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Abstract Animal models of peripheral nerve injury (PNI) serve as the fundamental basis for the investigations of nerve injury, regeneration, and neuropathic pain. The injury properties of such models, including the intensity and duration, significantly influence the subsequent pathological changes, pain development, and therapeutic efficacy. However, precise control over the intensity and duration of nerve injury remains challenging within existing animal models, thereby impeding accurate and comparative assessments of relevant cases. Here, a new model that provides quantitative and off‐body controllable injury properties via a magnetically controlled clamp, is presented. The clamp can be implanted onto the rat sciatic nerve and exert varying degrees of compression under the control of an external magnetic field. It is demonstrated that this model can accurately simulate various degrees of pathology of human patients by adjusting the magnetic control and reveal specific pathological changes resulting from intensity heterogeneity that are challenging to detect previously. The controllability and quantifiability of this model may significantly reduce the uncertainty of central response and inter‐experimenter variability, facilitating precise investigations into nerve injury, regeneration, and pain mechanisms.

Summary: Background: Synovitis has long been considered a common and modifiable inflammatory feature of osteoarthritis (OA), but current disease-modifying anti-inflammatory treatments appear ineffective in OA clinical trials. Elucidating the temporal relationship between synovitis and OA could provide insight into the role of synovitis in OA. Methods: We conducted a prospective cohort study based on the baseline and three-year follow-up data from the Xiangya Osteoarthritis (XO) Study. We assessed bidirectional associations between ultrasound-detected synovitis and radiographic and symptomatic OA at knee and hand sites using generalized estimating equations. Additionally, we performed bidirectional Mendelian randomization (MR) analyses to test these hypotheses utilising whole-genome sequencing data in the XO population. Age, sex, body mass index, smoking, alcohol consumption, educational level, physical activity, and joint injury history were adjusted for these analyses. Findings: A total of 2211, 2420, 2280, and 2600 participants were enrolled for analyses of radiographic knee OA (RKOA), symptomatic knee OA (SKOA), radiographic hand OA (RHOA) and symptomatic hand OA (SHOA), respectively. The baseline synovitis (i.e., with synovitis vs. without synovitis) was associated with the incident RKOA (76/277 vs. 557/3674 knees), SKOA (49/387 vs. 287/4213 knees), RHOA (171/358 vs. 686/3664 hands) and SHOA (35/689 vs. 76/4327 hands), with adjusted odds ratio (aORs) of 2.2 (95% CI 1.7–3.1), 2.0 (1.3–2.9), 3.4 (2.7–4.4), and 2.4 (1.5–3.8), respectively. The baseline RKOA (with OA vs. without OA: 409/1246 vs. 481/3758 knees), SKOA (200/576 vs. 675/4356 knees), RHOA (192/778 vs. 410/3723 hands), and SHOA (41/162 vs. 548/4285 hands) were also associated with the incident synovitis, with aORs of 3.4 (95% CI 2.9–4.1), 2.7 (2.1–3.4), 2.3 (1.8–2.9) and 1.9 (1.2–2.8), respectively. These bidirectional associations were stronger when more active synovitis was compared with the reference group (all P

Angiopteris nodosipetiolata Ting Wang tris, H.F.Chen & Y.H.Yan, a new fern of Marattiaceae, is described and illustrated. Morphologically, A. nodosipetiolata is similar to A. chingii with more than one naked pulvinus on the stipe and numerous jointed hairs on the undersides of the mature pinnae. However, the pinnae of A. nodosipetiolata are lanceolate and can reach up to 4–6 pairs, whereas they are elliptic and occur in 2–3 pairs in A. chingii. Phylogenetic and genetic distance analysis, based on the plastid genomes, also indicates that A. nodosipetiolata is not closely related to A. chingii. Currently, there are ca. 500 mature individuals in Gulinqing Nature Reserve and we suggest A. nodosipetiolata should be categorised as an Endangered (EN) species according to the criteria of IUCN.

Abstract Aiming at the engineering problem of roadway deformation and instability of swelling soft rock widely existed in Kailuan mining area, the mineral composition and microstructure of such soft rock were obtained by conducting scanning electron microscopy, X-ray diffraction experiments, uniaxial and conventional triaxial tests, and the law of softening and expanding of such soft rock and the failure mechanism of surrounding rock were identified. The combined support scheme of multi-level anchor bolt, bottom corner pressure relief and fractional grouting is proposed. The roadway supporting parameters are adjusted and optimized by FLAC3D numerical simulation, and three supporting methods of multi-layer anchor bolt, bottom corner pressure relief and fractional grouting are determined and their parameters are optimized. The study results show that: the total amount of clay minerals is 53–75%, pores, fissures, nanoscale and micron layer gaps are developed, providing a penetrating channel for water infiltration to soften the surrounding rock; the three-level anchor pressure-relief and grouting support technology can control the sinking amount of the roof within 170 mm, the bottom drum amount within 210 mm, the bolts of each level is evenly distributed in tension, and the maximum stress and bottom drum displacement in the pressure relief area are significantly reduced; the pressure-relief groove promotes the development of bottom corner cracks, accelerates the secondary distribution of peripheral stress, and weakens the effect of high stress on the shallow area. Using time or displacement as the index, optimizing the grouting time, filling the primary and excavation cracks, blocking the expansion and softening effect of water on the rock mass, realizing the dynamic unity of structural yielding pressure and surrounding rock modification, has guiding significance for the support control of soft rock roadway.

Abstract The colored calla lily is an ornamental floral plant native to southern Africa, belonging to the Zantedeschia genus of the Araceae family. We generated a high-quality chromosome-level genome of the colored calla lily, with a size of 1,154 Mb and a contig N50 of 42 Mb. We anchored 98.5% of the contigs (1,137 Mb) into 16 pseudo-chromosomes, and identified 60.18% of the sequences (694 Mb) as repetitive sequences. Functional annotations were assigned to 95.1% of the predicted protein-coding genes (36,165). Additionally, we annotated 469 miRNAs, 1,652 tRNAs, 10,033 rRNAs, and 1,677 snRNAs. Furthermore, Gypsy-type LTR retrotransposons insertions in the genome are the primary factor causing significant genome size variation in Araceae species. This high-quality genome assembly provides valuable resources for understanding genome size differences within the Araceae family and advancing genomic research on colored calla lily.

