Whole-genome sequencing of diverse wheat accessions uncovers genetic changes during modern breeding in China and the United States.

Breeding has dramatically changed the plant architecture of wheat (Triticum aestivum), resulting in the development of high-yielding varieties adapted to modern farming systems. However, how wheat breeding shaped the genomic architecture of this crop remains poorly understood. Here, we performed a comprehensive comparative analysis of a whole-genome resequencing panel of 355 common wheat accessions (representing diverse landraces and modern cultivars from China and the United States) at the phenotypic and genomic levels. The genetic diversity of modern wheat cultivars was clearly reduced compared to landraces. Consistent with these genetic changes, most phenotypes of cultivars from China and the United States were significantly altered. Of the 21 agronomic traits investigated, 8 showed convergent changes between the 2 countries. Moreover, of the 207 loci associated with these 21 traits, more than half overlapped with genomic regions that showed evidence of selection. The distribution of selected loci between the Chinese and American cultivars suggests that breeding for increased productivity in these 2 regions was accomplished by pyramiding both shared and region-specific variants. This work provides a framework to understand the genetic architecture of the adaptation of wheat to diverse agricultural production environments, as well as guidelines for optimizing breeding strategies to design better wheat varieties.

Engineering of the DNA replication and repair machinery to develop binary mutators for rapid genome evolution of Corynebacterium glutamicum.

Corynebacterium glutamicum is an important industrial workhorse for production of amino acids and chemicals. Although recently developed genome editing technologies have advanced the rational genetic engineering of C. glutamicum, continuous genome evolution based on genetic mutators is still unavailable. To address this issue, the DNA replication and repair machinery of C. glutamicum was targeted in this study. DnaQ, the homolog of ϵ subunit of DNA polymerase III responsible for proofreading in Escherichia coli, was proven irrelevant to DNA replication fidelity in C. glutamicum. However, the histidinol phosphatase (PHP) domain of DnaE1, the α subunit of DNA polymerase III, was characterized as the key proofreading element and certain variants with PHP mutations allowed elevated spontaneous mutagenesis. Repression of the NucS-mediated post-replicative mismatch repair pathway or overexpression of newly screened NucS variants also impaired the DNA replication fidelity. Simultaneous interference with the DNA replication and repair machinery generated a binary genetic mutator capable of increasing the mutation rate by up to 2352-fold. The mutators facilitated rapid evolutionary engineering of C. glutamicum to acquire stress tolerance and protein overproduction phenotypes. This study provides efficient tools for evolutionary engineering of C. glutamicum and could inspire the development of mutagenesis strategy for other microbial hosts.

High-intensity interval training ameliorates postnatal immune activation-induced mood disorders through KDM6B-regulated glial activation.

Postnatal immune activation (PIA) induces persistent glial activation in the brain and causes various neuropathologies in adults. Exercise training improves stress-related mood disorders; however, the role of exercise in psychiatric disorders induced by early-life immune activation and the association between exercise training and glial activation remain unclear. We compared the effects of different exercise intensities on the PIA model, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Both HIIT and MICT in adolescent mice inhibited neuroinflammation, remodeled synaptic plasticity, and improved PIA-induced mood disorders in adulthood. Importantly, HIIT was superior to MICT in terms of reducing inflammation and increasing body weight. RNA-seq of prefrontal cortex (PFC) tissues revealed a gene expression pattern, confirming that HIIT was more effective than MICT in improving brain glial cell activation through epigenetic modifications of KDM6B. We investigated the role of KDM6B, a specific histone lysine demethylation enzyme - histone 3 lysine 27 demethylase, in inhibiting glial activation against PIA-induced depression and anxiety by regulating the expression of IL-4 and brain-derived neurotrophic factor (BDNF). Overall, our data support the idea that HIIT improves PIA-induced mood disorders by regulating KDM6B-mediated epigenetic mechanisms and indicate that HIIT might be superior to MICT in improving mood disorders with PIA in mice. Our findings provide new insights into the treatment of anxiety and depression disorders.

Expression and clinical diagnostic value of CCHE1 in breast cancer.

