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CDK9 is the kinase subunit of positive transcription elongation factor b (P-TEFb) that enables RNA polymerase (Pol) II's transition from promoter-proximal pausing to productive elongation. Although considerable interest exists in CDK9 as a therapeutic target, little progress has been made due to lack of highly selective inhibitors. Here, we describe the development of i-CDK9 as such an inhibitor that potently suppresses CDK9 phosphorylation of substrates and causes genome-wide Pol II pausing. While most genes experience reduced expression, MYC and other primary response genes increase expression upon sustained i-CDK9 treatment. Essential for this increase, the bromodomain protein BRD4 captures P-TEFb from 7SK snRNP to deliver to target genes and also enhances CDK9's activity and resistance to inhibition. Because the i-CDK9-induced MYC expression and binding to P-TEFb compensate for P-TEFb's loss of activity, only simultaneously inhibiting CDK9 and MYC/BRD4 can efficiently induce growth arrest and apoptosis of cancer cells, suggesting the potential of a combinatorial treatment strategy.

Transcriptional elongation by RNA polymerase (Pol) II is essential for gene expression during cell growth and differentiation. The positive transcription elongation factor b (P-TEFb) stimulates transcriptional elongation by phosphorylating Pol II and antagonizing negative elongation factors. A reservoir of P-TEFb is sequestered in the inactive 7SK snRNP where 7SK snRNA and the La-related protein LARP7 are required for the integrity of this complex. Here, we show that P-TEFb activity is important for the epithelial–mesenchymal transition (EMT) and breast cancer progression. Decreased levels of LARP7 and 7SK snRNA redistribute P-TEFb to the transcriptionally active super elongation complex, resulting in P-TEFb activation and increased transcription of EMT transcription factors, including Slug, FOXC2, ZEB2, and Twist1, to promote breast cancer EMT, invasion, and metastasis. Our data provide the first demonstration that the transcription elongation machinery plays a key role in promoting breast cancer progression by directly controlling the expression of upstream EMT regulators.

PurposeTo explore the influence of corneal higher-order aberrations (HOAs) on dynamic visual acuity (DVA) post cataract surgery.MethodsA total of 27 patients with 45 eyes following cataract surgery were included in this study. The postoperative monocular object-moving DVA at the velocity of 20, 40, and 80 degrees per second (dps) were examined at 1 month. The total corneal HOAs were measured with Scheimpflug-based corneal topography. The correlation between postoperative DVA and HOAs was analyzed.ResultsSignificant difference was shown among DVA at different velocities (P < 0.001). The 20 dps DVA was significantly better than 40 (P < 0.001) and 80 (P < 0.001) dps DVA. No significant difference was observed between 40 and 80 dps DVA (P = 0.420). The vertical coma and the root mean square (RMS) of coma (RMScoma) were statistically correlated with 80 dps DVA (P < 0.05). The vertical trefoil, RMStrefoil and total RMSHOA were statistically correlated with 40 and 80 dps DVA (P < 0.05). The spherical aberration was not significantly associated with postoperative DVA (P > 0.05 for all velocites). The multivariate linear regression model revealed that age was a significant influential factor for 20 dps DVA (P = 0.002), and RMStrefoil (4 mm) and age were significantly associated with 40 and 80 dps DVA (P ≤ 0.01).ConclusionThe research demonstrated that larger corneal HOAs, especially coma and trefoil aberrations were significantly associated with worse high-speed DVA, but not spherical aberration post cataract surgery.

Chronic hepatitis (CH) encompasses a prevalent array of liver conditions that significantly contribute to global morbidity and mortality. Yiguanjian (YGJ) is a classical traditional Chinese medicine with a long history of medicinal as a treatment for CH. Although it has been reported that YGJ can reduce liver inflammation, the intricate mechanism requires further elucidation. We used network pharmacology approaches in this work, such as gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and network-based analysis of protein-protein interactions (PPIs), to clarify the pharmacological constituents, potential therapeutic targets, and YGJ signaling pathways associated with CH. Employing the random walk restart (RWR) algorithm, we identified GNAS, GNB1, CYP2E1, SFTPC, F2, MAPK3, PLG, SRC, HDAC1, and STAT3 as pivotal targets within the PPI network of YGJ-CH. YGJ attenuated liver inflammation and inhibited GNAS/STAT3 signaling in vivo. In vitro, we overexpressed the GNAS gene further to verify the critical role of GNAS in YGJ treatment. Our findings highlight GNAS/STAT3 as a promising therapeutic target for CH, providing a basis and direction for future investigations.

With the advent of artificial intelligence, ship segmentation has become a critical component in the development of intelligent maritime surveillance systems. However, due to the increasing number of ships and the increasingly complex maritime traffic environment, the target features in these ship images are often not clear enough, and the key details cannot be clearly identified, which brings difficulty to the segmentation task. To tackle these issues, we present an approach that leverages state-of-the-art technology to improve the precision of ship segmentation in complex environments. Firstly, we employ a multi-scale context features module using different convolutional kernels to extract a richer set of semantic features from the images. Secondly, an enhanced spatial pyramid pooling (SPP) module is integrated into the encoder’s final layer, which significantly expands the receptive field and captures a wider range of contextual information. Furthermore, we introduce an attention module with a multi-scale structure to effectively obtain the interactions between the encoding–decoding processes and enhance the network’s ability to exchange information between layers. Finally, we performed comprehensive experiments on the public SeaShipsSeg and MariBoatsSubclass open-source datasets to validate the efficacy of our approach. Through ablation studies, we demonstrated the effectiveness of each individual component and confirmed its contribution to the overall system performance. In addition, comparative experiments with current state-of-the-art algorithms showed that our MSCF-Net excelled in both accuracy and robustness. This research provides an innovative insight that establishes a strong foundation for further advancements in the accuracy and performance of ship segmentation techniques.

