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Human trophoblast cells are crucial for healthy pregnancy. However, whether the defective homologous recombination (HR) repair of dsDNA break (DSB) in trophoblast cells may induce miscarriage is completely unknown. Moreover, the abundance of BRCA1 (a crucial protein for HR repair), its recruitment to DSB foci, and its epigenetic regulatory mechanisms, are also fully unexplored. In this work, it is identified that a novel lnc‐HZ10, which is highly experssed in villous tissues of recurrent miscarriage (RM) vs their healthy control group, suppresses HR repair of DSB in trophoblast cell. Lnc‐HZ10 and AhR (aryl hydrocarbon receptor) form a positive feedback loop. AhR acts as a transcription factor to promote lnc‐HZ10 transcription. Meanwhile, lnc‐HZ10 also increases AhR levels by suppressing its CUL4B‐mediated ubiquitination degradation. Subsequently, AhR suppresses BRCA1 transcription; and lnc‐HZ10 (mainly 1‐447 nt) interacts with γ‐H2AX; and thus, impairs its interactions with BRCA1. BPDE exposure may trigger this loop to suppress HR repair in trophoblast cells, possibly inducing miscarriage. Knockdown of murine Ahr efficiently recovers HR repair in placental tissues and alleviates miscarriage in a mouse miscarriage model. Therefore, it is suggested that AhR/lnc‐HZ10/BRCA1 axis may be a promising target for alleviation of unexplained miscarriage. [ABSTRACT FROM AUTHOR]

BPDE (benzo(a)pyren‐7,8‐dihydrodiol‐9,10‐epoxide), a metabolite of environmental carcinogenic BaP, weakens the migration and invasion of human villous trophoblast cells and may further induce miscarriage. However, the underlying mechanisms remain largely unknown. In this study, we identified that in trophoblast Swan 71 and HTR‐8/SVneo cells, miR‐hz02 upregulates the level of lnc‐HZ02, which inhibits the expression of an RNA‐binding protein HuR. HuR could interact with FAK mRNA and promote its mRNA stability, thus upregulating the FAK level and the FAK/SRC/PI3K/AKT pathway, and finally maintaining the normal migration and invasion of trophoblast cells. If trophoblast cells are exposed to BPDE, both miR‐hz02 and lnc‐HZ02 are upregulated, which reduce the level of HuR, weaken the interactions of HuR with FAK mRNA, downregulate FAK level and the FAK/SRC/PI3K/AKT pathway, and finally inhibit cell migration and invasion. This study provides a novel scientific understanding of the dysfunctions of human trophoblast cells. [ABSTRACT FROM AUTHOR]

Abasic site as a common DNA lesion blocks DNA replication and is highly mutagenic. Protein interactions in T7 DNA replisome facilitate DNA replication and translesion DNA synthesis. However, bypass of an abasic site by T7 DNA replisome has never been investigated. In this work, we used T7 DNA replisome and T7 DNA polymerase alone as two models to study DNA replication on encountering an abasic site. Relative to unmodified DNA, abasic site strongly inhibited primer extension and completely blocked strand-displacement DNA synthesis, due to the decreased fraction of enzyme–DNA productive complex and the reduced average extension rates. Moreover, abasic site at DNA fork inhibited the binding of DNA polymerase or helicase onto fork and the binding between polymerase and helicase at fork. Notably and unexpectedly, we found DNA polymerase alone bypassed an abasic site on primer/template (P/T) substrate more efficiently than did polymerase and helicase complex bypass it at fork. The presence of gp2.5 further inhibited the abasic site bypass at DNA fork. Kinetic analysis showed that this inhibition at fork relative to that on P/T was due to the decreased fraction of productive complex instead of the average extension rates. Therefore, we found that protein interactions in T7 DNA replisome inhibited the bypass of DNA lesion, different from all the traditional concept that protein interactions or accessory proteins always promote DNA replication and DNA damage bypass, providing new insights in translesion DNA synthesis performed by DNA replisome. [ABSTRACT FROM AUTHOR]

