Japanese encephalitis virus NS1 and NS1' protein disrupts the blood-brain barrier through macrophage migration inhibitory factor-mediated autophagy.

Flaviviruses in the Japanese encephalitis virus (JEV) serogroup, such as JEV, West Nile virus, and St. Louis encephalitis virus, can cause severe neurological diseases. The nonstructural protein 1 (NS1) is a multifunctional protein of flavivirus that can be secreted by infected cells and circulate in the host bloodstream. NS1' is an additional form of NS1 protein with 52 amino acids extension at its carboxy-terminal and is produced exclusively by flaviviruses in the JEV serogroup. In this study, we demonstrated that the secreted form of both NS1 and NS1' can disrupt the blood-brain barrier (BBB) of mice, with NS1' exhibiting a stronger effect. Using the in vitro BBB model, we found that treatment of soluble recombinant JEV NS1 or NS1' protein increases the permeability of human brain microvascular endothelial cells (hBMECs) and leads to the degradation of tight junction proteins through the autophagy-lysosomal pathway. Consistently, NS1' protein exhibited a more pronounced effect compared to NS1 in these cellular processes. Further research revealed that the increased expression of macrophage migration inhibitory factor (MIF) is responsible for triggering autophagy after NS1 or NS1' treatment in hBMECs. In addition, TLR4 and NF-κB signaling was found to be involved in the activation of MIF transcription. Moreover, administering the MIF inhibitor has been shown to decrease viral loads and mitigate inflammation in the brains of mice infected with JEV. This research offers a novel perspective on the pathogenesis of JEV. In addition, the stronger effect of NS1' on disrupting the BBB compared to NS1 enhances our understanding of the mechanism by which flaviviruses in the JEV serogroup exhibit neurotropism.IMPORTANCEJapanese encephalitis (JE) is a significant viral encephalitis worldwide, caused by the JE virus (JEV). In some patients, the virus cannot be cleared in time, leading to the breach of the blood-brain barrier (BBB) and invasion of the central nervous system. This invasion may result in cognitive impairment, behavioral disturbances, and even death in both humans and animals. However, the mechanism by which JEV crosses the BBB remains unclear. Previous studies have shown that the flavivirus NS1 protein plays an important role in causing endothelial dysfunction. The NS1' protein is an elongated form of NS1 protein that is particularly produced by flaviviruses in the JEV serogroup. This study revealed that both the secreted NS1 and NS1' of JEV can disrupt the BBB by breaking down tight junction proteins through the autophagy-lysosomal pathway, and NS1' is found to have a stronger effect compared to NS1 in this process. In addition, JEV NS1 and NS1' can stimulate the expression of MIF, which triggers autophagy via the ERK signaling pathway, leading to damage to BBB. Our findings reveal a new function of JEV NS1 and NS1' in the disruption of BBB, thereby providing the potential therapeutic target for JE.

Single-cell RNA sequencing reveals the immune features and viral tropism in the central nervous system of mice infected with Japanese encephalitis virus.

Japanese encephalitis virus (JEV) is a neurotropic pathogen that causes lethal encephalitis. The high susceptibility and massive proliferation of JEV in neurons lead to extensive neuronal damage and inflammation within the central nervous system. Despite extensive research on JEV pathogenesis, the effect of JEV on the cellular composition and viral tropism towards distinct neuronal subtypes in the brain is still not well comprehended. To address these issues, we performed single-cell RNA sequencing (scRNA-seq) on cells isolated from the JEV-highly infected regions of mouse brain. We obtained 88,000 single cells and identified 34 clusters representing 10 major cell types. The scRNA-seq results revealed an increasing amount of activated microglia cells and infiltrating immune cells, including monocytes & macrophages, T cells, and natural killer cells, which were associated with the severity of symptoms. Additionally, we observed enhanced communication between individual cells and significant ligand-receptor pairs related to tight junctions, chemokines and antigen-presenting molecules upon JEV infection, suggesting an upregulation of endothelial permeability, inflammation and antiviral response. Moreover, we identified that Baiap2-positive neurons were highly susceptible to JEV. Our findings provide valuable clues for understanding the mechanism of JEV induced neuro-damage and inflammation as well as developing therapies for Japanese encephalitis.

Excessive immunosuppression by regulatory T cells antagonizes T cell response to schistosome infection in PD-1-deficient mice.

