The role of lysine-specific demethylase 6A (KDM6A) in tumorigenesis and its therapeutic potentials in cancer therapy.

Histone demethylation is a key post-translational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Lysine specific demethylase 6A (KDM6A, also known as UTX) is an Fe2+- and α-ketoglutarate- dependent oxidase which belongs to KDM6 Jumonji histone demethylase subfamily, and it can remove mono-, di- and tri-methyl groups from methylated lysine 27 of histone H3 (H3K27me1/2/3). Mounting studies indicate that KDM6A is responsible for driving multiple human diseases, particularly cancers and pharmacological inhibition of KDM6A is an effective strategy to treat varieties of KDM6A-amplified cancers in cellulo and in vivo. Although there are several reviews on the roles of KDM6 subfamily in cancer development and therapy, all of them only simply introduce the roles of KDM6A in cancer without systematically summarizing the specific mechanisms of KDM6A in tumorigenesis, which greatly limits the advances on the understanding of roles KDM6A in varieties of cancers, discovering targeting selective KDM6A inhibitors, and exploring the adaptive profiles of KDM6A antagonists. Herein, we present the structure and functions of KDM6A, simply outline the functions of KDM6A in homeostasis and non-cancer diseases, summarize the role of KDM6A and its distinct target genes/ligand proteins in development of varieties of cancers, systematically classify KDM6A inhibitors, sum up the difficulties encountered in the research of KDM6A and the discovery of related drugs, and provide the corresponding solutions, which will contribute to understanding the roles of KDM6A in carcinogenesis and advancing the progression of KDM6A as a drug target in cancer therapy.

Berberine as a potential agent for breast cancer therapy.

Breast cancer (BC) is a common malignancy that mainly occurred in women and it has become the most diagnosed cancer annually since 2020. Berberine (BBR), an alkaloid extracted from the Berberidacea family, has been found with broad pharmacological bioactivities including anti-inflammatory, anti-diabetic, anti-hypertensive, anti-obesity, antidepressant, and anticancer effects. Mounting evidence shows that BBR is a safe and effective agent with good anticancer activity against BC. However, its detailed underlying mechanism in BC treatment remains unclear. Here, we will provide the evidence for BBR in BC therapy and summarize its potential mechanisms. This review briefly introduces the source, metabolism, and biological function of BBR and emphasizes the therapeutic effects of BBR against BC via directly interacting with effector proteins, transcriptional regulatory elements, miRNA, and several BBR-mediated signaling pathways. Moreover, the novel BBR-based therapeutic strategies against BC improve biocompatibility and water solubility, and the efficacies of BBR are also briefly discussed. Finally, the status of BBR in BC treatment and future research directions is also prospected.

How does high C load affect nitrous oxide emission of subsurface wastewater infiltration system?

Subsurface wastewater infiltration systems (SWISs) have drawn much attention due to the lower operating costs, lower energy demands and absence of secondary pollutants requiring further treatment. The process of denitrification involves reduction of nitrate to nitrous oxide (N2O) and dinitrogen gas (N2). Though removal of nitrate is advantageous from a water quality perspective, N2O may contribute to adverse environmental effects. This study evaluated N2O emission at high C loading regimes. The results revealed that as the C load increased, N2O emission increased first and then decreased, indicating that carbon source was a limiting factor for the release of N2O from the denitrification process. Denitrification was the dominant process for the release of N2O at any of the given C loads. When the influent carbon load was in the range of 220-460 mg/L, the contribution of denitrification to N2O emissions came to 69.77-83.11% (feeding period) and 67.07-79.53% (rest period), respectively.

Does carbon-nitrogen ratio affect nitrous oxide emission and spatial distribution in subsurface wastewater infiltration system?

In order to evaluate the effects of carbon-nitrogen ratio (CNR) on nitrous oxide (N2O) emission and quantify N2O spatial distribution in subsurface wastewater infiltration system (SWIS), layered sampling method was introduced. Results showed that low N2O emission rate (1.43 mg/m2·h) and conversion rate (0.1% accounting for influent TN) were obtained when CNR increased up to as high as 10. The highest N2O emission (3.14 mg/m2·h) was observed at CNR of 6. Instead, independent of CNR variations, 0-75 cm was the main contributor for N2O emission. The results indicated that layered sampling method is necessary in revealing N2O spatial distribution in soil layers. Carbon source availability and nitrogen load and their ratio (i.e. CNR) determined N2O emission rate. CNR of medium level leads to an increase in N2O emission rate.

