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Anti-CRISPR proteins are very efficient for inhibiting CRISPR/Cas9-based genome editing tools in both herbaceous and woody plant species.

Purpose: The aim of this study was to analyze the anatomical and visual outcomes after internal limiting membrane (ILM) peeling or ILM flap insertion in highly myopic macular holes (HMMHs) and try to compare these two surgical techniques in large HMMHs. Methods: This is a retrospective, consecutive series study of patients with HMMH undergone vitrectomy from September 2016 to January 2021. We observed the outcomes of the HMMHs with ILM peeling and ILM flap insertion, respectively. Binary logistic regression and receiver operating characteristic (ROC) curve were used to analyze the relationship between the minimum linear diameter (MLD) of macular hole and the initial closure rate in ILM peeling group. Finally, we compared the surgical outcomes between these two surgical techniques in large HMMHs. Results: There were 69 HMMHs using ILM peeling with a mean MLD of 423.55 ± 190.99 µm and 33 HMMHs using ILM flap insertion with a mean MLD of 600.79 ± 187.85 µm. The initial type I closure rate was 86.9% (60/69) and 81.8% (27/33), respectively. MLD had a good correlation with the initial closure rate in HMMHs with ILM peeling (p = 0.046). The large HMMH (MLD >461.5 μm obtained by ROC curve) was present in 26 eyes with each surgical technique, and there was no significant difference of baseline characteristics between them. In large HMMHs, the initial closure rate of ILM peeling was 73.0% and that of ILM flap insertion was 84.6% (p = 0.499). Postoperative best-corrected visual acuity (BCVA) improved significantly in both groups (p < 0.001), and the BCVA at last follow-up was better in closed large HMMHs with ILM peeling (p = 0.034). Conclusion: In HMMHs with ILM peeling, the initial closure rate was decreased when MLD >461.5 μm. ILM peeling may obtain better functional prognosis in eyes with closed large macular holes compared with ILM flap insertion.

Electro-hydraulic servo system (EHSS) plays an important role in many industrial and military applications. However, its high-performance tracking control is still a challenging mission due to its nonlinear system dynamics and model uncertainties. In this paper, a novel adaptive robust integral method of the sign of the error (ARISE) with extended state observer (ESO) is proposed. Firstly, the nonlinear mathematical model of typical EHSS with modeling uncurtains and uncertain nonlinear is established. Then, ESO is used to estimate the state and lumped disturbance, of which the unknown parameter estimations can be updated by the novel adaptive law. Results shows that the novel controller achieves better tracking performance in maximum tracking error, average tracking error and standard deviation of the tracking error.

Introduction: To investigate the characteristics of macular pseudoholes (MPHs) with different foveal profiles and their impact on preoperative and postoperative visual acuity (VA). Methods: A retrospective review of 47 eyes from 46 consecutive patients with MPH who had undergone vitrectomy was conducted. The MPHs were classified into u-shape and v-shape according to the morphological description of the foveola base. The best-corrected visual acuity (BCVA), central foveal point thickness, parafoveal thickness, parafoveal inner and outer retinal thickness, stretched lamellar cleavage, microcystic macular edema (MME), disorganization of retinal inner layers (DRIL), and the integrity of outer retinal layers were recorded. Results: The eyes in the v-shaped group (n = 31) had lower BCVA, thicker retinal thickness, more intraretinal cleavage, MME, and DRIL than the u-shaped (n = 16) group (all p < 0.05). Multiple regression analysis revealed that the morphology of the foveola base was significantly related to the preoperative BCVA (p = 0.025). The VA was significantly improved in both groups, and the improvement was greater in the v-shaped group (p = 0.024). No significant difference was found in the postoperative BCVA between the two groups (all p > 0.05). Conclusion: The v-shape, reflecting the stretch in the foveola, had a significant impact on preoperative BCVA. However, the VA was improved after surgery whatever their initial foveal profile.

A novel polyurethane organohydrogel with anti-freezing, anti-drying, and electromagnetic shielding abilities was used as a magnetic responsive switch and strain sensor.

