Search

Neurofibromatosis type 1 is a rare genetic disorder, which is a benign nerve tumor resulting from aberrant growth of the cells of nerve sheath. NF1 patients were associated with multisystem involvement, characterized by neurofibroma, of which 50% were associated with plexus neurofibroma. Characteristically benign plexiform neurofibromas can cause pain, disfigurement, compression and functional changes. Although plexiform neurofibroma is common in the head and neck, the orbital plexiform neurofibroma is rare and easily confused with other orbital tumors. There is no consensus with regard to the treatment strategy of plexiform neurofibromas, current treatment has remained largely surgical, but comes with a high recurrence rate after partial removal. We describe a case of a 4-year-old patient with orbital plexiform neurofibroma who has a 3-year history of ptosis in the right eye. At the begining, we misdiagnosed it as hemangioma. After surgical resection, it was confirmed as plexiform neurofibroma by histopathological examination. One year after surgery, the tumor recurred, so surgical resection was performed again, and the ptosis was corrected. After that, the patients were followed up and examined annually, and no recurrence was found so far. This case shows that an infant or a child present with unilateral eye swelling and ptosis of the upper eyelid should be evaluated for orbital neurofibroma.

Objectives: Circular RNAs (circRNAs) have been found to have significant impacts on non-small cell lung cancer (NSCLC) progression through various mechanisms. However, the mechanism of circRNAs modulating tumor immune evasion in NSCLC has yet to be well-revealed. Materials and Methods: Through analyzing the expression profiles of circRNAs in NSCLC tissues, RNA FISH, pull-down assay, mass spectrometry analysis, and RIP, circCRIM1 was identified, and its interaction with IGF2BP1 was confirmed. The effects of circCRIM1 on modulating tumor immune evasion were explored via co-culture in vitro and in tumor xenograft models. Subsequently, we evaluated the regulatory effects of circCRIM1 on IGF2BP1 and screened its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circCRIM1 could regulate the stability of target mRNA. Results: circCRIM1 was downregulated in NSCLC, and its expression was positively correlated with favorable prognoses. Furthermore, circCRIM1 was more stable than its linear transcript and was mainly localized in the cytoplasm. Mechanistically, circCRIM1 destabilized HLA-F mRNA via competitive binding to IGF2BP1. Importantly, the overexpression of circCRIM1 suppressed the immune evasion of NSCLC and promoted the expressions of Granzyme B, IFN-γ, and TNF-α of CD8+ T and NK cell in vitro co-culture assays and tumor xenograft models. Conclusions: This study identifies circCRIM1 as a new tumor suppressor that inhibits tumor immune evasion through a competitive combination with IGF2BP1 to destabilize HLA-F mRNA.

Ischemic stroke causes cerebral hypoxia, while long non-coding RNA regulator of reprogramming is associated with hypoxia. To find a new intervention target to protect hypoxic cerebral tissue and a potential biomarker from reflecting the severity of hypoxia after ischemic stroke, our research explored the expression pattern and function of the regulator of reprogramming in cerebral hypoxia-induced injury. The expression pattern and the function of the regulator of reprogramming were explored in mice with middle cerebral artery occlusion, and human brain microvascular endothelial cells underwent oxygen-glucose deprivation treatment. A case-control study, including 223 ischemic stroke patients and 155 controls were also conducted to investigate its correlation with ischemic stroke clinical characteristics. Results showed that the regulator of reprogramming increased significantly in middle cerebral artery occlusion in mice (P < 0.05), and its level remained stable within 2 to 48 h after the implement of middle cerebral artery occlusion. Oxygen-glucose deprivation up-regulated the expression of regulator of reprogramming, and regulator of reprogramming promoted ASK-1/STRAP/14-3-3 complex formation to inhibit the activation of TNF-α/ASK-1-mediated apoptosis of human brain microvascular endothelial cells, while small interfering ribonucleic acid (RNA) targeting regulator of reprogramming amplified these effects. Regulator of reprogramming increased and maintained stable within 3 to 48 h of ischemic stroke onset in patients, and was negatively associated with the National Institutes of Health Stroke Scale (NIHSS) (r = -0.708, P < 0.001), high sensitivity C-reactive protein (Hs-CRP) (r = -0.683, P < 0.001) level, infarct volume (r = -0.579, P < 0.001), and modified Rankin scale (mRS) (r = -0.728, P < 0.001). These results indicate that the regulator of reprogramming can alleviate cerebral hypoxia-induced injury by suppressing TNFα-induced apoptosis of vascular endothelial cells.

Disordered metabolic states, which are characterised by hypoxia and elevated levels of metabolites, particularly lactate, contribute to the immunosuppression in the tumour microenvironment (TME). Excessive lactate secreted by metabolism-reprogrammed cancer cells regulates immune responses via causing extracellular acidification, acting as an energy source by shuttling between different cell populations, and inhibiting the mechanistic (previously ‘mammalian’) target of rapamycin (mTOR) pathway in immune cells. This review focuses on recent advances in the regulation of immune responses by lactate, as well as therapeutic strategies targeting lactate anabolism and transport in the TME, such as those involving glycolytic enzymes and monocarboxylate transporter inhibitors. Considering the multifaceted roles of lactate in cancer metabolism, a comprehensive understanding of how lactate and lactate-targeting therapies regulate immune responses in the TME will provide insights into the complex relationships between metabolism and antitumour immunity.

The soluble resistance-related calcium-binding protein (sorcin, SRI) serves as the calcium-binding protein for the regulation of calcium homeostasis and multidrug resistance. Although the mounting evidence suggests a crucial role of SRI in the chemotherapeutic resistance of certain types of tumors, insights into pan-cancer analysis of SRI are unavailable. Therefore, this study aimed to probe the multifaceted properties of SRI across the 33 cancer types. The SRI expression was analyzed via The Cancer Genome Atlas (TCGA) and Genotype Tissue-Expression (GTEX) database. The SRI genomic alterations and drug sensitivity analysis were performed based on the cBioPortal and the CellMiner database. Furthermore, the correlations among the SRI expression and survival outcomes, clinical features, stemness, tumor mutation burden (TMB), microsatellite instability (MSI), and immune cells infiltration were analyzed using TCGA data. The differential analysis showed that SRI was upregulated in 25 tumor types compared with the normal tissues. Aberrant expression of SRI was able to predict survival in different cancers. Further, the most frequent alteration of SRI genomic was amplification. Moreover, the aberrant SRI expression was related to stemness score, epithelial-mesenchymal-transition (EMT)-related genes, MSI, TMB, and tumor immune microenvironment in various types of cancer. TIMER database mining further found that the SRI expression was significantly correlated with the infiltration levels of various immune cells in certain types of cancer. Intriguingly, the SRI expression was negatively correlated with drug sensitivity of fluorouracil, paclitaxel, docetaxel, and isotretinoin. Our findings highlight the predictive value of SRI in cancer and provide insights for illustrating the role of SRI in tumorigenesis and drug resistance.

Breast cancer (BC) represents a molecularly and clinically heterogeneous disease. Recent progress in immunotherapy has provided a glimmer of hope for several BC subtypes. The relationship between N6-methyladenosine (m6A) modification and long non-coding RNAs (LncRNAs) is still largely unexplored in BC. Here, with the intention to dissect the landscape of m6A-related lncRNAs and explore the immunotherapeutic value of the m6A-related lncRNA signature, we identified m6A-related lncRNAs by co-expression analysis from The Cancer Genome Atlas (TCGA) and stratified BC patients into different subgroups. Furthermore, we generated an m6A-related lncRNA prognostic signature. Four molecular subtypes were identified by consensus clustering. Cluster 3 preferentially had favorable prognosis, upregulated immune checkpoint expression, and high level of immune cell infiltration. Twenty-one m6A-related lncRNAs were applied to construct the m6A-related lncRNA model (m6A-LncRM). Survival analysis and receiver operating characteristic (ROC) curves further confirmed the prognostic value and prediction performance of m6A-LncRM. Finally, high- and low-risk BC subgroups displayed significantly different clinical features and immune cell infiltration status. Overall, our study systematically explored the prognostic value of the m6A-related LncRNAs and identified a high immunogenicity BC subtype. The proposed m6A-related LncRNA model might serve as a robust prognostic signature and attractive immunotherapeutic targets for BC treatment.