Field study on N2O emission from subsurface wastewater infiltration system under variable loading rates and drying-wetting cycles.

In this field study, the impacts of influent loadings and drying-wetting cycles on N2O emission in a subsurface wastewater infiltration (SWI) system were investigated. N2O emitted under different operation conditions were quantified using static chamber and gas chromatograph techniques. N2O conversion rate decreased from 6.6 ± 0.1% to 2.7 ± 0.1% with an increase in hydraulic loading (HL) from 0.08 to 0.24 m3/m2·d. By contrast, N2O conversion rate increased with increasing pollutant loading (PL) up to 8.2 ± 0.5% (PL 4.2 g N/m2·d) above which conversion rate decreased, confirming that N2O production was under the interaction of nitrification and denitrification. Taking into consideration the pollutants (chemical oxygen demand (COD), NH4+-N, NO3--N and total nitrogen (TN)) removal ratio and N2O emission, optimal loading ranges and drying-wetting modes were suggested as HL 0.08-0.12 m3/m2·d, PL 3.2-3.7 g N/m2·d and 12 h:12 h, respectively. The results revealed that in SWI systems, conversion ratio of influent nitrogen to N2O could be between 4.5% and a maximum of 7.0%.

Distributions, sources and ecological risk of polycyclic aromatic hydrocarbons (PAHs) in subsurface water of urban old industrial relocation areas: A case study in Shenyang, China.

During a 12-month study period, the levels, distributions, sources and ecological risk of 16 polycyclic aromatic hydrocarbons (PAHs) were investigated in subsurface water of Shenyang (the largest urban industrial relocation base in China). The results showed that ΣPAH concentration ranged from 0.21 to 1.07 µg/L, in descending order as follows, summer, autumn, spring and winter. Comparing with the situations before relocation, there was a significant decrease in Fluorene, Phenanthrene and Anthracene levels. The content of Banzo[a]pyrene was in high level. Relatively high 16 EPA-PAHs concentrations were observed at downstream sites suggesting that after the industrial relocation, residual 16 EPA-PAHs in soil and sediments could be desorbed and resuspended in water. From a global perspective, contamination of subsurface water PAHs can be categorized as moderate level. Source analysis suggested that without industrial waste input, pyrogenic soureces were the major contributors for PAHs pollution in winter. Petrogenic and pyrogenic inputs were equally important sources for PAHs pollution in other seasons. Due to incomplete combustion of wood and coal, ecological risk of Banzo[a]pyrene was high in the winter, indicating that to alleviate 16 EPA-PAH contamination, segmented remediation and energy structure adjustment would be equally important in urban industrial relocation areas.

Surveillance results analysis of human brucellosis in Qinghai province in 2010 / 中国地方病学杂志

Objective To analyze the epidemic situation of human brucellosis in Qinghai province,in order to provide a theoretical basis for prevention and treatment of brucellosis.Methods Five counties in Qinghai province(Ping'an county,Haiyan county,Tianjun county,Dari county and Henan county) were selected as monitoring counties in 2010,and three or four townships were selected as monitoring points in each county.People aged 7 to 60 close contacted with livestock were monitored.The methods of rose bengal plate agglutination test(RBPT) and standard tube agglutination test (SAT) were used for serological testing.Brucellosis diagnosis was based on Brucellosis Diagnostic Criteria(WS 269-2007).Results A total of 2021 high-risk subjects from 5 counties were examined for brucellosis,and 76(by RBPT) of them were serologically confirmed with a positive rate of 3.76％ (76/2021),SAT positive 15 persons,the average positive rate was 0.74％ (15/2021).The number of infections was 15 cases,average prevalence was 0.74％(15/2021 ),and 3 new eases were discovered.The seasonal peak of incidence was from February to June.Most of the eases were reported dealing with slaughtering and fur processing.Conclusions The main reasons for epidemic rise are that the source of infection is not completely clear and weak awareness of self-protection in employees.So we must strengthen the quarantine,do surveillance on occupational groups and epidemic reporting work,carry out vocational training,strengthen publicity and education,and enhance the protection awareness.Thus brucellosis epidemic will be effectively controlled.