MCM8 interacts with DDX5 to promote R-loop resolution.

MCM8 has emerged as a core gene in reproductive aging and is crucial for meiotic homologous recombination repair. It also safeguards genome stability by coordinating the replication stress response during mitosis, but its function in mitotic germ cells remains elusive. Here we found that disabling MCM8 in mice resulted in proliferation defects of primordial germ cells (PGCs) and ultimately impaired fertility. We further demonstrated that MCM8 interacted with two known helicases DDX5 and DHX9, and loss of MCM8 led to R-loop accumulation by reducing the retention of these helicases at R-loops, thus inducing genome instability. Cells expressing premature ovarian insufficiency-causative mutants of MCM8 with decreased interaction with DDX5 displayed increased R-loop levels. These results show MCM8 interacts with R-loop-resolving factors to prevent R-loop-induced DNA damage, which may contribute to the maintenance of genome integrity of PGCs and reproductive reserve establishment. Our findings thus reveal an essential role for MCM8 in PGC development and improve our understanding of reproductive aging caused by genome instability in mitotic germ cells.

Adjusting Li+ Solvation Structures via Dipole-Dipole Interaction to Construct Inorganic-Rich Interphase for High-Performance Li Metal Batteries.

Practical applications of lithium metal batteries are limited by unstable solid electrolyte interphase (SEI) and uncontrollable dendrite Li deposition. Regulating the solvation structure of Li+ via modifying electrolyte components enables optimizing the structure of the SEI and realizing dendrite-free Li deposition. In this work, it is found that the ionic-dipole interactions between the electron-deficient B atoms in lithium oxalyldifluoro borate (LiDFOB) and the O atoms in the DME solvent molecule can weaken the interaction between the DME molecule and Li+, accelerating the desolvation of Li+. On this basis, the ionic-dipole interactions facilitate the entry of abundant anions into the inner solvation sheath of Li+, which promotes the formation of inorganic-rich SEI. In addition, the interaction between DFOB- and DME molecules reduces the highest occupied molecular orbital energy level of DME molecules in electrolytes, which improves the oxidative stability of the electrolytes system. As a result, the Li||Li cells in LiDFOB-containing electrolytes exhibit an excellent cyclability of over 1800 h with a low overpotential of 18.2 mV, and the Li||LiFePO4 full cells display a high-capacity retention of 93.4% after 100 cycles with a high Coulombic efficiency of 99.3%.

2D MXene/MBene Superlattice with Narrow Bandgap as Superior Electrocatalyst for High-Performance Lithium-Oxygen Battery.

Lithium-oxygen (Li-O2) battery with large theoretical energy density (≈3500 Wh kg-1) is one of the most promising energy storage and conversion systems. However, the slow kinetics of oxygen electrode reactions inhibit the practical application of Li-O2 battery. Thus, designing efficient electrocatalysts is crucial to improve battery performance. Here, Ti3C2 MXene/Mo4/3B2-x MBene superlattice is fabricated its electrocatalytic activity toward oxygen redox reactions in Li-O2 battery is studied. It is found that the built-in electric field formed by a large work function difference between Ti3C2 and Mo4/3B2-x will power the charge transfer at the interface from titanium (Ti) site in Ti3C2 to molybdenum (Mo) site in Mo4/3B2-x. This charge transfer increases the electron density in 4d orbital of Mo site and decreases the d-band center of Mo site, thus optimizing the adsorption of intermediate product LiO2 at Mo site and accelerating the kinetics of oxygen electrode reactions. Meanwhile, the formed film-like discharge products (Li2O2) improve the contact with electrode and facilitate the decomposition of Li2O2. Based on the above advantages, the Ti3C2 MXene/Mo4/3B2-x MBene superlattice-based Li-O2 battery exhibits large discharge specific capacity (17 167 mAh g-1), low overpotential (1.16 V), and superior cycling performance (475 cycles).

Optimized Lithium Ion Coordination via Chlorine Substitution to Enhance Ionic Conductivity of Garnet-Based Solid Electrolytes.

