Aims
In this study, the antifungal effect of cinnamaldehyde against Fusarium sambucinum and its underlying mechanisms were determined.
Methods and Results
Minimum inhibitory concentration and minimal ...fungicidal concentration of cinnamaldehyde were 3 and 4 mmol l−1 on spore germination and colony development assays in vitro, respectively. Furthermore, the lesion diameter of potato tubers and tuber slices inoculated with F. sambucinum was reduced by 76·9 and 69% after treatment with 4 mmol l−1 cinnamaldehyde. Cytometric analyses revelled that cinnamaldehyde significantly affected the integrity of cell membrane firstly, then decreased mitochondrial membrane potential and induced the accumulation of intracellular reactive oxygen species. Meanwhile, high‐performance liquid chromatography results indicated that 3 mmol l−1 cinnamaldehyde could reduce the ergosterol content by 67·94%. This effect was accompanied by a down‐regulation of ERG11, ERG6 and ERG4 which were involved in ergosterol biosynthesis.
Conclusion
Theses results suggest that cinnamaldehyde exerts strong antifungal activity against F. sambucinum, probably by affecting the ergosterol biosynthetic processes what leads to the disruption of cell membrane integrity.
Significance and Impact of the Study
Cinnamaldehyde is a predominant constituent and key flavour compound of cinnamon essential oil. It has been used as a food additive and flavorant. It is expected to be a novel and safe fungicide for controlling dry rot in potato tubes.
P. polyphylla Smith is used in traditional medicine in China, India and Nepal and is likely to be similarly used through most of its geographic range. China is at the centre of demand for P. ...polyphylla where it is used as an ingredient in several very successful Chinese medicinal herbal formulations. The Chinese e-commerce platform ‘alibaba.com’, for example, lists 97 P. polyphylla items offered by 46 Asian suppliers, of which 21 are situated in the Chinese mainland, 12 in Nepal, 7 in India, 2 in Pakistan, and 1 each in Bhutan, Hong Kong, Thailand, and Vietnam. Products offered include the crude drug (dried whole or cut rhizomes), extracts and formulations containing this herbal drug.
The aims of this review were to assess the scale of the P. polyphylla trade, reviewing evidence on the impacts of wild harvest on P. polyphylla populations and on the role of cultivation as an alternative to wild harvest.
Firstly, we reviewed published information on Paris population biology and studies on impacts of wild P. polyphylla harvest from across the geographic range of this species. Secondly, global trade data for P. polyphylla were analysed. Thirdly, we reviewed published information on P. polyphylla cultivation and made field visits to P. polyphylla cultivation areas in Yunnan and Sichuan.
Since the 1980s, there has been a 400-fold increase in the market price paid in China for P. polyphylla rhizomes, from 2.7 Chinese Yuan (CNY) per kg in the 1980s to market prices up to 1100 CNY per kg in 2017. Cross-border trade in dried P. polyphylla rhizomes occurs at three different scales. Firstly, an internal, national trade of P. polyphylla rhizomes within countries (such as India, Nepal and China). Secondly, trade in P. polyphylla rhizomes from Nepal (and possibly from Bhutan) to the two range states that have the largest traditional medicine trade in the world: China and India. Thirdly, trade in processed herbal products. In China, for example, P. polyphylla is widely used as an ingredient in several very successful herbal products, including a famous first aid treatment to stop bleeding. Some of these products are exported globally, in addition to entering into regional trade. Trade data in our review shows that c. 800–1050 t of P. polyphylla rhizomes are sold annually, significantly more than recorded in earlier studies. China is the only country where P. polyphylla is cultivated on a significant scale, although small-scale cultivation is taking place in India and Nepal.
Based on the criteria for the inclusion of species in CITES Appendix II (Art. IV 2(a)), there is compelling evidence for adding Paris polyphylla. At the same time, cultivation of P. polyphylla outside of high conservation value habitats needs to be encouraged and supported. One way of doing this may be to develop separate, traceable supply chains for cultivated supplies in order to distinguish them from wild harvested stocks.
