The effect of depression and anxiety on survival in patients with glioma: a systematic review and meta-analysis.

PURPOSE: Depression and anxiety's impact on glioma patient survival lacks consensus. Understanding these effects can highlight the importance of identifying depression and anxiety in glioma patients, and inform future treatments. This systematic review and meta-analysis aims to clarify the impact of depression and anxiety on glioma patient survival. METHODS: We conducted a systematic literature search of major databases, including PubMed, Embase, Web of Science Core Collection, Cochrane Library, and PsycINFO, from inception to June 2023, to identify relevant studies. Eligible studies were those that examined the association between depression, anxiety, or both, and survival outcomes in glioma patients. Data were extracted and analyzed using fixed-effects meta-analysis models to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 15 studies met the inclusion criteria, encompassing a diverse range of glioma patients across different clinical settings and stages. The meta-analysis revealed a statistically significant association between depression and reduced overall survival in glioma patients, with a pooled HR of 1.65 (95% CI: 1.41-1.83, 11 studies). The preliminary univariate meta-regression results indicate no impact of individual study characteristics on the effect size. Likewise, anxiety was associated with worse overall survival, with a pooled HR of 1.65 (95% CI: 1.18-2.31, 5 studies). CONCLUSIONS: This meta-analysis underscores the vital need to identify and treat depression and anxiety in glioma patients. Future research should explore the underlying mechanisms, aiding the creation of interventions enhancing both mental health and clinical outcomes for this vulnerable group.

Prospective applications of bioactive materials in orthopedic therapies: A review.

The biomedical application of biodegradable polymers for addressing bone-related diseases has garnered considerable attention in recent years. Advances in material technology have expanded the repertoire of materials suitable for orthopedic implants, with nanomaterials playing a pivotal role in replicating crucial surface properties akin to natural tissues. This comprehensive review explores the evaluation of bioactive glass ceramics, shedding light on their properties and applications. The synthesis of composites through composite manufacturing has emerged as a strategy to enhance biocompatibility and biomechanical characteristics. They are addressing challenges associated with conventional implants and nanomaterials, whether in the form of functional nano coatings or nanostructured surfaces, present opportunities to refine implant techniques. Novel developments in orthopedic biomaterials, such as smart biomaterials, porous structures, and 3D implants, offer stimuli-responsive behavior to achieve desired implant shapes and characteristics. Bioactive and biodegradable porous polymer/inorganic composite materials are explored for bone tissue engineering scaffolds, aiming to promote bone formation and regeneration. As a prospective direction, the integration of stem cells into scaffolds hints at the creation of next-generation synthetic/living hybrid biomaterials, displaying high adaptability in biological settings. This review establishes a foundation for nanotechnology-driven biomaterials by elucidating fundamental design factors crucial for orthopedic implant performance and their response to cell differentiation, proliferation, and adhesion.

Bone scaffolds-based localized drugs delivery for osteosarcoma: current status and future perspective.

A common malignant bone neoplasm in teenagers is Osteosarcoma. Chemotherapy, surgical therapy, and radiation therapy together comprise the usual clinical course of treatment for Osteosarcoma. While Osteosarcoma and other bone tumors are typically treated surgically, however, surgical resection frequently fails to completely eradicate tumors, and in turn becomes the primary reason for postoperative recurrence and metastasis, ultimately leading to a high rate of mortality. Patients still require radiation and/or chemotherapy after surgery to stop the spread of the tumor and its metastases, and both treatments have an adverse influence on the body's organ systems. In the postoperative management of osteosarcoma, bone scaffolds can load cargos (growth factors or drugs) and function as drug delivery systems (DDSs). This review describes the different kinds of bone scaffolds that are currently available and highlights key studies that use scaffolds as DDSs for the treatment of osteosarcomas. The discussion also includes difficulties and perspectives regarding the use of scaffold-based DDSs. The study may serve as a source for outlining efficient and secure postoperative osteosarcoma treatment plans.