Schistosomiasis is caused by parasitic flatworms known as schistosomes and affects over 200 million people worldwide. Prevention of T cell exhaustion by blockade of PD-1 results in clinical benefits to cancer patients and clearance of viral infections, however it remains largely unknown whether loss of PD-1 could prevent or cure schistosomiasis in susceptible mice. In this study, we found that S. japonicum infection dramatically induced PD-1 expression in T cells of the liver where the parasites chronically inhabit and elicit deadly inflammation. Even in mice infected by non-egg-producing unisex parasites, we still observed potent induction of PD-1 in liver T cells of C57BL/6 mice following S. japonicum infection. To determine the function of PD-1 in schistosomiasis, we generated PD-1-deficient mice by CRISPR/Cas9 and found that loss of PD-1 markedly increased T cell count in the liver and spleen of infected mice. IL-4 secreting Th2 cells were significantly decreased in the infected PD-1-deficient mice whereas IFN-γ secreting CD4+ and CD8+ T cells were markedly increased. Surprisingly, such beneficial changes of T cell response did not result in eradication of parasites or in lowering the pathogen burden. In further experiments, we found that loss of PD-1 resulted in both beneficial T cell responses and amplification of regulatory T cells that prevented PD-1-deficient T cells from unleashing anti-parasite activity. Moreover, such PD-1-deficient Tregs exert excessive immunosuppression and express larger amounts of adenosine receptors CD39 and CD73 that are crucial for Treg-mediated immunosuppression. Our experimental results have elucidated the function of PD-1 in schistosomiasis and provide novel insights into prevention and treatment of schistosomiasis on the basis of modulating host adaptive immunity.

H3K27me3 of Rnf19a promotes neuroinflammatory response during Japanese encephalitis virus infection.

Histone methylation is an important epigenetic modification that affects various biological processes, including the inflammatory response. In this study, we found that infection with Japanese encephalitis virus (JEV) leads to an increase in H3K27me3 in BV2 microglial cell line, primary mouse microglia and mouse brain. Inhibition of H3K27me3 modification through EZH2 knockdown and treatment with EZH2 inhibitor significantly reduces the production of pro-inflammatory cytokines during JEV infection, which suggests that H3K27me3 modification plays a crucial role in the neuroinflammatory response caused by JEV infection. The chromatin immunoprecipitation-sequencing (ChIP-sequencing) assay revealed an increase in H3K27me3 modification of E3 ubiquitin ligases Rnf19a following JEV infection, which leads to downregulation of Rnf19a expression. Furthermore, the results showed that Rnf19a negatively regulates the neuroinflammatory response induced by JEV. This is achieved through the degradation of RIG-I by mediating its ubiquitination. In conclusion, our findings reveal a novel mechanism by which JEV triggers extensive neuroinflammation from an epigenetic perspective.

The Influence of the Gut Microbiota on Alzheimer's Disease: A Narrative Review.

Alzheimer's disease (AD) is a common neurodegenerative disease that tends to occur in the elderly. The main symptom is hypomnesia. More and more older people are suffering from this disease worldwide. By 2050, 152 million people worldwide are expected to have AD. It is thought that the aggregation of amyloid-beta peptides and hyper-phosphorylated tau tangles contribute to AD. The microbiota-gut-brain (MGB) axis appears as a new concept. The MGB axis is a collection of microbial molecules produced in the gastrointestinal tract that influence the physiological function of the brain. In this review, we discuss how the gut microbiota (GM) and its metabolites affect AD in different ways. Dysregulation of the GM has been shown to be involved in various mechanisms involved in memory and learning functions. We review the current literature on the role of the entero-brain axis in the pathogenesis of AD and its potential role as a future therapeutic target in the treatment and/or prevention of AD.

Autophagy inhibitors alleviate Japanese encephalitis virus-induced cerebral inflammation in mice.

