Linking Interfacial Structure and Electrochemical Behaviors of Batteries by High-Resolution Electrocapillarity.

The electrode-electrolyte interface governs the kinetics and reversibility of all electrochemical processes. While theoretical models can calculate and simulate the structure and associated properties of this intriguing component, their validation by direct experimental measurement has been a long-standing challenge. Electrocapillarity is a classical technique that derives the interfacial structure through potential-dependent surface tensions, but its limited resolution has confined its application to ideal systems such as extremely diluted aqueous electrolytes. In this work, we revive this technique with unprecedented time resolution, which allows fast and precise extraction of intrinsic interfacial structure and properties for a wide spectrum of electrolytes, be it ideal or nonideal, aqueous or nonaqueous, dilute or superconcentrated. For the very first time, this new electrocapillarity enables the measurements of a set of interfacial quantities, such as ion concentration distribution and potential drop across Helmholtz planes. Applying it on Zn-battery electrolytes, we discovered that Cl- specific adsorption at the inner-Helmholtz plane results in unexpected Zn2+ aggregation at the outer-Helmholtz plane, and identified such a unique interfacial structure as the fundamental driving force for fast Zn deposition/stripping kinetics and crystallographic texturing. The renaissance of electrocapillarity brings a new tool to the understanding and design of new electrolytes for future battery systems.

Solvent-Mediated, Reversible Ternary Graphite Intercalation Compounds for Extreme-Condition Li-Ion Batteries.

Traditional Li-ion intercalation chemistry into graphite anodes exclusively utilizes the cointercalation-free or cointercalation mechanism. The latter mechanism is based on ternary graphite intercalation compounds (t-GICs), where glyme solvents were explored and proved to deliver unsatisfactory cyclability in LIBs. Herein, we report a novel intercalation mechanism, that is, in situ synthesis of t-GIC in the tetrahydrofuran (THF) electrolyte via a spontaneous, controllable reaction between binary-GIC (b-GIC) and free THF molecules during initial graphite lithiation. The spontaneous transformation from b-GIC to t-GIC, which is different from conventional cointercalation chemistry, is characterized and quantified via operando synchrotron X-ray and electrochemical analyses. The resulting t-GIC chemistry obviates the necessity for complete Li-ion desolvation, facilitating rapid kinetics and synchronous charge/discharge of graphite particles, even under high current densities. Consequently, the graphite anode demonstrates unprecedented fast charging (1 min), dendrite-free low-temperature performance, and ultralong lifetimes exceeding 10 000 cycles. Full cells coupled with a layered cathode display remarkable cycling stability upon a 15 min charging and excellent rate capability even at -40 °C. Furthermore, our chemical strategies are shown to extend beyond Li-ion batteries to encompass Na-ion and K-ion batteries, underscoring their broad applicability. Our work contributes to the advancement of graphite intercalation chemistry and presents a low-cost, adaptable approach for achieving fast-charging and low-temperature batteries.

Association between frailty and adverse outcomes in patients undergoing maintenance hemodialysis: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to determine the strength of the association between frailty and adverse outcomes in patients undergoing maintenance hemodialysis. DESIGN: A systematic review and meta-analysis. SETTING AND PARTICIPANTS: Patients aged ≥18 years who were undergoing maintenance hemodialysis. METHODS: PubMed, Web of Science, Embase, the Cochrane Library, Scopus, the China Knowledge Resource Integrated Database, the Wanfang Database and the Weipu Database were searched from inception until 11 April 2024. The reviewers independently selected the studies, extracted the data and evaluated the quality of the studies. Stata 15.1 software was used to perform the meta-analysis. RESULTS: A total of 36 articles were included in this study, including 56,867 patients. The primary outcome events in this study were mortality, hospitalization, and vascular access events. The secondary outcomes were depression, cognitive impairment, falls, fracture, sleep disturbances, and quality of life. This study suggested that frailty was associated with mortality in patients undergoing maintenance hemodialysis [hazard ratio (HR), 1.97; 95% CI, 1.62-2.40]. Frailty increased the risk of mortality in patients [odds ratio (OR), 2.33; 95% CI, 1.47-3.68]. In addition, we found that frailty was significantly associated with hospitalization in patients undergoing maintenance hemodialysis (OR, 2.47; 95% CI, 1.52-4.03). Patients who were undergoing maintenance hemodialysis and who were frail had a greater risk of hospitalization [RR, 1.47; 95% CI, 1.05-2.08] and emergency visits (RR, 2.28; 95% CI, 1.78-2.92). The results of this study also suggested that frailty was associated with a greater risk of vascular access events (HR, 1.72; 95% CI, 1.50-1.97). Finally, frailty increased the risk of depression (OR, 4.31; 95% CI, 1.83-10.18), falls and fractures, and reduced quality of life. CONCLUSIONS: The findings of this study suggested that frailty was an important predictor of adverse outcomes in patients undergoing maintenance hemodialysis. In the future, medical staff should regularly evaluate signs of weakness, formulate individual diagnosis and treatment plans, adjust dialysis plans according to the patient's condition, and reduce the occurrence of adverse events. REGISTRATION: The study protocol was registered on PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, number: CRD42023486239).

