MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase-anaphase transition by affecting cyclin B1 and Securin stabilization in meiotic oocyte.

Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.

A new isocoumarin derivative from endophytic fungus Pezicula neosporulosa VDB39 from Vaccinium dunalianum.

Four isocoumarin derivatives (1-4) and five phenols (5-9) were obtained from the endophytic fungus Pezicula neosporulosa VDB39, which was isolated from the branches of Vaccinium dunalianum Wight (Ericaceae). Compound 1 is a new derivative of isocoumarin. The structures were elucidated by spectroscopic methods. Single X-ray crystallography confirmed the absolute configuration of compound 1. Additionally, the antiphytopathogenic fungi activity of isocoumarin derivatives (1-4) was evaluated.

Breaking the vitrification limitation of monatomic metals.

The question of whether all materials can solidify into the glassy form proposed by Turnbull half a century ago remains unsolved. Some of the simplest systems of monatomic metals have not been vitrified, especially the close-packed face-centred cubic metals. Here we report the vitrification of gold, which is notoriously difficult to be vitrified, and several similar close-packed face-centred cubic and hexagonal metals using a method of picosecond pulsed laser ablation in a liquid medium. The vitrification occurs through the rapid cooling during laser ablation and the inhibition of nucleation by the liquid medium. Using this method, a large number of atomic configurations, including glassy configurations, can be generated simultaneously, from which a stable glass state can be sampled. Simulations demonstrate that the favourable stability of monatomic metals stems from the strong topological frustration of icosahedra-like clusters. Our work breaks the limitation of the glass-forming ability of matter, indicating that vitrification is an intrinsic property of matter and providing a strategy for the preparation and design of metallic glasses from an atomic configuration perspective.

Novel Alkaloids from Aspergillus fumigatus VDL36, an Endophytic Fungus Associated with Vaccinium dunalianum.

Eleven alkaloids (1-11) including seven new ones, 1-7, were isolated from the solid fermentation of Aspergillus fumigatus VDL36, an endophytic fungus isolated from the leaves of Vaccinium dunalianum Wight (Ericaceae), a perennial evergreen shrub distributed across the Southwest regions of China, Myanmar, and Vietnam. Their structures were elucidated on the basis of extensive spectroscopic methods. The isolates were evaluated for in vitro antifungal activities against five phytopathogenic fungi (Fusarium oxysporum, Coriolus versicolor, Fusarium solani, Botrytis cinerea, Fusarium graminearum). As a result, the new compounds fumigaclavine I (1), 13-ethoxycyclotryprostatin A (5), 13-dehydroxycyclotryprostatin A (6), and 12ß-hydroxy-13-oxofumitremorgin C (7) exhibited antifungal activities with MIC values of 7.8-62.5 µg/mL which were comparable to the two positive controls ketoconazole (MIC = 7.8-31.25 µg/mL) and carbendazim (MIC = 1.95-7.8 µg/mL). Furthermore, compounds 1 and 5 demonstrated potent protective and curative effects against the tomato gray mold in vivo. Preliminary structure-activity relationships of the tested indole diketopiperazine alkaloids indicate that the introduction of a substituent group at position C-13 enhances their biological activities.

The effectiveness of intervention in hepatitis C patients and improvement in their referral rate.

BACKGROUND: To investigate the effectiveness of the intervention with critical value management and push short messaging service (SMS), and to determine improvement in the referral rate of patients with positive hepatitis C antibody (anti-HCV). METHODS: No intervention was done for patients with positive anti-HCV screening results from 1 January 2015 to 31 October 2021. Patients with positive anti-HCV results at our hospital from 1 November 2021 to 31 July 2022 were informed vide critical value management and push SMS. For inpatients, a competent physician was requested to liaise with the infectious disease physician for consultation, and patients seen in the OPD (outpatient department) were asked to visit the liver disease clinic. The Chi-square correlation test, one-sided two-ratio test and linear regression were used to test the relationship between intervention and referral rate. RESULTS: A total of 638,308 cases were tested for anti-hepatitis C virus (HCV) in our hospital and 5983 of them were positive. 51.8% of the referred patients were aged 18-59 years and 10.8% were aged ≥75 years. The result of Chi-square correlation test between intervention and referral was p = .0000, p < .05. One-sided two-ratio test was performed for statistics of pre-intervention referral rate (p1) and post-intervention referral rate (p2). Normal approximation and Fisher's exact test for the results obtained were 0.000, p < .05, and the alternative hypothesis p1 - p2 < 0 was accepted. The linear regression equation was referral = 0.1396 × intervention + 0.3743, and the result model p = 8.79e - 09, p < .05. The model was significant, and the coefficient of intervention was 0.1396. CONCLUSIONS: The interventions of critical value management and push SMS were correlated with the referral rate of patients with positive anti-HCV.