Improved biohydrogen production by co-fermentation of corn straw and excess sludge: Insights into biochemical process, microbial community and metabolic genes.

The global climate change mainly caused by fossil fuels combustion promotes that zero-carbon hydrogen production through eco-friendly methods has attracted attention in recent years. This investigation explored the biohydrogen production by co-fermentation of corn straw (CS) and excess sludge (ES), as well as comprehensively analyzed the internal mechanism. The results showed that the optimal ratio of CS to ES was 9:1 (TS) with the biohydrogen yield of 101.8 mL/g VS, which was higher than that from the mono-fermentation of CS by 1.0-fold. The pattern of volatile fatty acids (VFAs) indicated that the acetate was the most preponderant by-product in all fermentation systems during the biohydrogen production process, and its yield was improved by adding appropriate dosage of ES. In addition, the content of soluble COD (SCOD) was reduced as increasing ES, while concentration of NH4+-N showed an opposite tendency. Microbial community analysis revealed that the microbial composition in different samples showed a significant divergence. Trichococcus was the most dominant bacterial genus in the optimal ratio of 9:1 (CS/ES) fermentation system and its abundance was as high as 41.8%. The functional genes prediction found that the dominant metabolic genes and hydrogen-producing related genes had not been significantly increased in co-fermentation system (CS/ES = 9:1) compared to that in the mono-fermentation of CS, implying that enhancement of biohydrogen production by adding ES mainly relied on balancing nutrients and adjusting microbial community in this study. Further redundancy analysis (RDA) confirmed that biohydrogen yield was closely correlated with the enrichment of Trichococcus.

Current developments and future perspectives of nanotechnology in orthopedic implants: an updated review.

Orthopedic implants are the most commonly used fracture fixation devices for facilitating the growth and development of incipient bone and treating bone diseases and defects. However, most orthopedic implants suffer from various drawbacks and complications, including bacterial adhesion, poor cell proliferation, and limited resistance to corrosion. One of the major drawbacks of currently available orthopedic implants is their inadequate osseointegration at the tissue-implant interface. This leads to loosening as a result of immunological rejection, wear debris formation, low mechanical fixation, and implant-related infections. Nanotechnology holds the promise to offer a wide range of innovative technologies for use in translational orthopedic research. Nanomaterials have great potential for use in orthopedic applications due to their exceptional tribological qualities, high resistance to wear and tear, ability to maintain drug release, capacity for osseointegration, and capability to regenerate tissue. Furthermore, nanostructured materials possess the ability to mimic the features and hierarchical structure of native bones. They facilitate cell proliferation, decrease the rate of infection, and prevent biofilm formation, among other diverse functions. The emergence of nanostructured polymers, metals, ceramics, and carbon materials has enabled novel approaches in orthopaedic research. This review provides a concise overview of nanotechnology-based biomaterials utilized in orthopedics, encompassing metallic and nonmetallic nanomaterials. A further overview is provided regarding the biomedical applications of nanotechnology-based biomaterials, including their application in orthopedics for drug delivery systems and bone tissue engineering to facilitate scaffold preparation, surface modification of implantable materials to improve their osteointegration properties, and treatment of musculoskeletal infections. Hence, this review article offers a contemporary overview of the current applications of nanotechnology in orthopedic implants and bone tissue engineering, as well as its prospective future applications.

Grain boundary plasticity initiated by excess volume.

Grain boundaries (GBs) serve not only as strong barriers to dislocation motion, but also as important carriers to accommodate plastic deformation in crystalline solids. During deformation, the inherent excess volume associated with loose atomic packing in GBs brings about a microscopic degree of freedom that can initiate GB plasticity, which is beyond the classic geometric description of GBs. However, identification of this atomistic process has long remained elusive due to its transient nature. Here, we use Au polycrystals to unveil a general and inherent route to initiating GB plasticity via a transient topological transition process triggered by the excess volume. This route underscores the general impact of a microscopic degree of freedom which is governed by a stress-triaxiality-based criterion. Our findings provide a missing perspective for developing a more comprehensive understanding of the role of GBs in plastic deformation.