OBJECTIVE: Breast cancer is a malignant tumor in the epithelial tissue of the breast gland. This study aimed to unveil the expression and clinical diagnostic value of lncRNA cervical cancer high-expressed 1 (CCHE1) in breast cancer. METHODS: CCHE1 expression in breast cancer tissues was evaluated by RT-qPCR. The relationship between the CCHE1 expression and clinicopathological features of breast cancer was analyzed with the chi-square test, and the survival of breast cancer patients was evaluated with the Kaplan-Meier method. The diagnostic value of CCHE1 expression for breast cancer was evaluated by using the receiver operating characteristics (ROC) curve. Breast cancer cell lines (SKBR3, T47D, BT474, and MCF-7) were cultured for detecting CCHE1 expression in the cells. MCF-7 cells were selected for the subsequent experiments, and the small interfering RNA of CCHE1 (si-CCHE1) and CCHE1 overexpression vector (pcDNA-CCHE1) were transfected into MCF-7 cells. The proliferation, migration, and invasive ability were assessed by CCK-8 and Transwell assays. The influence of CCHE1 on the growth of tumors was validated by nude mice xenograft assay. RESULTS: CCHE1 was up-regulated in breast cancer tissues and breast cancer cells. The high expression level of CCHE1 in cancer tissues of breast cancer patients was correlated with larger tumor size, advanced TNM stage, Ki-67 status, and lymph node metastasis. The area under the ROC curve for CCHE1 in the diagnosis of breast cancer was 0.983 (95% CI: 0.966-1.000), with a sensitivity of 95.00% and a specificity of 91.70%. The 5-year survival rate was higher in patients with low CCHE1 expression than those with high CCHE1 expression. Furthermore, restrained CCHE1 impeded proliferation, invasion, and migration of MCF-7 cells, as well as tumor growth in mice. CONCLUSION: Our study highlights that elevated expression of CCHE1 in breast cancer tissues, which is closely related to clinicopathologic features, has some clinical value in the diagnosis of the disease.

Polysaccharide-Based Coating with Excellent Antibiofilm and Repeatable Antifouling-Bactericidal Properties for Treating Infected Hernia.

In recent years, the utilization of medical devices has gradually increased and implantation procedures have become common treatments. However, patients are susceptible to the risk of implant infections. This study utilized chemical grafting to immobilize polyethylenimine (QPEI) and hyaluronic acid (HA) on the surface of the mesh to improve biocompatibility while being able to achieve antifouling antimicrobial effects. From the in vitro testing, PP-PDA-Q-HA exhibited a high antibacterial ratio of 93% against S. aureus, 93% against E. coli, and 85% against C. albicans. In addition, after five rounds of antimicrobial testing, the coating continued to exhibit excellent antimicrobial properties; PP-PDA-Q-HA also inhibits the formation of bacterial biofilms. In addition, PP-PDA-Q-HA has good hemocompatibility and cytocompatibility. In vivo studies in animal implantation infection models also demonstrated the excellent antimicrobial properties of PP-PDA-Q-HA. Our study provides a promising strategy for the development of antimicrobial surface medical materials with excellent biocompatibility.

Genome sequence of the progenitor of wheat A subgenome Triticum urartu.

Triticum urartu (diploid, AA) is the progenitor of the A subgenome of tetraploid (Triticum turgidum, AABB) and hexaploid (Triticum aestivum, AABBDD) wheat1,2. Genomic studies of T. urartu have been useful for investigating the structure, function and evolution of polyploid wheat genomes. Here we report the generation of a high-quality genome sequence of T. urartu by combining bacterial artificial chromosome (BAC)-by-BAC sequencing, single molecule real-time whole-genome shotgun sequencing 3 , linked reads and optical mapping4,5. We assembled seven chromosome-scale pseudomolecules and identified protein-coding genes, and we suggest a model for the evolution of T. urartu chromosomes. Comparative analyses with genomes of other grasses showed gene loss and amplification in the numbers of transposable elements in the T. urartu genome. Population genomics analysis of 147 T. urartu accessions from across the Fertile Crescent showed clustering of three groups, with differences in altitude and biostress, such as powdery mildew disease. The T. urartu genome assembly provides a valuable resource for studying genetic variation in wheat and related grasses, and promises to facilitate the discovery of genes that could be useful for wheat improvement.

Nicotinamide mononucleotide maintains cytoskeletal stability and fortifies mitochondrial function to mitigate oocyte damage induced by Triocresyl phosphate.