The role of autophagy in lung cancer is context-dependent and complex. Recent studies have reported the important role of autophagy in tumor immune escape. However, the association between autophagy and tumor-infiltrating lymphocytes (TILs) in early-stage lung adenocarcinoma (LUAD) remains unclear. In this study, we aimed to develop and validate the autophagy-related gene pair index (ATGPI) and autophagy clinical prognostic index (ACPI) in multiple LUAD cohorts, including The Cancer Genome Atlas (TCGA) cohort, Gene Expression Omnibus cohorts, and one cohort from Union Hospital, Wuhan (UH cohort), using a Cox proportional hazards regression model with the least absolute shrinkage and selection operator. Multivariate Cox regression analysis demonstrated that there was a significant difference in overall survival (OS) between patients with high and low ATGPI in the testing [hazard ratio (HR) = 1.97; P < 0.001] and TCGA validation (HR = 2.25; P < 0.001) cohorts. Time-dependent receiver operating characteristic curve analysis was also performed. We found that high ATGPI could accurately identify patients with early-stage LUAD with shorter OS, with the areas under the curve of 0.703 and 0.676 in the testing and TCGA validation cohorts, respectively. Concordance index (C-index) was used to evaluate the efficiency of ATGPI and ACPI. The C-index of ACPI was higher than that of ATGPI in the testing (0.71 vs. 0.66; P < 0.001), TCGA validation (0.69 vs. 0.65; P = 0.028), and UH (0.80 vs. 0.70; P = 0.015) cohorts. TIL analysis demonstrated that the proportions of tumor-infiltrating CD4+ T cells were lower in the high-ATGPI group than in the low-ATGPI group in both the TCGA validation and UH cohorts. These results indicate the potential clinical use of ATG signatures which are associated with TILs, in identifying patients with early-stage LUAD with different OS.

Objective The neutrophil-to-lymphocyte ratio (NLR) is recognised as a suitable prognostic biomarker in patients with breast cancer. Nevertheless, the efficacy of this biomarker in predicting the pathological complete response (pCR) and survival in patients with breast cancer receiving neoadjuvant chemotherapy (NACT) is still controversial. This meta-analysis aimed to identify the association between baseline NLR and the prognosis of patients with breast cancer treated with NACT.Design Meta-analysis.Data sources Relevant literature published before 1 May 2021 was searched using the Cochrane Library, Embase, PubMed and the Web of Science databases.Eligibility criteria All studies involving patients with breast cancer treated with NACT and peripheral blood pretreatment NLR recorded as a dichotomous variable were included.Data extraction and synthesis Two researchers independently extracted and evaluated OR/HR and its 95% CIs of survival outcomes and clinicopathological parameters.Results A total of 19 studies were identified. From each study, the impact of NLR on the pCR, OR and HR, with their 95% CIs were extracted and combined using either a random or fixed-effects model. The results indicate that a higher pCR in patients with a low NLR (OR 1.620, 95% CI 1.209 to 2.169, p＜0.001). In addition, an elevated NLR predicted lower disease-free survival (HR 2.269, 95% CI 1.557 to 3.307, p

Acidic gas penetration through the internal pressure sheath of a flexible riser tends to cause a corrosive environment in the annulus, reducing the service life of the flexible riser. Nanoparticles can act as gas barriers in the polymer matrix to slow down the gas permeation. Herein, we prepared PA11/SiO2 composites by the melt blending method. The effect of adding different amounts of SiO2 to PA11 on its gas barrier properties was investigated by conducting CO2 permeation tests between 20 °C and 90 °C. As the temperature increased, the lowest value of the permeability coefficient that could be achieved for the PA11 with different contents of SiO2 increased. The composites PA/0.5% SiO2 and PA/1.5% SiO2 had the lowest permeation coefficients in the glassy state (20 °C) and rubbery state (≥50 °C). We believe that this easy-to-produce industrial PA/SiO2 composite can be used to develop high-performance flexible riser barrier layers. It is crucial for understanding riser permeation behavior and enhancing barrier qualities.

The rich −SO3H groups enable sulfonated poly (ether ether ketone) (SPEEK) to possess excellent proton conductivities in proton exchange membrane (PEM), but cause excessive water absorption, resulting in the decline of dimensional stability. It is a challenge to resolve the conflict between conductivity and stability. Owing to its unique structural designability, covalent organic frameworks (COFs) have been used to regulate the performances of PEMs. The authors propose the use of COFs with acidic and basic groups for meeting the requirements of proton conductivity and dimensional stability. Herein, COFs containing different groups (sulfoacid, pyridine, and both) were uniformly dispersed into the SPEEK matrix by in situ synthesis, and the effects on the properties of SPEEK matrix PEMs were revealed. The sulfoacid group significantly improves proton conductivities. At 60 °C, under 95% RH, the conductivity of the SPEEK/TpPa−SO3H-20 composite membrane was 443.6 mS·cm−1, which was 3.3 times that of the pristine SPEEK membrane. The pyridine group reduced the swelling ratio at 50 °C from 220.7% to 2.4%, indicating an enhancement in dimensional stability. Combining the benefits of sulfoacid and pyridine groups, SPEEK/TpPa−(SO3H-Py) composite membrane has a conductivity of 360.3 mS·cm−1 at 60 °C and 95% RH, which is 1.86 times that of SPEEK, and its swelling ratio is 11.8%, about 1/20 of that of SPEEK membrane. The method of in situ combination and regulation of groups open up a way for the development of SPEEK/COFs composite PEMs.

Abstract Amnion‐derived prostaglandin E2 (PGE2) and cortisol are key to labor onset. Identification of a common transcription factor driving the expression of both cyclooxygenase‐2 (COX‐2) and 11β‐hydroxysteroid dehydrogenase 1 (11β‐HSD1), the key enzymes in their production, may hold the key to the treatment of pre‐term labor. Here, we have found that the CCAAT enhancer binding protein δ (C/EBPδ) is such a transcription factor which underlies the feed‐forward induction of COX‐2 and 11β‐HSD1 expression by their own products PGE2 and cortisol in human amnion fibroblasts so that their production would be ensured in the amnion for the onset of labor. Moreover, the abundance of C/EBPδ in the amnion increases along with COX‐2 and 11β‐HSD1 at term and further increases at parturition. Knockout of C/EBPδ in mice delays the onset of labor further supporting the concept. In conclusion, C/EBPδ pathway may be speculated to serve as a potential pharmaceutical target in the amnion for treatment of pre‐term labor.

The current reports of COVID-19 focus on the respiratory system, however, intestinal infections caused by SARS-CoV-2 are also worthy of attention. This paper reported persistence of intestinal SARS-CoV-2 infection leads to re-admission after pneumonia resolved in three cases with COVID-19.

Uveitis has been generally defined as the inflammation occurring in the intraocular tissues. Among them, non-infectious uveitis is a T cell-mediated autoimmune inflammatory response. Through systemic treatments for non-infectious uveitis are abundant, the main principle is to suppress the immune response. In this review, we reviewed the history of non-infectious uveitis systemic therapy, detailed the current status of systemic treatment, summarized the pros and cons of each treatment regimen, and expected some new treatments for non-infectious uveitis.