Toonanoronoids A-E, five new limonoids from Toona ciliata var. yunnanensis.

Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.

Histopathological and Immunohistochemical Mechanisms of Bone Marrow-Derived Mesenchymal Stem Cells in Reversion of Gastric Precancerous Lesions.

BACKGROUND: Gastric cancer (GC) stands as one of the most prevalent cancer types worldwide, holding the position of the second leading cause of cancer-related deaths. Gastric lesions represent pathological alterations to the gastric mucosa, with an elevated propensity to advance to gastric cancer. Limited research has explored the potential of stem cells in the treatment of gastric lesions. METHODS: This study aimed to explore the potential of intravenous transplantation of labeled bone marrow-derived mesenchymal stem cells (BMMSCs) to inhibit the progression of precancerous gastric lesions. RESULTS: In the gastric lesion disease model group, the rat tissue exhibited noteworthy mucosal atrophy, intestinal metaplasia, dysplasia, and inflammatory cell infiltration. Following the infusion of BMMSCs, a notable decrease in gastric lesions was found, with atrophic gastritis being the sole remaining lesion, which was confirmed by morphological and histological examinations. BMMSCs that were colonized at gastric lesions could differentiate into epithelial and stromal cells, as determined by the expression of pan-keratin or vimentin. The expression of vascular endothelial growth factor was significantly elevated following BMMSC transplantation. BMMSCs could also upregulate the production of humoral immune response cytokines, including interleukin (IL)-4 and IL-10, and downregulate the production of IL-17 and interferon-gamma, which could be highly associated with the cellular immune response and inflammation severity of the lesions. CONCLUSIONS: BMMSC transplantation significantly reduced inflammation and reversed gastric lesion progression.

Electronic structures and quantum capacitance of twisted bilayer graphene with defects based on three-band tight-binding model.

Twisted bilayer graphene (tBLG) with C vacancies would greatly improve the density of states (DOS) around the Fermi level (EF) and quantum capacitance; however, the single-band tight-binding model only considering pz orbitals cannot accurately capture the low-energy physics of tBLG with C vacancies. In this work, a three-band tight-binding model containing three p orbitals of C atoms is proposed to explore the modulation mechanism of C vacancies on the DOS and quantum capacitance of tBLG. We first obtain the hopping integral parameters of the three-band tight-binding model, and then explore the electronic structures and the quantum capacitance of tBLG at a twisting angle of θ = 1.47° under different C vacancy concentrations. The impurity states contributed by C atoms with dangling bonds located around the EF and the interlayer hopping interaction could induce band splitting of the impurity states. Therefore, compared with the quantum capacitance of pristine tBLG (∼18.82 µF cm-2) at zero bias, the quantum capacitance is improved to ∼172.76 µF cm-2 at zero bias, and the working window with relatively large quantum capacitance in the low-voltage range is broadened in tBLG with C vacancies due to the enhanced DOS around the EF. Moreover, the quantum capacitance of tBLG is further increased at zero bias with an increase of the C vacancy concentration induced by more impurity states. These findings not only provide a suitable multi-band tight-binding model to describe tBLG with C vacancies but also offer theoretical insight for designing electrode candidates for low-power consumption devices with improved quantum capacitance.

Interventing mitochondrial PD-L1 suppressed IFN-γ-induced cancer stemness in hepatocellular carcinoma by sensitizing sorafenib-induced ferroptosis.

Evidence recently showed that pleiotropic cytokine interferon-gamma (IFN-γ) in the tumor microenvironment (TME) plays a positive role in hepatocellular carcinoma (HCC) progression through the regulation of liver cancer stem cells (LCSCs) in HCC. The present study explored the role and potential mechanism of mitochondrial programmed cell death-ligand 1 (PD-L1) and its regulation of ferroptosis in modulating the cancer stemness of LCSCs. It was shown that mimicking TME IFN-γ exposure increased the LCSCs ratio and cancer stemness phenotypes in HCC cells. IFN-γ exposure inhibited sorafenib (Sora)-induced ferroptosis by enhancing glutathione peroxidase 4 (GPX4) expression as well reactive oxygen species (ROS) and lipid peroxidation (LPO) generation in LCSCs. Furthermore, IFN-γ exposure upregulated PD-L1 expression and its mitochondrial translocation, inducing dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and correlating with glycolytic metabolism reprogramming in LCSCs. The genetic intervention of PD-L1 promoted ferroptosis-dependent anti-tumor effects of Sora, reduced glycolytic metabolism reprogramming, and inhibited cancer stemness of HCC in vitro and in vivo. Our results revealed a novel mechanism that IFN-γ exposure-induced mitochondrial translocation of PD-L1 enhanced glycolytic reprogramming to mediate the GPX4-dependent ferroptosis resistance and cancer stemness in LCSCs. This study provided new insights into the role of mitochondrial PD-L1-Drp1-GPX4 signal axis in regulating IFN-γ exposure-associated cancer stemness in LCSCs and verified that PD-L1-targeted intervention in combination with Sora might achieve promising synergistic anti-HCC effects.