Abstract Background Brain microglia and macrophages (Mi/MΦ) can shift to a harmful or advantageous phenotype following an ischemic stroke. Identification of key molecules that regulate the transformation of resting Mi/MΦ could aid in the development of innovative therapies for ischemic stroke. The transcription factor signal transducer and activator of transduction 1 (STAT1) has been found to contribute to acute neuronal death (in the first 24 h) following ischemic stroke, but its effects on Mi/MΦ and influence on long-term stroke outcomes have yet to be determined. Methods We generated mice with tamoxifen-induced, Mi/MΦ-specific knockout (mKO) of STAT1 driven by Cx3cr1CreER. Expression of STAT1 was examined in the brain by flow cytometry and RNA sequencing after ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). The impact of STAT1 mKO on neuronal cell death, Mi/MΦ phenotype, and brain inflammation profiles were examined 3–5 days after MCAO. Neurological deficits and the integrity of gray and white matter were assessed for 5 weeks after MCAO by various neurobehavioral tests and immunohistochemistry. Results STAT1 was activated in Mi/MΦ at the subacute stage (3 days) after MCAO. Selective deletion of STAT1 in Mi/MΦ did not alter neuronal cell death or infarct size at 24 h after MCAO, but attenuated Mi/MΦ release of high mobility group box 1 and increased arginase 1-producing Mi/MΦ 3d after MCAO, suggesting boosted inflammation-resolving responses of Mi/MΦ. As a result, STAT1 mKO mice had mitigated brain inflammation at the subacute stage after MCAO and less white matter injury in the long term. Importantly, STAT1 mKO was sufficient to improve functional recovery for at least 5 weeks after MCAO in both male and female mice. Conclusions Mi/MΦ-targeted STAT1 KO does not provide immediate neuroprotection but augments inflammation-resolving actions of Mi/MΦ, thereby facilitating long-term functional recovery after stroke. STAT1 is, therefore, a promising therapeutic target to harness beneficial Mi/MΦ responses and improve long-term outcomes after ischemic stroke.

Aims: Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture). Methods: PubMed, Embase, and Cochrane Library were systematically searched to retrieve relevant articles published before 15 November 2022. Studies focusing on the correlation between selenium and BMD, OP, or fracture were included. Effect sizes included regression coefficient (β), weighted mean difference (WMD), and odds ratio (OR). According to heterogeneity, the fixed-effect or random-effect model was used to assess the association between selenium and bone health. Results: From 748 non-duplicate publications, 19 studies were included. We found a significantly positive association between dietary selenium intake (β = 0.04, 95% confidence interval (CI) 0.00 to 0.07, p = 0.029) as well as serum selenium (β = 0.13, 95% CI 0.00 to 0.26, p = 0.046) and BMD. Consistently, those with higher selenium intake had a lower risk of OP (OR = 0.47, 95% CI 0.31 to 0.72, p = 0.001), and patients with OP had a significantly lower level of serum selenium than healthy controls (WMD = -2.01, 95% CI -3.91 to -0.12, p = 0.037). High dietary selenium intake was associated with a lower risk of hip fracture (OR = 0.44, 95% CI 0.37 to 0.52, p < 0.001). Conclusion: Selenium was positively associated with BMD and inversely associated with OP; dietary selenium intake was negatively associated with hip fracture. The causality and therapeutic effect of selenium on OP needs to be investigated in future studies. Cite this article: Bone Joint Res 2023;12(7):423–432.

This is a paper in the field of process mineralogy. Dawudian crystalline graphite deposit is a extra large graphite deposit which located in the Langshan Mountain lying in the Bayan obo rift zone. To get some insight into the characteristics of Dawudian crystalline graphite deposit ore and its gangue minerals, this paper systematically studies the ore characteristics of Dawudian crystalline graphite deposit. Some modern analysis and testing methods were used. Such as X-ray diffraction analysis, rock ore identification, spectral semi quantitative analysis. The results show that: (1) The useful mineral of the ore is graphite, and the gangue minerals are mainly quartz, feldspar, muscovite, andalusite, pyrite, etc. (2) The maximum particle size of ore graphite flake is 2.5 ~ 3 mm, and the minimum is 0.001 mm, which is mostly concentrated between 0.01~0.05 mm. It is a fine flake microcrystalline graphite ore. (3) The fixed carbon grade of the main beneficial elements of the ore varies from 2.50% to 11.18%, generally from 3.00% to 7.00%, the average grade is 4.15%, the content of harmful components is 0.16%~4.23%, the content of P2O5 is 0.05%~0.79%, and the content of Fe2O3 is 3.89%~10.38%. The impurity minerals are mainly siliceous minerals and clay minerals. (4) The ore has no other comprehensive utilization value mineral except graphite.

Summary: Fibrotic scar is one of the main impediments to axon regeneration following spinal cord injury (SCI). In this study, we found that CD44 was upregulated during the formation of fibrotic scar, and blocking CD44 by IM7 caused downregulation of fibrosis-related extracellular matrix proteins at both 2 and 12 weeks post-spinal cord injury. More Biotinylated dextran amine (BDA)-traced corticospinal tract axons crossed the scar area and extended into the distal region after IM7 administration. A recovery of motor and sensory function was observed based on Basso Mouse Scale (BMS) scores and tail-flick test. In vitro experiments revealed that inhibiting CD44 and JAK2/STAT3 signaling pathway decreased the proliferation, differentiation, and migration of fibroblasts induced by the inflammatory supernatant. Collectively, these findings highlight the critical role of CD44 and its downstream JAK2/STAT3 signaling pathway in fibrotic scar formation, suggesting a potential therapeutic target for SCI.