Insight into the effect of large yellow croaker roe phospholipids on the physical properties of surimi gel and their interaction mechanism with myofibrillar protein.

BACKGROUND: The present study aimed to investigate the effects of large yellow croaker roe phospholipids (LYCRPLs) on the physical properties of surimi gels and to clarify their interaction mechanism with myofibrillar proteins (MPs) in terms of chemical forces and the spatial conformation. RESULTS: LYCRPLs could improve the gel strength, textural properties, rheological properties and water-holding capacity of surimi gels. Moreover, the interaction mechanism between LYCRPLs with MPs was revealed through intermolecular forces, Fourier transform infrared spectroscopy and ultraviolet visible absorption spectroscopy. The findings demonstrated that LYCRPLs enhanced the surface hydrophobicity and particle size of MPs, facilitating expansion and cross-linking of MPs. CONCLUSION: These results provide a theoretical basis for improving the characteristics of surimi gels and thus facilitate the application of LYCRPLs in the aquatic food industry. © 2023 Society of Chemical Industry.

Decabromodiphenyl ethane affects embryonic development by interfering with nuclear F-actin in zygotes and leads to cognitive and social disorders in offspring mice.

Decabromodiphenyl ethane (DBDPE) is a novel retardant. DBDPE is used in various flammable consumer products such as electronics, building materials, textiles, and children's toys. The presence of DBDPE in humans makes it extremely urgent to assess the health effects of DBDPE exposure. Here, we used female mice as an animal model to investigate the effects of DBDPE on embryonic development and offspring health. The results showed that 50 µg/kg bw/day of DBDPE exposure did not affect spindle rotation in oocytes after fertilization, but led to a decrease of pronuclei (PN) in zygotes. Further investigation found that DBDPE interferes with the self-assembly of F-actin in PN, resulting in PN reduction, DNA damage, and reduced expression of zygotic genome activating genes, and finally leading to abnormal embryonic development. More importantly, we found that maternal DBDPE exposure did not affect the growth and development of the first generation of offspring (F1) mice, but resulted in behavioral defects in F1 mice. Female F1 mice from DBDPE-exposed mothers exhibited increased motor activity and deficits in social behavior. Both female and male F1 mice from DBDPE-exposed mothers exhibited cognitive memory impairment. These results suggest that DBDPE has developmental toxicity on embryos and has a cross-generational interference effect. It is suggested that people should pay attention to the reproductive toxicity of DBDPE. In addition, it also provides a reference for studying the origin of neurological diseases and indicates that adult diseases caused by environmental pollutants may have begun in the embryonic stage.

Gasdermin E regulates the stability and activation of EGFR in human non-small cell lung cancer cells.

BACKGROUND: Lung cancer is the most lethal malignancy, with non-small cell lung cancer (NSCLC) being the most common type (~ 85%). Abnormal activation of epidermal growth factor receptor (EGFR) promotes the development of NSCLC. Chemoresistance to tyrosine kinase inhibitors, which is elicited by EGFR mutations, is a key challenge for NSCLC treatment. Therefore, more thorough understanding of EGFR expression and dynamics are needed. METHODS: Human non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of gasdermin E (GSDME) regulating EGFR stability by Western blot analysis, immunoprecipitation and immunofluorescence. GSDME and EGFR siRNAs or overexpression plasmids were used to characterize the functional role of GSDME and EGFR in vitro. EdU incorporation, CCK-8 and colony formation assays were used to determine the proliferation ability of non-small cell lung cancer cells. RESULTS: GSDME depletion reduced the proliferation of non-small cell lung cancer cells in vitro. Importantly, both GSDME-full length (GSDME-FL) and GSDME-N fragment physically interacted with EGFR. GSDME interacted with cytoplasmic fragment of EGFR. GSDME knockdown inhibited EGFR dimerization and phosphorylation at tyrosine 1173 (EGFRY1173), which activated ERK1/2. GSDME knockdown also promoted phosphorylation of EGFR at tyrosine 1045 (EGFRY1045) and its degradation. CONCLUSION: These results indicate that GSDME-FL increases the stability of EGFR, while the GSDME N-terminal fragment induces EGFR degradation. The GSDME-EGFR interaction plays an important role in non-small cell lung cancer development, reveal a previously unrecognized link between GSDME and EGFR stability and offer new insight into cancer pathogenesis. Video abstract.

