Advanced therapy medicinal products in China: Regulation and development

Abstract Advanced therapy medicinal products (ATMPs) have shown dramatic efficacy in addressing serious diseases over the past decade. With the acceleration and deepening of China's drug regulatory reforms, the country sees a continuous introduction of policies that encourage drug innovation. The capacity and efficiency of the Center for Drug Evaluation (CDE), National Medical Products Administration have significantly improved, where substantial resources have been allocated to ATMPs with major innovations and outstanding clinical values that satisfy urgent clinical needs. These changes have greatly stimulated the research and development of biological products in China, ushering in a period of explosive growth in the number of investigational new drug (IND) applications of ATMPs. Here, we described China's ATMP regulatory framework and analyzed data on IND applications for ATMPs submitted to CDE. The data show that China's ATMP industry is expanding dramatically, but lagging behind in terms of the innovative targets and the coverage of indications. However, in recent years, the diversity of product types, targets, and indications is growing. We discussed challenges and opportunities in ATMP regulation. Risk‐based regulation and cross‐discipline collaborations are encouraged to promote more ATMPs toward market authorization in China

Small kinetochore associated protein (SKAP) promotes UV-induced cell apoptosis through negatively regulating pre-mRNA processing factor 19 (Prp19).

Apoptosis is a regulated cellular suicide program that is critical for the development and maintenance of healthy tissues. Previous studies have shown that small kinetochore associated protein (SKAP) cooperates with kinetochore and mitotic spindle proteins to regulate mitosis. However, the role of SKAP in apoptosis has not been investigated. We have identified a new interaction involving SKAP, and we propose a mechanism through which SKAP regulates cell apoptosis. Our experiments demonstrate that both overexpression and knockdown of SKAP sensitize cells to UV-induced apoptosis. Further study has revealed that SKAP interacts with Pre-mRNA processing Factor 19 (Prp19). We find that UV-induced apoptosis can be inhibited by ectopic expression of Prp19, whereas silencing Prp19 has the opposite effect. Additionally, SKAP negatively regulates the protein levels of Prp19, whereas Prp19 does not alter SKAP expression. Finally, rescue experiments demonstrate that the pro-apoptotic role of SKAP is executed through Prp19. Taken together, these findings suggest that SKAP promotes UV-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19

Ubiquitylation of Rad51d Mediated by E3 Ligase Rnf138 Promotes the Homologous Recombination Repair Pathway.

Ubiquitylation has an important role as a signal transducer that regulates protein function, subcellular localization, or stability during the DNA damage response. In this study, we show that Ring domain E3 ubiquitin ligases RNF138 is recruited to DNA damage site quickly. And the recruitment is mediated through its Zinc finger domains. We further confirm that RNF138 is phosphorylated by ATM at Ser124. However, the phosphorylation was dispensable for recruitment to the DNA damage site. Our findings also indicate that RAD51 assembly at DSB sites following irradiation is dramatically affected in RNF138-deficient cells. Hence, RNF138 is likely involved in regulating homologous recombination repair pathway. Consistently, efficiency of homologous recombination decreased observably in RNF138-depleted cells. In addition, RNF138-deficient cell is hypersensitive to DNA damage insults, such as IR and MMS. And the comet assay confirmed that RNF138 directly participated in DNA damage repair. Moreover, we find that RAD51D directly interacted with RNF138. And the recruitment of RAD51D to DNA damage site is delayed and unstable in RNF138-depleted cells. Taken together, these results suggest that RNF138 promotes the homologous recombination repair pathway

Concentric gravity waves over Northern China observed by an airglow imager network and satellites

The first no-gap OH airglow all-sky imager network was established in northern China in February 2012. The network is composed of 6 all-sky airglow imagers that make observations of OH airglow gravity waves and cover an area of about 2000 km east and west and about 1400 km south and north. An unusual outbreak of Concentric Gravity Wave (CGW) events were observed by the network nearly every night during the first half of August 2013. These events were coincidentally observed by satellite sensors from FY-2, AIRS/Aqua, and VIIRS/Suomi NPP. Combination of the ground imager network with satellites provides multi-level observations of the CGWs from the stratosphere to the mesopause region. In this paper, two representative CGW events in August 2013 are studied in detail. First, is the CGW on the night of 13 August 2013, likely launched by a single thunderstorm. The temporal and spatial analyses indicate that the CGW horizontal wavelengths follow freely propagating waves based on a GW dispersion relation within 300 km from the storm center. In contrast, the more distant observed gravity wave field exhibits a smaller horizontal wavelength of ~20 km and our analysis strongly suggest this wave field represents a ducted wave. A second event, exhibiting multiple CGWs, was induced by two very strong thunderstorms on 09 August 2013. Multi-scale waves with horizontal wavelengths ranging from less than 10 km to 200 km were observed