Garnet-type solid-state electrolytes attract abundant attentions due to the broad electrochemical window and remarkable thermal stability while their poor ionic conductivity obstructs their widespread application in all-solid-state batteries. Herein, the enhanced ionic conductivity of garnet-type solid electrolytes is achieved by partially substituting O2- sites with Cl- anions, which effectively reduce Li+ migration barriers while preserving the highly conductive cubic phase of garnet-type solid-state electrolytes. This substitution not only weakens the anchoring effect of anions on Li+ to widen the size of Li+ diffusion channel but also optimizes the occupancy of Li+ at different sites, resulting in a substantial reduction of the Li+ migration barrier and a notable improvement in ionic conductivity. Leveraging these advantageous properties, the developed Li6.35La3Zr1.4Ta0.6O11.85-Cl0.15 (LLZTO-0.15Cl) electrolyte demonstrates high Li+ conductivity of 4.21×10-6 S cm-1. When integrated with LiFePO4 (LFP) cathode and metallic lithium anode, the LLZTO-0.15Cl electrolyte enables the solid-state battery to operate for more than 100 cycles with a high capacity retention of 76.61% and superior Coulombic efficiency of 99.48%. This work shows a new strategy for modulating anionic framework to enhance the conductivity of garnet-type solid-state electrolytes.

Ultrasound-Activated NIR Chemiluminescence for Deep Tissue and Tumor Foci Imaging.

Fluorescence imaging requires real-time external light excitation; however, it has the drawbacks of autofluorescence and shallower penetration depth, limiting its application in deep tissue imaging. At the same time, ultrasound (US) has high spatiotemporal resolution, deep penetrability, noninvasiveness, and precise localization of lesions; thus, it can be a promising alternative to light. However, US-activated luminescence has been rarely reported. Herein, an US-activated near-infrared (NIR) chemiluminescence (CL) molecule, namely, PNCL, is designed by protoporphyrin IX as a sonosensitizer moiety and a phenoxy-dioxetane precursor containing a dicyanomethyl chromone acceptor scaffold (NCL) as the US-responsive moiety. After therapeutic US radiation (1 MHz), the singlet oxygen (1O2), as an "intermediary", oxidizes the enol-ether bond of the NCL moiety and then emits NIR light via spontaneous decomposition. Combining the deep penetrability of US with a high signal-to-background ratio of NIR CL, the designed probe PNCL successfully realizes US-activated deep tissue imaging (∼20 mm) and selectively turns on signals in specific tumor foci. Bridging US chemistry with luminescence using an "intermediary" will provide new imaging methods for accurate cancer diagnosis.

The Aux/IAA protein TaIAA15-1A confers drought tolerance in Brachypodium by regulating abscisic acid signal pathway.

KEY MESSAGE: Overexpression of the Aux/IAA protein TaIAA15-1A from wheat improves drought tolerance by regulating the ABA signalling pathway in transgenic Brachypodium. Drought is a major abiotic stress that causes severe crop yield loss. Aux/IAA genes have been shown to be involved in drought stress responses. However, to the best of our knowledge, there has been little research on the molecular mechanism of the wheat Aux/IAA gene in the context of drought tolerance. In this study, we found that expression of the wheat Aux/IAA gene TaIAA15-1A was upregulated by PEG6000, NaCl, SA, JA, IAA and ABA. Transgenic plants overexpressing TaIAA15-1A showed higher drought tolerance than wild-type (WT) plants. The physiological analyses showed that the transgenic lines exhibited a higher survival rate, shoot length, and relative water content than the WT plants. The activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were enhanced in transgenic lines, causing a reduction in the hydrogen peroxide (H2O2) and superoxide anion radical (O2-) contents. Transcriptome analysis showed that TaIAA15-1A overexpression alters the expression of these genes involved in the auxin signalling pathway, ABA signalling pathway, phenolamides and antioxidant pathways. The results of exogenous ABA treatment suggested that TaIAA15-1A overexpression increased sensitivity to ABA at the germination and postgermination stages compared to WT plants. These results indicate that TaIAA15-1A plays a positive role in plant drought tolerance by regulating ABA-related genes and improving antioxidative stress ability and has potential application in genetically modified crops.