Deciduous woody plants like poplar (Populus spp.) have seasonal bud dormancy. It has been challenging to simultaneously delay the onset of bud dormancy in the fall and advance bud break in the spring, as bud dormancy, and bud break were thought to be controlled by different genetic factors. Here, we demonstrate that heterologous expression of the REVEILLE1 gene (named AaRVE1) from Agave (Agave americana) not only delays the onset of bud dormancy but also accelerates bud break in poplar in field trials. AaRVE1 heterologous expression increases poplar biomass yield by 166% in the greenhouse. Furthermore, we reveal that heterologous expression of AaRVE1 increases cytokinin contents, represses multiple dormancy-related genes, and up-regulates bud break-related genes, and that AaRVE1 functions as a transcriptional repressor and regulates the activity of the DORMANCY-ASSOCIATED PROTEIN 1 (DRM1) promoter. Our findings demonstrate that AaRVE1 appears to function as a regulator of bud dormancy and bud break, which has important implications for extending the growing season of deciduous trees in frost-free temperate and subtropical regions to increase crop yield.

Based on fully considering the actual differences in statistical indicators between Hong Kong, Macao, and nine cities in the Pearl River Delta, this paper constructs a high-quality urban development evaluation system that is suitable for the actual development of the Guangdong Hong Kong Macao Greater Bay Area. Entropy Weighted TOPSIS two-step method is used to process data and systematically investigate the changes in the high-quality development index of 11 cities in the Guangdong Hong Kong Macao Greater Bay Area from 2013 to 2020. The study found that: the Guangdong Hong Kong Macao Greater Bay Area thoroughly implemented the new development concept, and the high-quality development level continued to improve; The profound integration effect of Guangdong Hong Kong Macao Greater Bay Area appears, and the high-quality development of the region is promoted in coordination; The construction of the Guangdong Hong Kong Macao Greater Bay Area has strongly promoted the great practice of "one country, two systems" to achieve stability and prosperity.

Designing metal-metal oxide heteronanostructures with synergistic and superior activities (unattainable in the case of a single entity) is of great interest for a wide range of technological applications. Traditional synthetic strategies typically require reducing agents, stabilizing ligands, or high temperature reductive treatment to produce oxide-supported metals. Herein, a facile noble metal deposition strategy is developed to produce silver, gold, and platinum nanocrystals on the surface of hollow mesoporous cerium oxide nanospheres without any pretreatment. Unlike the galvanic replacement reaction, the developed protocol employs the innate reductive potential of CeO

To investigate the changes in the external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ) integrity and their relationship with visual outcomes after idiopathic epiretinal membranes peeling.Clinical records of 150 eyes from 144 consecutive patients who underwent vitrectomy were reviewed. The status of IZ, EZ, and ELM was assessed by spectral-domain optical coherence tomography at baseline and 1, 4, 10, and 24 months postoperatively.Sixty-one eyes presented with photoreceptor layer disruption preoperatively, and IZ disruption (40.7%) was the primary type. The best-corrected visual acuity (BCVA) in the photoreceptor disruption group was significantly lower than that in the intact group at baseline and the final follow-up. Of them, ELM + EZ + IZ disruption showed the worst BCVA (P = 0.001). After surgery, 62 eyes were observed with disruption aggravated. EZ + IZ disruption (51.0%) was the most frequent type at 1 month postoperatively. The eyes with longer symptom duration, better BCVA, earlier stage, thinner CFT at baseline, and combined cataract surgery more tended to be observed with photoreceptor damage progressed after surgery (P 0.05). There was no significant difference in the final BCVA between the eyes with and without damage progressed (P = 0.332). Finally, 28.1% of the eyes recovered photoreceptor continuity. The eyes with foveal photoreceptor integrity restored had better BCVA than those remaining discontinuous (P 0.001).ERM-induced photoreceptor disruption mainly manifests as IZ disruption and has a negative effect on BCVA, whereas surgery mainly causes EZ and IZ disruption, which does not have a significant impact on the final BCVA.