Abstract Background The coexistence of MRCS (microcornea, retinal dystrophy, cataract, and posterior staphyloma) syndrome and extremely long axis is rare since microcornea frequently accompanies with diminution of entire anterior segment and occasionally the whole globe. In the case presented here, combination of these two elements were identified, together with XFS (exfoliation syndrome). Case presentation A 66-year-old Han Chinese woman presented for consultation due to impaired vision which accompanied throughout her entire life span and worsened during the last 2 years. Combination of MRCS syndrome and extremely long axial length was evidently diagnosed in both eyes, with XFS confirmed in her right eye, but mutation screening failed to identify disease-causing sequence variants in some specific genes reported previously, including BEST1 and ARL2. However, likely pathogenic mutations in FBN2 gene were identified. Bilateral cataract phacoemulsification without intraocular lens implantation was performed using scleral tunnel incision and under general anesthesia. At 3-month follow-up, ocular recovery of the patient was satisfactory. Conclusions The case presented here exhibited rare coexistence of MRCS syndrome, extremely long axis and XFS. The complexity of her ocular abnormalities brought challenges to surgical management, in which multidisciplinary collaboration is often required. Furthermore, the genetic analysis in this case yielded a possible novel candidate gene for MRCS syndrome and provided evidence in support of genetic heterogeneity in this phenotype.

Objectives. To investigate the effect of 2% hydroxypropyl methylcellulose (HPMC) and bandage contact lens (BCL) on dry eye disease after cataract surgery. Methods. This prospective randomized controlled trial included 63 eyes which were divided into the balanced salt solution (BSS), HPMC, BCL, and combined HPMC and BCL (H&B) groups. The Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), and average tear break-up time were measured before cataract surgery and 30 days postoperatively. Differences in corneal nerve fiber (CNF) and dendritic cell (DC) density in various directions were evaluated and compared. The CNFs and DCs in central and infratemporal directions were observed using in vivo confocal microscopy. Data were evaluated using the Kruskal–Wallis rank-sum test and analysis of variance. Results. The differences in variations in OSDI and TMH after cataract surgery between the four groups were statistically significant (P

PurposeTo investigate the dynamic visual acuity (DVA) after implantation of toric bifocal or trifocal intraocular lens in age-related cataract patients.MethodsThis was a prospective randomized controlled trial. Of one hundred and twenty-four patients enrolled and randomized to receive unilateral phacoemulsification and toric trifocal (939 M/MP, Carl Zeiss Meditec AG, Jena, Germany) or toric bifocal (909 M, Carl Zeiss Meditec AG, Jena, Germany) intraocular lenses (IOL) implantation, ninety-nine patients completed the follow-up and were included in final analysis. Postoperatively, uncorrected and corrected distance (UDVA and CDVA), intermediate (UIVA and DCIVA) and near (UNVA and DCNVA) static visual acuity, manifest refraction and uncorrected and corrected distance DVA (UDDVA and CDDVA) at 20, 40 and 80 degrees per second (dps) were evaluated at one week, one month and three months.ResultsThree months postoperatively, the UDVA were 0.13 ± 0.11 and 0.14 ± 0.13 in the toric trifocal and bifocal IOL group, respectively. Significant better UIVA (trifocal, 0.17 ± 0.13 vs. bifocal, 0.23 ± 0.13, p = 0.037) and DCIVA (trifocal, 0.16 ± 0.11 vs. bifocal, 0.20 ± 0.12, p = 0.048) were observed in patients implanting toric trifocal than bifocal IOL at three months postoperatively. Patients implanted with toric bifocal IOL obtained better CDDVA at 80 dps (0.5607 ± 0.2032) than the trifocal group (0.6573 ± 0.2450, p = 0.039) at three months. Postoperative UDDVA and CDDVA at 20, 40 and 80 dps were significantly associated with age (p

Fusarium oxysporum is a soil-borne plant pathogen that can cause various plant diseases including cucumber wilt. An experiment was conducted to explore the physiological mechanism underlying the inhibitory activity of Cleome spinosa against the morphology and reproduction of F. oxysporum. Different concentrations of C. spinosa extracts.−0 (Z0), 5 (Z5), 15 (Z15), 30 (Z30), 45 (Z45), and 60 (Z60) mg·mL−1 were applied to F. oxysporum. Cleome spinosa extract significantly reduced the colony diameter (89.7 %) and dry mass (78.9 %) of F. oxysporum under the Z45 treatment. Moreover, spore formation was also significantly inhibited by C. spinosa extract. The spore number and germination rate decreased by 73.5 % and 83.0 %, respectively, under the Z45 treatment. The number of mycelia in the unit field of view was significantly reduced, and the mycelia were wizened with rough surfaces and more bends under the Z45 treatment. Hence, C. spinosa extracts severely damaged the morphology of F. oxysporum mycelia. Additionally, F. oxysporum could not adjust to the osmotic changes caused by C. spinosa extract, leading to membrane injury and electrolyte leakage. Finally, they impaired the antioxidant system in F. oxysporum, resulting in cell membrane injury.

Neuropeptide Y receptor Y2 (npy2r) is an important receptor gene involved in anxiety and feeding regulation in mammals. Since NPY receptors have different receptor gene deletions in mammals and teleost fish, it is not clear whether npy2r has the similar function in fish as in mammals. In this study, we used the CRISPR/Cas9 system to establish npy2r-deficient medaka (Oryzias latipes). Unexpectedly, the deletion of npy2r resulted in the npy2r+/− medaka were all-male, therefore, npy2r homozygous mutant lines could not be established. The deletion of npy2r increased the food intake in medaka, and the expression levels of appetite stimulating genes (agrp, npy) increased significantly, while the expression levels of anorexia factors (cck, pomc) decreased significantly. Moreover, the absence of npy2r significantly increased the total length and body weight of medaka. The mirror test and open field test showed that npy2r+/− medaka improved sociability and reduced anxiety-like behavior, qRT-PCR analysis showed that the expression levels of anxiety related genes (th1, th2, gr1, gr2, and mr) in npy2r+/− medaka were significantly decreased. So far, this is the first npy2r gene knockout model established in fish and demonstrates that npy2r plays an important role in the regulation of reproduction, feeding and anxiety in fish.