The Modulation of Sucrose Nonfermenting 1-Related Protein Kinase 2.6 State by Persulfidation and Phosphorylation: Insights from Molecular Dynamics Simulations.

SnRK2.6 (SUCROSE NONFERMENTING 1-RELATED PROTEIN KINASE2.6) has been characterized as a molecular switch for the intracellular abscisic acid (ABA) signal-transduction pathway. Normally, SnRK2.6 is kept in an "off" state, forming a binary complex with protein phosphatase type 2Cs (PP2Cs). Upon stressful conditions, SnRK2.6 turns into an "on" state by its release from PP2Cs and then phosphorylation at Ser175. However, how the "on" and "off" states for SnRK2.6 are fine-tuned, thereby controlling the initiation and braking processes of ABA signaling, is still largely unclear. SnRK2.6 activity was tightly regulated through protein post-translational modifications (PTM), such as persulfidation and phosphorylation. Taking advantage of molecular dynamics simulations, our results showed that Cys131/137 persulfidation on SnRK2.6 induces destabilized binding and weakened interactions between SnRK2.6 and HAB1 (HYPERSENSITIVE TO ABA1), an important PP2C family protein. This unfavorable effect on the association of the SnRK2.6-HAB1 complex suggests that persulfidation functions are a positive regulator of ABA signaling initiation. In addition, Ser267 phosphorylation in persulfidated SnRK2.6 renders a stable physical association between SnRK2.6 and HAB1, a key characterization for SnRK2.6 inhibition. Rather than Ser175, HAB1 cannot dephosphorylate Ser267 in SnRK2.6, which implies that the retained phosphorylation status of Ser267 could ensure that the activated SnRK2.6 reforms the binary complex to cease ABA signaling. Taken together, our findings expand current knowledge concerning the regulation of persulfidation and phosphorylation on the state transition of SnRK2.6 and provide insights into the fine-tuned mechanism of ABA signaling.

Characteristics and pollution risks of potentially toxic elements and nematode community structure on farm soil near coal mines.

As one of the most important coal-producing provinces of China, Shanxi Province has been concerned about soil potentially toxic elements (PTEs) contamination in recent years. The study aimed to determine the status and sources of PTEs contamination and evaluate the quality of the soil ecology. This study investigated the degree of 13 PTEs contamination. The sources and contributions of PTEs were traced by the absolute principal component score followed by a multiple linear regression model (APCS-MLR). And the status of the soil ecosystem was verified by evaluating the soil nematode community around the coal mining areas in Jinzhong. The results showed that the mean PTEs concentration of 5 trace elements were higher than the background values of Shanxi, and safe to considerable was indicated by the pollution and ecological risk values. Soil Hg was the most contaminated element, followed by Cd. The distribution of PTEs was determined by coal mining activities (44.72%) followed by agricultural practice (32.37%) and coal transportation (21.37%). The nematode genera Acrobeloides (4.01%), Aphelenchus (20.30%), Meloidogyne (11.95%) and Aporcelaimus (2.74%) could be regarded as bioindicators of soil PTEs contamination by their tolerance. Concentrations of soil Cr, Mn, Ti and Cd showed remarkable influences on the total nematode abundance, maturity index, enrichment index, structural index, Shannon-Wiener diversity index and Pielou index of soil nematode. It is an appropriate method to evaluate the status of soil PTEs contamination combining the response of a single nematode genus and the nematode community evaluation index.

Low-dose florfenicol and copper combined exposure during early life induced health risks by affecting gut microbiota and metabolome in SD rats.

The potential health risks associated with simultaneous presence of residues of heavy metals and antibiotics in the environment and food have been of wide concern. However, the adverse health effects of combined heavy metal and antibiotic exposure at low doses remain unclear. In this study, the effects of combined exposure to florfenicol and copper at low doses during early life on toxicity, gut microbiota, drug resistance genes, and the fecal metabolome were investigated in Sprague-Dawley (SD) rats. The results showed that combined exposure induced inflammatory responses and visceral injury as well as faster weight gain compared with florfenicol or copper exposure alone. Alpha and beta diversity indices indicated that the composition of the gut microbiota and the abundance of bacteria related to energy intake and disease in the combined exposure group were significantly altered. The increase in resistance genes (floR, fexA) induced by florfenicol exposure was suppressed under combined exposure to florfenicol and copper. The fecal metabolome also demonstrated that metabolic pathways related to energy intake and liver injury were significantly affected in the combined exposure group. In conclusion, this study shows that combined exposure to florfenicol and copper during early life can pose a nonnegligible health risk even if the exposure concentration of florfenicol or copper is below the safe limit.