Summary: Background: Since gut microbiome dysbiosis can cause inflammatory disorders by affecting host metabolism, we postulate that the gut microbiome and related metabolites could play a role in hand osteoarthritis. We characterised gut microbiome-related metabolites in people with symptomatic hand osteoarthritis (SHOA) in two independent cohorts. Methods: Using data collected from a large-sample community-based observational study (discovery cohort), we assessed the relations of the microbial function and plasma key metabolites related to altered microbial function with SHOA. Finally, we verified the relations of plasma metabolites to SHOA in an independent observational study (validation cohort). Findings: In the discovery cohort (n = 1359), compared to those without SHOA, participants with SHOA had significantly altered microbial functions related to tryptophan metabolism (Q = 0.025). Therefore we measured the plasma tryptophan metabolites and found that participants with SHOA had higher levels of 5-hydroxyindoleacetic acid (odds ratio [OR] = 1.25, 95% confidence interval [CI]: 1.09–1.42) and 5-hydroxytryptophol (OR = 1.13, 95% CI: 1.04–1.23), but lower levels of indole-3-lactic acid (ILA) (OR = 0.85, 95% CI: 0.72–1.00), skatole (OR = 0.93, 95% CI: 0.88–0.99) and 3-hydroxyanthranilic acid (OR = 0.90, 95% CI: 0.85–0.96). Findings from the validation cohort (n = 142) verified that lower levels of ILA were related to SHOA (OR = 0.70, 95% CI: 0.53–0.92). Interpretation: Alterations of the microbial function of tryptophan biosynthesis and tryptophan metabolites, especially lower levels of ILA, are associated with SHOA. These findings suggest the role of the microbiome and tryptophan metabolites in developing of SHOA and may contribute to future translational opportunities. Funding: National Key Research and Development Plan and National Natural Science Foundation of China.

Vascular cognitive impairment and dementia (VCID) represents a broad spectrum of cognitive decline secondary to cerebral vascular aging and injury. It is the second most common type of dementia, and the prevalence continues to increase. Nuclear factor erythroid 2-related factor 2 (NRF2) is enriched in the cerebral vasculature and has diverse roles in metabolic balance, mitochondrial stabilization, redox balance, and anti-inflammation. In this review, we first briefly introduce cerebrovascular aging in VCID and the NRF2 pathway. We then extensively discuss the effects of NRF2 activation in cerebrovascular components such as endothelial cells, vascular smooth muscle cells, pericytes, and perivascular macrophages. Finally, we summarize the clinical potential of NRF2 activators in VCID.

Objectives Knee synovitis is a highly prevalent and potentially curable condition for knee pain; however, its pathogenesis remains unclear. We sought to assess the associations of the gut fungal microbiota and the fungi–bacteria correlation network with knee synovitis.Methods Participants were derived from a community-based cross-sectional study. We performed an ultrasound examination of both knees. A knee was defined as having synovitis if its synovium was ≥4 mm and/or Power Doppler (PD) signal was within the knee synovium area (PD synovitis). We collected faecal specimens from each participant and assessed gut fungal and bacterial microbiota using internal transcribed spacer 2 and shotgun metagenomic sequencing. We examined the relation of α-diversity, β-diversity, the relative abundance of taxa and the interkingdom correlations to knee synovitis.Results Among 977 participants (mean age: 63.2 years; women: 58.8%), 191 (19.5%) had knee synovitis. β-diversity of the gut fungal microbiota, but not α-diversity, was significantly associated with prevalent knee synovitis. The fungal genus Schizophyllum was inversely correlated with the prevalence and activity (ie, control, synovitis without PD signal and PD synovitis) of knee synovitis. Compared with those without synovitis, the fungi–bacteria correlation network in patients with knee synovitis was smaller (nodes: 93 vs 153; edges: 107 vs 244), and the average number of neighbours was fewer (2.3 vs 3.2).Conclusion Alterations of gut fungal microbiota and the fungi–bacteria correlation network are associated with knee synovitis. These novel findings may help understand the mechanisms of the gut-joint axis in knee synovitis and suggest potential targets for future treatment.

Objective The pathogenesis of hand osteoarthritis (OA) remains unknown. Hyperuricaemia, which is related to inflammation, may play a role in hand OA, but evidence is lacking. In a large population-based study, we examined the association between hyperuricaemia and hand OA.Methods Participants were from the Xiangya OA Study, a community-based observational study. Hyperuricaemia was defined as serum urate >416 µmol/L in men and >357 µmol/L in women. Radiographic hand OA (RHOA) was defined as presence of the modified Kellgren-Lawrence grade ≥2 in any hand joint. Symptomatic hand OA (SHOA) was defined as presence of both self-reported symptoms and RHOA in the same hand. The associations of hyperuricaemia with RHOA or SHOA were examined using generalised estimating equations.Results Among 3628 participants, the prevalence of RHOA was higher in participants with hyperuricaemia than those with normouricaemia (26.9% vs 20.9%), with an adjusted OR (aOR) of 1.34 (95% CI 1.11 to 1.61). The associations were consistent in men (aOR 1.33, 95% CI 1.01 to 1.74) and women (aOR 1.35, 95% CI 1.05 to 1.74). Hyperuricaemia was mainly associated with bilateral RHOA (aOR 1.54, 95% CI 1.18 to 2.01) but not unilateral RHOA (aOR 1.13, 95% CI 0.89 to 1.45). Prevalence of SHOA was higher, although statistically insignificant, in participants with hyperuricaemia (aOR 1.39, 95% CI 0.94 to 2.07).Conclusion In this population-based study, hyperuricaemia was associated with a higher prevalence of hand OA. Future prospective studies are required to investigate the temporal relationship.Trial registration number NCT04033757.

TMEM16F is involved in many physiological processes such as blood coagulation, cell membrane fusion and bone mineralization. Activation of TMEM16F has been studied in various central nervous system diseases. High TMEM16F level has been also found to participate in microglial phagocytosis and transformation. Microglia-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer’s disease. However, few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer’s disease. In this study, we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in AD. We performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 inflammasome. Our results showed that TMEM16F was elevated in 9-month-old APP/PS1 mice. After TMEM16F knockdown in mice, spatial memory ability was improved, microglia polarization to the M2 phenotype was promoted, NLRP3 inflammasome activation was inhibited, cell apoptosis and Aβ plaque deposition in brain tissue were reduced, and brain injury was alleviated. We used amyloid-beta (Aβ25–35) to stimulate human microglia to construct microglia models of Alzheimer’s disease. The levels of TMEM16F, inducible nitric oxide synthase (iNOS), proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aβ25–35 treated group compared with that in the control group. TMEM16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3, reduced the release of proinflammatory factors interleukin-1, interleukin-6 and tumor necrosis factor-α, and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1β and interleukin-18. This inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist Nigericin. Our findings suggest that TMEM16F participates in neuroinflammation in Alzheimer’s disease through participating in polarization of microglia and activation of the NLRP3 inflammasome. These results indicate that TMEM16F inhibition may be a potential therapeutic approach for Alzheimer’s disease treatment.