With the continuous and rapid development of Cloud Computing, Big Data and Internet of Things, it is extremely critical to protect data with homomorphism, privacy and integrity. For this, Rezaeibagha et al. proposed a new cryptographic primitive, called homomorphic signcryption. However, the current homomorphic signcryption schemes either only support linear computation or are built on non-standard assumption. Therefore, it is interesting to design a leveled fully homomorphic signcryption (FHSC) scheme from the standard assumption. In this work, we present a leveled FHSC scheme from lattices. For this, we exert classical sign-then-encrypt method and surmount the difficulty of homomorphic multiplicative evaluation in the way of encrypting every elements. Moreover, we prove its indistinguishability against chosen plaintext attacks (IND-CPA) and strong unforgeability (SUF) under hard problems of standard lattices.

Abstract We evaluated how different degrees of air pollution affect the ocular surface of a cohort of human subjects in Beijing by correlating in-patient test outcomes with tear cytokines. A cross-sectional study involving 221 volunteers was carried out in different districts of Beijing. Air pollution indices were recorded for 7 d (including the visit day). The indices recorded were the air quality index (AQI), which is a dimensionless measure that quantitatively describes the state of air quality, concentrations of particulate matter smaller than 2.5 μm (PM2.5) and 10 μm (PM10), sulfur dioxide (SO2), ozone (O3), and nitrogen dioxide (NO2). The Ocular Symptom Disease Index (OSDI) questionnaire provided. Subsequently, subjects underwent slit-lamp examination, which included meibomian gland examination, conjunctival congestion score, conjunctivochalasis grade, tear meniscus height (TMH), tear breakup time (TBUT), corneal fluorescein staining (CFS), Schirmer I test, and conjunctival impression cytology. The concentrations of vascular endothelial growth factor (VEGF), interleukins (IL)-1β, IL-6 and IL-8 in tears were measured by microsphere-based immunoassay analysis. According to the value of the AQI, participants are divided into a slightly polluted (SP) group (n = 103) which the AQI value is less than or equal to 100 and a heavily polluted (HP) group (n = 118) whose AQI value is more than 100. Air pollution is related to ocular discomfort based on tear cytokine concentrations. PM2.5, PM10 and NO2 were positively correlated with OSDI, MG expressibility, meibum score, meiboscore, conjunctival congestion score, Schirmer I test value, TMH, goblet-cell density, concentrations of IL-6, and VEGF were negatively correlated with TBUT. PM2.5 and PM10 appear to be the major risk factors to the ocular surface, with NO2 being another important risk factor based on this study. The symptoms and signs of eye discomfort in the SP group were significantly less severe than those in the HP group, and tear cytokine concentrations (IL-6 and VEGF) were lower. Air pollution degrees were significantly correlated with tear cytokine concentrations, indicating an alteration of cytokine balance at the ocular surface under different degrees of air pollution.

Abstract Background Pyroptosis, especially microglial pyroptosis, may play an important role in central nervous system pathologies, including traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs), such as human umbilical cord MSCs (hUMSCs), has been a focus of brain injury treatment. Recently, MSCs have been found to play a role in many diseases by regulating the pyroptosis pathway. However, the effect of MSC transplantation on pyroptosis following TBI remains unknown. Tumor necrosis factor α stimulated gene 6/protein (TSG-6), a potent anti-inflammatory factor expressed in many cell types including MSCs, plays an anti-inflammatory role in many diseases; however, the effect of TSG-6 secreted by MSCs on pyroptosis remains unclear. Methods Mice were subjected to controlled cortical impact injury in vivo. To assess the time course of pyroptosis after TBI, brains of TBI mice were collected at different time points. To study the effect of TSG-6 secreted by hUMSCs in regulating pyroptosis, normal hUMSCs, sh-TSG-6 hUMSCs, or different concentrations of rmTSG-6 were injected intracerebroventricularly into mice 4 h after TBI. Neurological deficits, double immunofluorescence staining, presence of inflammatory factors, cell apoptosis, and pyroptosis were assessed. In vitro, we investigated the anti-pyroptosis effects of hUMSCs and TSG-6 in a lipopolysaccharide/ATP-induced BV2 microglial pyroptosis model. Results In TBI mice, the co-localization of Iba-1 (marking microglia/macrophages) with NLRP3/Caspase-1 p20/GSDMD was distinctly observed at 48 h. In vivo, hUMSC transplantation or treatment with rmTSG-6 in TBI mice significantly improved neurological deficits, reduced inflammatory cytokine expression, and inhibited both NLRP3/Caspase-1 p20/GSDMD expression and microglial pyroptosis in the cerebral cortices of TBI mice. However, the therapeutic effect of hUMSCs on TBI mice was reduced by the inhibition of TSG-6 expression in hUMSCs. In vitro, lipopolysaccharide/ATP-induced BV2 microglial pyroptosis was inhibited by co-culture with hUMSCs or with rmTSG-6. However, the inhibitory effect of hUMSCs on BV2 microglial pyroptosis was significantly reduced by TSG-6-shRNA transfection. Conclusion In TBI mice, microglial pyroptosis was observed. Both in vivo and in vitro, hUMSCs inhibited pyroptosis, particularly microglial pyroptosis, by regulating the NLRP3/Caspase-1/GSDMD signaling pathway via TSG-6. Video Abstract

Ischemic stroke is by far the most common cerebrovascular disease and a major burden to the global economy and public health. Trimethylamine-N-oxide (TMAO), a small molecule compound produced by the metabolism of intestinal microorganisms, is reportedly associated with the risk of stroke, as well as the severity and prognosis of stroke; however, this conclusion remains contentious. This article reviews the production of TMAO, TMAO’s relationship with different etiological types of ischemic stroke, and the possibility of reducing TMAO levels to improve the prognosis of ischemic stroke.