Triocresyl phosphate (TOCP) was commonly used as flame retardant, plasticizer, lubricant, and jet fuel additive. Studies have shown adverse effects of TOCP on the reproductive system. However, the potential harm brought by TOCP, especially to mammalian female reproductive cells, remains a mystery. In this study, we employed an in vitro model for the first time to investigate the effects of TOCP on the maturation process of mouse oocytes. TOCP exposure hampered the meiotic division process, as evidenced by a reduction in the extrusion of the first polar body from oocytes. Subsequent research revealed the disruption of the oocyte cell cytoskeleton induced by TOCP, resulting in abnormalities in spindle organization, chromosome alignment, and actin filament distribution. This disturbance further extended to the rearrangement of organelles within oocytes, particularly affecting the mitochondria. Importantly, after TOCP treatment, mitochondrial function in oocytes was impaired, leading to oxidative stress, DNA damage, cell apoptosis, and subsequent changes of epigenetic modifications. Supplementation with nicotinamide mononucleotide (NMN) alleviated the harmful effects of TOCP. NMN exerted its mitigating effects through two fundamental mechanisms. On one hand, NMN conferred stability to the cell cytoskeleton, thereby supporting nuclear maturation. On the other hand, NMN enhanced mitochondrial function within oocytes, reducing the excess reactive oxygen species (ROS), restoring meiotic division abnormalities caused by TOCP, preventing oocyte DNA damage, and suppressing epigenetic changes. These findings not only enhance our understanding of the molecular basis of TOCP induced oocyte damage but also offer a promising avenue for the potential application of NMN in optimizing reproductive treatment strategies.

Melatonin improves mouse oocyte quality from 2-ethylhexyl diphenyl phosphate-induced toxicity by enhancing mitochondrial function.

2-Ethylhexyl diphenyl phosphate (EHDPP) is a representative organophosphorus flame retardant (OPFR) that has garnered attention due to its widespread use and potential adverse effects. EHDPP exhibits cytotoxicity, genotoxicity, developmental toxicity, and endocrine disruption. However, the toxicity of EHDPP in mammalian oocytes and the underlying mechanisms remain poorly understood. Melatonin is a natural free radical scavenger that has demonstrated cytoprotective properties. In this study, we investigated the effect of EHDPP on mouse oocytes in vitro culture system and evaluated the rescue effect of melatonin on oocytes exposed to EHDPP. Our results indicated that EHDPP disrupted oocyte maturation, resulting in the majority of oocytes arrested at the metaphase I (MI) stage, accompanied by cytoskeletal damage and elevated levels of reactive oxygen species (ROS). Nevertheless, melatonin supplementation partially rescued EHDPP-induced mouse oocyte maturation impairment. Results of single-cell RNA sequencing (scRNA-seq) analysis elucidated potential mechanisms underlying these protective effects. According to the results of scRNA-seq, we conducted further tests and found that EHDPP primarily disrupts mitochondrial distribution and function, kinetochore-microtubule (K-MT) attachment, DNA damage, apoptosis, and histone modification, which were rescued upon the supplementation of melatonin. This study reveals the mechanisms of EHDPP on female reproduction and indicates the efficacy of melatonin as a therapeutic intervention for EHDPP-induced defects in mouse oocytes.

MicroRNA expression as a prognostic biomarker of tongue squamous cell carcinoma (TSCC): a systematic review and meta-analysis.

BACKGROUND: Recent studies have indicated that microRNA (miRNA) expression in tumour tissues has prognostic significance in Tongue squamous cell carcinoma (TSCC) patients. This study explored the possible prognostic value of miRNAs for TSCC based on published research. METHODS: A comprehensive literature search of multiple databases was conducted according to predefined eligibility criteria. Data were extracted from the included studies by two researchers, and HR results were determined based on Kaplan‒Meier curves according to the Tierney method. The Newcastle‒Ottawa Scale (NOS) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pro-GDT were applied to assess the quality of all studies. Publication bias was estimated by funnel plot, Egger's rank correlation test and sensitivity analysis. RESULTS: Eleven studies (891patients) were included, of which 6 reported up-regulated miRNAs and 7 mentioned down-regulated miRNAs. The pooled hazard ratio (HR) from the prognostic indicator overall survival (OS) was 1.34 (1.25-1.44), p < 0.00001, indicating a significant difference in miRNA expression between TSCC patients with better or worse prognosis. CONCLUSION: MiRNAs may have high prognostic value and could be used as prognostic biomarkers of TSCC.