Subband non-overlapping full duplex (SBFD) at gNB side within a conventional TDD band was considered as a key feature of 5G-Advanced to fulfill the challenging requirements of low latency and high uplink throughput emerging in vertical industry and industrial internet.Meanwhile, gNB-to-gNB cross-link interference handling needed to be enhanced to enable different TDD configurations for both public network (Macro) and vertical network (Micro) applied in the same frequency band.With a thorough analysis on the interference characteristic in the potential deployment scenarios for both different TDD configurations and subband non-overlapping full duplex, various feasible interference handling schemes to fulfill the challenging deployment requirements for vertical industry and industrial internet were presented, and the feasibility of above duplex enhancement schemes was checked via link budget, simulation and proof-of-concept prototype.

Abstract Background Several studies have examined gut microbiota and sarcopenia using 16S ribosomal RNA amplicon sequencing; however, this technique may not be able to identify altered specific species and functional capacities of the microbes. We performed shotgun metagenomic sequencing to compare the gut microbiome composition and function between individuals with and without sarcopenia. Methods Participants were from a community‐based observational study conducted among the residents of rural areas in China. Appendicular skeletal muscle mass was assessed using direct segmental multi‐frequency bioelectrical impedance and grip strength using a Jamar Hydraulic Hand dynamometer. Physical performance was evaluated using the Short Physical Performance Battery, 5‐time chair stand test and gait speed with the 6 m walk test. Sarcopenia and its severity were diagnosed according to the Asian Working Group for Sarcopenia 2019 algorithm. The gut microbiome was profiled by shotgun metagenomic sequencing to determine the microbial composition and function. A gut microbiota‐based model for classification of sarcopenia was constructed using the random forest model, and its performance was assessed using the area under receiver‐operating characteristic curve (AUC). Results The study sample included 1417 participants (women: 58.9%; mean age: 63.3 years; sarcopenia prevalence: 10.0%). β‐diversity indicated by Bray–Curtis distance (genetic level: P = 0.004; taxonomic level of species: P = 0.020), but not α‐diversity indicated by Shannon index (genetic level: P = 0.962; taxonomic level of species: P = 0.922), was significantly associated with prevalent sarcopenia. After adjusting for potential confounders, participants with sarcopenia had higher relative abundance of Desulfovibrio piger (P = 0.003, Q = 0.090), Clostridium symbiosum (P

In this study, based on a closed bomb test combined with computational fluid dynamics, a structural finite element method, and an acoustic boundary element method, a fluid-solid acoustic one-way coupling calculation model is established for the combustion process of energetic materials in a closed bomb, and the effectiveness of the model is verified by experiments. It is found that the maximum peak sound pressure increases exponentially with an increase in loading doses or gas pressure. However, a change in the combustion coefficient of the energetic materials has little effect on the noise generated during the combustion process in the closed bomb. When the combustion coefficient is reduced by a multiple of 16, the maximum transient sound pressure is reduced by 1.79 dB, and the sound pressure level in the frequency band is reduced by 1.75 dB. With an increase in shell thickness, the combustion noise of the energetic materials in the closed bomb decreases, and the reduction range of the combustion noise increases with the increase in shell thickness.

Traumatic brain injury (TBI) is commonly followed by intractable psychiatric disorders and long-term changes in affect, such as anxiety. The present study sought to investigate the effect of repetitive intranasal delivery of interleukin-4 (IL-4) nanoparticles on affective symptoms after TBI in mice. Adult male C57BL/6 J mice (10–12 weeks of age) were subjected to controlled cortical impact (CCI) and assessed by a battery of neurobehavioral tests up to 35 days after CCI. Neuron numbers were counted in multiple limbic structures, and the integrity of limbic white matter tracts was evaluated using ex vivo diffusion tensor imaging (DTI). As STAT6 is a critical mediator of IL-4-specific transcriptional activation, STAT6 knockout mice were used to explore the role of endogenous IL-4/STAT6 signaling axis in TBI-induced affective disorders. We also employed microglia/macrophage (Mi/Mϕ)-specific PPARγ conditional knockout (mKO) mice to test if Mi/Mϕ PPARγ critically contributes to IL-4-afforded beneficial effects. We observed anxiety-like behaviors up to 35 days after CCI, and these measures were exacerbated in STAT6 KO mice but mitigated by repetitive IL-4 delivery. We discovered that IL-4 protected against neuronal loss in limbic structures, such as the hippocampus and the amygdala, and improved the structural integrity of fiber tracts connecting the hippocampus and amygdala. We also observed that IL-4 boosted a beneficial Mi/Mϕ phenotype (CD206+/Arginase 1+/PPARγ+ triple-positive) in the subacute injury phase, and that the numbers of Mi/Mϕ appositions with neurons were robustly correlated with long-term behavioral performances. Remarkably, PPARγ-mKO completely abolished IL-4-afforded protection. Thus, CCI induces long-term anxiety-like behaviors in mice, but these changes in affect can be attenuated by transnasal IL-4 delivery. IL-4 prevents the long-term loss of neuronal somata and fiber tracts in key limbic structures, perhaps due to a shift in Mi/Mϕ phenotype. Exogenous IL-4 therefore holds promise for future clinical management of mood disturbances following TBI.

The development of high-throughput sequencing technology has made it possible to develop molecular markers such as EST-SSR from transcriptome sequences in non-model plants such as bulbous flowers. However, the EST-SSR markers that have been developed are weakly validated and low polymorphic due to the short read size and poor quality of the assembled sequences. This study therefore used the CandiSSR pipeline to identify 550 potential polymorphic SSR loci among 487 homologous unigenes based on the transcriptomic sequences of three varieties of colored calla lily, and 460 of these loci with appropriate flanking sequences were suitable for primer pairs design. A further validation with 200 randomly selected EST-SSRs demonstrated an increase of more than 30% and 100% in amplification validity and polymorphism, respectively, in comparison with our previous study. In addition, since most of the current varieties of colored calla lily are hybridized from a few species, which have low genetic diversity, we subsequently identified primary core germplasm for 160 colored calla lily accessions using the aforementioned 40 polymorphic EST-SSRs. It was concluded that the core germplasm containing 42 accessions derived from the M strategy incorporated into the software Power Core was the most representative of all 160 original germplasm, as evidenced by the preservation of 100% of the EST-SSR variation, with a higher level of genetic diversity and heterogeneity (Nei = 0.40, I = 0.66, PIC = 0.43). This study provides a practical example of polymorphism EST-SSR markers developed from multiple transcriptomes for non-model plants. A future breeding program for colored calla lily will also benefit from the core germplasm defined by those molecular markers.