Abstract Introduction Pentoxifylline may be an important approach to treat neonatal sepsis. However, its use has not been well established. We conduct a systematic review and meta-analysis to evaluate the efficacy of pentoxifylline treatment for neonatal sepsis. Methods PubMed, Embase, and the Cochrane Central Register of Controlled Trials are searched. Randomized controlled trials (RCTs) assessing the influence of pentoxifylline treatment on neonatal sepsis are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. This meta-analysis is performed using the random-effect model. Results Seven RCTs involving 439 patients are included in the meta-analysis. Compared with control intervention for neonatal sepsis, pentoxifylline treatment is associated with reduced hospital stay (Std. MD = -0.61; 95% CI = -0.93 to − 0.29; P = 0.0002) and metabolic acidosis (RR = 0.38; 95% CI = 0.22 to 0.66; P = 0.0006), but has no remarkable impact on mortality (RR = 0.59; 95% CI = 0.30 to 1.16; P = 0.13), serum TNF-α (Std. MD = -0.38; 95% CI = -1.29 to 0.52; P = 0.41), serum CRP (Std. MD = -0.25; 95% CI = -0.92 to 0.42; P = 0.47), plasma IL-6 (Std. MD = -0.13; 95% CI = -0.41 to 0.15; P = 0.37), disseminated intravascular coagulopathy (RR = 0.55; 95% CI = 0.25 to 1.21; P = 0.14), and oliguria/anuria (RR = 0.77; 95% CI = 0.28 to 2.16; P = 0.62). In addition, pentoxifylline treatment can significantly reduce mortality (RR = 0.50; 95% CI = 0.29 to 0.88; P = 0.02) after excluding the study conducted by Akdag during the sensivity analysis. Conclusions Pentoxifylline treatment may be associated with reduced mortality and hospital stay in neonatal sepsis.

Abstract Background To investigate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients with diabetic macular edema (DME) treated monthly with ranibizumab. Methods We retrospectively analyzed the medical records of all patients who received intravitreal ranibizumab (IVR) treatment for DME at the First Affiliated Hospital of Nanchang University between December 2015 and December 2017. Clinicopathological parameters, including NLR, were evaluated to identify predictors of better outcomes of IVR monotherapy. Results Ninety-one treatment-naïve eyes treated with IVR for DME were retrospectively analyzed in this study. Baseline best-corrected visual acuity (BCVA), neutrophils, NLR, monocyte-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were negatively correlated with the changes in BCVA at 24 weeks compared with the baseline, while baseline central retinal thickness and lymphocytes were positively correlated with the changes in BCVA at 24 weeks compared with the baseline. Multiple linear regression analysis revealed that NLR was independently associated with the mean change of BCVA between baseline and week 24. In addition, patients with NLR 2.27. Conclusion Pretreatment NLR is independently associated with the BCVA in DME patients treated with IVR, and higher pretreatment NLR may contribute to inferior BCVA outcomes.

Abstract Background Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neurotoxicity and histopathology in human neurodegenerative diseases. Here we report a protocol for the rapid development of a human cell culture model of neuroinflammatory astrogliosis using induced pluripotent stem cells (iPSCs). Methods Using RNA sequencing and in vitro cell assays, we measured transcriptional and cellular effects of chronic exposure of human iPSC-derived astrocytes to the cytokines TNFα (tumor necrosis factor alpha) or IL-1β (interleukin-1 beta). Results We show TNFα and IL-1β induce pro-inflammatory gene signatures but by widely different magnitudes. TNFα treatment results in 606 differential expressed genes, the suppression of glutamate-uptake, and increased phagocytic activity in astrocyte cultures. In contrast, IL-1β effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity. Conclusion Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. In particular, we reveal a model for robust TNFα-induced human astrogliosis suitable for the study of neurotoxic A1 astrocytes.

Abstract As a widely distributed species along the Irtysh River, Phoxinus phoxinus ujmonensis (Kaschtschenko, 1899) was used as a model to investigate genetic diversity and population structure as well as the influence of environmental factors on population genetics. In this study, we specifically developed 12 polymorphic microsatellite loci. The analysis of microsatellite and mtDNA markers revealed a high and a moderate genetic diversity across seven populations, respectively. Moderate differentiation was also detected among several populations, indicating the impact of habitat fragmentation and divergence. The absence of isolation by distance implied an extensive gene flow, while the presence of isolation by adaptation implied that these populations might be in the process of adapting to divergent habitats. Correlation analysis showed that abiotic factors like dissolved oxygen, pH, total dissolved solids, and conductivity in water as well as biotic factors like plankton diversity and fish species diversity had impact on genetic diversity and divergence in P. phoxinus ujmonensis populations. The results of this study will provide an insight into the effect of environmental factors on genetic diversity and contribute to the study of population genetics of sympatric species.

Abstract Background The clinical efficacy of definitive pelvic radiotherapy for primary tumors in patients with newly diagnosed organ metastatic cervical cancer is unclear. Therefore, we conducted a retrospective study to evaluate the efficacy of definitive pelvic radiotherapy combined with systemic chemotherapy in patients with organ metastatic cervical cancer. Methods We retrospectively analysed medical records from patients with newly diagnosed organ metastatic cervical cancer, all treated with chemotherapy at the Zhejiang Cancer Hospital between October 2006 and December 2016. Survival times were compared using the Kaplan-Meier method. The univariate log-rank method and multivariate Cox proportional hazard models were used to identify associated variables with survival. Results A total of 48 patients were identified from 11,982 primary cervical cancer patients and divided into two groups according to treatment mode: 36 patients received chemotherapy combined with definitive pelvic radiotherapy (group A), 12 patients underwent chemotherapy with/without palliative pelvic radiotherapy (group B). Median follow-up was 14.4 months (range, 4.6–114.7 months). Median overall survival (OS) for group A and group B was 17.3 and 10 months, respectively. Using the univariate analysis, group A was found to have a better OS than group B (p = 0.002). In multivariate analysis, group A (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15–0.67, p = 0.003) was associated with lower risk of death compared with group B. The main reason for treatment failure was found to be due to the progression of distant metastatic lesions in 36 patients (75%) from the whole cohort. Conclusion In this cohort of organ metastatic cervical cancer patients in good performance status, chemotherapy combined with definitive pelvic radiotherapy was associated with improved survival outcomes when compared with chemotherapy with/without palliative pelvic radiotherapy. Prospective trials evaluating definitive pelvic radiotherapy for newly diagnosed organ metastatic cervical cancer, therefore, are warranted.

Mitochondria are vital organelles in cells, regulating energy metabolism and apoptosis. Mitochondrial transcellular transfer plays a crucial role during physiological and pathological conditions, such as rescuing recipient cells from bioenergetic deficit and tumorigenesis. Studies have shown several structures that conduct transcellular transfer of mitochondria, including tunneling nanotubes (TNTs), extracellular vesicles (EVs), and Cx43 gap junctions (GJs). The intra- and intercellular transfer of mitochondria is driven by a transport complex. Mitochondrial Rho small GTPase (MIRO) may be the adaptor that connects the transport complex with mitochondria, and myosin XIX is the motor protein of the transport complex, which participates in the transcellular transport of mitochondria through TNTs. In this review, the roles of TNTs, EVs, GJs, and related transport complexes in mitochondrial transcellular transfer are discussed in detail, as well as the formation mechanisms of TNTs and EVs. This review provides the basis for the development of potential clinical therapies targeting the structures of mitochondrial transcellular transfer.