PurposeTo explore the composition of the ocular microbiome in patients with Meibomian gland dysfunction (MGD) using metagenomic nanopore sequencing.MethodsA total of 98 participants were recruited from September to December 2021, including 86 patients with MGD and 12 controls. Symptoms and signs of dry eye were assessed, and bacterial samples in the conjunctival sac (CS) and meibomian gland (MG) secretions were then identified by bacterial culture identification and metagenomic nanopore sequencing.ResultsThe positive rate of CS bacterial culture in the MGD group was significantly higher than that in the normal group. A more complex composition of bacterial genera was detected in the mild and moderate MGD groups than in the control. However, the severe MGD groups had the simplest composition of bacteria. Metagenomic nanopore sequencing detected more species of bacteria than traditional culture.ConclusionThe CS and MG of MGD patients may have different degrees of bacterial microbiota imbalance. Metagenomic nanopore sequencing technology provides a new way for us to understand the composition of “real-world” ocular surface microorganisms.

Abstract Background Highly myopic eyes differ in morphology from emmetropic eyes, and the correct estimation of the vitreous volume is difficult. To explore an effective method to estimate ocular volume using refractive factors in children. Methods This is a retrospective study of children with high myopia who visited the Shenzhen Shekou People’s Hospital (July-December 2018) before undergoing posterior scleral reinforcement surgery. Data on refractive factors and ocular 3D reconstruction imaging based on high-end CT were collected for linear correlation and linear regression analyses. Results Ten patients (20 eyes) were included. There are nine males and one female. They were 4 to 12 years of age. The spherical equivalent ranges from + 0.25 to -20.00 D. The cylindrical equivalent ranges from − 0.50 to -6.25 D. The AL(axial length, AL) ranges from 21.78 to 33.90 mm. The corneal curvature (mean) ranges from 42.44 to 46.75. The 3D reconstruction of the CT images shows that the ocular volume ranges from 4.591 to 10.988 ml. The ocular volume of the 20 eyes decreases with the increase of diopter and total curvature, both presenting a linear trend, with the Pearson correlation coefficients being − 0.776 (P

The medaka (Oryzias latipes) is an excellent vertebrate model for studying the development of the retina. Its genome database is complete, and the number of opsin genes is relatively small compared to zebrafish. Short wavelength sensitive 2 (sws2), a G-protein-coupled receptor expressed in the retina, has been lost in mammals, but its role in eye development in fish is still poorly understood. In this study, we established a sws2a and sws2b knockout medaka model by CRISPR/Cas9 technology. We discovered that medaka sws2a and sws2b are mainly expressed in the eyes and may be regulated by growth differentiation factor 6a (gdf6a). Compared with the WT, sws2a−/− and sws2b−/− mutant larvae displayed an increase in swimming speed during the changes from light to dark. We also observed that sws2a−/− and sws2b−/− larvae both swam faster than WT in the first 10 s of the 2 min light period. The enhanced vision-guided behavior in sws2a−/− and sws2b−/− medaka larvae may be related to the upregulation of phototransduction-related genes. Additionally, we also found that sws2b affects the expression of eye development genes, while sws2a is unaffected. Together, these findings indicate that sws2a and sws2b knockouts increase vision-guided behavior and phototransduction, but on the other hand, sws2b plays an important role in regulating eye development genes. This study provides data for further understanding of the role of sws2a and sws2b in medaka retina development.

This study aimed to investigate the association of between previously neglected oval cells located in the corneal vortex and dry eye disease (DED). This was an observational, prospective study involving 168 patients with different degrees of DED. In vivo confocal microscopy was used to observe the corneal subbasal nerves and Langerhans cells (LCs) in the corneal vortex and periphery. Bright and oval cells were also observed in the corneal vortex. An artificial intelligence technique was used to generate subbasal nerve fiber parameters. The patients were divided into the three groups based on the presence of inflammatory cells. Group 2 patients showed a significant increase in the corneal peripheral nerve maximum length and average corneal peripheral nerve density. Patients in group 3 had more LCs than other patients. A bright and oval cell was identified in the corneal vortex, which might be a type of immature LC related to the disease severity of DED.

PurposeThe study assessed the validity of impression cytology (IC) and in vivo confocal microscopy (IVCM) of lip mucosa compared with labial gland biopsy, anti-Sjögren’s syndrome A (SSA)/Ro antibody status, and classification criteria in suspected primary Sjögren’s syndrome (pSS) patients.MethodsClinically suspected pSS patients (n = 201) were enrolled consecutively and were divided into pSS (n = 56) and control (n = 145, only with dryness) groups according to the American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) criteria. All patients underwent lip mucosa IC (inflammatory cell density) and IVCM (epithelium/intrinsic layer thickness and labial gland density/diameter) analyses. The associations between IC/IVCM parameters and clinical/laboratory results were analyzed.ResultsThe absolute agreement between positive lip mucosal IC (≥50 cells/4 mm2) and the ACR-EULAR criteria (94.5%)/labial gland biopsy (95.5%) was good, with sensitivities of 82.1 and 85.2%, respectively, and a specificity of 99.3%. Compared with controls, IVCM revealed significant lip mucosal atrophy and glandular decreases in the pSS group (all P = 0.000). The sensitivities for diagnosing pSS corresponding to a lamina propria thickness ≤128 μm and a gland diameter ≤114 μm were 85.7 and 89.3%; the specificities were 90.3 and 95.9%, respectively. A combination of positive IC/IVCM and anti-SSA/Ro antibody results showed a high predictive value for diagnosing pSS.ConclusionsIC and IVCM could detect distinctive cellular and morphological changes in the lip mucosa of patients with pSS. These noninvasive and easy-to-perform examinations may be an alternative to labial gland biopsy for diagnosing pSS.