Potassium Improves Drought Stress Tolerance in Plants by Affecting Root Morphology, Root Exudates, and Microbial Diversity

Potassium (K) reduces the deleterious effects of drought stress on plants. However, this mitigation has been studied mainly in the aboveground plant pathways, while the effect of K on root-soil interactions in the underground part is still underexplored. Here, we conducted the experiments to investigate how K enhances plant resistance and tolerance to drought by controlling rhizosphere processes. Three culture methods (sand, water, and soil) evaluated two rapeseed cultivars’ root morphology, root exudates, soil nutrients, and microbial community structure under different K supply levels and water conditions to construct a defensive network of the underground part. We found that K supply increased the root length and density and the organic acids secretion. The organic acids were significantly associated with the available potassium decomposition, in order of formic acid > malonic acid > lactic acid > oxalic acid > citric acid. However, the mitigation had the hormesis effect, as the appropriate range of K facilitated the morphological characteristic and physiological function of the root system with increases of supply levels, while the excessive input of K could hinder the plant growth. The positive effect of K-fertilizer on soil pH, available phosphorus and available potassium content, and microbial diversity index was more significant under the water stress. The rhizosphere nutrients and pH further promoted the microbial community development by the structural equation modeling, while the non-rhizosphere nutrients had an indirect negative effect on microbes. In short, K application could alleviate drought stress on the growth and development of plants by regulating the morphology and secretion of roots and soil ecosystems

Sexual and reproductive health status and related knowledge among female migrant workers in Guangzhou, China: a cross-sectional survey

Objective: The objective of this study was to investigate the current sexual and reproductive health (SRH) status including SRH-related knowledge and associated factors, self-reported symptoms of reproductive tract infection (RTI), medical assistance seeking behavior, sexual experience and contraceptive use, reproductive information approach and reproductive service utilization among female migrant workers in Huangpu district, Guangzhou city, China. Study design: A cross-sectional study was conducted in 2008 in eight factories, which were selected randomly from 32 eligible factories in the Huangpu district in Guangzhou. Descriptive statistics were used to describe the SRH status of migrant workers. Factors associated with the level of SRH knowledge were determined by a logistic regression model. Results: Of 1346 female migrant workers, 831(61.7%) were unmarried and 515 (38.3%) were married. 27.2% of the unmarried respondents and 40.2% of the married respondents had suffered self-reported RTI symptoms. Among unmarried respondents, the median knowledge score was 5 points, compared to 8 points for the married. For unmarried migrant workers, factors associated with the knowledge level were age, education level, access to SRH information and service, sexual experiences and RTI symptoms. For married migrant workers, factors associated with the knowledge level were age, education level, access to SRH services and RTI symptoms. Conclusions: A high prevalence of self-reported RTI symptoms and a low knowledge level were found among young female migrant workers. Unmarried migrant workers are more vulnerable to SRH problems. Those findings demand more specific interventions targeting female migrants and in particular the unmarried

Ectopic expression of SKAP in HeLa cells promotes UV-induced apoptosis.

<p>(A) FACS analysis (PI incorporation) to analyze apoptosis of HeLa cells transfected with pcDNA-Flag or pcDNA-Flag-SKAP after treatment with TNFα (20 ng/ml), TRAIL (50 ng/ml), Staurosporine (STS, 0.2 μM) or 40 J/m² UV exposure. The percentage of apoptotic cells (% of total cells) was determined using EXPO32-ADC, and the results are shown as a bar graph (*p<0.05). The values represent the mean ± SD from three independent experiments. (B) HeLa cells were transfected with pcDNA-Flag or pcDNA-Flag-SKAP and exposed to 40 J/m² UV irradiation. FACS analysis was used to analyze apoptosis as described in (A). (C) Confirmation of SKAP expression in HeLa/Flag-SKAP stable cell line by immunoblot analysis. GAPDH was used as a loading control. (D) HeLa/Flag and HeLa/Flag-SKAP stable cells were treated with 40 J/m² UV irradiation. The cell lysates were analyzed by immunoblot with the antibodies indicated. GAPDH was used as a loading control.</p

Sexual and reproductive health status and related knowledge among female migrant workers in Guangzhou, China: a cross-sectional survey.

The objective of this study was to investigate the current sexual and reproductive health (SRH) status including SRH-related knowledge and associated factors, self-reported symptoms of reproductive tract infection (RTI), medical assistance seeking behavior, sexual experience and contraceptive use, reproductive information approach and reproductive service utilization among female migrant workers in Huangpu district, Guangzhou city, China.Journal Articleinfo:eu-repo/semantics/publishe