Calla lily (Zantedeschia spp.) have great aesthetic value due to their spathe-like appearance and richness of coloration. However, embryonic callus regeneration is absent from its current regeneration mechanism. As a result, constructing an adequate and stable genetic transformation system is hampered, severely hindering breeding efforts. In this research, the callus induction effectiveness of calla lily seed embryos of various maturities was evaluated. The findings indicated that mature seed embryos were more suitable for in vitro regeneration. Using orthogonal design experiments, the primary elements influencing in vitro regeneration, such as plant growth regulators, genotypes, and nanoscale materials, which was emergent uses for in vitro regeneration, were investigated. The findings indicated that MS supplemented with 6-BA 2 mg/L and NAA 0.1 mg/L was the optimal medium for callus induction (CIM); the germination medium (GM) was MS supplemented with 6-BA 2 mg/L NAA 0.2 mg/L and 1 mg/L CNTs, and the rooting medium (RM) was MS supplemented with 6-BA 2 mg/L NAA 0.7 mg/L and 2 mg/L CNTs. This allowed us to verify, in principle, that the Agrobacterium tumefaciens-mediated genetic transformation system operates under optimal circumstances using the GUS reporter gene. Here, we developed a seed embryo-based genetic transformation regeneration system, which set the stage for future attempts to create new calla lily varieties.

The MIKCC-type gene family plays important roles in plant growth, development, and tolerance of biotic and abiotic stress, especially during floral organ differentiation. However, there have been no studies of MIKCC-type genes in rose, and functional differentiation of family members has not been explored. In this study, we identified 42 MIKCC-type genes in rose, classified the genes into 12 subfamilies, and constructed a phylogenetic tree. We performed expression analysis of these genes, and found that expression patterns correlated with the predicted subfamily, indicating that the features of MIKCC-type genes were broadly conserved during evolution. Collinear analysis of MIKCC genes among Rosaceae species confirmed the occurrence of whole genome duplications (WGD) and revealed some species-specific MIKCC genes. Transcriptome analysis showed that the expression of some MIKCC-type genes responded to low temperatures (4°C, 24 h) during flower organ differentiation. These conserved, duplicated, and novel expression patterns of MIKCC-type genes may have facilitated the adaptation of rose to various internal and external environmental changes. The results of this study provide a theoretical basis for future functional analysis of the MIKCC genes in rose and investigation of the evolutionary pattern of the MIKCC gene family in the Rosaceae genome.

Phylogenomic studies based on plastid genome have resolved recalcitrant relationships among various plants, yet the phylogeny of Dennstaedtiaceae at the level of family and genera remains unresolved due to conflicting plastid genes, limited molecular data and incomplete taxon sampling of previous studies. The present study generated 30 new plastid genomes of Dennstaedtiaceae (9 genera, 29 species), which were combined with 42 publicly available plastid genomes (including 24 families, 27 genera, 42 species) to explore the evolution of Dennstaedtiaceae. In order to minimize the impact of systematic errors on the resolution of phylogenetic inference, we applied six strategies to generate 30 datasets based on CDS, intergenic spacers, and whole plastome, and two tree inference methods (maximum-likelihood, ML; and multispecies coalescent, MSC) to comprehensively analyze the plastome-scale data. Besides, the phylogenetic signal among all loci was quantified for controversial nodes using ML framework, and different topologies hypotheses among all datasets were tested. The species trees based on different datasets and methods revealed obvious conflicts at the base of the polypody ferns. The topology of the “CDS-codon-align-rm3” (CDS with the removal of the third codon) matrix was selected as the primary reference or summary tree. The final phylogenetic tree supported Dennstaedtiaceae as the sister group to eupolypods, and Dennstaedtioideae was divided into four clades with full support. This robust reconstructed phylogenetic backbone establishes a framework for future studies on Dennstaedtiaceae classification, evolution and diversification. The present study suggests considering plastid phylogenomic conflict when using plastid genomes. From our results, reducing saturated genes or sites can effectively mitigate tree conflicts for distantly related taxa. Moreover, phylogenetic trees based on amino acid sequences can be used as a comparison to verify the confidence of nucleotide-based trees.

Abstract Grading individual knee osteoarthritis (OA) features is a fine-grained knee OA severity assessment. Existing methods ignore following problems: (1) more accurately located knee joints benefit subsequent grades prediction; (2) they do not consider knee joints’ symmetry and semantic information, which help to improve grades prediction performance. To this end, we propose a SE-ResNext50-32x4d-based Siamese network with adaptive gated feature fusion method to simultaneously assess eight tasks. In our method, two cascaded small convolution neural networks are designed to locate more accurate knee joints. Detected knee joints are further cropped and split into left and right patches via their symmetry, which are fed into SE-ResNext50-32x4d-based Siamese network with shared weights, extracting more detailed knee features. The adaptive gated feature fusion method is used to capture richer semantic information for better feature representation here. Meanwhile, knee OA/non-knee OA classification task is added, helping extract richer features. We specially introduce a new evaluation metric (top±1 accuracy) aiming to measure model performance with ambiguous data labels. Our model is evaluated on two public datasets: OAI and MOST datasets, achieving the state-of-the-art results comparing to competing approaches. It has the potential to be a tool to assist clinical decision making.

Abstract Background There is paucity of data on the prevalence of ultrasound-detected synovial abnormalities in the general population, and the relationship between synovial changes and knee pain remains unclear. We examined the prevalence of synovial abnormalities on ultrasound and the relationship of these features with knee pain and radiographic osteoarthritis (ROA) in a community sample. Methods Participants aged 50 years or over were from the Xiangya Osteoarthritis Study, a community-based cohort study. Participants were questioned about chronic knee pain and underwent (1) ultrasonography of both knees to determine presence of synovial hypertrophy (≥ 4 mm), effusion (≥ 4 mm), and Power Doppler signal [PDS; yes/no]; and (2) standard radiographs of both knees (tibiofemoral and patellofemoral views) to determine ROA. Results There were 3755 participants (mean age 64.4 years; women 57.4%). The prevalence of synovial hypertrophy, effusion, and PDS were 18.1% (men 20.2%; women 16.5%), 46.6% (men 49.9%; women 44.2%), and 4.9% (men 4.9%; women 5.0%), respectively, and increased with age (P for trend