Controllable Pseudoelasticity in Metallic Nanocrystals by Grain Boundary Engineering.

Materials with pseudoelasticity can recover from large strains exceeding their elastic limits during unloading, making them promising damage-tolerant building blocks for advanced nanodevices. Nevertheless, a practical approach to realize controllable pseudoelastic behavior at nanoscale remains challenging. Here, we proposed a grain boundary (GB) engineering approach to endow metallic nanocrystals with a controllable pseudoelasticity. Both in situ nanomechanical testing and atomistic simulations demonstrate that such controllable pseudoelasticity is governed by the extension and contraction of an inherent stacking fault array at the GB. By precisely tuning GB misorientation and inclination, our simulation results reveal that metallic nanocrystals can exhibit tailored pseudoelastic performance across a broad spectrum of GBs in different face-centered cubic metals. These findings enrich our understanding of the intrinsic pseudoelasticity of GBs and provide a GB engineering approach toward metallic materials with reversible deformability.

Current advancements in therapeutic approaches in orthopedic surgery: a review of recent trends.

Recent advancements in orthopedic surgery have greatly improved the management of musculoskeletal disorders and injuries. This review discusses the latest therapeutic approaches that have emerged in orthopedics. We examine the use of regenerative medicine, including stem cell therapy and platelet-rich plasma (PRP) injections, to accelerate healing and promote tissue regeneration. Additionally, we explore the application of robotic-assisted surgery, which provides greater precision and accuracy during surgical procedures. We also delve into the emergence of personalized medicine, which tailors treatments to individual patients based on their unique genetic and environmental factors. Furthermore, we discuss telemedicine and remote patient monitoring as methods for improving patient outcomes and reducing healthcare costs. Finally, we examine the growing interest in using artificial intelligence and machine learning in orthopedics, particularly in diagnosis and treatment planning. Overall, these advancements in therapeutic approaches have significantly improved patient outcomes, reduced recovery times, and enhanced the overall quality of care in orthopedic surgery.

Revealing the room temperature superplasticity in bulk recrystallized molybdenum.

Body-centered cubic refractory metallic materials exhibit excellent high-temperature strength, but often suffer from brittle intergranular fracture due to the recrystallization-induced enrichment of trace elements at grain boundaries (GBs). Here, we report a fully-recrystallized pure molybdenum (Mo) material with room temperature (RT) superplasticity, fabricated by a facile method of powder metallurgy, Y-type hot rolling and annealing. By engineering the ultralow concentration of O at GBs, the inherent GB brittleness of Mo can be largely eliminated, which, in conjunction with high fractions of soft texture and low angle GBs, enables a significant development of ordered dislocation networks and the effective dislocation transmission across low angle GBs. Synergy of these factors greatly suppress the brittle intergranular fracture of Mo, contributing to an enhanced deformability of 108.7% at RT. These findings should have general implication for fabricating a broad class of refractory metals and alloys toward harsh applications.

Augmented Concentration of Isopentyl-Deoxynyboquinone in Tumors Selectively Kills NAD(P)H Quinone Oxidoreductase 1-Positive Cancer Cells through Programmed Necrotic and Apoptotic Mechanisms.