Japanese encephalitis (JE) is a zoonotic epidemic disease caused by Japanese encephalitis virus (JEV), and currently, no medicines are available to treat this disease. Autophagy modulators play an important role in the treatment of tumors, heart disease, and some viral diseases. The aim of this study was to investigate the effects of autophagy modulators on JEV infection and the host response in mice. The experimental mice were grouped as follows: DMEM (control), JEV, JEV+rapamycin (JEV+Rapa), JEV+wortmannin (JEV+Wort), JEV+chloroquine (JEV+CQ), Rapa, Wort, and CQ. The control group was treated with DMEM. The mice in other groups were infected with 105 PFU of JEV, and Rapa, Wort, and CQ were administered 2 h prior to JEV challenge and then administered daily for 10 consecutive days. All mice were monitored for neurological signs and survival. The damage of subcellular structures in the mouse brain was evaluated by transmission electron microscopy. The distribution of virus in the mouse brain was determined by RNAScope staining and immunohistochemical staining. The neuroinflammatory responses in the brain were examined via quantitative real-time PCR, and the signal pathways involved in neuroinflammation were identified by Western blot. The mice in the JEV+Wort and JEV+CQ groups showed milder neurological symptoms, less damage to the mitochondria in the brain tissue, and a higher survival rate than those in the JEV+Rapa and JEV groups. Compared with the JEV+Rapa and JEV groups, the distribution of JEV in the brain of mice in the JEV+Wort and JEV+CQ groups was lower, and the inflammatory response was weaker. No significant difference was observed in the expression of the PI3K/AKT/NF-κB pathway in mouse brain among the different groups. Our study suggests that the autophagy inhibitors Wort and CQ reduce JEV infection and weaken the inflammatory response, which does not depend on the PI3K/AKT/NF-κB pathway in mouse brain.

[Transurethral holmium laser enucleation of the prostate for benign prostatic hyperplasia in patients with a history of transrectal prostate biopsy].

OBJECTIVE: To evaluate the efficiency and safety of transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of BPH in patients with a history of transrectal prostate biopsy (TRPB). METHODS: We retrospectively analyzed the clinical data on 102 cases of BPH treated by HoLEP in our hospital between November 2015 and May 2017, of which 42 had received TRPB prior to HoLEP (the PB group) but not the other 60 (the non-TRPB ï¼»NPBï¼½ group). We compared the preoperative, perioperative and postoperative follow-up data between the two groups of patients. RESULTS: There were no statistically significant differences in the mean age, prostate volume, and preoperative post-void residual urine volume (PVR), IPSS, quality of life (QOL) score and maximum urinary flow rate (Qmax) between the two groups of patients. The preoperative PSA level was significantly higher in the PB than in the NPB group (ï¼»10.30 ± 3.62ï¼½ vs ï¼»2.62 ± 1.75ï¼½ µg/L, P < 0.01), and the operation time markedly longer in the former than in the latter (ï¼»78.00 ± 18.25ï¼½ vs ï¼»67.93 ± 15.89ï¼½ min, P < 0.01), particularly in the patients with an interval of <2 weeks between HoLEP and TRPB than in those with an interval of ≥2 weeks (ï¼»91.17 ± 16.51ï¼½ vs ï¼»68.13 ± 12.45ï¼½ min, P < 0.01). Statistically significant differences were not found in the postoperative hemoglobin level, continuous bladder irrigation duration, catheter-indwelling time and hospital stay, nor in the incidence rate of transient urinary incontinence between the PB and NPB groups (47.62% vs 45%, P = 0.794). There were no transurethral resection syndrome, bladder or rectal injury, or blood transfusion in either group, nor statistically significant differences in PVR, Qmax, IPSS and QOL score between the two groups of patients at 3, 6 or 12 months after operation. CONCLUSIONS: HoLEP is a safe and effective surgical treatment of BPH for patients with a history of TRPB, which can reduce the time and increase the safety of operation when performed at ≥2 weeks after TRPB.

Activation of neuronal N-methyl-D-aspartate receptor plays a pivotal role in Japanese encephalitis virus-induced neuronal cell damage.

BACKGROUND: Overstimulation of glutamate receptors, especially neuronal N-methyl-D-aspartate receptor (NMDAR), mediates excitatory neurotoxicity in multiple neurodegenerative diseases. However, the role of NMDAR in the regulation of Japanese encephalitis virus (JEV)-mediated neuropathogenesis remains undisclosed. The primary objective of this study was to understand the function of NMDAR to JEV-induced neuronal cell damage and inflammation in the central nervous system. METHODS: The effect of JEV-induced NMDAR activation on the progression of Japanese encephalitis was evaluated using the primary mouse neuron/glia cultures and a mouse model of JEV infection. A high-affinity NMDAR antagonist MK-801 was employed to block the activity of NMDAR both in vitro and in vivo. The subsequent impact of NMDAR blockade was assessed by examining the neuronal cell death, glutamate and inflammatory cytokine production, and JEV-induced mice mortality. RESULTS: JEV infection enhanced the activity of NMDAR which eventually led to increased neuronal cell damage. The data obtained from our in vitro and in vivo assays demonstrated that NMDAR blockade significantly abrogated the neuronal cell death and inflammatory response triggered by JEV infection. Moreover, administration of NMDAR antagonist protected the mice from JEV-induced lethality. CONCLUSION: NMDAR plays an imperative role in regulating the JEV-induced neuronal cell damage and neuroinflammation. Thus, NMDAR targeting may constitute a captivating approach to rein in Japanese encephalitis.