Immunomodulation holds therapeutic promise against brain injuries, but leveraging this approach requires a precise understanding of mechanisms. We report that CD8+CD122+CD49dlo T regulatory-like cells (CD8+ TRLs) are among the earliest lymphocytes to infiltrate mouse brains after ischemic stroke and temper inflammation; they also confer neuroprotection. TRL depletion worsened stroke outcomes, an effect reversed by CD8+ TRL reconstitution. The CXCR3/CXCL10 axis served as the brain-homing mechanism for CD8+ TRLs. Upon brain entry, CD8+ TRLs were reprogrammed to upregulate leukemia inhibitory factor (LIF) receptor, epidermal growth factor–like transforming growth factor (ETGF), and interleukin 10 (IL-10). LIF/LIF receptor interactions induced ETGF and IL-10 production in CD8+ TRLs. While IL-10 induction was important for the antiinflammatory effects of CD8+ TRLs, ETGF provided direct neuroprotection. Poststroke intravenous transfer of CD8+ TRLs reduced infarction, promoting long-term neurological recovery in young males or aged mice of both sexes. Thus, these unique CD8+ TRLs serve as early responders to rally defenses against stroke, offering fresh perspectives for clinical translation.

Parkinson’s disease (PD) is one of the most common neurodegenerative movement disorders worldwide. There are currently no cures or preventative treatments for PD. Emerging evidence indicates that mitochondrial dysfunction is closely associated with pathogenesis of sporadic and familial PD. Because dopaminergic neurons have high energy demand, cells affected by PD exhibit mitochondrial dysfunction that promotes the disease-defining the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The mitochondrion has a particularly important role as the cellular “powerhouse” of dopaminergic neurons. Therefore, mitochondria have become a promising therapeutic target for PD treatments. This review aims to describe mitochondrial dysfunction in the pathology of PD, outline the genes associated with familial PD and the factors related to sporadic PD, summarize current knowledge on mitochondrial quality control in PD, and give an overview of therapeutic strategies for targeting mitochondria in neuroprotective interventions in PD.

The power consumption of 5G UE is much serious than 4G UE due to larger bandwidth, massive MIMO, and higher data rate and has been one of the important reason affecting users’ experience of 5G network.3GPP has promoted the study and standardization of NR UE power saving techniques, which the R16 techniques is designed for RRC_connected mode and the started R17 techniques focus on RRC_idle mode.The power consumption of NR UE in RRC_idle was analyzed and compared with LTE UE.The power saving techniques to solve the power consumption in paging and tracking procedure were proposed and the power saving gain were also evaluated.The proposed techniques can reduce 5G UE power consumption and be applicable to future 5G commercial UE.

Aldo-keto reductase (AKR) 1C15, a member of the AKR superfamily, was recently identified and cloned, and reported to alleviate oxidative stress in endothelial cells in rodent lungs. However, its expression and role in the brain and ischemic brain diseases have not been investigated. AKR1C15 expression was detected with real-time PCR. Mouse ischemic stroke and ischemic preconditioning (IPC) were established with middle cerebral artery occlusion (MCAO) for 1 h or 12 min, respectively. Recombinant AKR1C15 was administered intraperitoneally, and stroke outcome was evaluated with neurobehavioral tests and infarct volumes. Rat primary brain cell cultures were subjected to oxygen–glucose deprivation (OGD) to mimic ischemic injury. Cell survival or in vitro blood–brain barrier (BBB) permeability was measured, and nitric oxide (NO) release was detected. Immunostaining and Western blotting were used to evaluate oxidative-stress-related protein expression. AKR1C15 administration decreased the infarct volume and neurological deficits 2d post-stroke, and its early (1-h) administration after IPC abolished the protection of IPC against stroke. In rat primary brain cell cultures, AKR1C15 was most abundantly expressed in brain microvascular endothelial cells (BMVECs) and microglia. Its expression decreased upon OGD in most cell types except for BMVECs and microglia. In primary neuronal cultures, AKR1C15 treatment prevented OGD-induced cell death accompanied by decreased levels of 4-hydroxynonenal, 8-hydroxy-2′-deoxyguanosine, and heme oxygenase-1. In BMVEC cultures, AKR1C15 treatment protected against OGD-induced cell death and in vitro BBB leakage. In primary microglial cultures, AKR1C15 reduced the release of NO upon proinflammatory stimulation. Our results provide a characterization of the novel antioxidant AKR1C15 and demonstrate its protective role against ischemic injury, both in vivo and in vitro. AKR1C15 may be a promising agent for ischemic stroke treatment.

Abstract Background Schwann cells (SCs) play a crucial role in Wallerian degeneration after peripheral nerve injury. The expression of genes in SCs undergo a series of changes, which greatly affect the proliferation and apoptosis of SCs as well as the fate of peripheral nerve regeneration. However, how do these genes regulate the proliferation and apoptosis of SCs remains unclear. Results SPP1 and PKCα were found upregulated after human median peripheral nerve injury, which promoted SCs proliferation and survival. The promoted proliferation and inhibited apoptosis by SPP1 were blocked after the treatment of PKCα antagonist Gö6976. Whereas, the inhibited proliferation and enhanced apoptosis induced by silence of SPP1 could be rescued by the activation of PKCα, which suggested that SPP1 functioned through PKCα. Moreover, both CD44 and αvβ3 were found expressed in SCs and increased after peripheral nerve injury. Silence of CD44 or β3 alleviated the increased proliferation and inhibited apoptosis induced by recombinant osteopontin, suggesting the function of SPP1 on SCs were dependent on CD44 and β3. Conclusion These results suggested that SPP1 promoted proliferation and inhibited apoptosis of SCs through PKCα signaling pathway by binding with CD44 and αvβ3. This study provides a potential therapeutic target for improving peripheral nerve recovery.

Abstract Background Myelin sheaths surrounding axons are critical for electrical signal transmission in the central nervous system (CNS). Diseases with myelin defects such as multiple sclerosis (MS) are devastating neurological conditions for which few effective treatments are available. Dysfunction of the dopaminergic system has been observed in multiple neurological disorders. Its role in myelin pathogenesis, however, is unclear. Methods This work used a combination of literature curation, bioinformatics, pharmacological and genetic manipulation, as well as confocal imaging techniques. Literature search was used to establish a complete set of genes which is associated with MS in humans. Bioinformatics analyses include pathway enrichment and crosstalk analyses with human genetic association studies as well as gene set enrichment and causal relationship analyses with transcriptome data. Pharmacological and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) genetic manipulation were applied to inhibit the dopaminergic signaling in zebrafish. Imaging techniques were used to visualize myelin formation in vivo. Results Systematic analysis of human genetic association studies revealed that the dopaminergic synapse signaling pathway is enriched in candidate gene sets. Transcriptome analysis confirmed that expression of multiple dopaminergic gene sets was significantly altered in patients with MS. Pathway crosstalk analysis and gene set causal relationship analysis reveal that the dopaminergic synapse signaling pathway interacts with or is associated with other critical pathways involved in MS. We also found that disruption of the dopaminergic system leads to myelin deficiency in zebrafish. Conclusions Dopaminergic signaling may be involved in myelin pathogenesis. This study may offer a novel molecular mechanism of demyelination in the nervous system.

