopanacis Cortex, thereby furnishing valuable insights into the exploration of novel COX-2 inhibitors derived from natural reservoirs.

Changes to physical activity behavior during the COVID-19 pandemic and their associated factors: a cross sectional survey of Mexican women.

BACKGROUND: On March 24, 2020, the Mexican Government established social distancing measures to address the outbreak of the COVID-19 pandemic. The resulting home confinement affected daily lifestyle habits such as eating, sleeping, and physical activity (PA). The objectives of this study were to determine changes in PA behaviors among Mexican women due to the COVID-19 pandemic and to assess potential factors associated with these changes. METHODS: This was a cross-sectional study based on an anonymous online questionnaire developed by the Task Force on Physical Activity for Persons with Disabilities (PAPD) within the International Society of Physical and Rehabilitation Medicine (ISPRM). Descriptive, quantitative statistics were used for data analysis. A Chi-squared (χ²) test was used to explore associations between dependent and independent variables. RESULTS: A total of 1882 surveys were completed. Among the respondents, 53.3% declared that their PA was reduced during the pandemic, 26.6% reported similar PA behavior, and 20.1% declared that their PA had increased during the pandemic. Lower PA behavior during the pandemic was associated with lower education levels, stricter pandemic constraints, obesity, and lower self-perceived functioning levels. A statistically significant association between poorer self-perceived mental health and decreased PA behaviors was also found. Respondents who were younger, self-perceived as unimpaired, not overweight, and whose income was not impacted by COVID-19 were associated with higher levels of reported physical and mental health. CONCLUSIONS: The study results identify disparities experienced in PA behavior during the COVID-19 pandemic among Mexican women and highlights the need for social support for PA participation.

Microbial signatures of health, gingivitis, and periodontitis.

The subgingival crevice harbors diverse microbial communities. Shifts in the composition of these communities occur with the development of gingivitis and periodontitis, which are considered as successive stages of periodontal health deterioration. It is not clear, however, to what extent health- and gingivitis-associated microbiota are protective, or whether these communities facilitate the successive growth of periodontitis-associated taxa. To further our understanding of the dynamics of the microbial stimuli that trigger disruptions in periodontal homeostasis, we reviewed the available literature with the aim of defining specific microbial signatures associated with different stages of periodontal dysbiosis. Although several studies have evaluated the subgingival communities present in different periodontal conditions, we found limited evidence for the direct comparison of communities in health, gingivitis, and periodontitis. Therefore, we aimed to better define subgingival microbiome shifts by merging and reanalyzing, using unified bioinformatic processing strategies, publicly available 16S ribosomal RNA gene amplicon datasets of periodontal health, gingivitis, and periodontitis. Despite inherent methodological differences across studies, distinct community structures were found for health, gingivitis, and periodontitis, demonstrating the specific associations between gingival tissue status and the subgingival microbiome. Consistent with the concept that periodontal dysbiosis is the result of a process of microbial succession without replacement, more species were detected in disease than in health. However, gingivitis-associated communities were more diverse than those from subjects with periodontitis, suggesting that certain species ultimately become dominant as dysbiosis progresses. We identified the bacterial species associated with each periodontal condition and prevalent species that do not change in abundance from one state to another (core species), and we also outlined species co-occurrence patterns via network analysis. Most periodontitis-associated species were rarely detected in health but were frequently detected, albeit in low abundance, in gingivitis, which suggests that gingivitis and periodontitis are a continuum. Overall, we provide a framework of subgingival microbiome shifts, which can be used to generate hypotheses with respect to community assembly processes and the emergence of periodontal dysbiosis.

A novel model of controlling PD-L1 expression in ALK+ anaplastic large cell lymphoma revealed by CRISPR screening.

The success of programmed cell death protein 1 (PD-1)/PD-L1-based immunotherapy highlights the critical role played by PD-L1 in cancer progression and reveals an urgent need to develop new approaches to attenuate PD-L1 function by gaining insight into how its expression is controlled. Anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALK+ ALCL) expresses a high level of PD-L1 as a result of the constitutive activation of multiple oncogenic signaling pathways downstream of ALK activity, making it an excellent model in which to define the signaling processes responsible for PD-L1 upregulation in tumor cells. Here, using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 library screening, we sought a comprehensive understanding of the molecular effectors required for PD-L1 regulation in ALK+ ALCL. Indeed, we determined that PD-L1 induction is dependent on the nucleophosmin-ALK oncoprotein activation of STAT3, as well as a signalosome containing GRB2/SOS1, which activates the MEK-ERK and PI3K-AKT signaling pathways. These signaling networks, through STAT3 and the GRB2/SOS1, ultimately induce PD-L1 expression through the action of transcription factors IRF4 and BATF3 on the enhancer region of the PD-L1 gene. IRF4 and BATF3 are essential for PD-L1 upregulation, and IRF4 expression is correlated with PD-L1 levels in primary ALK+ ALCL tissues. Targeting this oncogenic signaling pathway in ALK+ ALCL largely inhibited the ability of PD-L1-mediated tumor immune escape when cocultured with PD-1-positive T cells and natural killer cells. Thus, our identification of this previously unrecognized regulatory hub not only accelerates our understanding of the molecular circuitry that drives tumor immune escape but also provides novel opportunities to improve immunotherapeutic intervention strategies.