Correlation between chronic headaches and the rectus capitis posterior minor muscle: A comparative analysis of cross-sectional trail.

Objective We aimed to investigate the morphological changes and potential correlation between chronic headaches and the rectus capitis posterior minor muscle (RCPmi). Methods Comparison of RCPmi between patients with chronic headaches and healthy adult volunteers were collected using magnetic resonance imaging (MRI) and Mimics software. Results Among the 235 MRI images analyzed, the data between the two groups were considered statistically significant. The number of males was larger than that of females ( p < 0.001) and the headache group showed greater hypertrophy than the control group in both males ( p < 0.001) and females ( p = 0.001). Conclusions Chronic headaches were correlated with the RCPmi. Patients with chronic headaches suffered from more obvious hypertrophy than that of the control group. Additionally, it was supposed that RCPmi hypertrophy may be one pathogenesis of the chronic headaches.

TCDD promoted EMT of hFPECs via AhR, which involved the activation of EGFR/ERK signaling.

One critical step of second palatal fusion is the newly formed medial epithelia seam (MES) disintegration, which involves apoptosis, epithelial to mesenchymal transition (EMT), and cell migration. Although the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces cleft palate at high rates, little is known about the effects of TCDD exposure on the fate of palatal epithelial cells. By using primary epithelial cells isolated from human fetal palatal shelves (hFPECs), we show that TCDD increased cell proliferation and EMT, as demonstrated by increased the epithelial markers (E-cadherin and cytokeratin14) and enhanced the mesenchymal markers (vimentin and fibronectin), but had no effect on cell migration and apoptosis. TCDD exposure led to a dose-dependent increase in Slug protein expression. Coimmunoprecipitation revealed that TCDD promoted AhR to form a protein complex with Slug. ChIP assay confirmed that TCDD exposure recruited AhR to the xenobiotic responsive element of Slug promoter. Knockdown of AhR by siRNA remarkably weakened TCDD-induced binding of AhR to the XRE promoter of slug, thereby suppressed TCDD-induced vimentin. Further experiment showed that TCDD stimulated EGFR phosphorylation did not influence the TGFß3/Smad signaling; whereas TCDD increased phosphorylation of ERK1/2 and p38 with no effect on activation of JNK. By using varieties of inhibitors, we confirmed that TCDD promoted proliferation and EMT of hFPECs via activation of EGFR/ERK pathway. These data make a novel contribution to the molecular mechanism of cleft palate by TCDD.

Effect of TCDD on the fate of epithelial cells isolated from human fetal palatal shelves (hFPECs).

Cleft palate is caused by the failure of palatal midline epithelial cells to disintegrate, which is necessary for palatal mesenchymal confluence. Although 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure is linked to cleft palate at a high rate, the mechanism remains to be elucidated. The present study was designed to determine the effects of TCDD on the fate of epithelial cell isolated from human fetal palatal shelves (hFPECs). We demonstrate that TCDD increased cell proliferation and promoted the progression of cells from G1 to S phase as well as increased the number of cells entering the G2/M phase. We found that TCDD has no measurable effect on apoptosis of hFPECs. The protein level assays revealed that TCDD increased cyclin-dependent kinases 4 (cdk4), cyclin D1, cyclin E and p21 (Waf1/Cip1) but not cdk2, bcl-2, cyclin B1 and cyclin A. Furthermore, TCDD activated PI3K/AKT signaling, and the PI3K inhibitor, LY294002, partially abrogated TCDD-induced cell proliferation and gene modulations. TCDD treatment increased CYP1A1 mRNA and protein levels, which indicated the activation of AhR signaling. Knockdown of the AhR with siRNA suppressed TCDD-induced cell proliferation and PI3K/AKT signaling activation. Taken together, these data demonstrated that TCDD is able to promote growth of hFPECs through AhR-dependent activation of the PI3K/AKT pathway, which may account for the underlying mechanism by which TCDD causes a failure of palatal fusion.