Hydrogen Sulfide-Linked Persulfidation Maintains Protein Stability of ABSCISIC ACID-INSENSITIVE 4 and Delays Seed Germination.

Hydrogen sulfide (H2S) is an endogenous gaseous molecule that plays an important role in the plant life cycle. The multiple transcription factor ABSCISIC ACID INSENSITIVE 4 (ABI4) was precisely regulated to participate in the abscisic acid (ABA) mediated signaling cascade. However, the molecular mechanisms of how H2S regulates ABI4 protein level to control seed germination and seedling growth have remained elusive. In this study, we demonstrated that ABI4 controls the expression of L-CYSTEINE DESULFHYDRASE1 (DES1), a critical endogenous H2S-producing enzyme, and both ABI4 and DES1-produced H2S have inhibitory effects on seed germination. Furthermore, the ABI4 level decreased during seed germination while H2S triggered the enhancement of the persulfidation level of ABI4 and alleviated its degradation rate, which in turn inhibited seed germination and seedling establishment. Conversely, the mutation of ABI4 at Cys250 decreased ABI4 protein stability and facilitated seed germination. Moreover, ABI4 degradation is also regulated via the 26S proteasome pathway. Taken together, these findings suggest a molecular link between DES1 and ABI4 through the post-translational modifications of persulfidation during early seedling development.

Metal-Organic Frameworks for Electrocatalytic Sensing of Hydrogen Peroxide.

The electrochemical detection of hydrogen peroxide (H2O2) has become more and more important in industrial production, daily life, biological process, green energy chemistry, and other fields (especially for the detection of low concentration of H2O2). Metal organic frameworks (MOFs) are promising candidates to replace the established H2O2 sensors based on precious metals or enzymes. This review summarizes recent advances in MOF-based H2O2 electrochemical sensors, including conductive MOFs, MOFs with chemical modifications, MOFs-composites, and MOF derivatives. Finally, the challenges and prospects for the optimization and design of H2O2 electrochemical sensors with ultra-low detection limit and long-life are presented.

Changes in asphericity of anterior and posterior corneal surfaces for mild-moderate and high myopia after topography-guided FS-LASIK.

PURPOSE: To compare changes in asphericity of anterior and posterior corneal surfaces for different myopia patients after corneal topography-guided femtosecond-assisted laser in situ keratomileuses (FS-LASIK), and to analyze correlations between asphericity of corneal surfaces and preoperative spherical equivalence (SEQ). METHODS: In this prospective study, 59 patients who underwent corneal topography-guided FS-LASIK surgery were enrolled and divided into the mild-moderate myopia group (67 eyes) and the high myopia group (44 eyes). Postoperative follow-ups were performed at 1, 3, and 6 months. Postoperative changes in aspherical coefficient (Q values), corneal higher-order aberrations (HOAs), and spherical aberrations (Z40) were compared between the two groups. Relevance between Q value changes and SEQ, HOAs, and Z40 as well as between SEQ and changes of HOAs and Z40 was analyzed. RESULTS: There was a significant increase in Q values of the anterior (each diameter) and posterior (6-8 mm) corneal surface in both groups than before surgery (P < 0.001). Q values of corneal anterior (each diameter) and posterior (7-9 mm) surface in the high group were considerably larger than the mild-moderate group (P < 0.05). Corneal anterior surface HOAs and Z40 values in the high group largely exceeded those of the mild-moderate group (P < 0.001). The preoperative SEQ was linearly correlated with postoperative anterior Q change (ΔQ), HOAs change (ΔHOAs), and spherical aberration change (ΔZ40). CONCLUSION: The changes of corneal asphericity in patients with high myopia were greater than mild-moderate myopia, with more corneal HOAs and Z40 introduced when corneal topography-guided FS-LASIK was conducted.