Silicon (Si) enhances plant tolerance to various biotic and abiotic stressors such as salinity, drought, and heat. In addition, Si can be biomineralized within plants to form organic carbon-containing phytoliths that can have ecosystem-level consequences by contributing to long-term carbon sequestration. Si is taken up and transported in plants via different transporter proteins such as influx transporters (e.g., Lsi1, Lsi6) and efflux transporters (e.g., Lsi2). Additionally, the imported Si can be deposited in plant leaves via silicification process using the Siliplant 1 (e.g., Slp1) protein. Functional homologs of these proteins have been reported in different food crops. Here, we performed a genome-wide analysis to identify different Si transporters and Slp1 homologs in the bioenergy crop poplar (Populus trichocarpa Torr. and A. Gray ex W. Hook). We identified one channel-type Si influx transporter (PtLsi1; Potri.017G083300), one Si efflux transporter (PtLsi2; Potri.012G144000) and two proteins like Slp1 (PtSlp1a; Potri.004G168600 and PtSlp1b; Potri.009G129900) in the P. trichocarpa genome. We found a unique sequence (KPKPPVFKPPPVPI) in PtSlp1a which is repeated six times. Repeated presence of this sequence in PtSlp1a indicates that this protein might be important for silicification processes in P. trichocarpa. The mutation profiles of different Si transporters in a P. trichocarpa genome-wide association study population identified significant and impactful mutations in Potri.004G168600 and Potri.009G129900. Using a publically accessible database (http://bar.utoronto.ca/eplant_poplar/), digital expression analysis of the putative Si transporters in P. trichocarpa found low to moderate expression in the anticipated tissues, such as roots and leaves. Subcellular localization analysis found that PtLsi1/PtLsi2 are localized in the plasma membrane, whereas PtSlp1a/PtSlp1b are found in the extracellular spaces. Protein–Protein interaction analysis of PtLsi1/PtLsi2 identified Delta-1-pyrroline-5-carboxylate synthase (P5CS) as one of the main interacting partners of PtLsi2, which plays a key role in proline biosynthesis. Proline is a well-known participant in biotic and abiotic stress tolerance in plants. These findings will reinforce future efforts to modify Si accumulation for enhancing plant stress tolerance and carbon sequestration in poplar.

To observe the characteristics of highly myopic macular holes (HMMHs) with macular retinoschisis (MRS) by optical coherence tomography (OCT) and explore the possible relationship between HMMHs and different types of MRS.We consecutively reviewed the clinical data and OCT images of the patients with HMMHs from June 2015 to February 2021. Then we picked eyes with MRS from these HMMHs for analysis. The minimum linear diameter (MLD), basal diameter (BD), and height (H) of HMMHs were measured. HMMHs were grouped according to the extent or layer involvement of the concomitant MRS and the characteristics were compared among groups. The impact of MRS on the MLD of macular hole was analyzed with multivariable linear regression.We included 127 patients with MRS from 168 HMMHs (75.5%) for analysis. According to the different classification systems, the most frequent type of MRS in HMMHs was S3 (foveal but not entire macular area MRS) (62.2%) and both inner- and outer- (I/O-MRS) involved types. In our study, HMMHs with more extensive MRS had larger MLD, larger BD, larger H, and poorer best-corrected visual acuity (BCVA). Meanwhile, HMMHs with outer layer-involved MRS (outer MRS and I/O-MRS) had larger BD than HMMH with only inner layer-involved MRS. (All P 0.05) Multivariable linear regression further illustrated only the extent of MRS was significantly associated with the MLD of HMMH, while there was no significant correlation between the involved retinal layers and the MLD of HMMH.HMMH with MRS presented as a predominant type in HMMHs. The MRS was always with a relatively large extent and involved both inner and outer layers. MLD of HMMH was mainly affected by the extent of MRS.