Design and fabrication of complicated diffractive optical elements on multiple curved surfaces.

Fabrication of multiple arbitrary diffractive optical elements (DOEs) on multiple curved surfaces is always a challenge; here we propose an effective optimization method to fabricate complicated DOEs on several curved surfaces at the same time. First we design phase distribution to modulate complicated three-dimensional (3D) intensity distribution on multiple curved surfaces simultaneously, and then by exposure, the intensity distribution is transferred into the pure-phase or depth distribution. Numerical simulations and optical fabrication are performed for different intensity distributions: 3D binary patterns and 3D gray level patterns, on two or three curved surfaces, and both are in nice agreement. Since multiple DOEs are fabricated on curved surfaces simultaneously, the collimation of different curved surfaces is avoided, and it could improve the fabrication efficiency. It is expected that this proposed method would be employed in various precision 3D optical fabrication and processing in the future.

3D optical intensity modulation on curved surfaces by optimization method and its application to fabricate arbitrary patterns.

We present a method to design the pure-phase distribution based on phase optimization for realizing the three-dimensional (3D) intensity modulation on curved surfaces (CS) and apply it to fabricate desired 3D patterns on CS. 3D intensity patterns are reconstructed numerically as well as fabricated experimentally on CS with high quality, which demonstrates the validity of the method. Since the arbitrary phase profile of diffractive optical elements (DOEs) on CS can be mapped into the 3D optical intensity distribution on CS, the method can be directly applied to fabricate any desired DOEs on CS. As far as we know, it is the first time to design the pure-phase distribution for realizing the 3D intensity modulation on CS and apply it to fabricate arbitrary patterns on CS.

Mediation of the association between screen time and suicidality by overweight/obesity and perceived overweight: results from the youth risk behavior surveillance system of the United States.

Aim: Adolescent suicide is a major public health concern, and modifiable risk factors associated with adolescent suicide remain poorly understood. This study aimed to assess the association between screen time and overweight/obesity and self-perceived overweigh and suicidality in adolescents. Methods: Adolescents from the United States Youth Risk Behavior Surveillance System (YRBSS) between 2013 and 2019 were included in this cross-sectional study. The outcome was suicidality, including considered suicide, made a suicide plan, attempted suicide, and injurious suicide attempt. Multivariable logistic regression model was used to investigate the associations between screen time, overweight/obesity, self-perceived overweight, and suicidality, and expressed as odds ratio (OR) and 95% confidence interval (CI). Mediation analysis was used to explore the role of overweight/obesity and self-perceived overweight on the association between screen time and suicidality. Results: A total of 30,731 adolescents were included, of which 6,350 (20.65%) had suicidality, including 5,361 (17.45%) with considered suicide, 4,432 (14.42%) with made a suicide plan, 2,300 (7.45%) with attempted suicide, and 677 (2.21%) with injurious suicide attempt. Adolescents with screen time ≥3h were related to higher odds of suicidality (OR=1.35, 95%CI: 1.23-1.46), overweight/obesity (OR=1.27, 95%CI: 1.19-1.38), and self-perceived overweight (OR=1.38, 95%CI: 1.30-1.48) after adjusting confounders. Adolescents with overweight/obesity (OR=1.30, 95%CI: 1.19-1.43) and self-perceived overweight (OR=1.54, 95%CI: 1.39-1.70) were associated with higher odds of suicidality. The association between screen time and suicidality was 4.67% mediated by overweight/obesity and 9.66% mediated by self-perceived overweight. Moreover, the mediating role of overweight/obesity was observed only in females, whereas there were no sex differences in the mediating effect of self-perceived overweight. Conclusion: Both overweight/obesity and self-perceived overweight mediated the association between screen time and suicidality.

Correlation of the serum cell division cycle 42 with CD4+ T cell subsets and in-hospital mortality in Stanford type B aortic dissection patients.