Lung and breast cancers rank as two of the most common and lethal tumors, accounting for a substantial number of cancer-related deaths worldwide. While the past two decades have witnessed promising progress in tumor therapy, developing targeted tumor therapies continues to pose a significant challenge. NAD(P)H quinone oxidoreductase 1 (NQO1), a two-electron reductase, has been reported as a promising therapeutic target across various solid tumors. ß-Lapachone (ß-Lap) and deoxynyboquinone (DNQ) are two NQO1 bioactivatable drugs that have demonstrated potent antitumor effects. However, their curative efficacy has been constrained by adverse effects and moderate lethality. To enhance the curative potential of NQO1 bioactivatable drugs, we developed a novel DNQ derivative termed isopentyl-deoxynyboquinone (IP-DNQ). Our study revealed that IP-DNQ treatment significantly increased reactive oxygen species generation, leading to double-strand break (DSB) formation, PARP1 hyperactivation, and catastrophic energy loss. Notably, we discovered that this novel drug induced both apoptosis and programmed necrosis events, which makes it entirely distinct from other NQO1 bioactivatable drugs. Furthermore, IP-DNQ monotherapy demonstrated significant antitumor efficacy and extended mice survival in A549 orthotopic xenograft models. Lastly, we identified that in mice IP-DNQ levels were significantly elevated in the plasma and tumor compared with IB-DNQ levels. This study provides novel preclinical evidence supporting IP-DNQ efficacy in NQO1+ NSCLC and breast cancer cells.

IP-DNQ induces mitochondrial dysfunction and G2/M phase cell cycle arrest to selectively kill NQO1-positive pancreatic cancer cells.

Pancreatic cancer is among the top five leading causes of cancer-related deaths worldwide, with low survival rates. Current therapies for pancreatic cancer lack tumor specificity, resulting in harmful effects on normal tissues. Therefore, developing tumor-specific agents for the treatment of pancreatic cancer is critical. NAD(P)H:quinone oxidoreductase 1 (NQO1), highly expressed in pancreatic cancers but not in normal tissues, makes NQO1 bioactivatable drugs a potential therapy for selectively killing NQO1-positive cancer cells. Our previous studies have revealed that novel NQO1 bioactivatable drug deoxynyboquinone (DNQ) is ten-fold more potent than the prototypic NQO1 bioactivatable drug ß-lapachone in killing of NQO1-positive cancer cells. However, DNQ treatment results in high-grade methemoglobinemia, a significant side effect that limits clinical development. Here, we report for the first time on a DNQ derivative, isopentyl-deoxynboquinone (IP-DNQ), which selectively kills pancreatic ductal adenocarcinoma cells in an NQO1-dependent manner with equal potency to the parent DNQ. IP-DNQ evokes massive ROS production and oxidative DNA lesions that results in PARP1 hyperactivation, mitochondrial catastrophe and G2/M-phase arrest, leading to apoptotic and necrotic programmed cell death. Importantly, IP-DNQ treatment causes mild methemoglobinemia in vivo, with a three-fold improvement in the maximum tolerated dose compared to DNQ, while significantly suppresses tumor growth and extends the lifespan of mice in subcutaneous and orthotopic pancreatic cancer xenograft models. Our study demonstrates that IP-DNQ is a promising therapy for NQO1-positive pancreatic cancers and may enhance the efficacy of other anticancer drugs. IP-DNQ represents a novel approach to treating pancreatic cancer with the potential to improve patient outcomes.

Pt-induced atomic-level tailoring towards paracrystalline high-entropy alloy.

Paracrystalline state achieved in the diamond system guides a direction to explore the missing link between amorphous and crystalline states. However, such a state is still challenging to reach in alloy systems in a controlled manner. Here, based on the vast composition space and the complex atomic interactions in the high-entropy alloys (HEAs), we present an "atomic-level tailoring" strategy to create the paracrystalline HEA. The addition of atomic-level Pt with the large and negative mixing enthalpy induces the local atomic reshuffling around Pt atoms for the well-targeted local amorphization, which separates severe-distorted crystalline Zr-Nb-Hf-Ta-Mo HEA into the high-density crystalline MRO motifs on atomic-level. The paracrystalline HEA exhibits high hardness (16.6 GPa) and high yield strength (8.37 GPa) and deforms by nanoscale shear-banding and nanocrystallization modes. Such an enthalpy-guided strategy in HEAs can provide the atomic-level tailoring ability to purposefully regulate structural characteristics and desirable properties.