Abstract Objective Middle‐age patients with retinal detachment (RD) exhibit a loss of visual information, and previous studies of functional magnetic resonance imaging (fMRI) have demonstrated abnormal spontaneous activity in the RD brain. Therefore, this study assessed changes in local functional connectivity density (lFCD) and long‐range functional connectivity density (longFCD) in middle‐age RD patients during resting‐state FC. Methods In total, 32 middle‐age patients with RD (18 men and 14 women), and 32 age‐, sex‐, and education‐matched normal controls (NCs) (18 men and 14 women) were recruited and underwent functional magnetic resonance examination in the resting state. Two‐sample t test was performed to compare lFCD and longFCD between groups. Receiver operating characteristic (ROC) curves were generated to distinguish middle‐age RD patients from NCs. Results Compared with NCs, middle‐age RD patients demonstrated increased lFCD values in the right inferior temporal gyrus, and increased longFCD values in the bilateral inferior frontal gyri, left superior and middle frontal gyrus, bilateral inferior temporal gyri, and left cerebellum posterior lobe. Middle‐age RD patient exhibited decreased lFCD values in the left cuneus, right lingual gyrus, and left middle frontal gyrus. They also had lower longFCD values in the left lingual gyrus and left inferior occipital gyrus. ROC curve analysis showed excellent accuracy of the specific areas under the curve. Conclusion Our results reveal that middle‐age RD patients exhibited variations of binarized lFCD and longFCD in specific brain areas, which provides insight into the pathological mechanism of RD patients with acute visual loss.

It is well recognized that aphid infestation severely reduces crop yield and further leads to significant economic loss. Therefore, accurately and efficiently detecting aphids is of vital importance in pest management. However, most existing detection methods suffer from unsatisfactory performance without fully considering the aphid characteristics, including tiny size, dense distribution, and multi-viewpoint data quality. In addition, existing clustered tiny-sized pest detection methods improve performance at the cost of time and do not meet the real-time requirements. To address the aforementioned issues, we propose a robust aphid detection method with two customized core designs: a Transformer feature pyramid network (T-FPN) and a multi-resolution training method (MTM). To be specific, the T-FPN is employed to improve the feature extraction capability by a feature-wise Transformer module (FTM) and a channel-wise feature recalibration module (CFRM), while the MTM aims at purifying the performance and lifting the efficiency simultaneously with a coarse-to-fine training pattern. To fully demonstrate the validity of our methods, abundant experiments are conducted on a densely clustered tiny pest dataset. Our method can achieve an average recall of 46.1% and an average precision of 74.2%, which outperforms other state-of-the-art methods, including ATSS, Cascade R-CNN, FCOS, FoveaBox, and CRA-Net. The efficiency comparison shows that our method can achieve the fastest training speed and obtain 0.045 s per image testing time, meeting the real-time detection. In general, our TD-Det can accurately and efficiently detect in-field aphids and lays a solid foundation for automated aphid detection and ranking.

Perfluorosulfonic acid (PFSA) polymer is considered as a proton exchange membrane material with great potential. Nevertheless, excessive water absorption caused by abundant sulfonic acid groups makes PFSA have low dimensional stabilities. In order to improve the dimensional stability of PFSA membranes, nanofibers are introduced into PFSA membranes. However, because nanofibers lack proton conducting groups, it usually reduces the proton conductivities of PFSA membranes. It is a challenge to improve dimensional stabilities while maintaining high proton conductivities. Due to the structural designability, covalent organic frameworks (COFs) with proton conductive groups are chosen to improve the overall performance of PFSA membranes. Herein, COFs synthesized in situ on three-dimensional PAN nanofibers were introduced into PFSA to prepare PFSA@PAN/TpPa-SO3H sandwiched membranes. The PFSA@PAN/TpPa-SO3H-5 composite membrane exhibited outstanding proton conductivity, which reached 260.81 mS·cm−1 at 80 °C and 100% RH, and only decreased by 4.7% in 264 h. The power density of a single fuel cell with PFSA@PAN/TpPa-SO3H-5 was as high as 392.7 mW·cm−2. Compared with the pristine PFSA membrane, the conductivity of PFSA@PAN/TpPa-SO3H-5 increased by 70.0 mS·cm−1, and the area swelling ratio decreased by 8.1%. Our work provides a novel strategy to prepare continuous proton transport channels to simultaneously improve conductivities and dimensional stabilities of proton exchange membranes.

The surfaces of trichoid sensilla on male moth antennae have been sculpted over evolutionary time to capture pheromone odorant molecules emitted by the females of their species and transport the molecules in milliseconds into the binding protein milieu of the sensillum lumen. The capture of pheromone molecules likely has been optimized by the topographies and spacings of the numerous ridges and pores on these sensilla. A monolayer of free lipids in the outer epicuticle covers the sensillar surfaces and must also be involved in optimal pheromone odorant capture and transport. Using electro-conductive atomic force microscopy probes, we found that electrical surface potentials of the pores, ridges and flat planar areas between ridges varied in consistent ways, suggesting that there is a heterogeneity in the distribution of surface lipid mixtures amongst these structures that could help facilitate the capture and transport of pheromone molecules down through the pores. We also performed experiments using peak force atomic force microscopy in which we heated the sensilla to determine whether there is a temperature-related change of state of some of the surface lipid exudates such as the prominent domes covering many of the pores. We found that these exudates were unaffected by heating and did not melt or change shape significantly under high heat. Additionally, we measured and compared the topographies of the trichoid sensilla of five species of moths, including the distributions, spacings, heights and diameters of ridges, pores and pore exudates.

Serum amyloid A1 (SAA1) is an acute phase protein produced mainly by the liver to participate in immunomodulation in both sterile and non-sterile inflammation. However, non-hepatic tissues can also synthesize SAA1. It remains to be determined whether SAA1 synthesized locally in the placenta participates in parturition via eliciting inflammatory reactions. In this study, we investigated this issue by using human placenta and a mouse model. We found that SAA1 mRNA and protein were present in human placental villous trophoblasts, which was increased upon syncytialization as well as treatments with lipopolysaccharides (LPS), tumor necrosis factor-α (TNF-α), and cortisol. Moreover, significant increases in SAA1 abundance were observed in the placental tissue or in the maternal blood in spontaneous deliveries without infection at term and in preterm birth with histological chorioamnionitis. Serum amyloid A1 treatment significantly increased parturition-pertinent inflammatory gene expression including interleukin-1β (IL-1β), IL-8, TNF-α, and cyclooxygenase-2 (COX-2), along with increased PGF2α production in syncytiotrophoblasts. Mouse study showed that SAA1 was present in the placental junctional zone and yolk sac membrane, which was increased following intraperitoneal administration of LPS. Intraperitoneal injection of SAA1 not only induced preterm birth but also increased the abundance of IL-1β, TNF-α, and COX-2 in the mouse placenta. Conclusively, SAA1 can be synthesized in the human placenta, which is increased upon trophoblast syncytialization. Parturition is accompanied with increased SAA1 abundance in the placenta. Serum amyloid A1 may participate in parturition in the presence and absence of infection by inducing the expression of inflammatory genes in the placenta.

The global pandemic of COVID-19 cases caused by infection with SARS-CoV-2 is ongoing, with no approved antiviral intervention. We describe here the effects of treatment with interferon (IFN)-α2b in a cohort of confirmed COVID-19 cases in Wuhan, China. In this uncontrolled, exploratory study, 77 adults hospitalized with confirmed COVID-19 were treated with either nebulized IFN-α2b (5 mU b.i.d.), arbidol (200 mg t.i.d.) or a combination of IFN-α2b plus arbidol. Serial SARS-CoV-2 testing along with hematological measurements, including cell counts, blood biochemistry and serum cytokine levels, and temperature and blood oxygen saturation levels, were recorded for each patient during their hospital stay. Treatment with IFN-α2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP. These findings suggest that IFN-α2b should be further investigated as a therapy in COVID-19 cases.