The lung microbiome, vitamin D, and the tuberculous granuloma: A balance triangle.

Mycobacterium tuberculosis (Mtb) has the extraordinary ability to persist for decades within granulomas in the human host. These histopathological structures involved in both protection and pathogenesis, are subject to various influences from the host systemically and through micro-niche environments. Despite the fact that vitamin D (VD) has a key role in macrophage activation and mycobacterial clearance in the early stages of Mtb infection, the overall role of VD in granuloma maintenance or functionality has been scarcely studied. VD deficiency has long time been known to influence on gut microbiota composition, and recent studies have shown that it can also impact on respiratory microbiome. The human microbiota plays an important role in pathogen colonization resistance, and it has been proposed to play a potential role in TB pathogenesis. In this article, we have reviewed current knowledge on the interaction between VD, the lung microbiome and TB, and propose mechanisms by which the tuberculous granuloma's outcome could be modulated by these two factors. The determinants of the final fate of lung granulomas are still unclear, and deciphering the underlying drivers of Mtb infection outcome within those structures is of critical importance.

Influence of DNA extraction on oral microbial profiles obtained via 16S rRNA gene sequencing.

BACKGROUND AND OBJECTIVE: The advent of next-generation sequencing has significantly facilitated characterization of the oral microbiome. Despite great efforts in streamlining the processes of sequencing and data curation, upstream steps required for amplicon library generation could still influence 16S rRNA gene-based microbial profiles. Among upstream processes, DNA extraction is a critical step that could represent a great source of bias. Accounting for bias introduced by extraction procedures is important when comparing studies that use different methods. Identifying the method that best portrays communities is also desirable. Accordingly, the aim of this study was to evaluate bias introduced by different DNA extraction procedures on oral microbiome profiles. DESIGN: Four DNA extraction methods were tested on mock communities consisting of seven representative oral bacteria. Additionally, supragingival plaque samples were collected from seven individuals and divided equally to test two commonly used DNA extraction procedures. Amplicon libraries of the 16S rRNA gene were generated and sequenced via 454-pyrosequencing. RESULTS: Evaluation of mock communities revealed that DNA yield and bacterial species representation varied with DNA extraction methods. Despite producing the lowest yield of DNA, a method that included bead beating was the only protocol capable of detecting all seven species in the mock community. Comparison of the performance of two commonly used methods (crude lysis and a chemical/enzymatic lysis+column-based DNA isolation) on plaque samples showed no effect of extraction protocols on taxa prevalence but global community structure and relative abundance of individual taxa were affected. At the phylum level, the latter method improved the recovery of Actinobacteria, Bacteroidetes, and Spirochaetes over crude lysis. CONCLUSION: DNA extraction distorts microbial profiles in simulated and clinical oral samples, reinforcing the importance of careful selection of a DNA extraction protocol to improve species recovery and facilitate data comparison across oral microbiology studies.

Treatment of polycystic liver disease: a hypothesis, patient characteristics, short and long-term results.

BACKGROUND: Non-total liver resecting invasive treatment of polycystic liver disease has different recurrence rates. The aim of this study is to illustrate why the recurrence rates are different. We established a hypothesis that the cyst number is a constant in polycystic liver disease in a patient's lifetime. MATERIAL AND METHODS: We selected 287 patients with polycystic liver, in which 35 patients had the record of liver volume, while other 252 patients had the record of length of right liver. Data were divided into 5 groups in terms of age. The intergroup comparison with different ages and clinical files of patients were analyzed. RESULTS: The mean difference was statistically insignificant when compared amongst groups in the lengths of right liver respectively. Symptom recurrence rates (q) were 19.05 and 17.65% respectively after cyst aspiration-sclerotherapy and non-cyst aspiration-sclerotherapy. CONCLUSION: The cyst number is a constant in patients with non-massive or massive polycystic liver disease in their lifetime.