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Fritillaria cirrhosa D. Don bulbs contain alkaloids and are one of the most intensively exploited alpine Himalayan medicinal species. In terms of proprietary medicines, our study shows that 210 F. ...cirrhosa products are offered by 46 suppliers, most of which (44) are situated in China and two in Nepal. A widespread commercial use is as one of the main ingredients in cough syrups. A well known example is "Nin Jiom Pei Pa Koa Herbal Cough & Throat Syrup", which typically contains more F. cirrhosa than any other herbal ingredient in the formulation. The biggest market for F. cirrhosa bulbs is China, where demand exceeds supply of this wild harvested species for use in traditional Chinese medicine (TCM). Cross-border trade from Nepal to China occurs in significant quantities. Bhutan also imports F. cirrhosa bulbs from Nepal. In addition, F. cirrhosa is registered as an active ingredient in traditional herbal medicinal preparations in Australia, Canada, Hong Kong SAR, Malaysia, Republic of Korea, Singapore and Taiwan. There is also an export trade in F. cirrhosa to Europe. Assessing how much F. cirrhosa is traded is complex, however, due to a “look-alike” challenge, as nine Chinese Fritillaria species are traded in Europe (Fritillaria cirrhosa, F. delavayi, F. hupehensis, F. pallidiflora, F. przewalskii, F. thunbergii, F. unibracteata, F. ussuriensis and F. walujewii).
The aims of this review were to assess the scale of the global trade in F. cirrhosa, and to synthesise studies of the impacts of wild harvest on F. cirrhosa populations and on the extent of emerging cultivation initiatives as an alternative to wild harvest.
Firstly, we reviewed published information on studies on impacts of wild F. cirrhosa harvest from across the geographic range of this species. Secondly, global trade data for F. cirrhosa were analysed.
The principal demand for F. cirrhosa bulbs is in China, where hundreds of different companies produce Fritillaria preparations. Trade data also show that in 2013, China exported over 44 tonnes of F. cirrhosa bulbs to Taiwan and 26.7 tonnes to the Republic of Korea. Extensive commercial use and limited wild stocks result in a high price (2000 – 3800 CNY per kg (around US$ 303 –560 per kg in 2017)) for F. cirrhosa bulbs. Prices of cultivated Fritillaria bulbs are much lower (600–680 CNY per kg in 2017) than wild harvested bulbs. But due to very specific growth requirements of F. cirrhosa, cultivation is not yet able to meet total demand. The consequence is continued exploitation of wild stocks. At the same time, however, an increasing proportion of the demand is met by cultivation of alternative Fritillaria species that are easier to grow than F. cirrhosa. The air-dry mass of F. cirrhosa bulbs varies between 0.0917 and 0.1116 g per bulb. This represents 8960 – 10,900 bulbs/kg or 8.9 – 10.9 million bulbs per tonne. Current demand therefore represents billions of bulbs per year.
Demand for F. cirrhosa bulbs, particularly from China, makes this species one of the most intensively harvested alpine Himalayan medicinal bulbs. Although F. cirrhosa is listed as a Class III protected species in China, billions of these tiny, wild harvested bulbs are sold per year. Due to demand exceeding supply, the price of F. cirrhosa bulbs has increased dramatically. Between 2002 and 2017, for example, the price of wild harvested F. cirrhosa bulbs increased over nine-fold, from the equivalent of US$60 in 2002 to US$560 per kg in 2017. To date, cultivation has been unable to meet the entire market demand for F. cirrhosa bulbs, although other Fritillaria species are successfully cultivated on a larger scale.
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In this work, the antibacterial activity and mechanism of chloroform fraction obtained from aqueous extract of mugwort leaves against Staphylococcus aureus were investigated. The extract showed ...obvious antibacterial activity against S. aureus which the minimum inhibitory concentration and minimum bactericidal concentration were determined to be 3·0 and 6·0 mg ml−1 respectively. The mechanism study suggested that the extract could destroy the integrity of the S. aureus cell walls and increase the permeability of cell membrane in a certain concentration, but it could not kill S. aureus in a short time. Instead, the extract could make bacteria in a state of apoptosis for a long time, interfere with the normal physiological metabolism of bacteria, and eventually make bacteria die, which was confirm by scanning electronic microscope.
Significance and Impact of the Study: Since ancient times, Mugwort (Artemisia argyi L.) has been widely used as a traditional medicine for many diseases including bacterial infectious diseases; therefore, it plays a very important role in protecting people’s health. Previous studies have proved that the essential oil of mugwort has antibacterial activity; however, the antibacterial activity of the non‐volatile components of it is still unknown. In this work, the antibacterial activity and mechanism of aqueous extract of mugwort leaves were investigated for the first time. The results obtained from this study provide a scientific basis for revealing the antibacterial activity of the non‐volatile components of mugwort, and lays a foundation for further development and utilization of mugwort.