[Comparison of the virtual surgical planning position of maxilla and condyle with the postoperative real position in patients with mandibular protrusion].

OBJECTIVE: To compare the difference between virtual surgical planning (VSP) position and postoperative real position of maxilla and condyle, and to explore the degree of intraoperative realization of VSP after orthognathic surgery. METHODS: In this study, 36 patients with mandibular protrusion deformity from January 2022 to December 2022 were included. All the patients had been done bilateral sagittal split ramus osteotomy (SSRO) combined with Le Fort Ⅰ osteotomy under guidance of VSP. The VSP data (T0) and 1-week postoperative CT (T1) were collected, the 3D model of postoperative CT was established and segmented into upper and lower jaws in CCMF Plan software. At the same time, accor-ding to the morphology of palatal folds, the virtual design was registered with the postoperative model, and the unclear maxillary dentition in the postoperative model was replaced. Then the postoperative model was matched with VSP model by registration of upper skull anatomy that was not affected by the operation. The three-dimensional reference plane and coordinate system were established. Selecting anatomical landmarks and their connections of condyle and maxilla for the measurement, we compared the coordinate changes of marker points in three directions, and the angle changes between the line connecting the marker points and the reference plane to analyze the positional deviation and the angle deviation of the postoperative condyle and maxilla compared to VSP. RESULTS: The postoperative real position of the maxilla deviates from the VSP by nearly 1 mm in the horizontal and vertical directions, and the anteroposterior deviation was about 1.5 mm. In addition, most patients had a certain degree of counterclockwise rotation of the maxilla after surgery. Most of the bilateral condyle moved forward, outward and downward (the average distance deviation was 0.15 mm, 1.54 mm, 2.19 mm, respectively), and rotated forward, outward and upward (the average degree deviation was 4.32°, 1.02°, 0.86°, respectively) compared with the VSP. CONCLUSION: VSP can be mostly achieved by assistance of 3D printed occlusal plates, but there are certain deviations in the postoperative real position of maxilla and condyle compared with VSP, which may be related to the rotation axis of the mandible in the VSP. It is necessary to use patient personalized condylar rotation axis for VSP, and apply condylar positioning device to further improve surgical accuracy.

Generation of a Hydrophobic Protrusion on Nanoparticles to Improve the Membrane-Anchoring Ability and Cellular Internalization.

Controlling the nanoparticle-cell membrane interaction to achieve easy and fast membrane anchoring and cellular internalization is of great importance in a variety of biomedical applications. Here we report a simple and versatile strategy to maneuver the nanoparticle-cell membrane interaction by creating a tunable hydrophobic protrusion on Janus particles through swelling-induced symmetry breaking. When the Janus particle contacts cell membrane, the protrusion will induce membrane wrapping, leading the particles to docking to the membrane, followed by drawing the whole particles into the cell. The efficiencies of both membrane anchoring and cellular internalization can be promoted by optimizing the size of the protrusion. In vitro, the Janus particles can quickly anchor to the cell membrane in 1 h and be internalized within 24 h, regardless of the types of cells involved. In vivo, the Janus particles can effectively anchor to the brain and skin tissues to provide a high retention in these tissues after intracerebroventricular, intrahippocampal, or subcutaneous injection. This strategy involving the creation of a hydrophobic protrusion on Janus particles to tune the cell-membrane interaction holds great potential in nanoparticle-based biomedical applications.

The perception and interpretation of malaria among Chinese construction workers in sub-Saharan Africa: a qualitative study.