Observation of an isothermal glass transition in metallic glasses.

Glass transition, commonly manifested upon cooling a liquid, is continuous and cooling rate dependent. For decades, the thermodynamic basis in liquid-glass transition has been at the center of debate. Here, long-time isothermal annealing was conducted via molecular dynamics simulations for metallic glasses to explore the connection of physical aging in supercooled liquid and glassy states. An anomalous two-step aging is observed in various metallic glasses, exhibiting features of supercooled liquid dynamics in the first step and glassy dynamics in the second step, respectively. Furthermore, the transition potential energy is independent of initial states, proving that it is intrinsic for a metallic glass at a given temperature. We propose that the observed dynamic transition from supercooled liquid dynamics to glassy dynamics could be glass transition manifested isothermally. On this basis, glass transition is no longer cooling rate dependent, but is shown as a clear phase boundary in the temperature-energy phase diagram. Hence, a modified out-of-equilibrium phase diagram is proposed, providing new insights into the nature of glass transition.

Determining the Electron Scattering from Interfacial Coulomb Scatterers in Two-Dimensional Transistors.

Two-dimensional (2D) transistors are promising for potential applications in next-generation semiconductor chips. Owing to the atomically thin thickness of 2D materials, the carrier scattering from interfacial Coulomb scatterers greatly suppresses the carrier mobility and hampers transistor performance. However, a feasible method to quantitatively determine relevant Coulomb scattering parameters from interfacial long-range scatterers is largely lacking. Here, we demonstrate a method to determine the Coulomb scattering strength and the density of Coulomb scattering centers in InSe transistors by comprehensively analyzing the low-frequency noise and transport characteristics. Moreover, the relative contributions from long-range and short-range scattering in the InSe transistors can be distinguished. This method is employed to make InSe transistors consisting of various interfaces a model system, revealing the profound effects of different scattering sources on transport characteristics and low-frequency noise. Quantitatively accessing the scattering parameters of 2D transistors provides valuable insight into engineering the interfaces of a wide spectrum of ultrathin-body transistors for high-performance electronics.

Above-Room-Temperature Ferromagnetism in Copper-Doped Two-Dimensional Chromium-Based Nanosheets.

Two-dimensional ferromagnetic materials (2D-FMs) are expected to become ideal candidates for low-power, high-density information storage in next-generation spintronics devices due to their atomically ultrathin and intriguing magnetic properties. However, 2D-FMs with room-temperature Curie temperatures (Tc) are still rarely reported, which greatly hinders their research progress and practical applications. Herein, ultrathin Cu-doped Cr7Te8 FMs were successfully prepared and can achieve above-room-temperature ferromagnetism with perpendicular magnetic anisotropy via a facile chemical vapor deposition (CVD) method, which can be controlled down to an atomic thin layer of ∼3.4 nm. STEM-EDX quantitative analysis shows that the proportion of Cu to metal atoms is ∼5%. Moreover, based on the anomalous Hall effect (AHE) measurements in a six-terminal Hall bar device without any encapsulation as well as an out-of-plane magnetic field, the maximum Tc achieved ∼315 K when the thickness of the sample is ∼28.8 nm; even the ultrathin 7.6 nm sample possessed a near-room-temperature Tc of ∼275 K. Meanwhile, theoretical calculations elucidated the mechanism of the ferromagnetic enhancement of Cu-doped Cr7Te8 nanosheets. More importantly, the ferromagnetism of CVD-synthesized Cu-doped CrSe nanosheets can also be maintained above room temperature. Our work broadens the scope on room-temperature ferromagnets and their heterojunctions, promoting fundamental research and practical applications in next-generation spintronics.

High-temperature magnetically topological candidate material Mn3Bi2Te6.