Multiple myeloma (MM) is the second most common hematologic malignancy and the incidence of MM in mainland China in 2016 was 1.15/100 000.With the development of China's aging society, the incidence ...of MM is expected to increase year by year. Immunotherapy for MM has become the fourth pillar of therapy after autologous hematopoietic stem cell transplantation, immunomodulators, and proteasome inhibitors, and is the most active area of MM treatment. Nine new drugs have been approved for multiple myeloma treatment in China, and three are expected to be approved in 2024, which will focus on immunotherapy. There are many ambiguities about the current status of research and utilization in this emerging field in China. Determining the optimal integration of these therapies into the treatment regimen for Chinese MM patients constitutes a critical challenge for clinicians. Immunotherapy for MM primarily encompasses two major categories: antibody-based drug therapy and cellular immunotherapy. Antibody-based medications
The digestive tract development in goat kids around weaning is vital to the establishment of digestion and absorption function, growth, and health of adults. The objective was to explore the effects ...of age and solid feed on the anatomical and morphological development of the gastrointestinal tract of Laiwu Black goat kids. Forty-eight female Laiwu Black goats at 8 ages (1, 7, 14, 28, 42, 56, 70, and 84 d; 6 goats per group) were selected and killed for anatomical and morphological analysis. The goats experienced the following 4 diet phases: maternal colostrum (MC; d 1, d 7), maternal milk (MM; d 14, d 28), maternal milk plus solid diet (MMSD; d 42, d 56) and only solid diet (OSD; d 70, d 84). The body and carcass weights were not significantly changed during MC and MM phases but changed during the MMSD phase. The absolute growth of body and carcass weights were higher in the MMSD phase than in MM phase. In addition, the dressing percentage was the highest in the MMSD phase. The body size indices evolved progressively and increased over time. The percentage of internal and external organs to body weight decreased over time, whereas the percentage to complex stomach percentage increased. The rumen and omasum weight experienced synchronous absolute growth over time, especially in the OSD phase. In contrast, the absolute growth of the reticulum and abomasum was the highest in MMSD and MC phases, respectively. After weaning, the goats showed the highest papillae height, lamina propria, muscle layer thickness, and epithelial thickness. The OSD phase showed the highest colonic mucosa thickness, ileal villus height, and ileal muscle layer thickness. The crypt depth was higher in the MMSD phase than in the MM phase. Moreover, the crypt depth and muscle layer thickness of jejunum increased over time. Furthermore, duodenal crypt depth, muscle layer thickness, and epithelial thickness increased in the OSD phase compared with other stages. In conclusion, the histological investigation supports the improvement of the morphological development of the digestive tract and the growth performance in the solid feed phase. It is recommended to add solid food as early as 4 wk old.
The incidence and mortality trends of prostate cancer remain unknown in China. We examined secular trends in prostate cancer incidence and mortality rates and the net age, period, and cohort effects ...on them.
Trends were estimated using joinpoint regression, and the net age, period, and cohort effects were estimated by an age-period-cohort (APC) model with an intrinsic estimator (IE) algorithm.
Age-specific mortality rates of prostate cancer (1990–2017) were collected from the Global Burden of Disease (GBD) 2017 study, and the average annual percent change (AAPC) and relative risks (RRs) analyzed by joinpoint regression and APC model.
Age-standardized rates significantly rose by 2.75% (95% confidence interval CI: 2.6, 2.9) for incidence but declined by 0.26% (95% CI: −0.4, −0.2) for mortality from 1990 to 2017. The joinpoint regression analysis showed that incidence rates significantly rose in all age groups, but mortality rates decreased in these age groups over the past three decades. In addition, compared to the younger age groups (15-19, 20-24, 25-29, 30-34, 35-39 and 40-44 age group), the older age groups (50-54, 55-59, 60-64 and 75-79 age group) showed more substantial increases in incidence and slighter declines in mortality. The age effect on incidence and mortality showed sharp increasing trends from 40 to 79 years, and period effect showed both of them continuously increased with advancing period, but cohort effect showed substantial decreasing trends from 1917–1921 to 2002–2006 birth cohort.