Human social conditions predict the risk of exposure to zoonotic parasites in companion animals in East and Southeast Asia.

BACKGROUND: A recent dramatic surge in pet ownership has been observed across metropolitan areas in Asia. To date, there is a dearth of information on the risk associated with pet ownership for the transmission of parasites on a large scale in Asia, despite this continent giving rise to the largest burden of zoonotic infections worldwide. METHODS: We explored the nature and extent of zoonotic internal (endo-) and external (ecto-) parasites and arthropod-borne pathogens in 2381 client-owned dogs and cats living in metropolitan areas of eight countries in East and Southeast Asia using reliable diagnostic tests and then undertook extensive statistical analyses to define predictors of exposure to zoonotic pathogens. RESULTS: The estimated ORs for overall parasite infections are 1.35 [95% CIs 1.07;1.71] in young animals and 4.10 [1.50;11.2] in the animal group older than 15 years as compared with adult animals, 0.61 [0.48;0.77] in neutered animals as compared to unneutered animals, 0.36 [0.26;0.50] in animals living in urban areas as compared with rural areas, 1.14 [1.08;1.21] for each 1 °C increase of annual mean temperature which varies from 12.0 to 28.0 °C, and 0.86 [0.78;0.95] for each year of life expectancy which varies from 70.9 to 83.3 years. CONCLUSIONS: Here we highlight the influence of human life expectancy and the neutering status of the animals, which reflect increased living standards through access to education and human and veterinary health care, to be both strongly associated with exposure to zoonotic parasites. An integrated approach of local and international authorities to implement and manage educational programs will be crucial for the control of zoonotic infections of companion animals in Asia.

Parasites live on or inside animals or humans and can cause disease. Companion animals (pets) with parasites present a potential risk to the health of their owners, as certain kinds of parasites (known as zoonotic parasites) can affect both animal and human health. Here, we investigated whether human social conditions are associated with zoonotic parasite infections in companion animals in East and Southeast Asia. We found that higher human life expectancy and neutering of the companion animals were associated with fewer zoonotic parasite infections in the animals. These findings highlight the need for an enhanced commitment of local authorities to establish prevention campaigns, including education programs, against zoonotic pathogens. These measures will play a crucial role in alleviating the impact of these diseases in companion animals and humans in Asia.

Revealing the pulse-induced electroplasticity by decoupling electron wind force.

Micro/nano electromechanical systems and nanodevices often suffer from degradation under electrical pulse. However, the origin of pulse-induced degradation remains an open question. Herein, we investigate the defect dynamics in Au nanocrystals under pulse conditions. By decoupling the electron wind force via a properly-designed in situ TEM electropulsing experiment, we reveal a non-directional migration of Σ3{112} incoherent twin boundary upon electropulsing, in contrast to the expected directional migration under electron wind force. Quantitative analyses demonstrate that such exceptional incoherent twin boundary migration is governed by the electron-dislocation interaction that enhances the atom vibration at dislocation cores, rather than driven by the electron wind force in classic model. Our observations provide valuable insights into the origin of electroplasticity in metallic materials at the atomic level, which are of scientific and technological significances to understanding the electromigration and resultant electrical damage/failure in micro/nano-electronic devices.