Human trophoblast cells play important role in embryo-fetal development. However, trophoblast cells are sensitive to environmental carcinogens. Recently, we have discovered that BPDE inhibits trophoblast cell migration, invasion and proliferation, and also increases trophoblast cell apoptosis. Ferroptosis is a newly identified iron-dependent non-apoptotic programmed cell death. Whether BPDE might induce trophoblast cell ferroptosis is completely unknown. In this work, we have discovered that ferroptosis does occur in BPDE-treated human trophoblast cells. Iron metabolism up-regulates intracellular free Fe2+ level, produces excessive ROS (reactive oxygen species), and accelerates lipid peroxidation. GPX4 efficiently eliminates ROS and inhibits lipid peroxidation. Thus, ferroptosis is well suppressed due to the balance of these two pathways in healthy trophoblast cells. However, BPDE exposure could promote iron metabolism, increase intracellular free Fe2+ level, produce excessive ROS, and result in lipid peroxidation. Meanwhile, BPDE also down-regulates GPX4 expression level by promoting its proteasomal degradation, which eventually produces excessive ROS and induces lipid peroxidation. Thus, BPDE exposure induces trophoblast cell ferroptosis by unbalancing these two pathways, providing new insight in understanding BPDE-induced dysfunctions of human trophoblast cells. • BPDE exposure induces human trophoblast cell ferroptosis. • BPDE exposure increases intracellular free Fe2+ level and ROS level. • BPDE promotes GPX4 proteasomal degradation and reduces its protein level. • BPDE produces excessive ROS and induces lipid peroxidation. [ABSTRACT FROM AUTHOR]

The increased installation capacity of grid-connected household photovoltaic (PV) systems has been witnessed worldwide, and the power grid is facing the challenges of overvoltage during peak power generation and limited frequency regulation performance. With the dual purpose of enhancing the power grid safety and improving the PV utilization rate, the maximum feed-in active power can be regulated by modifying the maximum power point tracking (MPPT) algorithm and battery energy storage (BES) accessibility as control instructions. However, the existing methods not only waste installed PV capacity, but it becomes no longer accessible when the state of charge (SOC) of the BES approaches its upper limit. In response to the above problem, this paper proposes a power limit control strategy to coordinate the MPPT algorithm and the BES accessibility. The proposed strategy directly controls the inverter output current according to the power limit instructions from the electric operation control centers, leading to a bus voltage difference. The difference serves as a control signal for BES and PV. Under a power-limiting scenario, priority is given to power regulation through energy storage to absorb the limited active power. When the SOC of the BES reaches the upper limit of charging, modification of the PV MPPT algorithm facilitates the inverter output power to meet the power limit requirements. To further verify the effectiveness of the proposed power limit control strategy, both simulation and experimental studies are conducted, which consistently indicated a synchronized inverter current with grid voltage and a rapid power response of the power-limiting instruction within 0.2 s. The power limit control strategy not only improves the PV energy utilization but also supports the safe and reliable operation of the power gird in the context of soaring renewable energy penetration. [ABSTRACT FROM AUTHOR]

Power systems optimization is generally subject to the compromise between performance and cost. The 2021 Texas grid outage illustrates the worldwide dangers for the regional-centralized power grid, with comparable advantages to safety and flexibility for the distributed energy system. The storage of household batteries helps balance grid load and increase system stability and flexibility. However, household storage battery is still not widely used today because of its high costs. Currently, research on increasing household battery storage applicability is focused largely on optimizing economic strategies, such as configuration, dispatching and subsidy policies, which rely substantially more on technologies and financial perspectives. Consumers are not 'rational' individuals, and non-economic incentives can affect their decisions without raising prices. This paper consequently proposes to encourage users to acquire household battery storage to increase efficiency of power dispatching and economic advantages based on behavioral economics. In this paper, an empirical research builds upon the utility model of behavioral economics incentives and purchase willingness. Moreover, the multi-objective genetic algorithm is utilized to optimize the dispatching of household battery storage by using grid variance and user revenues as optimizing goals. The results of this paper show that the behavioral economics incentive improves intention to buy the household battery energy storage by 10.7% without raising subsidies. By improving the energy dispatching strategy, peak-load shifting performance and user revenues are improved by 4.2% and 10.6%, respectively. [ABSTRACT FROM AUTHOR]