Bone marrow mesenchymal stem cells (BMSCs) can effectively alleviate liver fibrosis, but the efficacy of cell therapy alone is insufficient. In recent years, a combination of traditional Chinese medicine (TCM) and cell therapy has been increasingly used to treat diseases in clinical trials. Ferulic acid (FA) is highly effective in treating liver fibrosis, and a combination of cells and drugs is being tested in clinical trials. Therefore, we combined BMSCs and Ferulic acid to treat CCl4-induced fibrosis and determine whether this combination was more effective than single treatment. We used BMSCs and FA to treat CCl4-induced fibrosis in rat models, observed their therapeutic effects, and investigated the specific mechanism of this combination therapy in liver fibrosis. We created a BMSC/hepatic stellate cell (HSC) coculture system and used FA to treat activated HSCs to verify the specific mechanism. Then, we used cytochalasin D and angiotensin II to investigate whether BMSCs and FA inactivate HSCs through cytoskeletal rearrangement. MiR-19b-3p was enriched in BMSCs and targeted TGF-β receptor II (TGF-βR2). We separately transfected miR-19b-3p into HSCs and BMSCs and detected hepatic stellate cell activation. We found that the expression of the profibrotic markers α-SMA and COL1-A1 was significantly decreased in the combination group of rats. α-SMA and COL1-A1 levels were also significantly decreased in the HSCs with the combination treatment. Cytoskeletal rearrangement of HSCs was inhibited in the combination group, and RhoA/ROCK pathway gene expression was decreased. Following angiotensin II treatment, COL1-A1 and α-SMA expression increased, while with cytochalasin D treatment, profibrotic gene expression decreased in HSCs. The expression of COL1-A1, α-SMA and RhoA/ROCK pathway genes was decreased in the activated HSCs treated with a miR-19b-3p mimic, indicating that miR-19b-3p inactivated HSCs by suppressing RhoA/ROCK signalling. In contrast, profibrotic gene expression was significantly decreased in the BMSCs treated with the miR-19b-3p mimic and FA or a miR-19b-3p inhibitor and FA compared with the BMSCs treated with the miR-19b-3p mimic alone. In conclusion, the combination therapy had better effects than FA or BMSCs alone. BMSC and FA treatment attenuated HSC activation and liver fibrosis by inhibiting cytoskeletal rearrangement and delivering miR-19b-3p to activated HSCs, inactivating RhoA/ROCK signalling. FA-based combination therapy showed better inhibitory effects on HSC activation.

Multi-object tracking (MOT) is a topic of great interest in the field of computer vision, which is essential in smart behavior-analysis systems for healthcare, such as human-flow monitoring, crime analysis, and behavior warnings. Most MOT methods achieve stability by combining object-detection and re-identification networks. However, MOT requires high efficiency and accuracy in complex environments with occlusions and interference. This often increases the algorithm’s complexity, affects the speed of tracking calculations, and reduces real-time performance. In this paper, we present an improved MOT method combining an attention mechanism and occlusion sensing as a solution. A convolutional block attention module (CBAM) calculates the weights of space and channel attention from the feature map. The attention weights are used to fuse the feature maps to extract adaptively robust object representations. An occlusion-sensing module detects an object’s occlusion, and the appearance characteristics of an occluded object are not updated. This can enhance the model’s ability to extract object features and improve appearance feature pollution caused by the short-term occlusion of an object. Experiments on public datasets demonstrate the competitive performance of the proposed method compared with the state-of-the-art MOT methods. The experimental results show that our method has powerful data association capability, e.g., 73.2% MOTA and 73.9% IDF1 on the MOT17 dataset.

Background. Evaluate the effect of the miRNA-106a/20b on the efficacy of DCs pulsed with GSCs in activating GSC-specific T cell responses. Methods. We cultured GSCs and prepared GSC antigen lysates by apoptosis. Then, immature DCs were pulsed with GSC antigen lysates in vitro. STAT3 levels in DCs were assessed by Western blotting, and the expression of CD80, CD86, and MHC-II was tested by fluorescence-activated cell sorting. The production and secretion of the cytokines IL-6, IL-12, TNF-α, and IL-10 in DCs induced by GSCs were determined by enzyme-linked immunosorbent assay. Finally, the cytotoxic functions of T cells stimulated by GSC-DC fusion cells transfected with a miR-106a/20b mimic in vitro and the antitumour activity in vivo were detected. Results. We found that the levels of miR-106a/20b were downregulated, but the expression of STAT3 was significantly upregulated. Simultaneously, the inhibition of STAT3 in the fusion cells by STAT3-specific siRNA caused significant upregulation of the expression of CD80, CD86, and MHC-II, and the secretion of the cytokines IL-6 and IL-12 was substantially increased, IL-10 was markedly decreased. These findings revealed that STAT3 is an important regulator of DC maturation. Furthermore, the interactional binding sites between the 3′-untranslated region (3′-UTR) of STAT3 mRNA and miR-106a/20b were predicted by bioinformatics and verified by a dual-luciferase assay. Moreover, the reduction in STAT3 levels in GSC-DCs enhanced the generation of CD8+ T cells and reduced the generation of Foxp3+ regulatory T cells. Meanwhile, the secretion of the T cell cytokine IFN-γ was significantly increased. Further research showed that DCs after miR-106a/20b-mimics transfection could promote the inhibition of GSC proliferation by T cells in vitro and suppress tumour growth in vivo. Conclusions. This study indicted that the miR-106a/20b activation could be one of the important molecular mechanisms leading to enhance antitumour immune responses of GSC-mediated DCs, which downregulated the expression of STAT3 to alleviate its the inhibitory effect.

Purkinje cells (PCs) are large GABAergic projection neurons of the cerebellar cortex, endowed with elaborate dendrites that receive a multitude of excitatory inputs. Being the only efferent neuron of the cerebellar cortex, PCs project to cerebellar nuclei and control behaviors ranging from movement to cognition and social interaction. Neural cell adhesion molecule 1 (NCAM1) is widely expressed in the embryonic and postnatal development of the brain and plays essential roles in neuronal migration, axon pathfinding and synapse assembly. However, despite its high expression levels in cerebellum, little is known to date regarding the role(s) of NCAM1 in PCs development. Among other aspects, elucidating how the expression of NCAM1 in PCs could impact their postnatal migration would be a significant achievement. We analyzed the Acp2 mutant mouse (nax: naked and ataxia), which displays excessive PC migration into the molecular layer, and investigated how the excessive migration of PCs along Bergmann glia could correlate to NCAM1 expression pattern in early postnatal days. Our Western blot and RT-qPCR analysis of the whole cerebellum show that the protein and mRNA of NCAM1 in wild type are not different during PC dispersal from the cluster stage to monolayer formation. However, RT-qPCR analysis from FACS-based isolated PCs shows that Ncam1 is significantly upregulated when PCs fail to align and instead overmigrate into the molecular layer. Our results suggest two alternative interpretations: (1) NCAM1 promotes excessive PC migration along Bergmann glia, or (2) NCAM1 upregulation is an attempt to prevent PCs from invading the molecular layer. If the latter scenario proves true, NCAM1 may play a key role in PC monolayer formation.