KP372-1-Induced AKT Hyperactivation Blocks DNA Repair to Synergize With PARP Inhibitor Rucaparib via Inhibiting FOXO3a/GADD45α Pathway.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have exhibited great promise in the treatment of tumors with homologous recombination (HR) deficiency, however, PARPi resistance, which ultimately recovers DNA repair and cell progress, has become an enormous clinical challenge. Recently, KP372-1 was identified as a novel potential anticancer agent that targeted the redox enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), to induce extensive reactive oxygen species (ROS) generation that amplified DNA damage, leading to cancer cell death. To overcome PARPi resistance and expand its therapeutic utility, we investigated whether a combination therapy of a sublethal dose of KP372-1 with a nontoxic dose of PARPi rucaparib would synergize and enhance lethality in NQO1 over-expressing cancers. We reported that the combination treatment of KP372-1 and rucaparib induced a transient and dramatic AKT hyperactivation that inhibited DNA repair by regulating FOXO3a/GADD45α pathway, which enhanced PARPi lethality and overcame PARPi resistance. We further found that PARP inhibition blocked KP372-1-induced PARP1 hyperactivation to reverse NAD+/ATP loss that promoted Ca2+-dependent autophagy and apoptosis. Moreover, pretreatment of cells with BAPTA-AM, a cytosolic Ca2+ chelator, dramatically rescued KP372-1- or combination treatment-induced lethality and significantly suppressed PAR formation and γH2AX activation. Finally, we demonstrated that this combination therapy enhanced accumulation of both agents in mouse tumor tissues and synergistically suppressed tumor growth in orthotopic pancreatic and non-small-cell lung cancer xenograft models. Together, our study provides novel preclinical evidence for new combination therapy in NQO1+ solid tumors that may broaden the clinical utility of PARPi.

Clinical effectiveness of different types of bone-anchored maxillary protraction devices for skeletal Class III malocclusion: Systematic review and network meta-analysis.

Objective: This study aimed to estimate the clinical effects of different types of bone-anchored maxillary protraction devices by using a network meta-analysis. Methods: We searched seven databases for randomized and controlled clinical trials that compared bone-anchored maxillary protraction with tooth-anchored maxillary protraction interventions or untreated groups up to May 2021. After literature selection, data extraction, and quality assessment, we calculated the mean differences, 95% confidence intervals, and surface under the cumulative ranking scores of eleven indicators. Statistical analysis was performed using R statistical software with the GeMTC package based on the Bayesian framework. Results: Six interventions and 667 patients were involved in 18 studies. In comparison with the tooth-anchored groups, the bone-anchored groups showed significantly more increases in Sella-Nasion-Subspinale (°), Subspinale-Nasion-Supramentale(°) and significantly fewer increases in mandibular plane angle and the labial proclination angle of upper incisors. In comparison with the control group, Sella-Nasion-Supramentale(°) decreased without any statistical significance in all treated groups. IMPA (angle of lower incisors and mandibular plane) decreased in groups with facemasks and increased in other groups. Conclusions: Bone-anchored maxillary protraction can promote greater maxillary forward movement and correct the Class III intermaxillary relationship better, in addition to showing less clockwise rotation of mandible and labial proclination of upper incisors. However, strengthening anchorage could not inhibit mandibular growth better and the lingual inclination of lower incisors caused by the treatment is related to the use of a facemask.

Hierarchical twinning governed by defective twin boundary in metallic materials.

Dense networks of deformation twins endow metals and alloys with unprecedented mechanical properties. However, the formation mechanism of these hierarchical twin structures remains under debate, especially their relations with the imperfect nature of twin boundaries (TBs). Here, we investigate the intrinsic deformability of defective TBs in face-centered cubic metallic materials, where the inherent kinks on a set of primary TBs are demonstrated to facilitate the formation of secondary and hierarchical nanotwins. This defect-driven hierarchical twinning propensity is critically dependent on the kink height, which proves to be generally applicable in a variety of metals and alloys with low stacking fault energies. As a geometric extreme, a fivefold twin can be constructed via this self-activated hierarchical twinning mechanism. These findings differ from the conventional twinning mechanisms, enriching our understanding of twinning-mediated plasticity in metallic materials.