Insect olfactory sensing is crucial for finding food, mating, and oviposition preference. Odorant receptors (ORs) play a central role in the transmission of odorant signals into the environment by the peripheral olfactory system. Therefore, the identification and functional study of ORs are essential to better understand olfactory mechanisms in insects. OR studies on Diptera insects are primarily performed on Drosophila and mosquitoes, but few studies have been reported in Tephritidae. In this study, we examined three candidate ORs (BminOR3, BminOR12, and BminOR16) from Bactrocera minax. Our analysis of tissue expression revealed that the three BminORs were expressed in the antennae, with no difference between the male and female. In in vitro heterologous expression system of Xenopus oocytes. BminOR3/BminOrco responded strongly to 1-octen-3-ol, BminOR12/BminOrco responded to eight compounds [methyl salicylate, benzaldehyde, (Z)-3-hexenyl acetate, butyl acrylate, butyl propionate, 1-octanol, (S)-(+)-carvone and benzyl alcohol], and BminOR16/BminOrco slightly responded to undecanol. Our results concluded that BminOR3, BimOR12, and BminOR16 could play an important role in host-finding and oviposition positioning in B. minax.

Background Severe early childhood caries (S-ECC) is mainly caused by the interaction of microbiota and environmental factors. However, the metabolic profiles of S-ECC microbial communities and the community-level microbial responses to carbohydrates and amino acids are poorly understood. Methods We collected supragingival plaques from 15 caries-free (CF) and 14 S-ECC children. Cultivation on Biolog AN microplates together with next-generation sequencing was used to analyze sole carbon source utilization patterns and microbial responses to sucrose, lactose and phenylalanine. Results S-ECC plaques had greater overall metabolic activity than those of CF ones. Comparing with CF, S-ECC plaques utilized more sucrose and lactose but less phenylalanine and then had greater response to carbohydrates. A remarkable increase of non-mutans Streptococci was observed in sucrose and lactose consumption. Lactose led to less differently distributed taxa than sucrose in both CF and S-ECC groups. Sucrose made the originally different S-ECC and CF communities eventually became similar to each other, but they remained dissimilar in lactose. Conclusion S-ECC plaques had more active interaction with cariogenic carbohydrates like sucrose and lactose than healthy plaques. We supported lactose has less cariogenicity compared with sucrose from microbial community structural aspect. Phenylalanine may have a potentially inhibitory effect on caries development.

With the widespread clinical use of drug combinations, the incidence of drug–drug interactions (DDI) has significantly increased, accompanied by a variety of adverse reactions. Drug transporters play an important role in the development of DDI by affecting the elimination process of drugs in vivo, especially in the pathological state. Tubulointerstitial fibrosis (TIF) is an inevitable pathway in the progression of chronic kidney disease (CKD) to end-stage renal disease. Here, the dynamic expression changes of eleven drug transporters in TIF kidney have been systematically investigated. Among them, the mRNA expressions of Oat1, Oat2, Oct1, Oct2, Oatp4C1 and Mate1 were down-regulated, while Oat3, Mrp2, Mrp4, Mdr1-α, Bcrp were up-regulated. Pearson correlation analysis was used to analyze the correlation between transporters and Creatinine (Cr), OCT2 and MATE1 showed a strong negative correlation with Cr. In contrast, Mdr1-α exhibited a strong positive correlation with Cr. In addition, the pharmacokinetics of cimetidine, ganciclovir, and digoxin, which were the classical substrates for OCT2, MATE1 and P-glycoprotein (P-gp), respectively, have been studied. These results reveal that changes in serum creatinine can indicate changes in drug transporters in the kidney, and thus affect the pharmacokinetics of its substrates, providing useful information for clinical use.

Background/Aims: Fish is a protein-rich food and is increasingly favored by consumers. It has been well recognized that the flesh composition of fish is closely related to its maturation and growth stage, but few studies have explored these differences. Additionally, hormone residues in fish after artificial induction of reproduction also attract consumer concern. In this study, we attempt to address these concerns by using a combination of transcriptomics and metabolomics analyses to identify key regulated pathways, genes, and metabolites that may affect the flesh nutrition of one typical aquaculture species in China, blunt snout bream (Megalobrama amblycephala). Methods: The four groups of fish were used for transcriptomics and metabolomics analyses, including one-year-old immature (group I), two-year-old immature (group II), two-year-old mature (group III) and successfully spawned (group IV) female M. amblycephala after artificial induction of reproduction. Results: We identified a total of 1460 differential compounds and 1107 differentially expressed unigenes in muscle among the different groups. Differential metabolites related to fish age (group II vs group I, group III vs group I) were largely enriched in “Glycerophospholipid metabolism”, “Linoleic acid metabolism”, “α-Linolenic acid metabolism”, and “Biosynthesis of unsaturated fatty acids”. Between these two pairwise comparisons, metabolites that are beneficial to human health, such as docosapentaenoic acid, α-Linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid were found to be significantly decreased in two-year-old (group II, group III) compared with one-year-old (group I) M. amblycephala. Only one differential metabolite related to fish maturation, a triglyceride, was detected between groups III and II. Transcriptomics data showed that differently expressed genes (between group III vs group II, group III vs group I) related to maturation were highly enriched in “Cell adhesion molecules (CAMs)”, “Sphingolipid metabolism” and “Phagosome”. DEGs (between group II vs group I, group III vs group I) relating to fish age were enriched in the “cGMP-PKG signaling pathway”, “FoxO signaling pathway”, and “AMPK signaling pathway”. The gene-metabolite interaction network showed pivotal genes, including fumarate hydratase and GNPAT, which played a major role in the regulation of glycerphospholipid metabolism. The nutritional components were also measured, which verified the metabolomics results. Moreover, the metabolomics results showed that after 24 hours of artificial hormone injection, the drug was completely metabolized. Conclusion: Integrated analysis demonstrated that the nutrition value of fish fillet was much more related to fish age compared with maturation status in M. amblycephala females.

This study investigated the changes in interhemispheric functional connectivity (FC) of the whole brain in open globe injury (OGI) patients, using voxel-mirrored homotopic connectivity (VMHC), and their relationships with clinical features. Totally, 16 male and 2 female acute OGI patients and 18 sex, age, and education-matched healthy volunteers were enrolled in the study. All subjects were scanned through functional magnetic resonance imaging (fMRI). Receiver operating characteristic (ROC) curves analyses had been used to identify the VMHC in these brain areas could be used as biomarkers to distinguish OGI and from healthy control (HC). The mean VMHC values in multiple brain areas and clinical OGI manifestations were evaluated with a Pearson correlation analysis. OGI patients had significantly decreased VMHC in the bilateral calcarine/lingual/cuneus (BA18, 19, 30) and middle occipital gyrus (BA18, 19). The OGI patients had abnormal interhemispheric FC in the dorsal visual pathway, which may represent the pathophysiological mechanism that underlies acute vision loss after OGI.

