The Isoelectronic Dopant in the Z-Scheme SnS2/ß-As Heterostructure Enhancing Photocatalytic Overall Water Splitting.

The catalytic field aims to decrease reaction barriers, accelerate reaction processes, and enhance the selectivity toward a target product. This study uses first-principles calculations to design a modified direct Z-scheme SnS2/ß-As heterostructure as a potential photocatalyst for overall water splitting. Our previous investigations have demonstrated that the SnS2/ß-As heterostructure can realize a hydrogen evolution reaction (HER) under light, while the oxygen evolution reaction (OER) follows a pathway involving the intermediate HOOH*. Interestingly, by substituting an S atom of SnS2 with a Se or Te atom, the rate-determining step of the OER is significantly reduced from 3.76 eV to 2.56 or 2.22 eV. Moreover, the OER can occur directly without the transition via HOOH*. Isoelectronic doping effectively trades off the adsorption strength of OER intermediates and promotes the OER process. This work highlights the dual benefits of isoelectronic doping, namely lowering the reaction barrier of the rate-determining step and promoting the selectivity of end products. These findings provide insights into the rational design of high-efficiency photocatalysts for water splitting.

The polarized electric field of CdTe/B4C3 heterostructure efficiently promotes its photocatalytic overall water splitting.

Inspired by natural photosynthesis, two-dimensional van der Waals (vdW) heterostructures are considered as promising photocatalysts for solar-driven water splitting and they attract ever-growing interest. A type-II vdW hetero-photocatalyst (CdTe/B4C3) integrating the polarized CdTe into metal-free B4C3 was constructed, which could achieve solar-driven spontaneous overall water splitting at pH = 0-7 and exhibit a high solar-to-hydrogen (STH) efficiency of 19.64%. Our calculation results show that the interlayer interaction between the CdTe and B4C3 monolayers in the heterostructure creates an interfacial electric field enhanced by the intrinsic dipole of polarized CdTe, which accelerates the effective separation of photogenerated carriers and makes the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) take place separately on the B4C3 and CdTe layers. Furthermore, the CdTe/B4C3 heterostructure has decent band edge positions to promote the redox reaction to decompose water due to the significant electrostatic potential difference in the CdTe/B4C3 heterostructure and it could trigger spontaneous redox reaction under light at pH = 0-7. This work is helpful for us to design type-II heterojunction photocatalysts with high efficiency of photogenerated carrier separation for overall water splitting.

DMEP induces mitochondrial damage regulated by inhibiting Nrf2 and SIRT1/PGC-1α signaling pathways in HepG2 cells.

Dimethoxyethyl phthalate (DMEP) is an environmental endocrine disruptor. However, research into the underlying mechanisms of DMEP mitochondrial toxicity is still in its infancy. We therefore expect to understand whether DMEP induced mitochondrial damage in HepG2 cells and the associated signaling pathways. DMEP (0.125, 0.25, 0.5, 1 and 2 mM) exposure for 48 h induced a notable increment in reactive oxygen species (ROS), malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate transaminase (AST) and 8-hydroxydeoxyguanosine (8-OHdG) in hepG2 cells, resulting in cellular oxidative stress. Low doses of DMEP upregulated nuclear factor E2-related factor 2 (Nrf2) and downstream protein haeme oxygenase-1 (HO-1) levels and high doses down-regulated their levels. Nrf2 levels increased after ROS scavenging by N-acetyl-L-cysteine (NAC), which indicated that the Nrf2 pathway may be affected by oxidative stress. We also found that DMEP decreased ATP content, mitochondrial copy number (mtDNA), translocase of the outer membrane subunit 20 (TOM20) expression, mitochondria-encoded genes CO1, CO2, CO3, ATP6, ATP8 expression, inhibited mitochondrial biogenesis pathway, down-regulated sirtuin 1(SIRT1), PPAR gamma co-activator 1 alpha (PGC-1α), Nuclear respiratory factor 1(Nrf1), Mitochondrial transcription factor A (TFAM) content and activated PINK1/Parkin autophagy pathway. DMEP also activated the mitochondrial apoptotic pathway, causing cytochrome c cytoplasmic translocation and caspase 3 cleavage. What's more, DMEP activated the Nuclear factor-κB (NF-κB) pathway and levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were significantly upregulated, causing an inflammatory response. In summary, DMEP can cause inflammatory response and oxidative stress in HepG2 cells, inhibited the Nrf2 pathway and mitochondrial biogenesis, and induced autophagy and apoptosis. And oxidative stress at least partially affected the Nrf2 pathway and mitochondrial biogenesis SIRT1/PGC-1α pathway.