Scale Effect of Land Cover Classification from Multi-Resolution Satellite Remote Sensing Data.

Land cover data are important basic data for earth system science and other fields. Multi-source remote sensing images have become the main data source for land cover classification. There are still many uncertainties in the scale effect of image spatial resolution on land cover classification. Since it is difficult to obtain multiple spatial resolution remote sensing images of the same area at the same time, the main current method to study the scale effect of land cover classification is to use the same image resampled to different resolutions, however errors in the resampling process lead to uncertainty in the accuracy of land cover classification. To study the land cover classification scale effect of different spatial resolutions of multi-source remote sensing data, we selected 1 m and 4 m of GF-2, 6 m of SPOT-6, 10 m of Sentinel-2, and 30 m of Landsat-8 multi-sensor data, and explored the scale effect of image spatial resolution on land cover classification from two aspects of mixed image element decomposition and spatial heterogeneity. For the study area, we compared the classification obtained from GF-2, SPOT-6, Sentinel-2, and Landsat-8 images at different spatial resolutions based on GBDT and RF. The results show that (1) GF-2 and SPOT-6 had the best classification results, and the optimal scale based on this classification accuracy was 4-6 m; (2) the optimal scale based on linear decomposition depended on the study area; (3) the optimal scale of land cover was related to spatial heterogeneity, i.e., the more fragmented and complex was the space, the smaller the scale needed; and (4) the resampled images were not sensitive to scale and increased the uncertainty of the classification. These findings have implications for land cover classification and optimal scale selection, scale effects, and landscape ecology uncertainty studies.

The inhibitory effect of paeoniflorin on reactive oxygen species alleviates the activation of NF-κB and MAPK signalling pathways in macrophages.

Paeoniflorin (PF) has been proven to possess a protective effect in some inflammatory diseases, but the underlying mechanism remains unclear. Macrophages play central roles in inflammatory responses and LPS-stimulated RAW264.7 macrophage is an ideal model for studying the anti-inflammatory effects and mechanisms of drugs. Thus, it was used to explore the anti-inflammatory mechanism of PF in this study. The results showed that PF markedly attenuated the activation of NF-κB, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen activated protein kinase (p38) signalling pathways induced by LPS exposure. In addition, PF pretreatment dose-dependently suppressed the production of cytokines and the expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Concomitantly, PF pretreatment dramatically inhibited the accumulation of intracellular reactive oxygen species (ROS) without affecting the phagocytosis of macrophages. Furthermore, it has proved the scavenging effect of PF on ROS was involved in the anti-inflammatory process. This study provides a novel aspect to the understanding of the anti-inflammatory mechanism of PF.

Decabromodiphenyl ethane exposure damaged the asymmetric division of mouse oocytes by inhibiting the inactivation of cyclin-dependent kinase 1.

Decabromodiphenyl ethane (DBDPE) is a new brominated flame retardant and is widely added to flammable materials to prevent fire. Because it has been continuously detected in a variety of organisms and humans, it is important to reveal the biological toxicity of DBDPE. However, the influence of DBDPE for female reproduction is unclear. In this study, we investigated whether and how DBDPE exposure affects oocyte development. Female mice as a model were orally exposed to DBDPE by 0, 0.05, 0.5, 5, 50 µg/kg bw/day for 30 days (0.05 µg/kg bw/day is close to the environmental exposure concentration). We found that exposure of mice to DBDPE did not affect the first polar body extrusion (PBE) of oocytes. Strikingly, however, asymmetric division of oocytes was markedly impaired in 5 and 50 µg/kg bw/day DBDPE exposed group, which resulted in oocytes with larger polar bodies (PBs). Then, we further explored and found that DBDPE exposure inhibited the spindle migration and membrane protrusion in oocytes during anaphase of meiosis I (anaphase I), thereby impairing asymmetric division. Additionally, we found that DBDPE exposure suppressed the inactivation of cyclin-dependent kinase 1 (Cdk1), resulting in the decrease of cytoplasmic formin2 (FMN2)-mediated F-actin polymerization in oocytes at the onset of anaphase I. Simultaneously, DBDPE exposure damaged the structural integrity of the spindle and the perpendicular relationship between spindle and cortex. These together led to the failure of spindle migration and membrane protrusion required for oocytes asymmetric division. Finally, DBDPE exposure injured the development of blastocysts, leading to blastocyst apoptosis.