The Mn-Bi-Te family displaying magnetism and non-trivial topological properties has received extensive attention. Here, we predict that the antiferromagnetic structure of Mn3Bi2Te6with three MnTe layers is energetically stable and the magnetic energy difference of Mn-Mn is enhanced four times compared with that in the single MnTe layer of MnBi2Te4. The predicted Néel transition point is raised to 102.5 K, surpassing the temperature of liquid nitrogen. The topological properties show that with the variation of the MnTe layer from a single layer to three layers, the system transforms from a non-trivial topological phase to a trivial topological phase. Interestingly, the ferromagnetic state of Mn3Bi2Te6is a topological semimetal and it exhibits a topological transition from trivial to non-trivial induced by the magnetic transition. Our results enrich the Mn-Bi-Te family system, offer a new platform for studying topological phase transitions, and pave a new way to improve the working temperature of magnetically topological devices.

Geological timescales' aging effects of lunar glasses.

Physical aging is a long-lasting research hot spot in the glass community, yet its long-term effects remain unclear because of the limited experimental time. In this study, we discover the extraordinary aging effects in five typical lunar glassy particles with diameters ranging from about 20 to 53 micrometers selected from Chang'e-5 lunar regolith. It is found that geological time scales' aging can lead to unusually huge modulus enhancements larger than 73.5% while much weaker effects on hardness (i.e., varies decoupling evolutions of Young's modulus and hardness during aging) in these lunar glassy samples. Such extraordinary aging effects are primarily attributed to the natural selected complex glassy compositions and structures, consistent with high entropy and minor element doping criteria, prevailing under the special lunar conditions and the extensive aging time for the lunar glasses. This study offers valuable insights for developing high-performance and stable glassy materials for radiation protection and advanced space explorations.

Identification of an LDLR variant in a Chinese familial hypercholesterolemia and its relation to ROS/NLRP3-Mediated pyroptosis in hepatic cells.

BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant hereditary disease. Its early diagnosis and intervention significantly improve the patient's quality of life. However, there are few types of research on the FH pathogenic genes in China. METHODS: In this study, we recruited a family diagnosed with FH and used whole exome sequencing (WES) to analyze the proband variants. Intracellular cholesterol level, reactive oxygen species (ROS) level, and the expression of pyroptosis-related genes were detected after overexpression of wild-type or variant LDLR in L02 cells. RESULTS: A heterozygous missense variant predicted to be deleterious to LDLR (c.1879G > A, p.Ala627Thr) was identified in the proband. Mechanistically, intracellular cholesterol level, ROS level, and the expression of pyroptosis-related genes, nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3), gasdermin D (GSDMD), interleukin (IL) -18, IL-1ß was elevated in the variant LDLR group, which was attenuated by inhibition of ROS. CONCLUSIONS: FH is associated with a variant (c.1879G>A, p.Ala627Thr) in the LDLR gene. Regarding the mechanism, the ROS/NLRP3-mediated pyroptosis in hepatic cells may contribute to the pathogenesis of the LDLR variant.

Thermal Expansion Neutralization Enhancing the Cycling Stability of Ni-Rich LiNi0.6Co0.2Mn0.2O2 Cathode Material.

As promising cathode candidates with advantageous capacity and price superiority for lithium-ion batteries, Ni-rich materials are severely impeded in the practical application due to their poor microstructural stability induced by the intrinsic Li+/Ni2+ cation mixing and mechanical stress accumulation upon cycling. In this work, a synergetic approach is demonstrated to improve the microstructural and thermal stabilities of Ni-rich LiNi0.6Co0.2Mn0.2O2 (NCM622) cathode material through taking advantage of the thermal expansion offset effect of the LiZr2(PO4)3 (LZPO) modification layer. The optimized NCM622@LZPO cathode exhibits a significantly enhanced cyclability with a capacity retention of 67.7% after 500 cycles at 0.2 C and delivers a specific capacity of 115 mAh g-1 with a capacity retention of 64.2% after 300 cycles under 55 °C. Exploiting the chemical environment analysis of the Ni element detected by the synchrotron radiation technique, it is found that the mixing degree of Li+/Ni2+ cations in the bulk Ni-rich material can be effectively depressed through interfacial Zr4+ doping during the preparation of the LZPO-modified material. Additionally, time- and temperature-dependent powder diffraction spectra were collected to monitor the structure evolutions of pristine NCM622 and NCM622@LZPO cathodes in the initial cycles and under various temperatures, revealing the contribution of negative thermal expansion LZPO coating in promoting microstructural stability of the bulk NCM622 cathode. The introduction of NTE functional compounds might provide a universal strategy to address the stress accumulation and volume expansion issues of various cathode materials for advanced secondary-ion batteries.