The ability to stack multiple genes in plants is of great importance in the development of crops with desirable traits but can be challenging due to limited selectable marker options. Here we establish split selectable marker systems using protein splicing elements called “inteins” for Agrobacterium-mediated co-transformation in plants. First, we show that such a split selectable marker system can be used effectively in plants to reconstitute a visible marker, RUBY, from two non-functional fragments through tobacco leaf infiltration. Next, to determine the general applicability of our split selectable marker systems, we demonstrate the utility of these systems in the model plants Arabidopsis and poplar by successfully stacking two reporters eYGFPuv and RUBY, using split Kanamycin or Hygromycin resistance markers. In conclusion, this method enables robust plant co-transformation, providing a valuable tool for the simultaneous insertion of multiple genes into both herbaceous and woody plants efficiently.

The genus Populus has long been used for environmental, agroforestry and industrial applications worldwide. Today Populus is also recognized as a desirable crop for biofuel production and a model tree for physiological and ecological research. As such, various modern biotechnologies, including CRISPR/Cas9-based techniques, have been actively applied to Populus for genetic and genomic improvements for traits such as increased growth rate and tailored lignin composition. However, CRISPR/Cas9 has been primarily used as the active Cas9 form to create knockouts in the hybrid poplar clone ‘717-1B4’ (Populus tremula x P. alba clone INRA 717-1B4). Alternative CRISPR/Cas9-based technologies, e.g., those involving modified Cas9 for gene activation and base editing, have not been evaluated in most Populus species for their efficacy. Here we employed a deactivated Cas9 (dCas9)-based CRISPR activation (CRISPRa) technique to fine-tune the expression of two target genes, TPX2 and LecRLK-G which play important roles in plant growth and defense response, in hybrid poplar clone ‘717-1B4’ and poplar clone ‘WV94’ (P. deltoides ‘WV94’), respectively. We observed that CRISPRa resulted in 1.2-fold to 7.0-fold increase in target gene expression through transient expression in protoplasts and Agrobacterium-mediated stable transformation, demonstrating the effectiveness of dCas9-based CRISPRa system in Populus. In addition, we applied Cas9 nickase (nCas9)-based cytosine base editor (CBE) to precisely introduce premature stop codons via C-to-T conversion, with an efficiency of 13%-14%, in the target gene PLATZ which encodes a transcription factor involved in plant fungal pathogen response in poplar clone ‘717-1B4’. Overall, we showcase the successful application of CRISPR/Cas-based technologies in gene expression regulation and precise gene engineering in two Populus species, facilitating the adoption of emerging genome editing tools in woody species.

The Salicaceae family is of growing interest in the study of dioecy in plants because the sex determination region (SDR) has been shown to be highly dynamic, with differing locations and heterogametic systems between species. Without the ability to transform and regenerateSalixin tissue culture, previous studies investigating the mechanisms regulating sex in the genusSalixhave been limited to genome resequencing and differential gene expression, which are mostly descriptive in nature, and functional validation of candidate sex determination genes has not yet been conducted. Here we used Arabidopsis to functionally characterize a suite of previously identified candidate genes involved in sex determination and sex dimorphism in the bioenergy shrub willowSalix purpurea. Six candidate master regulator genes for sex determination were heterologously expressed in Arabidopsis, followed by floral proteome analysis. In addition, 11 transcription factors with predicted roles in mediating sex dimorphism downstream of the SDR were tested using DAP-Seq in both male and femaleS. purpureaDNA. The results of this study provide further evidence to support models for the roles ofARR17andGATA15as master regulator genes of sex determination inS. purpurea, contributing to a regulatory system that is notably different from that of its sister genusPopulus. Evidence was also obtained for the roles of two transcription factors, anAP2/ERFfamily gene and a homeodomain-like transcription factor, in downstream regulation of sex dimorphism.

Virus-assisted delivery of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system represents a promising approach for editing plant genomes. Among the CRISPR/Cas systems, CRISPR/Cas9 is most widely used; however, to pack the relatively large size of the CRISPR/Cas9 system into viral vectors with confined packaging capacity is challenging. To address this technical challenge, we developed a strategy based on split inteins that splits the required CRISPR/Cas9 components across a dual-vector system. The CRISPR/Cas reassembles into an active form following co-infection to achieve targeted genome editing in plant cells. An intein-mediated split system was adapted and optimized in plant cells by a successful demonstration of split-eYGFPuv expression. Using a plant-based biosensor, we demonstrated for the first time that the split-nCas9 can induce efficient base editing in plant cells. We identified several split sites for future biodesign strategies. Overall, this strategy provides new opportunities to bridge different CRISPR/Cas9 tools including base editor, prime editor, and CRISPR activation with virus-mediated gene editing.