Cryptococcosis is an infection caused by the yeast-like fungus Cryptococcus neoformans. Pulmonary cryptococcosis is typically identified as a single mass or as multiple nodules, while endobronchial lesions are quite rare. Here we report an uncommon case of pulmonary cryptococcosis presenting as endobronchial lesion in an immunocompetent patient. A 49-year-old male patient complained of intermittent cough with hemoptysis for two years. Computerized tomography of the chest showed a filling defect in the basal segment of the right lower lobe bronchus. A flexible bronchoscopic examination revealed a white smooth-surfaced polypoid lesion completely occluding the medial basal segment of the right lower lobe bronchus. The diagnosis was confirmed by bronchial biopsy under bronchoscopy, and the histopathologic findings showed the organisms were Cryptococcal neoformans. The patient was treated with fluconazole at a dose of 400 mg daily. The endobronchial lesion was found rapidly diminished after 18 days of therapy, and disappeared after 6.5 months of therapy by repeated fiberoptic bronchoscopy. Then the patient continued fluconazole for another 2.5 months. During the total 16 months' follow-up visits, the patient repeated CT scanning for five times, the results of which were all normal. The patient's symptoms disappeared as well, and now he is still under follow-up. This case highlights the fact that pulmonary cryptococcosis can present as endobronchial lesions even in immunocompetent subjects, mimicking lung tumor. Pathological confirmation is important to establish the definite diagnosis. Keywords: Case report, Cryptococcosis, Endobronchial mass, Pulmonary cryptococcosis

Video object and human action detection are applied in many fields, such as video surveillance, face recognition, etc. Video object detection includes object classification and object location within the frame. Human action recognition is the detection of human actions. Usually, video detection is more challenging than image detection, since video frames are often more blurry than images. Moreover, video detection often has other difficulties, such as video defocus, motion blur, part occlusion, etc. Nowadays, the video detection technology is able to implement real-time detection, or high-accurate detection of blurry video frames. In this paper, various video object and human action detection approaches are reviewed and discussed, many of them have performed state-of-the-art results. We mainly review and discuss the classic video detection methods with supervised learning. In addition, the frequently-used video object detection and human action recognition datasets are reviewed. Finally, a summarization of the video detection is represented, e.g., the video object and human action detection methods could be classified into frame-by-frame (frame-based) detection, extracting-key-frame detection and using-temporal-information detection; the methods of utilizing temporal information of adjacent video frames are mainly the optical flow method, Long Short-Term Memory and convolution among adjacent frames.

Background: Vaccine hesitancy, associated with medical mistrust, confidence, complacency and knowledge of vaccines, presents an obstacle to the campaign against the coronavirus disease 2019 (COVID-19). The relationship between vaccine hesitancy and conspiracy beliefs may be a key determinant of the success of vaccination campaigns. This study provides a conceptual framework to explain the impact of pathways from conspiracy beliefs to COVID-19 vaccine hesitancy with regard to medical mistrust, confidence, complacency and knowledge of vaccines. Methods: A non-probability study was conducted with 1015 respondents between 17 April and 28 May 2021. Conspiracy beliefs were measured using the coronavirus conspiracy scale of Coronavirus Explanations, Attitudes, and Narratives Survey (OCEANS), and vaccine conspiracy beliefs scale. Medical mistrust was measured using the Oxford trust in doctors and developers questionnaire, and attitudes to doctors and medicine scale. Vaccine confidence and complacency were measured using the Oxford COVID-19 vaccine confidence and complacency scale. Knowledge of vaccines was measured using the vaccination knowledge scale. Vaccine hesitancy was measured using the Oxford COVID-19 vaccine hesitancy scale. Confirmatory factor analysis (CFA) was used to evaluate the measurement models for conspiracy beliefs, medical mistrust, confidence, complacency, and knowledge of vaccines and vaccine hesitancy. The structural equation modeling (SEM) approach was used to analyze the direct and indirect pathways from conspiracy beliefs to vaccine hesitancy. Results: Of the 894 (88.1%) respondents who were willing to take the COVID-19 vaccine without any hesitancy, the model fit with the CFA models for conspiracy beliefs, medical mistrust, confidence, complacency and knowledge of vaccines, and vaccine hesitancy was deemed acceptable. Conspiracy beliefs had significant direct (β = 0.294), indirect (β = 0.423) and total (β = 0.717) effects on vaccine hesitancy; 41.0% of the total effect was direct, and 59.0% was indirect. Conspiracy beliefs significantly predicted vaccine hesitancy by medical mistrust (β = 0.210), confidence and complacency (β = 0.095), knowledge (β = 0.079) of vaccines, explaining 29.3, 11.0, and 13.2% of the total effects, respectively. Conspiracy beliefs significantly predicted vaccine hesitancy through the sequential mediation of knowledge of vaccines and medical mistrust (β = 0.016), explaining 2.2% of the total effects. Conspiracy beliefs significantly predicted vaccine hesitancy through the sequential mediation of confidence and complacency, and knowledge of vaccines (β = 0.023), explaining 3.2% of the total effects. The SEM approach indicated an acceptable model fit (χ2/df = 2.464, RMSEA = 0.038, SRMR = 0.050, CFI = 0.930, IFI = 0.930). Conclusions: The sample in this study showed lower vaccine hesitancy, and this study identified pathways from conspiracy beliefs to COVID-19 vaccine hesitancy in China. Conspiracy beliefs had direct and indirect effects on vaccine hesitancy, and the indirect association was determined through medical mistrust, confidence, complacency, and knowledge of vaccines. In addition, both direct and indirect pathways from conspiracy beliefs to vaccine hesitancy were identified as intervention targets to reduce COVID–19 vaccine hesitancy.

Plants have evolved various self-defense mechanisms against insect feeding. There are many reports regarding both direct and indirect defense mechanisms in seed-plant. However, only direct defenses on ferns were considered and the indirect defense mechanism has never been reported. In this study, it was observed that the fern Hypolepis punctata can attract the assassin bug Sclomina erinacea in the field. We collected and analyzed volatiles from H. punctata healthy individuals and the ones wounded by Bertula hadenalis, using dynamic headspace and GC-MS. We recorded the electroantennogram responses of antennae of S. erinacea to different standards of volatile compounds identified from the GC-MS analysis. We also analyzed the behavior of male and female S. erinacea adults in response to volatiles collected from H. punctata using a Y-tube olfactometer. The results showed that a number of volatile compounds were produced when the fern was damaged by B. hadenalis. Electroantennography and Y-tube olfactometer results showed that some herbivore-induced volatiles and volatiles from undamaged leaves could attract S. erinacea. Our research suggests that H. punctata can attract insect predators by releasing herbivory-induced volatile organic compounds, and for the first time we found ferns may also have indirect defense mechanisms using volatile organic compounds.

The distribution of Triplophysa yarkandensis is restricted to Xinjiang’s Tarim River basin. We collected 119 T. yarkandensis samples from nine geographic populations in the Tarim River basin and utilized the RAD-seq method for SNP genotyping. In this study, a total of 164.81 Gb bases were generated with the Illumina platform, and 129,873 candidate SNPs were obtained with the Stacks pipeline for population genetic analyses. High levels of genetic diversity were detected among nine populations. The AMOVA results showed that the majority of genetic variations originated from among populations (FST = 0.67), and the pairwise FST values ranged from 0.4579 to 0.8736, indicating high levels of genetic differentiation among these populations. The discriminate analysis of principal components (DAPCs) and neighbor joining (NJ) tree revealed that the nine populations could be separated into two clusters (i.e., south and north populations), and modest genetic differentiation between south and north populations was observed, while the individuals from several populations were not clustered together by geographical location. The evidence of two genetic boundaries between south and north populations (except TTM) was supported by barrier analysis. The Bayesian skyline plotting indicated that T. yarkandensis populations in the Tarim River basin had not experienced genetic bottlenecks, and the effective population size remained stable. This study first clarified the genetic diversity and differentiation of T. yarkandensis populations in the Tarim River basin, and it provided valuable molecular data for conservation and management of natural populations.