Clinical effects of maxillary protraction in different stages of dentition in skeletal class III children: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the effectiveness of using maxillary protraction during different stages of the dentition by assessing changes in the jaws and inclination of incisors. MATERIALS AND METHODS: MEDLINE (PubMed), Embase, Cochrane, Web Of Science, China National Knowledge Infrastructure and Wanfang Databases were searched without time limitations up to 15 January 2022. Google Scholar was used to search grey literature. We included cohort studies that compared the effect of maxillary protraction by analysing primary outcomes and were grouped in age-related conditions. Mean differences and 95% confidence intervals were used for statistical analysis, followed by Grading of Recommendations Assessment, Development and Evaluation analysis. RESULTS: Six studies were finally included. The heterogeneity test showed P ≥ .1 and I2  ≤ 50%, and a fixed-effect model was applied. Patients in the early treatment group (ETG) were mainly in the early-mixed dentition stage, while patients in the late treatment group (LTG) were in the late-mixed and early-permanent dentition stage. Meta-analysis showed that there were no statistical differences (P > .05) between the ETG and LTG groups in terms of SNA (the angle composed by point Sella-Nasion-Subspinale), SNB (the angle composed by point Sella-Nasion-Supramentale), ANB (the angle composed by point Subspinale-Nasion-Supramentale), Wits, U1/SN (the angle composed by the axis of upper incisors and Sella-Nasion plane) and L1/MP (the angle composed by the axis of lower incisors and the mandibular plane). CONCLUSION: Our analysis showed that maxillary protraction applied in the late-mixed or early-permanent dentition stage did not cause different effects on the maxillary growth, the correction of the intermaxillary relationship, the inhibition of mandibular growth and dental tipping of skeletal class III patients when compared to that in the early-mixed dentition stage. Collectively, these data provide a theoretical basis for widening the applicable age period of maxillary protraction and choosing the best treatment opportunity for children patients after a comprehensive assessment.

Embryonic exposure to fenbuconazole inhibits gametogenesis in adult zebrafish by targeting gonads not brain.

Fenbuconazole (FBZ) is widely used in agriculture. The current study was conducted to evaluate the influence of embryonic exposure to FBZ on reproduction in adult zebrafish. Embryos were exposed to 5, 50 and 500 ng/L FBZ for 72 h and then raised in clean water until adulthood. The result showed that the percentage of mature gametes was significantly reduced in adult zebrafish. The fertilization rate and survival rate of F1 embryos were decreased when the exposed fish were mated with untreated fish. The transcription of brain gnrh3, fshß and lhγ in adult fish was upregulated, while the levels of 17ß-estradiol and testosterone were not significantly changed in all treated groups, indicating that the reproduction-related genes in brain was not responsible for the reduced reproductive ability. The downregulated transcription of fshr, lhr, ar and esr2 in the gonads indicated the dysfunction of Sertoli and Leydig cells. Notably, downregulated transcription and upregulated methylation levels of genes related to germ cells were observed in treated F0 larvae and adult gonads. The elevated methylation levels of piwil1 and dnmt6 in the testes and vasa and dazl in the ovary were matched with the alterations in the expression of these genes, suggesting that germ cells are the main targets of FBZ. These results provide new mechanism underlying reproductive toxicity in fish caused by chemicals, and give potential retroactive biomarkers for monitoring reproductive toxic pollutants.

Twinning-assisted dynamic adjustment of grain boundary mobility.

Grain boundary (GB) plasticity dominates the mechanical behaviours of nanocrystalline materials. Under mechanical loading, GB configuration and its local deformation geometry change dynamically with the deformation; the dynamic variation of GB deformability, however, remains largely elusive, especially regarding its relation with the frequently-observed GB-associated deformation twins in nanocrystalline materials. Attention here is focused on the GB dynamics in metallic nanocrystals, by means of well-designed in situ nanomechanical testing integrated with molecular dynamics simulations. GBs with low mobility are found to dynamically adjust their configurations and local deformation geometries via crystallographic twinning, which instantly changes the GB dynamics and enhances the GB mobility. This self-adjust twin-assisted GB dynamics is found common in a wide range of face-centred cubic nanocrystalline metals under different deformation conditions. These findings enrich our understanding of GB-mediated plasticity, especially the dynamic behaviour of GBs, and bear practical implication for developing high performance nanocrystalline materials through interface engineering.