Topology of vibrational modes predicts plastic events in glasses.

The plastic deformation of crystalline materials can be understood by considering their structural defects such as disclinations and dislocations. Although also glasses are solids, their structure resembles closely the one of a liquid and hence the concept of structural defects becomes ill-defined. As a consequence it is very challenging to rationalize on a microscopic level the mechanical properties of glasses close to the yielding point and to relate plastic events to structural properties. Here we investigate the topological characteristics of the eigenvector field of the vibrational excitations of a two-dimensional glass model, notably the geometric arrangement of the topological defects as a function of vibrational frequency. We find that if the system is subjected to a quasistatic shear, the location of the resulting plastic events correlate strongly with the topological defects that have a negative charge. Our results provide thus a direct link between the structure of glasses prior their deformation and the plastic events during deformation.

High-risk HPV prevalence and genotype distribution among women in Liaocheng, Shandong Province, China from 2016 to 2022.

Human papilloma virus (HPV) infection and its associated disease are major problems affecting millions of individuals around the world. The distribution of HPV genotypes is specific to different areas and different populations. Therefore, understanding the prevalence and genotype distribution of HPV in different populations in different geographical regions is essential to optimize HPV vaccination strategies and to maximize vaccine effects. In this study, 34,076 women from January 2016 to July 2022 were retrospectively analyzed at Liaocheng People's Hospital. Of these, 7540 women were high-risk HPV positive and the infection rate was 22.13%. The top ten genotypes were as follows in descending order: HPV16, HPV52, HPV58, HPV53, HPV39, HPV59, HPV66, HPV51, HPV18, and HPV56 and the least frequent genotypes were, in order, HPV 26, HPV45, and HPV82. The HPV16 positive infection rate was 25.37% and was reduced with the increase in the number of individuals who had undergone HPV screening. The HPV52 infection rate increased with increasing numbers of individuals undergoing HPV screening, and then remained unchanged. The proportion of 20-29-year-olds among all positive women began to decrease since the vaccine was available in 2018. The 30-39-year-old group accounted for the highest percentage of positive women, and the 50-59-year-old group of HPV-positive women with cervical cancer accounted for most infections. This study confirmed that HPV16, HPV52, HPV 58, and HPV53 is widely distributed in this population and the total HR-HPV infection rate remains high in this region. Our findings indicate that prevention of HPV infection in this region still faces important challenges.

Pressure-Induced Structural Phase Transition and Enhanced Interlayer Coupling in Two-Dimensional Ferromagnet CrSiTe3.

The two-dimensional van der Waals ferromagnetic semiconductor CrSiTe3 has attracted growing interest as an intrinsic topological magnet. Both superconductivity and enhancement of ferromagnetism, usually competing for orders, have been observed in CrSiTe3 at high pressure. However, the high-pressure structure of CrSiTe3 is still unclear, setting obstacles in understanding pressure-induced novel physics. Here, combining the Raman spectra and first-principles calculations, the structure of CrSiTe3 at high pressure has been clarified. The interlayer breathing mode located at ∼42.1 cm-1 has been observed for the first time in CrSiTe3 by ultralow-frequency Raman spectroscopy at high pressure. Theoretical calculations confirm a phase transition from the R3̅ phase to the R3 phase accompanying noticeable enhancement of the Curie temperature. Our results highlight ultralow-frequency Raman spectroscopy combined with high pressure for detecting and modulating the structure and interlayer coupling of two-dimensional materials.

Distinct relaxation mechanism at room temperature in metallic glass.

How glasses relax at room temperature is still a great challenge for both experimental and simulation studies due to the extremely long relaxation time-scale. Here, by employing a modified molecular dynamics simulation technique, we extend the quantitative measurement of relaxation process of metallic glasses to room temperature. Both energy relaxation and dynamics, at low temperatures, follow a stretched exponential decay with a characteristic stretching exponent ß = 3/7, which is distinct from that of supercooled liquid. Such aging dynamics originates from the release of energy, an intrinsic nature of out-of-equilibrium system, and manifests itself as the elimination of defects through localized atomic strains. This finding is also supported by long-time stress-relaxation experiments of various metallic glasses, confirming its validity and universality. Here, we show that the distinct relaxation mechanism can be regarded as a direct indicator of glass transition from a dynamic perspective.