We report photochromic polyamide 6 (PA6) which was synthesized by hydrolyzed ring-opening polymerization of ε-caprolactam with spiropyran (SP) embedded in the polymer chains. It indicated that crystallinity degree of the resulting copolymers was decreased since only PA6 segments can crystallize with increasing content of SP modifier. Meanwhile, toughness of photochromic PA6 was decreased. The photochromic property analysis indicated that the sample with more flexibility and more content of SP was more sensitive to UV light at the beginning of irradiation than other samples and its color after being irradiated for 1 min tended to reddish. Investigation revealed that the UV-vis absorbance of SP-PA6-3 had negligible decay after 10 cycles, which indicated SP-modified PA6 possessed excellent photoresponse reversibility and fatigue resistance.

Lysyl oxidase-like 2 (LOXL2) is an enzyme that promotes scaffolding of extracellular matrix proteins. Here the authors show that LOXL2 is crucial for pressure-overload induced cardiac fibrosis, and that antibody-mediated inhibition or genetic disruption ofLoxl2in mice shows therapeutic potential for treatment of cardiac fibrosis.

Nacre-like composite films with different ratios of graphene oxide (GO), polyvinyl alcohol (PVA) and carboxylated single-walled carbon nanotubes (SWCNTs) were prepared by solvent evaporation and chemical reduction. Changes in the microstructure, mechanical properties, electrical properties and thermal stability of the composite films were studied. It was found that the cross-section of the composite films had a regular inter-layer alternating structure. Meanwhile, introduction of SWCNTs not only improved the mechanical properties but also the in-plane (σp) and through-thickness (σt) conductivities of the composite films. The tensile strength of the composite film reached 62.8 MPa. The σp and σt of the composite film reached 806 S/m and 479 S/m, respectively, 300 times and 490 times greater than the values obtained prior to the addition of the SWCNTs. Furthermore, the thermal stability of the composite film was also improved. Keywords: Nacre-like structure, Graphene oxide, Polyvinyl alcohol, Single-walled carbon nanotubes

Because of the considerable advantages of functional molecules as well as supramolecules, such as the low cost, light weight, flexibility, and large area preparation via the solution method, molecular electronics has grown into an active and rapidly developing research field over the past few decades. Beyond those well-known advantages, a very long spin relaxation time of π-conjugated molecules, due to the weak spin-orbit coupling, facilitates a pioneering but fast-growing research field, known as molecular spintronics. Recently, a series of sustained progresses have been achieved with various π-conjugated molecular matrixes where spin transport is undoubtedly an important point for the spin physical process and multifunctional applications. Currently, most studies on spin transport are carried out with a molecule-based spin valve, which shows a typical geometry with a thin-film molecular layer sandwiched between two ferromagnetic electrodes. In such a device, the spin transport process has been demonstrated to have a close correlation with spin relaxation time and charge carrier mobility of π-conjugated molecules. In this review, the recent advances of spin transport in these two aspects have been systematically summarized. Particularly, spin transport in π-conjugated molecular materials, considered as promising for spintronics development, have also been highlighted, including molecular single crystal, cocrystal, solid solution as well as other highly ordered supramolecular structures.

Anthocyanins belong to the group of flavonoid compounds broadly distributed in plant species responsible for attractive colors. In black rice (Oryza sativa L.), they are present in the stems, leaves, stigmas, and caryopsis. However, there is still no scientific evidence supporting the existence of compartmentalization and trafficking of anthocyanin inside the cells. In the current study, we took advantage of autofluorescence with anthocyanin’s unique excitation/emission properties to elucidate the subcellular localization of anthocyanin and report on the in planta characterization of anthocyanin prevacuolar vesicles (APV) and anthocyanic vacuolar inclusion (AVI) structure. Protoplasts were isolated from the stigma of black and brown rice and imaging using a confocal microscope. Our result showed the fluorescence displaying magenta color in purple stigma and no fluorescence in white stigma when excitation was provided by a helium–neon 552 nm and emission long pass 610–670 nm laser. The fluorescence was distributed throughout the cell, mainly in the central vacuole. Fluorescent images revealed two pools of anthocyanin inside the cells. The diffuse pools were largely found inside the vacuole lumen, while the body structures could be observed mostly inside the cytoplasm (APV) and slightly inside the vacuole (AVI) with different shapes, sizes, and color intensity. Based on their sizes, AVI could be grouped into small (Ф < 0.5 um), middle (Ф between 0.5 and 1 um), and large size (Ф > 1 um). Together, these results provided evidence about the sequestration and trafficking of anthocyanin from the cytoplasm to the central vacuole and the existence of different transport mechanisms of anthocyanin. Our results suggest that stigma cells are an excellent system for in vivo studying of anthocyanin in rice and provide a good foundation for understanding anthocyanin metabolism in plants, sequestration, and trafficking in black rice.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13052-019-0697-8

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), a lung disease that may progress to systemic organ involvement and in some cases, death. The identification of the earliest predictors of progressive lung disease would allow for therapeutic intervention in those cases. In an earlier clinical study, individuals with moderate COVID-19 were treated with either arbidol (ARB) or inhaled interferon (IFN)-α2b +/−ARB. IFN treatment resulted in accelerated viral clearance from the upper airways and in a reduction in the circulating levels of the inflammatory biomarkers IL-6 and C-reactive protein (CRP). We have extended the analysis of this study cohort to determine whether IFN treatment had a direct effect on virus-induced lung abnormalities and also to ascertain whether any clinical or immune parameters are associated with worsening of lung abnormalities. Evidence is provided that IFN-α2b treatment limits the development of lung abnormalities associated with COVID-19, as assessed by CT images. Clinical predictors associated with worsening of lung abnormalities include low CD8+ T cell numbers, low levels of circulating albumin, high numbers of platelets, and higher levels of circulating interleukin (IL)-10, IL-6, and C-reactive protein (CRP). Notably, in this study cohort, IFN treatment resulted in a higher percentage of CD8+ T cells, lower tumor necrosis factor (TNF)-α levels and, as reported earlier, lower IL-6 levels. Independent of treatment, age and circulating levels of albumin and CRP emerged as the strongest predictors of the severity of lung abnormalities.

As one of the most prevalent human infectious diseases, dental caries results from dysbiosis of the oral microbiota driven by multiple factors. However, most of caries studies were cross-sectional and mainly focused on the differences in the oral microbiota between caries-free (CF) and caries-affected (CA) populations, while little is known about the dynamic shift in microbial composition, and particularly the change in species association pattern during disease transition. Here, we reported a longitudinal study of a 12-month follow-up of a cohort of 3-year-old children. Oral examinations and supragingival plaque collections were carried out at the beginning and every subsequent 6 months, for a total of three time points. All the children were CF at enrollment. Children who developed caries at 6-month follow-up but had not received any dental treatment until the end of the study were incorporated into the CA group. Children who remained CF at the end of the study were incorporated into the CF group. Using Illumina Miseq Sequencing of the 16S rRNA gene, we monitored the shift of supragingival microbiome during caries initiation and progression in children who developed caries over the 12-month study period. Intriguingly, principle coordinates analyses revealed two major shifting patterns in microbial structures during caries initiation and progression in CA group, but not in CF group. Dynamic co-occurring OTU network study showed that compared to CF group, there was significant increase in both number and intensity of correlations between microbial taxa, as well as the formation of tight clusters of specific bacteria in CA group. Furthermore, there were enhanced correlations, positive ones between CA-enriched taxa, and negative ones between CF-enriched and CA-enriched species within CA group. Our data suggested coordinated microbial interactions could be essential to caries pathogenesis. Most importantly, our study indicated that significant microbial shifts occur not only during caries development, but even in the sub-clinical state. Using supragingival microbiome profiles, we were able to construct a caries-onset prediction model with a prediction accuracy of 93.1%. Our study indicated that the microbial shifts prior to the onset of caries might potentially be used for the early diagnosis and prediction of caries.