The structural organization of the liver in the Chinese fire-bellied newt (Cynops orientalis) / Organización estructural del hígado en el tritón de vientre de fuego chino (Cynops orientalis)

The morphology of Chinese fire-bellied newt liver consists of 5 lobes, with exception of a few individual differences present, which are composed by a number of hepatic lobules. Passing through the center of the lobules, a central vein radiates and is arranged in orderly row from one to several layers. The interval of the hepatic cords or masses are irregular and variable sinusoid. The hepatic sinusoidal wall consists of one layer endothelial cells or Macrophagocytus stellatus (Kupffer cells), which have protrusions and elongations. The intervals of the hepatic cells have perisinusoidal space (space of Disse). The hepatic cell is polygonal in shape with uniform, round or oval nucleus, 17.8­12.4um in diameter, mean 14.2 um 2-6 nucleoli, nuclear-cytoplasmic volume ratio was 0.24:1. There is a lot of pigmentation in the hepatic parenchyma.

La morfología del hígado del tritón de vientre de fuego chino está constituida por 5 lóbulos, excepto unos pocos que presentan diferencias individuales, los cuales se componen de una gran cantidad de lóbulos hepáticos. Pasando por el centro de los lóbulos, se encuentra una vena central radial y los organiza en cordones o placas hepáticas. La vena central es delgada de 61,6-30,2 um de diámetro, con una media 42 de um. Los hepatocitos alrededor de la vena central están organizados en filas ordenadas por una a varias capas. El intervalo de los cordones hepáticos o masas es irregular y sinusoidal variable. La pared del sinusoide hepático está formada por una capa de células endoteliales o macrófagos hepáticos (células de Kupffer) que tienen protuberancias y elongaciones. El intervalo de las células hepáticas tienen el espacio perisinusoidal (de Disse). La célula hepática es de forma poligonal con un núcleo redondo u oval uniforme de 17,8-12,4 um de diámetro, con una media 14,2um. 2 a 6 nucléolos, con un radio de volumen nuclear-citoplasmático de 0,24:1. Hay una gran cantidad de pigmentación en el parénquima hepático.

The changes of organelle ultrastructure and Ca2+ homeostasis in maize mesophyll cells during the process of drought-induced leaf senescence

The changes of cell ultra structure as well as Ca2+ homeostasis involved in the drought-induced maize leaf senescence was investigated. Meanwhile, many indicatives of leaf senescence including thiobarbituric acid reactive substance (MDA), electrolyte leakage (EL), and chlorophyll along with soluble proteins were also detected during the process. The Polyethylene glycol6000(PEG6000)-incubated detached leaves showed a slight increase in the MDA content and electrolyte leakage during the first 30 min of our detection, which was corresponded to an unobvious alteration of the cell ultrastructure. Other typical senescence parameters measured in whole leaf exhibited a moderate elevation as well. Thereafter, however, the EL and MDA rose to a large extent, which was correlated with a dramatic damage to the cell ultrastructure with concomitant sharp decrease in the chlorophyll and soluble proteins content. The deposits of calcium antimonite, being an indicator for Ca2+ localization, were observed in the vacuoles as well as intercellular spaces in the leaves grown under normal condition. Nevertheless, after PEG treatment, it was revealed a distinct increment of Ca2+ in the cytoplasm as well as chloroplasts and nuclei. Moreover, with long-lasting treatment of PEG to the detached leaves, the concentration of Ca2+ as described above showed a continuous increment which was consist with the remarked alteration of physiological parameters and severe damage to the ultrastructure of cells, all of which indicated the leaf senescence. Such drought-induced leaf senescence might result from a loss of the cell's capability to extrude Ca2+. All above findings give us a good insight into the important role of Ca2+ homeostasis in the process of leaf senescence accelerated by the drought stress.

The influence of wind on the water age in the tidal Rappahannock River.

Wind plays an important role in regulating mixing/stratification, estuarine circulation, and transport timescale in estuaries. A three-dimensional model was used to investigate the effect of wind on transport time by using the concept of water age (WA) in the tidal Rappahannock River, a western tributary of the Chesapeake Bay, USA. The model was calibrated for water level, current, and salinity. A series of experiments regarding the effects of wind on WA was conducted under various dynamic conditions. The effect of wind on transport timescale depends strongly on the competition between the wind and buoyancy forcings, and on the pre-status of the circulation. A down-estuary wind generally decreases WA along the estuary. An up-estuary wind increases WA substantially because it changes the vertical mixing and estuarine circulation more significantly. When the buoyancy forcing increases, the up-estuary wind effect decreases whereas the down-estuary wind effect increases. A 2-day period wind pulse with a maximum speed of 15 ms(-1) can alter WA for 3 days; but the wind influence on WA lasts up to 40 days in the simulation. Both local and non-local wind forcings alter WA distribution. The local wind enhances vertical mixing and changes the gravitational circulation in the downstream portion of the estuary whereas it enhances transport in the freshwater portion of the estuary. Consequently, the local wind has a significant impact on WA distribution. In contrast, the non-local wind does not change the gravitational circulation significantly by imposing setup (setdown) of water level at the open boundary, resulting in a lesser impact on WA distribution.