This study aimed to evaluate fixation stability and position changes after epiretinal membrane (ERM) surgery.This is a retrospective study that included 60 consecutive eyes with idiopathic ERM. All patients received comprehensive ophthalmic examinations preoperatively and 1, 4, and 10 months postoperatively. Main outcome measures included fixation stability and position, bivariate contour ellipse area, and preferred retinal locus.The number of patients with stable fixation and predominantly central fixation was increased significantly after ERM surgery (61.7 vs. 73.3%, P = 0.001; 41.7 vs. 71.7%, P = 0.037). The correlation analysis showed that the preoperative factors associated with improved postoperative fixation stability were a larger bivariate contour ellipse area value (P0.001), poorer visual acuity (P = 0.002), advanced stage (P = 0.002), thicker central fovea thickness (P = 0.015), and a longer preferred retinal locus-fovea distance (P = 0.025). As for the improved fixation location, the associated preoperative factors were age (P = 0.003), central fovea thickness (P = 0.044), and preferred retinal locus-fovea distance (P0.001).Our observations point to the changes of fixation parameters in patients after ERM surgery. We found that patients with preoperative unstable, eccentric fixation and poor BCVA can significantly benefit from the surgery. This result indicates that even in patients with severe macular damage, the ERM surgery still has great benefits in recovering visual function.

Under the effects of complex geological and stress environments, burst hazards continue to be a major challenge for underground space utilization and deep resources exploration as its occurrence can lead to personnel causalities, equipment damage and structural collapse. Considering the stress path experienced by in-situ coal body, cyclic loading appears in quite various forms for instance shearer cutting, overlying strata breakage, hydro-fracturing and blasting, during tunnel, mining and underground space utilizing process. The stability of the underground coal body subject to periodic loading/unloading stress is extremely important for maintain the function of designed engineering structure for waste storage, safe mining, roadway development, gas recovery, carbon sequestration and so on. The mechanical properties of hard rock subject to cyclic fatigue loads has been intensively investigated by many researchers as the rock burst induced by supercritical loads has long been a safety risk and engineering problems for civil and tunneling engineering under deep overburden. More recently, the mechanical properties of coal samples under cyclic fatigue loads is investigated from the aspect of hysteresis, energy dissipation and irreversible damage as the burst hazards of brittle coal is rising in many countries. However, the crack propagation and fracture pattern of brittle coal need more research to understand the micro mechanism of burst incubation subject to cyclic fatigue loads as brittle coal can store more elastic strain energy and rapidly release the energy when its ultimate strength once reached. This research studied the internal crack status corresponding to different cyclic fatigue loading stage of brittle coal samples. The AE monitoring was applied during the uniaxial and cyclic loading process of brittle coal samples to record the crack intensity of samples at different loading stages. The damage evolution curve corresponding to loading status was then determined. The fracture pattern of coal samples determined by micro-CT scan was observed and discussed. It has been found by this paper that brittle coal of uniaxial compression tests demonstrated sudden failure caused by major splitting fracture while that of cyclic fatigue tests experienced progressive failure with mixture fracture network.