Objective: Cell division cycle 42 (CDC42) regulates CD4+ T-cell differentiation and participates in vascular stiffness and atherosclerosis and is involved in the progression of Stanford type B aortic dissection (TBAD). This study aimed to explore the correlation between serum CDC42 level and CD4+ T cell subsets and in-hospital mortality in TBAD patients. Methods: Serum CDC42 and peripheral blood T-helper (Th) 1, Th2, and Th17 cells were detected in 127 TBAD patients by enzyme-linked immunosorbent assay and flow cytometry, respectively. Serum CDC42 was also quantified in 30 healthy controls. Results: Serum CDC42 was decreased in TBAD patients vs. healthy controls (median [interquartile range (IQR)]: 418.0 (228.0-761.0) pg/ml vs. 992.0 (716.3-1,445.8) pg/ml, P < 0.001). In TBAD patients, serum CDC42 was negatively correlated with Th17 cells (P = 0.001), but not Th1 (P = 0.130) or Th2 cells (P = 0.098). Seven (5.5%) patients experienced in-hospital mortality. Serum CDC42 was reduced in patients who experienced in-hospital mortality vs. those who did not (median (IQR): 191.0 (145.0-345.0) pg/ml vs. 451.5 (298.3-766.8) pg/ml, P = 0.006). By receiver operating characteristic analysis, serum CDC42 showed a good ability for estimating in-hospital mortality [area under curve = 0.809, 95% confidence interval (CI) = 0.662-0.956]. By the multivariate logistic regression analysis, elevated serum CDC42 [odd ratio (OR) = 0.994, 95% CI = 0.998-1.000, P = 0.043] was independently correlated with lower risk of in-hospital mortality, while higher age (OR = 1.157, 95% CI = 1.017-1.316, P = 0.027) was an independent factor for increased risk of in-hospital mortality. Conclusion: Serum CDC42 negatively associates with Th17 cells and is independently correlated with decreased in-hospital mortality risk in TBAD patients.

Distribution and correlation of iron oxidizers and carbon-fixing microbial communities in natural wetlands.

Most microaerophilic Fe(II)-oxidizing bacteria (mFeOB) belonging to the family Gallionellaceae are autotrophic microorganisms that can use inorganic carbon to drive carbon sequestration in wetlands. However, the relationship between microorganisms involved in Fe and C cycling is not well understood. Here, soil samples were collected from different wetlands to explore the distribution and correlation of Gallionella-related mFeOB and carbon-fixing microorganisms containing cbbL and cbbM genes. A significant positive correlation was found between the abundances of mFeOB and the cbbL gene, as well as a highly significant positive correlation between the abundances of mFeOB and the cbbM gene, indicating the distribution of mFeOB in co-occurrence with carbon-fixing microorganisms in wetlands. The mFeOB were mainly dominated by Sideroxydans lithotrophicus ES-1 and Gallionella capsiferriformans ES-2 in all wetland soils. The structures of the carbon-fixing microbial communities were similar in these wetlands, mainly consisting of Alphaproteobacteria, Betaproteobacteria, and Gammaproteobacteria. The extractable Fe(II) concentrations affected the community composition of mFeOB, resulting in a significant difference in the relative abundances of the dominant FeOB. The main factors affecting cbbL-related microbial communities were dissolved inorganic carbon and oxygen, soil redox potential, and sodium acetate-extracted Fe(II). The composition of cbbM-related microbial communities was mainly affected by acetate-extracted Fe(II) and soil redox potential. In addition, the positive correlation between these functional microorganisms suggests that they play a synergistic role in Fe(II) oxidation and carbon fixation in wetland soil ecosystems. Our results suggest a cryptic relationship between mFeOB and carbon-fixing microorganisms in wetlands and that the microbial community structure can be effectively altered by regulating their physicochemical properties, thus affecting the capacity of carbon sequestration.

Wrinkling and Strengthening Behaviors in the Two-Layer-Sheet Hot-Forming-Quenching Integrated Process for an Al-Cu-Mg-Alloy Thin-Walled Curved-Surface Shell.