[Study on Characterization and Content Determination Method of Silver in Chitosan Antibacterial Gel].

OBJECTIVE: To characterize the silver in chitosan antibacterial gel, and to establish a method for the determination of silver content in samples. METHODS: The silver in the samples was analysed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and single particle inductively coupled plasma mass spectrometry (SP-ICP-MS). Microwave digestion was adopted to digest the chitosan antibacterial gel, and then the content of silver was determined by flame atomic absorption spectrometry. RESULTS: The analysises showed that the particle size of silver in chitosan antibacterial gel was about 150~ 200 nm. The silver showed good linearity in the concentration range of 25~250 µg/L (y=0.000 35x+0.001 7, r=0.999 9). The recovery rate (n=9) was 98.5%. CONCLUSIONS: SEM, EDS and SP-ICP-MS can be used for the characterization of silver particles in chitosan antibacterial gel. Microwave digestion-flame atomic absorption spectrophotometry method is simple, practicable, high precision and high quantitative accuracy, which is suitable for the quantitative analysis of silver in chitosan antibacterial gel.

[In Vitro Fatigue Test of Lung Volume Reduction Loop].

Lung volume reduction loop uses bronchoscopic lung volume reduction(BLVR) technology to compress and collapse the necrotic emphysema tissue and exhaust the internal gas to achieve the purpose of lung volume reduction to treat emphysema. After the lung volume reduction loop is implanted into the human body, the compressed part of the lung tissue tends to expand with breathing, which makes the lung volume reduction loop expand into a linear trend periodically. Fatigue resistance is one of the most important performance indexes of the lung volume reduction loop. In the paper, Z-direction vibration fatigue machine was used to simulate the changes of human respiratory cycle movement to test the fatigue performance of lung volume reduction loop, which can provide some reference for the test method of in vitro fatigue performance of lung volume reduction related products in the future.

Relationships between leaf δ15 N and leaf metallic nutrients.

RATIONALE: Nitrogen (N) isotopic ratios (δ15 N values) of plants are primarily determined by the δ15 N values of their N sources. Metallic nutrients affect plant N uptake. However, there is little knowledge of the relationships between leaf δ15 N values and leaf metallic nutrients. The δ15 N values are often lower in soil nitrate (NO3 - ) than in ammonium (NH4 + ) due to large isotopic fractionation during nitrification. Plants acquire more NO3 - than NH4 + when accumulating high potassium (K), calcium (Ca) and magnesium (Mg) to maintain charge balance. In addition, plants that absorb more NO3 - than NH4 + increase the soil pH and decrease the availability of iron (Fe), manganese (Mn) and zinc (Zn). We therefore hypothesized that leaf δ15 N values correlate negatively with K, Ca and Mg contents, while positively with Fe, Mn and Zn contents. METHODS: Leaves of non-N-fixing plants were sampled across an approx. 6000 km transect in China and their δ15 N values and metallic nutrient content were determined using elemental analyzer/isotope ratio mass spectrometry. RESULTS: Inconsistent with the hypothesis, leaf δ15 N values correlated positively with leaf K, Ca and Mg, indicating higher δ15 N values of soil NO3 - than NH4 + . Higher δ15 N values of soil NO3 - revealed stronger denitrification than nitrification in the study regions because isotopic fractionation occurs during both processes. Leaf δ15 N values correlated negatively with Fe, relating to decreases in soil Fe availability, which might be attributed to oxidation of Fe2+ to Fe3+ supplying electrons for denitrification, while greater uptake of NO3 - than NH4 + of plants increases soil pH. Leaf δ15 N values correlated positively with Zn and did not correlate with Mn. These observed relationships between leaf δ15 N values and metallic nutrients, except Mn, were independent of vegetation or soil types. CONCLUSIONS: This study has enriched our knowledge of associations between metallic nutrients and N cycling in plant-soil systems, especially for the roles of Fe in soil N transformations and K, Ca and Mg in plant N uptake.