Direct electrochemical generation of supercooled sulfur microdroplets well below their melting temperature.

Supercooled liquid sulfur microdroplets were directly generated from polysulfide electrochemical oxidation on various metal-containing electrodes. The sulfur droplets remain liquid at 155 °C below sulfur's melting point (Tm = 115 °C), with fractional supercooling change (Tm - Tsc)/Tm larger than 0.40. In operando light microscopy captured the rapid merging and shape relaxation of sulfur droplets, indicating their liquid nature. Micropatterned electrode and electrochemical current allow precise control of the location and size of supercooled microdroplets, respectively. Using this platform, we initiated and observed the rapid solidification of supercooled sulfur microdroplets upon crystalline sulfur touching, which confirms supercooled sulfur's metastability at room temperature. In addition, the formation of liquid sulfur in electrochemical cell enriches lithium-sulfur-electrolyte phase diagram and potentially may create new opportunities for high-energy Li-S batteries.

Protective effect of surfactin on copper sulfate-induced inflammation, oxidative stress, and hepatic injury in zebrafish.

Surfactin, an antibacterial peptide, produced by various Bacillus subtilis strains, have broad-spectrum antibacterial and immune-enhancing functions. In this study, we investigated the anti-inflammatory, antioxidant, and hepatoprotective effect of surfactin on zebrafish (Danio rerio) larvae following their exposure to copper sulfate (CuSO4 ). The mature AB wild-type and a transgenic line of zebrafish larvae that expressed enhanced GFP (EGFP) named Tg (Lyz:EGFP) were exposed to 0, 20, 40, and 60 µg/mL surfactin after incubation with 3.2 µg/mL CuSO4 for 2 h from 72 h postfertilization (hpf). Different endpoints, such as migration of GFP-labeled neutrophils, analysis of inflammatory cytokines and transaminases, markers of oxidation, expression of certain genes, and histological changes of liver, were studied to evaluate the function of surfactin. The protein expression levels of NF-κBp65, TNF-α, cyclooxygenase-2 (COX-2), and iNOS were determined in murine macrophage RAW 264.7 cells by western blotting. Our results show that surfactin reduced migration of neutrophils and relieved hepatic injury. In addition, surfactin reduced the index levels of inflammatory factors, oxidative stress response, and improved hepatic function. Surfactin also significantly inhibited the expression of IL-1ß, IL-8, TNF-α, nitric oxide, NF-κBp65, COX-2, and iNOS, and increased the expression of IL-10. Thus, our results demonstrate that surfactin has anti-inflammatory, antioxidant, and hepatoprotective activities. Surfactin has potential as a novel inflammation and immune adjustment.

Lithium metal stripping beneath the solid electrolyte interphase.

Lithium stripping is a crucial process coupled with lithium deposition during the cycling of Li metal batteries. Lithium deposition has been widely studied, whereas stripping as a subsurface process has rarely been investigated. Here we reveal the fundamental mechanism of stripping on lithium by visualizing the interface between stripped lithium and the solid electrolyte interphase (SEI). We observed nanovoids formed between lithium and the SEI layer after stripping, which are attributed to the accumulation of lithium metal vacancies. High-rate dissolution of lithium causes vigorous growth and subsequent aggregation of voids, followed by the collapse of the SEI layer, i.e., pitting. We systematically measured the lithium polarization behavior during stripping and find that the lithium cation diffusion through the SEI layer is the rate-determining step. Nonuniform sites on typical lithium surfaces, such as grain boundaries and slip lines, greatly accelerated the local dissolution of lithium. The deeper understanding of this buried interface stripping process provides beneficial clues for future lithium anode and electrolyte design.

Exposure to Melamine cyanuric acid in adolescent mice caused emotional disorder and behavioral disorder.