Abstract Background Patients with chondrocalcinosis may suffer from a series of symptoms resembling acute gouty arthritis or septic arthritis, but the aetiology and pathogenesis of chondrocalcinosis have not been fully elucidated yet. This study was aimed to assess serum zinc and copper concentrations, as well as the ratio of serum copper to zinc concentrations (Cu/Zn ratio), in relation to the prevalence of knee chondrocalcinosis. Methods Data included in this analysis were retrieved from a large population-based cross-sectional study. A bilateral knee anteroposterior radiograph was obtained from each subject. Radiographic knee chondrocalcinosis was diagnosed if definite linear cartilage calcification was detected. Serum zinc and copper concentrations were measured using the spectrophotometric flow injection methods by Roche modular P800. The relations of serum zinc and copper concentrations and Cu/Zn ratio to the prevalence of knee chondrocalcinosis were examined using generalized estimating equations, respectively. Results The prevalence of knee chondrocalcinosis was 1.2% in the sample of this study (n = 12,362). In comparison with the lowest tertile, the odds ratios (ORs) of knee chondrocalcinosis adjusted by age, sex and body mass index were 0.74 (95% CI 0.50–1.09) in the second and 0.56 (95% CI 0.36–0.86) in the third tertiles of serum zinc concentrations (P for trend = 0.009), were 1.26 (95% CI 0.77–2.05) in the second and 2.01 (95% CI 1.25–3.24) in the third tertile of serum copper concentrations (P for trend = 0.003), and were 1.02 (95% CI 0.61–1.69) in the second and 2.23 (95% CI 1.38–3.59) in the third tertile of Cu/Zn ratio (P for trend

It is difficult for optical correlator to recognize the target with large rotation distortion by using existing filters. To solve this problem, a new neural network model is constructed based on the physical recognition process of planar integrated 2F optical correlator. The new optical filter is optimized by training the neural network. The planar integrated 2F optical correlator can output sharp correlation peaks by using the new filter to recognize targets with arbitrary rotation distortion. Compared with the traditional OTSDF filter, the average increase of correlation peak index is up to 1402.4%, while the recognition performance of distortion invariant is also better than the new NNCRF filter. The simulation and experimental results show that the optical filter designed in this paper can effectively solve the problem of weak recognition ability of optical correlator for rotating distortion targets, especially for large angle rotating distortion targets.

Abstract Objective To examine the correlation between dietary selenium (Se) intake and the prevalence of osteoporosis (OP) in the general middle-aged and older population in China. Methods Data for analyses were collected from a population based cross-sectional study performed at the Xiangya Hospital Health Management Centre. Dietary Se intake was evaluated using a validated semi-quantitative food frequency questionnaire. OP was diagnosed on the basis of bone mineral density scans using a compact radiographic absorptiometry system. The correlation between dietary Se intake and the prevalence of OP was primarily examined by multivariable logistic regression. Results This cross-sectional study included a total of 6267 subjects (mean age: 52.2 ± 7.4 years; 42% women), and the prevalence of OP among the included subjects was 9.6% (2.3% in men and 19.7% in women). Compared with the lowest quartile, the energy intake, age, gender and body mass index (BMI)-adjusted odds ratios of OP were 0.72 (95% confidence interval [CI] 0.55–0.94), 0.72 (95% CI 0.51–1.01) and 0.47 (95% CI 0.31–0.73) for the second, third and fourth quartiles of dietary Se intake, respectively (P for trend = 0.001). The results remained consistent in male and female subjects. Adjustment for additional potential confounders (i.e., smoking status, drinking status, physical activity level, nutritional supplements, diabetes, hypertension, fibre intake, and calcium intake) did not cause substantial changes to the results. Conclusions In the middle-aged and older humans, participants with lower levels of dietary Se intake have a higher prevalence of OP in a dose-response manner.

Recent advances in communication enable individuals to use phones and computers to access information on the web. E-commerce has seen rapid development, e.g., Alibaba has nearly 12 hundred million customers in China. Click-Through Rate (CTR) forecasting is a primary task in the e-commerce advertisement system. From the traditional Logistic Regression algorithm to the latest popular deep neural network methods that follow a similar embedding and MLP, several algorithms are used to predict CTR. This research proposes a hybrid model combining the Deep Interest Network (DIN) and eXtreme Deep Factorization Machine (xDeepFM) to perform CTR prediction robustly. The cores of DIN and xDeepFM are attention and feature cross, respectively. DIN follows an adaptive local activation unit that incorporates the attention mechanism to adaptively learn user interest from historical behaviors related to specific advertisements. xDeepFM further includes a critical part, a Compressed Interactions Network (CIN), aiming to generate feature interactions at a vectorwise level implicitly. Furthermore, a CIN, plain DNN, and a linear part are combined into one unified model to form xDeepFM. The proposed end-to-end hybrid model is a parallel ensemble of models via multilayer perceptron. CIN and xDeepFM are trained in parallel, and their output is fed into a multilayer perceptron. We used the e-commerce Alibaba dataset with the focal loss as the loss function for experimental evaluation through online complex example mining (OHEM) in the training process. The experimental result indicates that the proposed hybrid model has better performance than other models.