Persistent high-risk human papillomavirus (HPV) infection is the pivotal cause of cervical carcinogenesis. HPV types distribution varies greatly by region, and its long-term changes of prevalence remain to be fully characterized in China. Here, the largest population of 198,111 consecutive women who underwent routine cervical screening were investigated from 2015 to 2021 in Guangzhou, south China. The results showed that the overall HPV prevalence was 21.66% (42,911/198,111), and the annual prevalence increased significantly from 2015 to 2021 (p < 0.001). HPV52, 16, 58, CP8304, 51, 53, 39, and 68 were the most prevalent HPV types. The relative HPV-positive rate correlated positively with the progression of cervical intraepithelial neoplasia (p < 0.001); HPV16 was the predominant carcinogenic type, followed by HPV52 and HPV18. HPV infections were significantly age-specific, and 26.51% (11,375/42,911) of cases were caused by multiple HPV types. In addition, HPV infections typically cleared over a median time of 16 (interquartile range 9–31) months, and the clearance of HPV16 was significantly faster than that of other types (p < 0.001). These findings may serve as a guide for local governments to evaluate HPV vaccination and cervical cancer prevention strategies in south China.

Background Enterovirus (EV) infections are being increasingly seen in younger infants, often being more severe than in older children. The risk factors of EV infection in infants have been inadequately investigated till date. Methods We conducted a retrospective study on hospitalized children with laboratory-confirmed EV infection (50 infants aged 0–3 months and 65 older than 3 months) at a tertiary care center in China. Prevalence, clinical characteristics, and genetic features of the virus were analyzed, and independent predictors for severe infection were assessed. Results Clinical findings showed that severe infection was more common in infants aged 0–3 months than in older children (78.0% vs. 35.4%, p p p Conclusions Our data indicated that EV-B types mainly cause severe infection in infants aged 0–3 months. Therefore, knowledge about EV-B types could have implications in designing effective intervention and prevention strategies for young infants with severe EV infection.

As mining progresses into deep ore deposits in Australia, geo-hazards such as coal burst and outbursts are becoming a major concern for mine workers. The occurrence of geo-hazards involved the ejection of coal lumps and sometimes large volumes of hazardous gases such as methane and carbon dioxide. Whilst it is extremely important to de-stress and de-gas the seam and adjacent strata before roadway development and install competent support systems such as steel mesh and bolt, the last line of protection will be the installation of a protective canopy on the Continuous Miner (CM), which is typically used for roadway developments, to shield mine workers from these deadly dynamic impacts of coal and rock resulting from a burst or outburst. This paper aims to introduce the design, manufacture and testing of an innovative modular protective structure on the CM in underground coal mines. The developed protective system can be easily assembled in the underground mining environment and provide a high level of protection against flying debris hazards in the event of a coal burst. The extensive experimental program and numerical simulations have confirmed the high performance of the protective system against high-speed impact loading by single and multiple coal rocks and projectiles.

Three complexes [Fe2(L)2Cl4] (1), [Co2(L)2Cl4] (2) and [Ni(L)2Cl2]·CH2Cl2 (3) were synthesized and characterized. Complex 1 exhibits a slow magnetic relaxation behaviour. Complexes 1–3 are catalytically active toward the OER.

CRISPR construct design is a key step in the practice of genome editing, which includes identification of appropriate Cas proteins, design and selection of guide RNAs (gRNAs), and selection of regulatory elements to express gRNAs and Cas proteins. Here, we review the choices of CRISPR-based genome editors suited for different needs in plant genome editing applications. We consider the technical aspects of gRNA design and the associated computational tools. We also discuss strategies for the design of multiplex CRISPR constructs for high-throughput manipulation of complex biological processes or polygenic traits. We provide recommendations for different elements of CRISPR constructs and discuss the remaining challenges of CRISPR construct optimization in plant genome editing.