Direct optical activation of microbial rhodopsins in deep biological tissue suffers from ineffective light delivery because visible light is strongly scattered and absorbed. NIR light has deeper tissue penetration, but NIR-activation requires a transducer that converts NIR light into visible light in proximity to proteins of interest. Lanthanide-doped upconversion nanoparticles (UCNPs) are ideal transducer as they absorb near-infrared (NIR) light and emit visible light. Therefore, UCNP-assisted excitation of microbial rhodopsins with NIR light has been intensively studied by electrophysiology technique. While electrophysiology is a powerful method to test the functional performance of microbial rhodopsins, conformational changes associated with the NIR light illumination in the presence of UCNPs remain poorly understood. Since UCNPs have generally multiple emission peaks at different wavelengths, it is important to reveal if UCNP-generated visible light induces similar structural changes of microbial rhodopsins as conventional visible light illumination does. Here, we synthesize the lanthanide-doped UCNPs that convert NIR light to blue light. Using these NIR-to-blue UCNPs, we monitor the NIR-triggered conformational changes in sensory rhodopsin II from Natronomonas pharaonis (NpSRII), blue light-sensitive microbial rhodospsin, by FTIR spectroscopy. FTIR difference spectrum of NpSRII was recorded under two different excitation conditions: (ⅰ) with conventional blue light, (ⅱ) with UCNP-generated blue light upon NIR excitation. Both spectra display similar spectral features characteristic of the long-lived M photointermediate state during the photocycle of NpSRII. This study demonstrates that NIR-activation of NpSRII mediated by UCNPs takes place in a similar way to direct blue light activation of NpSRII.

Varied welding process parameters result in different welding energy inputs and welding residual stresses, significantly impacting the vibro-acoustic characteristics. This work investigated the influence of different welding energy inputs on the vibro-acoustic characteristics of the stiffened plate structure. Several experiments on the stiffened plate structure with different welding energy inputs were conducted regarding modal, underwater vibration, and acoustic radiation. The results revealed that welding energy input had the most significant impact on the first-order natural frequency, and the impact first becomes higher and subsequently decreases as welding energy input increases. The welding energy input had relatively little effect on the peak point distribution of vibration and acoustic radiation curves but could affect the peak point amplitude. With the increase in welding energy input, the overall vibration acceleration level and sound radiation level in each frequency band decreased and then increased. The best result was obtained when the welding energy input was 167 J/cm with a welding current of 200 A, a welding voltage of 25 V, and a welding speed of 3.02–3.06 mm/s. Based on construction technology, this research can provide some instructive insights for enhancing the acoustic stealth performance of ships and marine structures.

This study aimed to evaluate the change patterns in corneal intrinsic aberrations and nerve density after cataract surgery in dry eye disease. The preoperative, 1- and 3-month postoperative dry eye-related parameters were obtained by the Oculus keratograph and the ocular surface disease index questionnaire. The corneal intrinsic aberrations were measured using the Pentacam HR system. In vivo confocal microscopy was performed to observe the vortical and peripheral corneal nerves. An artificial intelligence technique run by the deep learning model generated the corneal nerve parameters. Corneal aberrations on the anterior and total corneal surfaces were significantly increased at 1 month compared with the baseline (p < 0.05) but gradually returned to the baseline by 3 months (p > 0.05). However, the change in posterior corneal aberration lasted up to 3 months (p < 0.05). There was a significant decrease in the corneal vortical nerve maximum length and average density after the operation (p < 0.05), and this damage lasted approximately 3 months. The corneal vortical nerve maximum length and average density were negatively correlated with the anterior corneal surface aberrations before and 1 month after the operation (correlation coefficients, CC = −0.26, −0.25, −0.28; all p < 0.05). Corneal vortex provided a unique site to observe long-term corneal nerve injury related to eye dryness. The continuous damage to the corneal vortical nerve may be due to the continuous dry eye state.

A fluid model of the magnetized sheath has been built using ion motion equation, ion continuity equation, Poisson's equation, and Boltzmann's relationship of electron for plasma-based low-energy ion implantation (PBLEII) inner surface modification of a tube. Along the central axis from the middle piece to the end, the maximum ion impact energy decreases from 1600 to 400 eV, the maximum ion impact angle increases from 7° to 60°, and an implantation dose peak of about twice as much as other place appears near the nozzle. The implantation dose just can compensate for the ion impact energy and angle because the mass transfer mechanism of PBLEII is thermal diffusion and low-energy ion implantation. The uniformity of the modification effect is acceptable along the axial direction of the tube.

Abstract Transplantation of endothelial progenitor cells (EPCs) is a proven safe and effective method for treatment of cerebral ischemia in animal experiments. However, safety and efficacy need to be determined in clinical trials. We performed a two‐center, randomized, placebo‐controlled phase I/IIa trial with blinded outcome assessment on 18 patients with acute cerebral infarct within the middle cerebral artery territory, and followed for up to 4 years. Autologous ex vivo expanded EPCs were injected intravenously in the EPC group, and patients who received saline or autologous bone marrow stromal cells served as control groups. Mortality of any cause, adverse events, and new‐onset comorbidities were monitored. Changes in neurological deficits were assessed at different time points. We found no toxicity events or infusional or allergic reactions in any treated group. Three patients in the placebo group died during the 4‐year follow‐up. We found that the EPC group had fewer serious adverse events compared with the placebo‐controlled group, although there were no statistical differences in mortality among the three groups. Furthermore, there was no significant difference in neurological or functional improvement observed among the three groups, except for the Scandinavia Stroke Scale score at 3 months between the EPC group and placebo‐controlled group. Autologous transplantation of EPCs appears to improve long‐term safety in acute cerebral infarct patients, supporting the feasibility of this novel method for treatment of ischemic stroke (ClinicalTrials.gov: NCT01468064). Stem Cells Translational Medicine 2019;8:14–21