Effects of 1,4-dihydropyridine derivatives on cell injury and mTOR of HepG2 and 3D-QSAR study.

1,4-dihydropyridine derivatives (1,4-DHPs) are a class of drugs used to treat cardiovascular diseases, but these drugs can cause liver injury. To reveal the toxicity characteristics of these compounds, we used a series of assays, including cell viability, enzyme activity detection, and western blotting, to investigate the toxicity of seven kinds of 1,4-DHPs (0-100 µM) on HepG2 cells and establish 3D-QSAR model based on relevant toxicity data. After HepG2 cells were treated with 1,4-DHPs for 24 h, high-dose (100 µM) 1,4-DHPs decreased cell viability to varying degrees, while ROS and MDA contents were significantly increased, and ATP content was reduced. Moreover, with the concentration of 100 µM 1,4-DHPs (Nimodipine, Nitrendipine, Cilnidipine, and Manidipine) were markedly inhibited the phosphorylation levels of mTOR protein. The results of the 3D-QSAR model showed that the non-cross validation coefficient (R2) and cross validation coefficient (Q2) of the model were 0.982 and 0.652, respectively. Combined with external validation and the Williams diagram, the model showed good predictability and application domain. Based on the CoMSIA 3D contour map, the introduction of large volume and hydrogen bond receptor groups on the carbonyl oxygen side chains of the 1,4-DHPs ring 3- and 5- was beneficial for reducing the toxicity of 1,4-DHPs. The results of this study could supplement information on the cytotoxicity of 1,4-DHPs, and could provide theoretical support for predicting the toxicity of 1,4-DHPs.

NMN Alleviates NP-Induced Learning and Memory Impairment Through SIRT1 Pathway in PC-12 Cell.

Nonylphenol (NP) is widely used in the chemical industry; it accumulates in organisms through environmental contamination and causes learning memory impairment. Nicotinamide mononucleotide (NMN) has been found to have a positive effect on the treatment of central nervous-related diseases. This study aimed to investigate the protective effect of NMN on NP-induced learning memory-related impairment in vitro and to further identify the underlying mechanisms. The results showed that NP induced oxidative stress and impaired the cholinergic system, 5-HT system in PC-12 cells. NMN alleviated NP-induced learning and memory impairment at the molecular level through alleviating oxidative stress and protective effects on the 5-HT system and cholinergic system. The 50 µM NP group significantly reduced the NAD+ content, and the relative expression of SIRT1, PGC-1α, Nrf2, MAOA, BDNF, and p-TrkB were significantly downregulated. Co-treatment of NMN with NP significantly reduced oxidative stress, improved the homeostasis of 5-HT and cholinergic system, enhanced the intracellular NAD+ content, and significantly upregulated the expression of SIRT1 pathway proteins. SIRT1 inhibitors reduced the expression of SIRT1 pathway-related proteins, which implied the impairment of learning and memory by NP and the protective effect of NMN might be achieved through the SIRT1-mediated PGC-1α/MAOA/BDNF signaling pathway. Overall, this study not only help us to understand the toxic mechanism of NP on learning memory impairment in vitro, but also have important reference significance to further explore the health care value of NMN and promote the development of related functional foods.

DBP induced autophagy and necrotic apoptosis in HepG2 cells via the mitochondrial damage pathway.