BACKGROUND: Cooperation between China and Africa is deepening, and business, trade, and people-to-people exchanges are growing closer together, especially in the infrastructure construction field. At the same time, malaria has become a serious health concern for Chinese construction workers in Africa, who are at increased risk of infection and complications due to lack of immunity and exposure to high-transmission environments. One of the biggest challenges in fighting malaria is their lack of knowledge and misinterpretations about the disease, which can impact their need for interventions, adherence to treatments, and health services. This study aims to determine the perception and interpretation of malaria among Chinese construction workers in sub-Saharan Africa. METHODS: Semi-structured interviews were conducted with 20 Chinese construction workers in sub-Saharan Africa. Some early respondents initially made contact through two Chinese construction companies in Africa, while the rest of the participants were engaged via a snowball method by the early participants. NVivo10, a qualitative research data management software and a thematic approach, was used to analyze the data and create themes. In order to achieve the general study goals, an inductive content analysis was applied. RESULTS: The study classified participants' perceptions and interpretations of malaria into four categories: flu-like malaria, the rumors of malaria, the hard-to-explain confusion about malaria, and the special interpretation of malaria. CONCLUSION: Malaria poses major health issues to Chinese construction workers in sub-Saharan Africa who lack immunity and live in an environment of high transmission. Their dearth of awareness and misunderstanding of malaria impacts their prevention and treatment behaviors and health outcomes. This study adopts qualitative methods to examine their perceptions and interpretations of malaria, which can serve as a source for future health management strategies.

Multi-disciplinary cooperation for the micro-elimination of hepatitis C in China: a hospital-based experience.

BACKGROUND: Hepatitis C virus (HCV) infection is one of the main causes of liver cancer and imposes an enormous social and economic burden. The blood-borne virus screening policy for preventing iatrogenic infections renders hospitals important for identifying individuals infected with hepatitis C. Therefore, we aimed to investigate the establishment of a multi-disciplinary cooperation model in medical institutions to leverage the screening results of patients with hepatitis C. Our objective is to ensure that patients receive timely and effective diagnosis and treatment, thereby enabling the elimination of hepatitis C by 2030. METHOD: A multi-disciplinary cooperation model was established in October 2021. This retrospective study was based on the establishment of antibody-positive and HCV RNA-positive patient databases. A Chi-square test was used to compare the HCV RNA confirmation rate in anti-HCV-positive patients, as well as the hepatitis C diagnosis rate and treatment rate in RNA-positive patients before and after the multi-disciplinary cooperation. A multivariable logistic regression was used to analyse the factors affecting the treatment of patients with hepatitis C. In addition, we examined changes in the level of hepatitis C knowledge among medical staff. RESULTS: After the implementation of the multi-disciplinary cooperation model, the RNA confirmation rate of hepatitis C antibody-positive patients increased from 36.426% to 88.737%, the diagnostic accuracy rate of RNA-positive patients increased from 67.456% to 98.113%, and the treatment rate of patients with hepatitis C increased from 12.426% to 58.491%. Significant improvements were observed among the clinicians regarding their ability to understand the characteristics of hepatitis C (93.711% vs. 58.861%), identify people at high risk (94.340% vs. 53.797%), manage patients with hepatitis C after diagnosis (88.679% vs. 67.089%), and effectively treat hepatitis C (84.277% vs. 51.899%). Multi-disciplinary cooperation in medical institutions was the most important factor for patients to undergo HCV treatment (odds ratio: 0.024, 95% confidence interval: 0.007-0.074). CONCLUSIONS: This study showed that the use of a multi-disciplinary cooperation model to utilise the results of HCV antibody screening fully in patients through further tracking, referral, and treatment may facilitate the detection and treatment of patients with hepatitis C and accelerate the elimination of HCV in China.

Study on the use and effectiveness of malaria preventive measures reported by employees of chinese construction companies in Western Africa in 2021.