Melamine cyanuric acid (MCA) is a flame retardant linked by hydrogen bonds between melamine and cyanuric acid. MCA is used in an excellent series of phosphorus and nitrogen flame retardants. MCA can harm the kidney, liver, testis, and spleen cells. However, the effects of MCA on the emotions and behaviour of adolescent mice have not yet been investigated. In this article, male mice were exposed to MCA at 10, 20, and 40 mg/kg for four weeks. MCA exposure resulted in enhanced mouse locomotor and nocturnal activity. We also observed anxiety-like and depression-like behaviours. Moreover, after MCA exposure, the serum concentrations of thyroid-related hormones were changed, and the mRNA levels were affected. In short, MCA exposure can cause behavioural and emotion disorders.

The toxic effects and possible mechanisms of decabromodiphenyl ethane on mouse oocyte.

Decabromodiphenyl ethane (DBDPE), a widely used new brominated flame retardant, is added into flammable materials to achieve fire retardation. As it is continuously detected in the environment, it has become an emerging environmental pollutant. However, the effects of DBDPE exposure on oocyte maturation and its underlying mechanisms remain unknown. This study found that DBDPE exposure inhibited the rate of germinal vesicle breakdown (GVBD), first polar body extrusion (PBE) and fertilization of mouse oocytes. After 14 h of exposure to DBDPE, metaphase II (MII) oocytes showed that the hardness of zona pellucida (ZP) markedly increased and that the spindle morphology was abnormal. Moreover, DBDPE exposure induced abnormal mitochondrial distribution, mitochondrial dysfunction, and ATP deficiency. Simultaneously, DBDPE exposure down-regulated the expression of antioxidant-related genes (Sod2, Gpx1) and increased the level of reactive oxygen species (ROS) in oocytes. The results of immunofluorescence and qRT-PCR revealed that autophagy occurred in DBDPE-treated oocytes with high expression of autophagy-related protein (LC3) and genes (Lc3, Beclin1). Meanwhile, DBDPE significantly up-regulated the protein (Bax) and mRNA (Bax, Caspase3) levels of pro-apoptosis genes. However, the protein and mRNA expression of anti-apoptosis genes Bcl-2 was dramatically down-regulated in DBDPE-exposed oocytes. Collectively, DBDPE exposure impaired mitochondrial function, causing oxidative damage, autophagy and apoptosis in oocytes.

[Identification of pathogenic variant in a Chinese pedigree affected with non-syndromic cleft lip and palate].

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with non-syndromic cleft lip and cleft palate (NSCLP). METHODS: With informed consent obtained, members of the pedigree were subjected to clinical examination and history taking to exclude syndromic cleft lip and palate. One affected member was subjected to whole-exome sequencing and bioinformatics analysis. Candidate variant was verified by Sanger sequencing and co-segregation analysis of her family members and 100 unrelated healthy individuals. RESULTS: Whole-exome sequencing and co-segregation analysis showed that all affected members of this pedigree have carried a heterozygous missense c.253A>G (p.Cys85Arg) variant in exon 4 of the IRF6 gene, which has co-segregated with the phenotype and was not found among the 100 unrelated healthy individuals. CONCLUSION: The missense c.253A>G variant in exon 4 of the IRF6 gene probably underlay the NSCLP in this pedigree.

Strong texturing of lithium metal in batteries.

Lithium, with its high theoretical specific capacity and lowest electrochemical potential, has been recognized as the ultimate negative electrode material for next-generation lithium-based high-energy-density batteries. However, a key challenge that has yet to be overcome is the inferior reversibility of Li plating and stripping, typically thought to be related to the uncontrollable morphology evolution of the Li anode during cycling. Here we show that Li-metal texturing (preferential crystallographic orientation) occurs during electrochemical deposition, which governs the morphological change of the Li anode. X-ray diffraction pole-figure analysis demonstrates that the texture of Li deposits is primarily dependent on the type of additive or cross-over molecule from the cathode side. With adsorbed additives, like LiNO3 and polysulfide, the lithium deposits are strongly textured, with Li (110) planes parallel to the substrate, and thus exhibit uniform, rounded morphology. A growth diagram of lithium deposits is given to connect various texture and morphology scenarios for different battery electrolytes. This understanding of lithium electrocrystallization from the crystallographic point of view provides significant insight for future lithium anode materials design in high-energy-density batteries.

In Situ X-ray Absorption Spectroscopic Investigation of the Capacity Degradation Mechanism in Mg/S Batteries.