The thin-walled curved-surface component is an important structural element in aerospace. Wrinkling, springback and thermal distortion occur easily when forming these components. To form thin-walled components with high precision and strength, a two-layer-sheet hot-forming-quenching integrated process was proposed, in which wrinkling is prevented by thickening the upper sheet and springback is reduced by solution and die quenching. Selecting an appropriate upper sheet is crucial to suppress wrinkling and accomplish effective die quenching. The effect of the upper sheet on the wrinkling and strengthening behaviors of an Al-Cu-Mg-alloy melon-petal shell was thus studied in detail. The anti-wrinkle mechanism was analyzed through numerical simulation. The forming quality, including forming precision, deformation uniformity and strength, were further evaluated. The wrinkle gradually decreased with the increasing thickness of the upper sheet, resulting from the depressed compressive stress at the edge of the target sheet. A defect-free specimen with a smooth surface was finally formed when the thickness of the upper sheet reached three times that of the target sheet. The profile deviation was ±0.5 mm. Excellent thickness uniformity in a specimen can be obtained with a maximum thinning rate of 6%. The full strength, ranging from 455 to 466 MPa, can be obtained in all regions of the specimen, indicating that effective strengthening can be accomplished with the two-layer-sheet die quenching. The results indicated that high forming quality and full strength can be obtained in a two-layer-sheet hot-forming-quenching integrated process. This research has great potential for engineering applications using aluminum-alloy curved-surface thin-walled components.

Biological determinants perpetuating the transmission dynamics of mosquito-borne flaviviruses.

Mosquito-borne flaviviruses present a major public health concern. Their transmission is sustained in a cycle between mosquitoes and vertebrate hosts. However, the dynamicity of the virus-mosquito-host triad has not been completely understood. Herein, we discussed determinants of viral, vertebrate host, and mosquito origins that ensure virus adaptability and transmission in the natural environment. In particular, we provided insights into how proteins and RNAs of flaviviruses, blood parameters and odours of humans, and gut microbiota, saliva, and hormones of mosquitoes coordinate with each other to perpetuate the virus transmission cycle. A better knowledge of mechanisms permitting flaviviruses dissemination in nature can provide opportunities for establishing new virus-controlling strategies and could guide future epidemic and pandemic preparedness.

Arbuscular mycorrhizal fungi increase crop yields by improving biomass under rainfed condition: a meta-analysis.

BACKGROUND: Rainfed agriculture plays key role in ensuring food security and maintain ecological balance. Especially in developing areas, most grain food are produced rainfed agricultural ecosystem. Therefore, the increase of crop yields in rainfed agricultural ecosystem becomes vital as well as ensuring global food security. METHODS: The potential roles of arbuscular mycorrhizal fungi (AMF) in improving crop yields under rainfed condition were explored based on 546 pairs of observations published from 1950 to 2021. RESULTS: AMF inoculation increased 23.0% crop yields based on 13 popular crops under rainfed condition. Not only was crop biomass of shoot and root increased 24.2% and 29.6% by AMF inocula, respectively but also seed number and pod/fruit number per plant were enhanced markedly. Further, the effect of AMF on crop yields depended on different crop groups. AMF improved more yield of N-fixing crops than non-N-fixing crops. The effect of AMF changed between grain and non-grain crops with the effect size of 0.216 and 0.352, respectively. AMF inoculation enhances stress resistance and photosynthesis of host crop in rainfed agriculture. CONCLUSION: AMF increased crop yields by enhancing shoot biomass due to the improvement of plant nutrition, photosynthesis, and stress resistance in rainfed field. Our findings provide a new view for understanding the sustainable productivity in rainfed agroecosystem, which enriched the theory of AMF functional diversity. This study provided a theoretical and technical way for sustainable production under rainfed agriculture.

Corresponding risk factors between cognitive impairment and type 1 diabetes mellitus: A narrative review.

Type 1 diabetes mellitus (T1DM) is a type of diabetes caused by the destruction of pancreatic ß cells and the absolute lack of insulin secretion. T1DM usually starts in adolescence or develops directly as a severe disease state of ketoacidosis. T1DM and its complications make many people suffer and have psychological problems, which make us have to pay more attention to the prevention and early control of T1DM. Cognitive impairment (CI) is one of the major complications of T1DM. It can further develop into Alzheimer's disease, which can seriously affect the quality of life of the elderly. Furthermore, the relationship between T1DM and CI is unclear. Hence, we conducted a narrative review of the existing literature through a PubMed search. We summarized some risk factors that may be associated with the cognitive changes in T1DM patients, including onset age and duration, education and gender, glycemic states, microvascular complications, glycemic control, neuropsychology and emotion, intestinal flora, dyslipidemia, sleep quality. We aimed to provide some content related to CI in T1DM, and hoped that it could play a role in early prediction and treatment to reduce the prevalence.