Tumor necrosis factor (TNF) is a pleiotropic cytokine that has both pro-inflammatory and anti-inflammatory functions. The biological functions of TNF are mediated by two receptors, TNF receptor type I (TNFR1) and TNF receptor type II (TNFR2). TNFR1 is expressed universally on almost all cell types and has been extensively studied, whereas TNFR2 is mainly restricted to immune cells and some tumor cells and its role is far from clarified. Studies have shown that TNFR2 mediates the stimulatory activity of TNF on CD4+Foxp3+ regulatory T cells (Tregs) and CD8+Foxp3+ Tregs, and is involved in the phenotypic stability, proliferation, activation, and suppressive activity of Tregs. TNFR2 can also be expressed on CD8+ effector T cells (Teffs), which delivers an activation signal and cytotoxic ability to CD8+ Teffs during the early immune response, as well as an apoptosis signal to terminate the immune response. TNFR2-induced abolition of TNF receptor-associated factor 2 (TRAF2) degradation may play an important role in these processes. Consequently, due to the distribution of TNFR2 and its pleiotropic effects, TNFR2 appears to be critical to keeping the balance between Tregs and Teffs, and may be an efficient therapeutic target for tumor and autoimmune diseases. In this review, we summarize the biological functions of TNFR2 expressed on CD8+Foxp3+ Tregs and CD8+ Teffs, and highlight how TNF uses TNFR2 to coordinate the complex events that ultimately lead to efficient CD8+ T cell-mediated immune responses.

Objective To investigate the underlying functional network brain-activity changes in patients with adult comitant exotropia strabismus (CES) and the relationship with clinical features using the voxel-wise degree centrality (DC) method. Methods A total of 30 patients with CES (17 men, 13 women), and 30 healthy controls (HCs; 17 men, 13 women) matched in age, sex, and education level participated in the study. DC was used to evaluate spontaneous brain activity. Receiver operating characteristic (ROC) curve analysis was conducted to distinguish CESs from HCs. The relationship between mean DC values in various brain regions and behavioral performance was examined with correlation analysis. Results Compared with HCs, CES patients exhibited decreased DC values in the right cerebellum posterior lobe, right inferior frontal gyrus, right middle frontal gyrus and right superior parietal lobule/primary somatosensory cortex (S1), and increased DC values in the right superior temporal gyrus, bilateral anterior cingulate, right superior temporal gyrus, and left inferior parietal lobule. However, there was no correlation between mean DC values and behavioral performance in any brain regions. Conclusions Adult comitant exotropia strabismus is associated with abnormal brain network activity in various brain regions, possibly reflecting the pathological mechanisms of ocular motility disorders in CES.

BACKGROUND:Using salivary microbiota as an accurate proxy for monitoring supragingival microbiota remains controversial because their relationship remains unclear. The eruption of permanent teeth and the exfoliation of primary teeth in mixed dentition greatly alter microbial habitats, which may cause compositional shifts of oral microbiota from childhood to adults. OBJECTIVE:This study's purpose was to assess whether saliva represents a suitable sample for monitoring supragingival microbiota in healthy people, and to explore how the replacement process of deciduous teeth with permanent teeth in mixed dentition influences microbiota within the oral cavity. DESIGN:Samples of saliva and of supragingival plaque from permanent and deciduous teeth were collected separately from 20 healthy children with mixed dentition. To characterize their microbial communities, we used the V3-V4 hypervariable region of the bacterial 16S rRNA gene sequence. RESULTS:Saliva harbored a less even and less diverse community than did the plaque. Discriminating genera, namely Rothia and Streptococcus, contributed to the saliva and plaque differentiation. About half of predicted KEGG pathways varied between the plaque and saliva communities. Oral bacteria showed significantly associations between their supragingival and salivary states. We identified 20 supragingival plaque-related genera in saliva, such as Corynebacterium, Capnocytophaga, Fusobacterium, and Neisseria. Additionally, the relative abundance of Actinobacteria peaked in the permanent teeth plaque but subsided in deciduous teeth plaque and saliva. The exfoliation of deciduous teeth and eruption of permanent teeth might be related to the reported fluctuation in the relative abundance of Actinobacteria from primary dentition to permanent dentition within the oral cavity. The variation between PT and DT was due mainly to permanent teeth being enriched in Actinomyces and deciduous teeth in Treponema. CONCLUSION:These results suggested that the supragingival plaque-related bacteria could be suitable candidates when sampling saliva for monitoring supragingival microbiota. The replacement process of deciduous teeth with permanent teeth in mixed dentition might be related to the reported age-maturation of phylum Actinobacteria in the oral cavity.

Background: Preeclampsia (PE) is a serious idiopathic disease posing a threat to both mothers and fetuses′ lives during pregnancy, whose main diagnostic criteria include hypertension with proteinuria. However, American College of Obstetricians and Gynecologists (ACOG) updated the diagnostic criteria for PE and reduced the diagnostic value of proteinuria for patients with PE. Qualitative analysis of the diagnostic value of 24-h proteinuria for patients with PE in China was conducted to evaluate the diagnostic criteria value in the latest ACOG guideline. Methods: Complete clinical data of 65 patients with hypertensive disorder in pregnancy (HDP) were collected. All patients were delivered to and hospitalized in Renji Hospital. Adverse outcome was defined in case of the emergence of any serious complication for a mother or the fetus. A retrospective study was conducted according to ACOG guideline, to analyze the relationship between each diagnostic criteria of ACOG guideline and maternal and perinatal outcomes. Spearman correlation test was used to detect the association between each diagnostic criterion, its corresponding value, and the adverse pregnancy outcome. Logistic regression was performed to verify the result of Spearman correlation test. Results: Of 65 HDP patients, the percentage of adverse pregnancy outcome was 63.1%. Adverse pregnancy outcomes constitute diversification. There were 55 cases with 24-h proteinuria value ≥0.3 g, of which the adverse outcome rate was 74.5%. While adverse pregnancy outcomes did not appear in the rest 10 HDP patients with proteinuria

Background: Interleukin (IL)-27 has been reported to have anti-proliferate and anti-angiogenic activities on cancer cells. However, the involvement of IL-27 in malignant pleural effusion (MPE) remains unknown. Thus, in this research, we compared the immune functions of IL-27, interferon (IFN)-γ, and IL-17 on lung cancer cells and revealed the regulatory mechanism of IL-27 in MPE. Methods: The distribution of IL-27 in both MPE and blood was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The expressions of cytokine receptors and the levels of the phosphorylated signal transducer and activator of transcription (STAT) signalings were detected by flow cytometry. As well as the effects of proliferation, apoptosis, migration, and adherent activity of IL-27, IFN-γ, and IL-17 on lung cancer cells were also explored. Results: The expression of IL-27 was increased in MPE when compared with blood (147.3 ± 25.1 pg/ml vs. 100.3 ± 13.9 pg/ml, P = 0.04). IL-27 was noted to suppress both proliferation (18.33 ± 0.21 vs. 27.77 ± 0.88, P = 0.0005) and migration (1.82 ± 0.44 vs. 3.13 ± 0.07, P = 0.04) of A549 cells, but obviously promoted apoptosis of A549 cells (9.47 ± 1.14 vs. 4.96 ± 0.17, P = 0.02) by activating STAT1 signaling. Interestingly, IL-27 played totally opposite effects on A549 cells by activating STAT3 pathway. Moreover, IL-27 exerted different intercellular adherent activities of A549 cells to pleural mesothelial cell monolayer by activating different STAT signalings. Conclusions: IL-27 might exert an important immune regulation on lung cancer cells in human pleural malignant environment.