(1) Background: Dry eye is a multifactorial disease of the ocular surface, the incidence of which has been increasing sharply. The pathogenesis of dry eye, especially in terms of the bacterial flora, has drawn great attention. Additionally, the potential treatment methods need to be explored. (2) Methods: We reviewed more than 100 studies and summarized them briefly in a review. (3) Results: We summarized the bacterial communities found on the ocular surface in the general population and patients with dry eye and found a relationship between dry eye and antibiotic therapy. We identified the possible mechanisms of bacteria in the development of dry eye by discussing factors such as the destruction of the antibacterial barrier, infectious diseases, microbiome homeostasis, inflammatory factors on the ocular surface and vitamin deficiency. (4) Conclusion: We systematically reviewed the recent studies to summarize the bacterial differences between patients with dry eye and the general population and brought up several possible mechanisms and possible treatment targets.

Mass suspension of anthropogenic activities is extremely rare, the quarantine due to the coronavirus disease 2019 (COVID-19) represents a natural experiment to investigate the impact of anthropogenic activities on air quality. The mitigation of air pollution during the COVID-19 lockdown has been reported from a global perspective; however, the air pollution levels vary in different regions. This study initiated a novel synthesis of multiple-year satellite observations, national ground measurements towards SO2, NO2 and O3 and meteorological conditions to evaluate the impact of the COVID-19 lockdown in Beihai, a specific city in a less developed area in southwest China, to reveal the potential implications of control strategies for air pollution. The levels of the major air pollutants during the COVID-19 lockdown (LP) and during the same period of previous years (SP) were compared and a series of statistical tools were applied to analyze the sources of air pollution in Beihai. The results show that air pollutant levels decreased with substantial diversity during the LP. Satellite-retrieved NO2 and SO2 levels during the LP decreased by 5.26% and 22.06%, while NO2, SO2, PM2.5 and PM10 from ground measurements during the LP were 25.6%, 2.7%, 22.2% and 22.2% lower than during SP, respectively. Ground measured SO2 concentrations during the LP were only 2.7% lower than during the SP, which may be attributed to uninterrupted essential industrial activities, such as power plants. Polar plots analysis shows that NO2 concentrations were strongly associated with local emission sources, such as automobiles and local industry. Additionally, the much lower levels of NO2 concentrations during the LP and the absence of an evening peak may highlight the significant impact of the traffic sector on NO2. The decrease in daily mean O3 concentrations during the LP may be associated with the reduction in NO2 concentrations. Indications in this study could be beneficial for the formulation of atmospheric protection policies.

Purchase order financing (POF) and buyer direct financing (BDF) are both innovative financing schemes aiming to help financial constrained suppliers secure financing for production. In this paper, we investigate the interaction mechanism between suppliers’ financing strategy selection and manufacturers’ loans offering strategy adoption under two innovative financing schemes. We developed an evolutionary game model to effectively investigate the interaction mechanism between suppliers and manufacturers and analyzed the evolutionary stable strategies of the game model. Then we used system dynamics to present the performance of the evolutionary game model and took a sensitivity analysis to verify the theoretical results. The main conclusions are as follows: in the supply chain, to deal with the noncooperation among suppliers and manufacturers on innovative financing schemes, the revenue of manufacturers, the rate of manufacturer loan, and the proper financial risk factor should be relatively high.

Purpose. The purpose is to compare the outcomes of implantation of trifocal intraocular lenses (TIOLs) and extended depth of focus (EDOF) intraocular lenses (IOLs). Methods. A comprehensive search of PubMed, Cochrane Library, EMBASE, and ClinicalTrial.gov was conducted in March 2020 to identify relevant studies. A meta-analysis of the results was performed. Patients implanted with EDOF IOLs or TIOLs in previous studies were included. The primary outcomes of the study were uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), and defocus curve. Results. TIOLs and EDOF IOLs provided comparable binocular UDVA (MD = -0.01, 95% CI: -0.04, 0.03, logMAR). However, EDOF IOLs provided better UIVA (MD: -0.08, 95% CI: -0.14, -0.01, logMAR) and worse UNVA (MD: 0.10, 95% CI: 0.06, 0.14, logMAR) than TIOLs. Fewer patients achieved spectacle independence after implantation of EDOF IOLs (RR: 0.74, 95% CI: 0.63, 0.87) than after implantation of TIOLs, especially for near vision (RR = 0.82, 95% CI: 0.68, 0.99). There was no statistically significant difference in contrast sensitivity (CS) under photopic or mesopic conditions with both IOLs. Patient satisfaction after implantation of both IOLs was high. Conclusion. EDOF IOLs and TIOLs provide comparable distance vision. However, EDOF IOLs provide better intermediate vision and worse near vision than TIOLs. The advantages of EDOF IOLs over TIOLs in terms of CS, aberrations, and visual disturbance are not significant. Patients are satisfied with both types of IOLs.

Purpose. To comparatively evaluate the safety and satisfaction of bandage contact lens (BCL) and eye patching in patients after cataract surgery. Methods. Sixteen (32 eyes) patients who planned to undergo bilateral cataract surgery were recruited. The two eyes of each patient were randomly divided into 2 groups. Group A and Group B were instructed to wear BCLs immediately at the end of the surgery until one week and eye patch immediately after surgery until one day, respectively. Visual analog scales of ten specific symptoms, Visual Function Index (VF-14) questionnaire, and best-corrected visual acuity (BCVA) were conducted on the first day before the surgery and Day 1 and Day 7 after surgery. Oculus keratography was conducted on the first day before surgery and on Day 7. Patient satisfaction was determined on Day 1. Moreover, bacterial species in the conjunctival sac, meibomian gland secretions, and BCLs were subsequently identified using 16S rRNA gene sequencing. Results. The patient satisfaction scores of Group A were higher than Group B. Group A were more motivated to choose the same treatment and were more likely to recommend BCLs to others. No statistically significant differences were found in bacterial culture positivity between the groups. The differences in ocular signs and symptoms between the two groups were not statistically significant. There were no significant differences in the BCVA and VF-14 between the groups at any time point. Conclusions. BCLs could be safely and effectively used in patients after cataract surgery.