BACKGROUND: As malaria continues to be a significant global public health concern, especially in Sub-Saharan Africa, Chinese workers in Africa are at increased risk of malaria. The effectiveness of malaria prevention measures implemented by Chinese companies and workers is a question that may correlate with the malaria infection rate in this population. This study explored the use and effectiveness of malaria prevention measures for Chinese employees in West Africa to provide a reference for companies and individuals on improving malaria prevention and control. METHODS: Using a cross-sectional approach, we surveyed 256 participants in 2021, mainly from Nigeria, Mali, Côte d'Ivoire, Ghana, Guinea, Sierra Leone, and Senegal in West Africa. The survey duration is from July to the end of September 2021. We selected two companies from the 2020 ENR "World's Largest 250 International Contractors" list, which featured 6 Chinese companies, all of which are state-owned and have a 61.9% market share in Africa. The participants were Chinese workers with more than a year of work experience in construction companies in Africa. A 20-minute WeChat-based structured online questionnaire was used to obtain information on malaria infection status and malaria prevention measures. Descriptive statistical analysis, chi-square test, principal components analysis, and ordinal logistic regression analysis are used to analyze the data obtained. The difference in Statistical significance was set at P < 0.05. RESULTS: Ninety six (37.5%) participants contracted malaria more than once within a year. The principal components analysis found a low correlation between public and individual preventive measures. No significant correlation was found between public preventive measures and malaria infection (p > 0.05), while standardized use of mosquito nets (P = 0.016) and pesticide spraying (P = 0.047) contributed significantly to fewer malaria infections at the individual level, but the removal of vegetation around houses (P = 0.028) at the individual level related to higher malaria infection. CONCLUSIONS: In our sample of Chinese construction workers going to Africa, some individual preventive measures had a stronger association with malaria prevention than a variety of public environmental measures. Furthermore, individual and public preventive measures were not associated with each other. Both of these findings are surprising and require further investigation in larger and more diverse samples. This- study provides important clues about the challenges that risk reduction programs face for migrant workers from China and elsewhere.

The effect of ambient temperature and risk of cardiovascular disease hospitalization in China: a meta-analysis.

The effect of ambient temperature on relative risk (RR) of cardiovascular disease (CVD) is different in China than in other countries due to the different geographical environment, climate the different inter- and intra-individual characteristics of the population within China. It is therefore important to integrate information to evaluate the impact of temperature on RR of CVD in China. We performed a meta-analysis to evaluate the effect of temperature on RR of CVD. The Web of Science, Google Scholar, and China National Knowledge Infrastructure databases were searched back to 2022 and nine studies were included in the study. The Cochran Q test and I2 statistics were used to assess heterogeneity, while Egger's test was used to assess publication bias. The pooled estimated size of the relationship between ambient temperature and CVD hospitalization in the random effect model was 1.2044 (95%CI: 1.0610-1.3671) for the cold effect and 1.1982 (95%CI: 1.0166-1.4122) for the heat effect. The Egger's test showed a potential publication bias for the cold effect, whereas there was no apparent publication bias for the heat effect. There is a significant effect of ambient temperature on RR of CVD for both the cold effect and heat effect. The effect of socioeconomic factors should be considered more thoroughly in future studies.

Chlorpyrifos-induced dysregulation of synaptic plasticity in rat hippocampal neurons.

Chlorpyrifos (CPF) is a widely used organophosphorus pesticide. Increasing evidence has shown that exposure to CPF in early life might induce neurodevelopmental disorders, but the pathogenesis remains uncertain. Synaptic plasticity plays a crucial role in neurodevelopment. This study aimed to investigate the effect of CPF on synaptic plasticity in hippocampal neurons and establish the cellular mechanism underlying these effects. Using CPF-exposed rat and primary hippocampal neurons model, we analyzed the impact of CPF on the synaptic morphology, the expression level of a presynaptic protein, a postsynaptic protein and ionotropic glutamate receptors (iGluRs), as well as the effects on the Wnt/ß-catenin pathway. We found that the synapses were shortened, the spines were decreased, and the expression of synaptophysin (Syp), postsynaptic density-95 (PSD-95), GluN1, GluA1 and Wnt7a, as well as active ß-catenin in primary hippocampal neurons was decreased. Our study suggests that CPF exposure induced dysregulation of synaptic plasticity in rat hippocampal neurons, which might provide novel information regarding the mechanism of CPF-induced neurodevelopmental disorders.

Influence of a new abutment design concept on the biomechanics of peri-implant bone, implant components, and microgap formation: a finite element analysis.