Dpo4 is a representative model of Y-family DNA polymerase and is therefore one of the most intensively studied DNA polymerase. 6 mA, an epigenetic marker, plays important roles in regulation of various biological processes. However, its effects on DNA replication by Dpo4 is completely unknown. Here, we found that 6 mA and its intermediate Hyp inhibits primer extension by Dpo4, showing an obvious blockage just one nucleotide before 6 mA or Hyp. 6 mA reduces dTTP incorporation efficiency, next-base extension efficiency, binding affinity of DNA to Dpo4, binding affinity of dTTP to Dpo4-DNA complex, the fraction of productive Dpo4 or productive ternary complex, and the burst incorporation rate, explaining the inhibition effects of 6 mA on DNA replication by Dpo4. Hyp is similar to G and dCTP is preferentially incorporated opposite Hyp by Dpo4, resulting in A:T to G:C mutation. Relative to dTTP incorporation opposite unmodified A, Hyp reduces dCTP incorporation efficiency, next-base extension efficiency, the priority in extension beyond correct pair, binding affinity of Dpo4 to DNA, binding of dCTP to Dpo4-DNA complex, and the burst incorporation efficiency, explaining the inhibition effects of Hyp on DNA replication by Dpo4. This work provides insight in the effects of epigenetically modified 6 mA and Hyp on DNA replication by a representative Y-family DNA polymerase Dpo4. [ABSTRACT FROM AUTHOR]

In this Chapter, we systematically and comprehensively described various environmental harmful factors. They were classified into four aspects: physical factors, chemical factors, biological factors, and physiological and psychological stress factors. Their classification, modes of presence, toxicity and carcinogenicity, routes of exposure to human and toxic effects on the female reproductive health were introduced. It is expected that the exposure routes could be controlled and eliminated, and the pathogenic mechanism of environmental harmful factors should be investigated and explained to protect female reproductive health.

N 6 -methyladenine (6mA), a newly identified epigenetic modification, plays important roles in regulation of various biological processes. However, the effect of 6mA on DNA replication has been little addressed. In this work, we investigated how 6mA affected DNA replication by DNA polymerase of Pseudomonas aeruginosa Phage PaP1 (gp90 exo - ). The presence of 6mA, as well as its intermediate hypoxanthine (Hyp), inhibited DNA replication by gp90 exo - . The 6mA reduced dTTP incorporation efficiency by 10-fold and inhibited next-base extension efficiency by 100-fold. Differently, dCTP was preferentially incorporated opposite Hyp among four dNTPs. Gp90 exo - reduced the extension priority beyond the 6mA:T pair rather than the 6mA:C mispair and preferred to extend beyond Hyp:C rather than the Hyp:T pair. Incorporation of dTTP opposite 6mA and dCTP opposite Hyp showed fast burst phases. The burst rate and burst amplitude were both reduced for 6mA compared with unmodified A. Moreover, the total incorporation efficiency ( k pol / K d,dNTP ) was decreased for dTTP incorporation opposite 6mA and dCTP incorporation opposite Hyp compared with dTTP incorporation opposite A. 6mA reduced the incorporation rate ( k pol ), and Hyp increased the dissociation constant ( K d,dNTP ). However, 6mA or Hyp on template did not affect the binding of DNA polymerase to DNA in binary or ternary complexes. This work provides new insight into the inhibited effects of epigenetic modification of 6mA on DNA replication in PaP1.