Objectives The present study aimed to investigate the distribution of lymphocyte subsets and cytokines expression in the peripheral blood of bitumen fumes-exposed workers. Methods In this study, 129 workers from molding and roasting workshops were recruited as the exposed group and 99 office and quality inspection staff were chosen as the control. The polycyclic aromatic hydrocarbons (PAHs) levels of bitumen fumes in individual and fixed-point air samples and the urinary levels of 1-hydroxypyrene (1-OH-P), 1-hydroxynaphthols (1-OH-N) and 2-hydroxynaphthols (2-OH-N) in workers were measured using High Performance Liquid Chromatography. The lymphocyte subsets and serum cytokines concentrations were analyzed by flow cytometry and cytometric bead array, respectively. Results The median values of PAHs were 0.08 mg/m3 for permissible concentration-time weighted average and 0.12 mg/m3 for permissible concentration-short term exposure (PC-STEL) in molding and roasting workshops, which were higher than that in the control area (< 0.01 mg/m3). Multivariate linear regression models were used to adjust for influential covariates, including age, gender, work age, smoking status, and alcohol consumptions. After adjusting for these covariates, we compared levels of urinary PAHs metabolites, the percentages of lymphocyte subsets, and serum cytokines concentrations between the two groups. The 1-OH-P, 1-OH-N, and 2-OH-N levels in the urine of bitumen fumes exposed workers were significantly higher than that in the controls (P < 0.05). Compared with the control group, the percentage of the natural killer (NK) cell (CD56+ cell) was significantly increased in the exposed group (P < 0.001). There was a significant decrease in the percentages of CD3+ T cell, CD4+ T cell, and CD8+ T cell in the exposed group compared to the control (P < 0.001). The serum levels of interleukin-1β (IL-1β) and IL-6 in bitumen fumes exposed workers were significantly higher than that of the controls (P < 0.05). Moreover, positive correlations were observed between the serum levels of IL-1β, IL-6, and urinary 1-OH-P levels in bitumen fumes-exposed workers, respectively (P < 0.05). There were no significant differences in the serum levels of IL-8, tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1β (MIP-1β) and monocyte chemotactic protein-1 (MCP-1) between the exposed group and the control group (P > 0.05). Conclusion Our study suggested that low dose of bitumen fumes exposure could decrease the percentage of T cell, increase the percentage of NK cell and stimulate the release of serum IL-1β and IL-6 in the peripheral blood of exposed workers. The serum levels of IL-1β and IL-6 were positive correlated with the urinary 1-OH-P levels in bitumen fumes exposed workers. These results may inform the search for potential effective biomarkers and provide evidences for early health monitoring in workers occupationally exposed to bitumen fumes.

Plant synthetic biology and genetic engineering depend on the controlled expression of transgenes of interest, which relies heavily on the use ofAgrobacterium-mediated transformation. Here we establish a novel split selectable marker system using protein splicing elements called “inteins” forAgrobacterium-mediated co-transformation in plants. This method enables robust co-transformation inArabidopsisand poplar, providing a novel strategy for the simultaneous insertion of multiple genes into both herbaceous and woody plants.

Numerous studies have demonstrated that type 2 diabetes (T2D) is closely linked to the occurrence of Alzheimer’s disease (AD). Nevertheless, the underlying mechanisms for this association are still unknown. Insulin resistance (IR) hallmarked by hyperinsulinemia, as the earliest and longest-lasting pathological change in T2D, might play an important role in AD. Since hyperinsulinemia has an independent contribution to related disease progressions by promoting inflammation in the peripheral system, we hypothesized that hyperinsulinemia might have an effect on microglia which plays a crucial role in neuroinflammation of AD. In the present study, we fed 4-week-old male C57BL/6 mice with a high-fat diet (HFD) for 12 weeks to establish IR model, and the mice treated with standard diet (SD) were used as control. HFD led to obesity in mice with obvious glucose and lipid metabolism disorder, the higher insulin levels in both plasma and cerebrospinal fluid, and aberrant insulin signaling pathway in the whole brain. Meanwhile, IR mice appeared impairments of spatial learning and memory accompanied by neuroinflammation which was characterized by activated microglia and upregulated expression of pro-inflammatory factors in different brain regions. To clarify whether insulin contributes to microglial activation, we treated primary cultured microglia and BV2 cell lines with insulin in vitro to mimic hyperinsulinemia. We found that hyperinsulinemia not only increased microglial proliferation and promoted M1 polarization by enhancing the production of pro-inflammatory factors, but also impaired membrane translocation of glucose transporter 4 (GLUT4) serving as the insulin-responding glucose transporter in the processes of glucose up-taking, reduced ATP production and increased mitochondrial fission. Our study provides new perspectives and evidence for the mechanism underlying the association between T2D and AD.

Shrub willows (