Phthalate esters (PAEs) are widely present in human tissues and pose significant health risks. In this study, HepG2 cells were treated with 0.0625, 0.125, 0.25, 0.5 and 1 mM Dibutyl phthalate (DBP) for 48 h to investigate mitochondrial toxicity. The results showed that DBP caused mitochondrial damage, autophagy, apoptosis and necroptosis; Transcriptomics analysis identified that MAPK and PI3K were significant factors in the cytotoxic changes induced by DBP; N-Acetyl-L-cysteine (NAC), SIRT1 activator, ERK inhibitor, p38 inhibitor and ERK siRNA treatments counteracted the changes of SIRT1/PGC-1α and Nrf2 pathway-related proteins, autophagy and necroptotic apoptosis proteins induced by DBP. While PI3K and Nrf2 inhibitors exacerbated the changes in SIRT1/PGC-1α, Nrf2-associated proteins and autophagy and necroptosis proteins induced by DBP. In addition, the autophagy inhibitor 3-MA alleviated the increase in DBP-induced necroptosis proteins. These results suggested that DBP-induced oxidative stress activated the MAPK pathway, inhibited the PI3K pathway, which in turn inhibited the SIRT1/PGC-1α pathway and Nrf2 pathway, thereby causing cell autophagy and necroptosis.

Effect of DEHP and DnOP on mitochondrial damage and related pathways of Nrf2 and SIRT1/PGC-1α in HepG2 cells.

Di-2-ethylhexyl phthalate (DEHP) and Dioctyl phthalate (DnOP) are widely used as plasticizers in various industries for which the consequent health problems are of great concern. In this context, we treated HepG2 cells with DEHP or DnOP for 48 h. The results showed that DEHP and DnOP caused increase in oxygen species (ROS), malondialdehyde (MDA), Alanine aminotransferase (ALT) and Aspartate transaminase (AST). The proteins NF⁃E2-related factor 2 (Nrf2) and haemeoxygenase-1 (HO-1), were significantly down-regulated. Subsequently, the mitochondrial structure was disrupted, and the ATP content, the mitochondrial copy number as well as the expression of the corresponding mitochondrial genes were also reduced. The expression of sirtuin 1(SIRT1), PPAR gamma co-activator 1 alpha (PGC-1α), Nuclear respiratory factor 1(Nrf1), Mitochondrial transcription factor A (TFAM) on the SIRT1/PGC-1α pathway were significantly reduced. Finally, neither DEHP nor DnOP was found to induce apoptosis, but could significantly up-regulate Light chain 3 II (LC3II) levels. In conclusion, DEHP and DnOP could induce HepG2 cell damage via mitochondria, probably by causing oxidative stress, inhibiting the Nrf2 pathway and inhibiting the mitochondrial biogenesis pathway, which leads to excessive autophagy and cell death. DEHP and DnOP differ in the Nrf2 pathway, autophagic pathway and MAPK pathway, which may be structurally related.

Comparative Analysis of Whey Proteins in Human Milk Using a Data-Independent Acquisition Proteomics Approach during the Lactation Period.

Human milk (HM) is the primary source of nutrients and bioactive components that supports the growth and development of infants. However, the proteins present in human milk may change depending on the period of lactation. In this light, the objective of the present study was to evaluate the effect of lactation period on HM utilizing a data-independent acquisition (DIA) approach to identify the differences in HM whey protein proteomes. As part of the study, whey proteins of January, February, and June in human milk were studied. The results identified a total of 1563 proteins in HM whey proteins of which 114 groups were subunits of differentially expressed proteins as revealed by cluster analysis. Protein expression was observed to be affected by the period of lactation with expression levels of plasminogen, thrombospondin-1, and tenascin higher during January, keratin, type I cytoskeletal 9 highest in February, and transcobalamin-1 highest in June. The results of this study contribute to expand our understanding of the human whey proteome but also provide strong evidence for the nutritional difference of HM during different lactation periods.