The endothelial lining of cerebral microvessels is damaged relatively early after cerebral ischemia/reperfusion (I/R) injury and mediates blood-brain barrier (BBB) disruption, neurovascular injury, and long-term neurological deficits. I/R induces BBB leakage within 1 h due to subtle structural alterations in endothelial cells (ECs), including reorganization of the actin cytoskeleton and subcellular redistribution of junctional proteins. Herein, we show that the protein peroxiredoxin-4 (Prx4) is an endogenous protectant against endothelial dysfunction and BBB damage in a murine I/R model. We observed a transient upregulation of Prx4 in brain ECs 6 h after I/R in wild-type (WT) mice, whereas tamoxifen-induced, selective knockout of Prx4 from endothelial cells (eKO) mice dramatically raised vulnerability to I/R. Specifically, eKO mice displayed more BBB damage than WT mice within 1 to 24 h after I/R and worse long-term neurological deficits and focal brain atrophy by 35 d. Conversely, endothelium-targeted transgenic (eTG) mice overexpressing Prx4 were resistant to I/R-induced early BBB damage and had better long-term functional outcomes. As demonstrated in cultures of human brain endothelial cells and in animal models of I/R, Prx4 suppresses actin polymerization and stress fiber formation in brain ECs, at least in part by inhibiting phosphorylation/ activation of myosin light chain. The latter cascade prevents redistribution of junctional proteins and BBB leakage under conditions of Prx4 repletion. Prx4 also tempers microvascular inflammation and infiltration of destructive neutrophils and proinflammatory macrophages into the brain parenchyma after I/R. Thus, the evidence supports an indispensable role for endothelial Prx4 in safeguarding the BBB and promoting functional recovery after I/R brain injury. [ABSTRACT FROM AUTHOR]

Rockburst is globally regarded as one of the most severe and complicated mining dynamic disasters to predict or control. Generally, the occurrence mechanism of rockbursts can be considered as a process of the elastic strain energy accumulation, emancipation, transmission, and occurrence. Tracing to the source, the reasons for large accumulation of elastic strain energy in coal and rock mass are the high stress of the roof layer that loads on the coal and rock masses around the mining space coupling effect with the natural horizontal tectonic stress. In this study, using the minimum energy theory and elasticity theory, the analytical formula for calculating elastic strain energy of the roof cantilever beam structure acting on the coal body load in front of the working face is deduced. Accordingly, we achieved a method of using hydraulic fracturing to improve the roof structure. In detail, we use a high-pressure jet to cut the cantilever roof structure, which can make a prelocated fracture surface, and then utilize the packers to make sure that the injected high-pressure fracturing fluid is propagating along the prelocated fracture surface and can cut off the cantilever roof structure eventually to prevent rockbursts in advance. Due to the rockburst occurrence mechanism and the quantitatively elastic strain energy analytical formula, a preconditioning water jet cutting induced fracture surface to create orientation-controllable hydraulic fracture strategy is proposed to guard against the high hazard caused by the massive elastic strain energy, which accumulated in the coal body in front of the working face and coal pillar.

The vibration and noise that resulted from turbomachinery, such as fans, compressors, and centrifugal pumps, are known to bring considerable disturbance and pollution to the machine itself, the environment, and the operators. Hence, how to cope with the vibration and noise has become a recent research focus. With the advancement of materials science, more and more new nanomaterials have been applied in the field of noise and vibration reduction. To be specific, carbon-based nanomaterials, such as carbon fibers, carbon nanotubes, and graphenes, have achieved outstanding results. Carbon nanocomposites, such as carbon nanofibers, carbon nanotubes, and graphenes, are characterized by their low densities, high strengths, and high elastic moduli, all of which made carbon nanocomposites the most promising vibration and noise-reduction composites, thanks to their damping properties, compatibilities, noise and vibration absorption qualities, and wide wave-absorbing frequency bands. In light of this, this paper summarizes the progresses and application prospects of such carbon nanocomposites as carbon nanofibers, carbon nanotubes, and graphenes in the field of turbomachinery vibration and noise reduction.

Recovery from spinal cord injury (SCI) remains an unsolved problem. As a major component of the SCI lesion, the glial scar is primarily composed of scar-forming astrocytes and plays a crucial role in spinal cord regeneration. In recent years, it has become increasingly accepted that the glial scar plays a dual role in SCI recovery. However, the underlying mechanisms of this dual role are complex and need further clarification. This dual role also makes it difficult to manipulate the glial scar for therapeutic purposes. Here, we briefly discuss glial scar formation and some representative components associated with scar-forming astrocytes. Then, we analyze the dual role of the glial scar in a dynamic perspective with special attention to scar-forming astrocytes to explore the underlying mechanisms of this dual role. Finally, taking the dual role of the glial scar into account, we provide several pieces of advice on novel therapeutic strategies targeting the glial scar and scar-forming astrocytes.

Artemisinin (ART) is a widely used antimalarial drug, but its mechanism of action is poorly understood. Here, Bridgford et al. show that ART kills parasites by a two-pronged mechanism, causing protein damage and compromising proteasome function, and that accumulation of proteasome substrates activates the ER stress response.

Brain ischemic preconditioning (IPC) with mild ischemic episodes is well known to protect the brain against subsequent ischemic challenges. However, the underlying mechanisms are poorly understood. Here we demonstrate the critical role of the master redox transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), in IPC-mediated neuroprotection and blood-brain barrier (BBB) preservation. We report that IPC causes generation of endogenous lipid electrophiles, including 4-hydroxy-2-nonenal (4-HNE), which release Nrf2 from inhibition by Keap1 (via Keap1-C288) and inhibition by glycogen synthase kinase 3β (via GSK3β-C199). Nrf2 then induces expression of its target genes, including a new target, cadherin 5, a key component of adherens junctions of the BBB. These effects culminate in mitigation of BBB leakage and of neurological deficits after stroke. Collectively, these studies are the first to demonstrate that IPC protects the BBB against ischemic injury by generation of endogenous electrophiles and activation of the Nrf2 pathway through inhibition of Keap1- and GSK3β-dependent Nrf2 degradation. Keywords: Stroke, Neuroprotection, Ischemic tolerance, Electrophile, Lipid peroxidation, VE-cadherin, Conditioning

In this paper, an optical correlator which adopts planar integrated 2F structure and optimal tradeoff synthetic discriminant function filter is proposed to improve the system integration and the recognition ability. The specialized digital microlens is designed for the correlator to replace the physical lens. By the theoretical analysis, the structural design conditions and parameters of the correlator are given, and the system volume is 63.1 cm3 which is only half of the planar integrated 4F optical correlator. Moreover, simulations and experimental research works reveal that the correlator can achieve stable recognition to the input object of distortion with scaling (52%, 150%), rotation (-50°, +42°), and existed scaling (72%, 130%) and rotation (-36°, +38°) simultaneously. Theoretical analysis and experimental results indicate that the planar integrated optical correlator with compact structure and high integration has good performance of distortion invariant recognition.