Incidence and prognostic factors of primary thyroid lymphoma and construction of prognostic models for post-chemotherapy and postoperative patients: a population-based study.

BACKGROUND: Primary thyroid lymphoma (PTL) is a rare thyroid malignancy, there are few large sample studies on PTL and no standardized treatment regimen has been established due to the rarity. The aims of this study were to explore the incidence and prognostic factors of PTL and construct visual prognostic prediction models for post-chemotherapy and postoperative patients. METHODS: The incidence of PTL in 1975-2017 was extracted from the US Surveillance, Epidemiology, and End Results (SEER) database, then assessed using joinpoint regression software. A total of 1616 eligible PTL patients diagnosed in 1998-2016 were brought into prognostic analysis. Multivariate Cox regression analyses were carried out to reveal independent prognostic elements for overall survival (OS) and cancer-specific survival (CSS). RESULTS: PTL incidence showed a relatively steady increase in 1975-1994, which annual percent change (APC) was 4.0%, and steady decreasing in 1994-2017(APC - 2.4%). Age, marital status, lymphoma Ann Arbor stage, histological subtypes, surgery, chemotherapy, and radiation were significantly correlated to OS and CSS. Nomograms were constructed to predict OS and CSS in post-chemotherapy and postoperative PTL patients separately, and were verified to have good reliability. CONCLUSIONS: The incidence of PTL increased and subsequently decreased. We revealed the prognostic implications and constructed reliable nomograms for post-chemotherapy and postoperative PTL patients.

A novel colorimetric immunoassay based on enzyme-regulated instant generation of Turnbull's blue for the sensitive determination of ochratoxin A.

The aim of this study was to develop a novel colorimetric sensing method based on enzyme-regulated instant generation of Turnbull's blue, serving as a chromogenic agent, for a sensitive immunoassay for the determination of ochratoxin A (OTA). Unlike the traditional enzyme-linked immunosorbent assay (ELISA), the chromogenic reaction reported herein relies on the immediate formation of Turnbull's blue. K3[Fe(CN)6] rapidly forms a coordinate bond with iron(ii), yielding a blue product. Meanwhile, glucose oxidase (GOx) catalyzes glucose hydrolysis to produce hydrogen peroxide (H2O2), which was used to inhibit the formation of Turnbull's blue by oxidizing iron(ii) to iron(iii). Thus, Turnbull's blue was generated in an enzyme-regulated manner. Accordingly, a competitive-type colorimetric enzyme immunoassay was established using a GOx based nanolabel. Under optimal conditions, the absorbance increased upon increasing the target OTA concentration in the range of 0.01-10 ng mL-1 with a detection limit of 8.3 pg mL-1 estimated at the 3Sblank level. The assay accuracy was validated by analyzing spiked wine samples. The present results potentially provide novel insights into the development of Turnbull's blue-based biological detection methods and colorimetric immunoassay strategies.

Applications of Life Cycle Assessment in the Chocolate Industry: A State-of-the-Art Analysis Based on Systematic Review.

Chocolate is a popular food for its unique flavor and taste, rich nutritional value, and the psychological values brought to people. The raw material production of chocolate, product manufacturing, sales and transportation have different degrees of environmental impact. This review explores the environmental hot spots in the life cycle of chocolate and puts forward corresponding suggestions for the improvement. By applying a systematic review method, this paper collected 25 articles on life cycle assessment (LCA) of the environmental impact of the chocolate industry. It is found that the life cycle of chocolate has the highest environmental impact in the raw material production and chocolate manufacturing stages (accounting for 77-97% of total impacts), among which milk powder, sugar and cocoa derivatives are the important contributors to significant environmental burden. Dark chocolate generates the lowest carbon emissions (1.67 kg CO2 eq/kg product) among existing chocolate categories, while the chocolate confectionery products release the highest carbon emissions (6.76 kg CO2 eq/kg product) among chocolate-containing products. Improvement measures are proposed for reducing environmental impacts and for selecting environmentally friendly product formulae. This study can provide benchmarking for the chocolate industry and improves the understanding of life cycle environmental impacts of chocolate products.