BACKGROUND: A new two-piece abutment design consisting of an upper prosthetic component and tissue-level base has been introduced; however, the biomechanical behavior of such a design has not been documented. This study aimed to investigate the effect of a two-piece abutment design on the stress in the implant components and surrounding bone, as well as its influence on microgap formation. METHODS: To simulate the implant models in the mandibular left first molar area, we established nine experimental groups that included three bone qualities (type II, III, and IV) and three implant-abutment designs (internal bone level, tissue level, and a two-piece design). After the screw was preloaded, the maximum occlusal (600 N) and masticatory (225 N) forces were established. Finite element analysis was performed to analyze the maximum and minimum principal stresses on the peri-implant bone; the von Mises stresses in the implants, abutments, bases, and screws, and the microgaps at the implant-abutment, implant-base, and base-abutment interfaces. RESULTS: For all three loading methods, the two-piece abutment design and bone-level connection exhibited similarities in the maximum and minimum principal stresses in the peri-implant bone. The von Mises stresses in both screws and bases were greater for the two-piece design than for the other connection types. The smallest microgap was detected in the tissue-level connection; the largest was observed at the implant-base interface in the two-piece design. CONCLUSIONS: The present study found no evidence that the abutment design exerts a significant effect on peri-implant bone stress. However, the mechanical effects associated with the base and screws should be noted when using a two-piece abutment design. The two-piece abutment design also had no advantage in eliminating the microgap.

Evaluation of HZX-960, a novel DCN1-UBC12 interaction inhibitor, as a potential antifibrotic compound for liver fibrosis.

Liver fibrosis is a very common health problem and currently lacks effective treatments. Cullin RING E3 ligases (CRLs) regulate the turnover of ∼20% of mammalian cell proteins. Neddylation, the process by which NEDD8 is covalently attached to cullin proteins through sequential enzymatic reactions, is critical for the activation of CRLs and was recently found to be elevated in liver fibrosis. NEDD8-activating enzyme E1-specific inhibition led to the reduced liver damage characterized by decreased apoptosis, inflammation, and fibrosis. However, the relevance of a co-E3 ligase, DCN1, in liver fibrosis remains unclear. Here, a novel and potent DCN1-UBC12 interaction inhibitor HZX-960 was discovered with an IC50 value of 9.37 nmol/L, which could inhibit the neddylation of cullin3. Importantly, we identified that HZX-960 treatment could attenuate transforming growth factor ß-induced liver fibrotic responses by reducing the deposition of collagen I and α-smooth muscle actin, and upregulating cellular NF-E2-related factor 2, hemeoxygenase 1, and NADPH quinone oxidoreductase-1 levels in two hepatic stellate cell lines. Additionally, DCN1 was shown to be unregulated in CCl4-induced mice liver tissue, and liver fibrotic signaling in mice was reduced by HZX-960. Therefore, our data demonstrated that HZX-960 possessed anti-liver fibrosis ability and that DCN1 may be a potential therapeutic target for liver fibrosis treatment.

Real-Time Imaging of Stress in Single Spherulites and Its Relaxation at the Single-Particle Level in Semicrystalline Polymers.

Crystallization-induced microscopic stress and its relaxation play a vital role in understanding crystallization behavior and mechanism. However, the real-time measurements for stress and its relaxation seem to be an unachievable task due to difficulties in simultaneous labeling, spatiotemporal discrimination, and continuous quantification. We designed a micron-sized fluorescent probe, whose fluorescence can respond to stress-induced environmental rigidity and whose three-dimensional (3D) flow can respond to stress relaxation. Using the as-prepared fluorescent probe, we established a versatile strategy to realize the real-time 3D imaging of stress and its relaxation in the crystallization process. The rigidity-responsive fluorescence clearly indicated the stress, while the 3D flow movement could quantify the stress relaxation. It is revealed that stress in spherulites increased dramatically as a result of the suppression of stress relaxation in polymer melts. The developed method provides a novel avenue to simultaneously detect stress and its relaxation in various semicrystalline polymers at the single-particle level. This success would achieve the microscopic ways to guide the development of advanced crystallization-dependent materials.

Meta-hologram enabled by a double-face copper-cladded metasurface based on reflection-transmission amplitude coding.

Here, we propose a double-face copper-cladded meta-hologram that can efficiently manipulate the amplitude of electromagnetic waves in both transmission and reflection spaces, depending on the polarization state of the incident electromagnetic wave. The proposed meta-hologram is validated by encoding the transmission-reflection amplitude information of two independent images into a single metasurface. The holographic images obtained from measurements agree qualitatively with simulation results. The proposed metasurface presents a novel, to the best of our knowledge, scheme for electromagnetic wavefront control in the whole space and overcomes the limitations of narrow frequency band operation.