The Mg/S battery is attractive because of its high theoretical energy density and the abundance of Mg and S on the earth. However, its development is hindered by the lack of understanding to the underlying electrochemical reaction mechanism of its charge-discharge processes. Here, using a unique in situ X-ray absorption spectroscopic tool, we systematically study the reaction pathways of the Mg/S cells in Mg(HMDS)2-AlCl3 electrolyte. We find that the capacity degradation is mainly due to the formation of irreversible discharge products, such as MgS and Mg3S8, through a direct electrochemical deposition or a chemical disproportionation of intermediate polysulfide. In light of the fundamental understanding, we propose to use TiS2 as a catalyst to activate the irreversible reaction of low-order MgS x and MgS, which results in an increased discharging capacity up to 900 mAh·g-1 and a longer cycling life.

Vertically Aligned and Continuous Nanoscale Ceramic-Polymer Interfaces in Composite Solid Polymer Electrolytes for Enhanced Ionic Conductivity.

Among all solid electrolytes, composite solid polymer electrolytes, comprised of polymer matrix and ceramic fillers, garner great interest due to the enhancement of ionic conductivity and mechanical properties derived from ceramic-polymer interactions. Here, we report a composite electrolyte with densely packed, vertically aligned, and continuous nanoscale ceramic-polymer interfaces, using surface-modified anodized aluminum oxide as the ceramic scaffold and poly(ethylene oxide) as the polymer matrix. The fast Li+ transport along the ceramic-polymer interfaces was proven experimentally for the first time, and an interfacial ionic conductivity higher than 10-3 S/cm at 0 °C was predicted. The presented composite solid electrolyte achieved an ionic conductivity as high as 5.82 × 10-4 S/cm at the electrode level. The vertically aligned interfacial structure in the composite electrolytes enables the viable application of the composite solid electrolyte with superior ionic conductivity and high hardness, allowing Li-Li cells to be cycled at a small polarization without Li dendrite penetration.

Shell-Protective Secondary Silicon Nanostructures as Pressure-Resistant High-Volumetric-Capacity Anodes for Lithium-Ion Batteries.

The nanostructure design of a prereserved hollow space to accommodate 300% volume change of silicon anodes has created exciting promises for high-energy batteries. However, challenges with weak mechanical stability during the calendering process of electrode fabrication and poor volumetric energy density remain to be solved. Here we fabricated a pressure-resistant silicon structure by designing a dense silicon shell coating on secondary micrometer particles, each consisting of many silicon nanoparticles. The silicon skin layer significantly improves mechanical stability, while the inner porous structure efficiently accommodates the volume expansion. Such a structure can resist a high pressure of over 100 MPa and is well-maintained after the calendering process, demonstrating a high volumetric capacity of 2041 mAh cm-3. In addition, the dense silicon shell decreases the surface area and thus increases the initial Coulombic efficiency. With further encapsulation with a graphene cage, which allows the silicon core to expand within the cage while retaining electrical contact, the silicon hollow structure exhibits a high initial Coulombic efficiency and fast rise of later Coulombic efficiencies to >99.5% and superior stability in a full-cell battery.

Melatonin reduces two-cell block via nonreceptor pathway in mice.

Embryo development block seriously limits the success of in vitro embryo production and assisted reproductive technology. Although numerous researchers have explored this problem, it remains to be solved. In this study, we found that melatonin supplementation at 10-8 and 10-9 M in M16 significantly reduced two-cell block of mouse embryos. When those melatonin-treated four-cell embryos were transplanted into the oviducts of female recipient mice, the litter sizes were significantly increased compared with those of the controls. Mechanism study discovered that melatonin treatment markedly reduced reactive oxygen species and mitochondrial superoxide. Quantitative polymerase chain reaction revealed that melatonin significantly upregulated the transcription of catalase, superoxide dismutase 2, glutathione peroxidase, and the antiapoptotic factors Bcl-2 and Bcl-x while downregulated the transcription of pro-apoptotic genes p53 and Bax. In addition, we found Dux, an important gene which promotes zygotic genome activation, and zygotic genes (zinc finger and SCAN4B and eukaryotic translation initiation factor 1A) were all increased after melatonin treatment. Melatonin membrane receptors have two isoforms, melatonin receptor 1 and 2 (MT1, MT2). Further studies with luzindole (a nonselective MT1 and MT2 antagonist) demonstrated that the beneficial effects of melatonin on reducing two-cell block were not mediated by the melatonin membrane receptors. This study shows that melatonin can be used for improving the embryo quality and production efficiency cultured in vitro and also identifies the underlying mechanism by which melatonin decreases two-cell block.