Age effect on incidence and mortality presented an increasing trend in older people, and period effect showed increasing trends. The incidence rate of prostate cancer is increasing at an alarming rate in all age groups, which may adversely impact the mortality rates. Mortality began to increase since 2005; thus, timely intervention should be conducted, especially for earlier birth cohorts at high risk.
•Incidence rates of prostate cancer are increasing at an alarming rate in all age groups.•Mortality rates decreased in all age groups, while ASMR began to increase since 2005.•Age effect: incidence and mortality showed sharply increasing trends in older people.•Period effect: incidence and mortality continuously increased with advancing period.•Cohort effect: incidence and mortality decreased from earlier to later birth cohorts.
A nivolumab dosage regimen of 480mg intravenously (i.v.) every 4weeks (Q4W) was approved by FDA for the majority of the approved indications for nivolumab.
The proposed new dosage regimen was ...supported by pharmacokinetic modeling and simulation, dose/exposure–response relationships for efficacy and safety in the indicated patient populations, and the clinical safety data with the 480mg Q4W dosage regimen. Pharmacokinetic exposures achieved with 480mg Q4W were predicted for 4166 patients in 21 clinical studies with various types of solid and hematological tumors. Exposure–response analyses were conducted to predict 480mg Q4W safety and efficacy across all FDA-approved indications for nivolumab.
For the overall population, the geometric mean exposure achieved with 480mg i.v. Q4W was 5.2% higher for steady state Cavg and 15.6% lower for Ctrough than those with 3mg/kg i.v. Q2W, the approved dosage regimen. The simulated concentration–time course achieved with 480mg Q4W regimen was below the median concentration achieved with 10mg/kg i.v. Q2W that was also studied in clinical trials. The predicted probability of adverse events was similar between 480mg Q4W and that observed with the 3mg/kg Q2W regimen. Efficacy results were found to be similar between Q2W and Q3W dosage regimens in patients with renal cell carcinoma. The predicted efficacy for each indication suggested that the efficacy with 480mg Q4W is unlikely to be compromised compared with that observed with 3mg/kg Q2W.
The model-informed analyses of predicted exposure, efficacy and safety based on data from extensive clinical experience with nivolumab suggest that the benefit–risk profile of 480mg Q4W regimen is comparable to the approved 3mg/kg Q2W regimen, thus providing the regulatory basis for the approval of 480mg Q4W regimen in the absence of clinical efficacy data with this new dosage regimen.
Long-Pulse Laser-induced cavitation bubbles have been identified to hold significant applications in various fields, such as industry and medicine. In this study, the dynamics of cavitation bubbles, ...induced by a 2.94 μm wavelength Er:YAG laser with an energy of 20 ±1 mJ and transmitted via sapphire fiber optics into distilled water at different temperatures, were investigated. The adiabatic expansion theory was utilized to predict the maximum length (Lmax) and the maximum width (Wmax) of the cavitation bubbles at different liquid temperatures. Excellent alignment was observed between the theoretical predictions and the experimental data. Using this theory, the local overheated liquid temperature was deduced to be ∼180 °C during the formation of cavitation bubbles. It was found that as the liquid temperature increased, the collapse position of the cavitation bubbles, relative to the normalized distance (γ) from the fiber end face, decreased. This study reveals the importance of considering the potential risk of damage to fiber optics from the shockwaves and microjet streams generated by cavitation bubbles in high-temperature conditions.
A high O3 episode with the large increases in surface ozone by 21-42 ppbv and the nocturnal surface O3 levels exceeding 70 ppbv was observed in the region between Xiamen and Quanzhou over the ...southeastern coast of China during 12-14 June 2014, before the Typhoon Hagibis landing. Variations in the surface O3, NO2, CO and meteorology during the Typhoon Hagibis event clearly suggest a substantial impact of the peripheral downdrafts in the large-scale typhoon circulation on such an O3 episode excluding the contributions of photochemical production and the horizontal transport. The influence of vertical O3 transport from the upper troposphere and lower stratosphere (UTLS) region on high surface O3 levels is further confirmed by a negative correlation between surface O3 and CO concentrations as well as dry surface air observed during the O3 episode. This study provides observational evidence of typhoon-driven intrusion of O3 from the UTLS region to surface air, revealing a significant effect of such a process of stratosphere-troposphere exchange (STE) of O3 on tropospheric O3 and ambient air quality.
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