This study proposes a three-index flow-based mixed integer formulation to solve a two-echelon location routing problem with simultaneous pickup and delivery. In this formulation, pickup and delivery demands can be addressed using the same vehicle in each echelon of the network to reduce costs and increase logistics efficiency. We solve such NP-hard problem by developing a multistart hybrid heuristic with path relinking (MHH-PR) which is composed of local search and a variable neighbourhood descent algorithm. In the algorithm, three constructive heuristics are applied to generate diversified initial solutions, and path relinking is introduced for intensification and postoptimisation. Results indicate that MHH-PR can reduce the gap between the near optimal and global optimal solutions by 1%-2%. The proposed algorithm significantly improves computational efficiency by reducing the computational time of more than 10 min for existing cases involving 20 nodes to less than 10 s.

Purpose. To assess the effects of oral vitamin B1 and mecobalamin on dry eye disease (DED) and patient satisfaction with treatment. Methods. In this randomized controlled study, DED patients were divided into 4 groups based on treatment: group 1, only artificial tears; group 2, corticosteroid eye drops and artificial tears; group 3, oral vitamin B1, mecobalamin, and artificial tears; and group 4, oral vitamin B1, mecobalamin, corticosteroid eye drops, and artificial tears. DED symptoms, signs, and patient satisfaction with treatment were assessed at baseline and at 1 and 2 months after treatment. Results. In total, 152 eyes from 76 patients (age, 55.25 ± 18.16 years) were included. In group 3, there were significant differences in dryness, foreign body sensation, burning, and tear film breakup time first (TBUTF) between 1 and 2 months after treatment and in satisfaction scores before and after treatment (P

Aberrant lipid metabolism is an established hallmark of cancer cells. In particular, ether lipid levels have been shown to be elevated in tumors, but their specific function in cancer remains elusive. We show here that the metabolic enzyme alkylglyceronephosphate synthase (AGPS), a critical step in the synthesis of ether lipids, is up-regulated across multiple types of aggressive human cancer cells and primary tumors. We demonstrate that ablation of AGPS in cancer cells results in reduced cell survival, cancer aggressiveness, and tumor growth through altering the balance of ether lipid, fatty acid, eicosanoid, and fatty acid-derived glycerophospholipid metabolism, resulting in an overall reduction in the levels of several oncogenic signaling lipids. Taken together, our results reveal that AGPS, in addition to maintaining ether lipids, also controls cellular utilization of fatty acids, favoring the generation of signaling lipids necessary for promoting the aggressive features of cancer. [ABSTRACT FROM AUTHOR]

Lysosomal acid phosphatase 2 (Acp2) mutant mice (naked-ataxia, nax) have a severe cerebellar cortex defect with a striking reduction in the number of granule cells. Using a combination of in vivo and in vitro immunohistochemistry, Western blotting, BrdU assays, and RT-qPCR, we show downregulation of MYCN and dysregulation of the SHH signaling pathway in the nax cerebellum. MYCN protein expression is significantly reduced at P10, but not at the peak of proliferation at around P6 when the number of granule cells is strikingly reduced in the nax cerebellum. Despite the significant role of the SHH–MycN pathway in granule cell proliferation, our study suggests that a broader molecular pathway and additional mechanisms regulating granule cell development during the clonal expansion period are impaired in the nax cerebellum. In particular, our results indicate that downregulation of the protein synthesis machinery may contribute to the reduced number of granule cells in the nax cerebellum.

A spontaneous mutation in the lysosomal acid phosphatase (Acp2) enzyme (nax: naked–ataxia) in experimental mice results in delayed hair appearance and severe cytoarchitectural impairments of the cerebellum, such as a Purkinje cell (PC) migration defect. In our previous investigation, our team showed that Acp2 expression plans a significant role in cerebellar development. On the other hand, the dopaminergic system is also a player in central nervous system (CNS) development, including cerebellar structure and function. In the current investigation, we have explored how Acp2 can be involved in the regulation of the dopaminergic pathway in the cerebellum via the regulation of dopamine receptor expression and patterning. We provided evidence about the distribution of different dopamine receptors in the developing cerebellum by comparing the expression of dopamine receptors on postnatal days (P) 5 and 17 between nax mice and wild–type (wt) littermates. To this aim, immunohistochemistry and Western blot analysis were conducted using five antibodies against dopamine receptors (DRD1, –2, –3, –4, and –5) accompanied by RNAseq data. Our results revealed that DRD1, –3, and –4 gene expressions significantly increased in nax cerebella but not in wt, while gene expressions of all 5 receptors were evident in PCs of both wt and nax cerebella. DRD3 was strongly expressed in the PCs’ somata and cerebellar nuclei neurons at P17 in nax mice, which was comparable to the expression levels in the cerebella of wt littermates. In addition, DRD3 was expressed in scattered cells in a granular layer reminiscent of Golgi cells and was observed in the wt cerebella but not in nax mice. DRD4 was expressed in a subset of PCs and appeared to align with the unique parasagittal stripes pattern. This study contributes to our understanding of alterations in the expression pattern of DRDs in the cerebellum of nax mice in comparison to their wt littermates, and it highlights the role of Acp2 in regulating the dopaminergic system.

Tumor initiating cells or cancer stem cells (CSCs) play an important role in the initiation, development, metastasis, and recurrence of tumors. However, traditional therapies have limited effects against CSCs and targeting these cells is crucial when developing new therapeutic strategies against cancer. One potentially targetable factor is CD47, a member of the immunoglobulin superfamily. This protein acts as an anti-phagocytic “don't eat me” signal and is often found expressed by cancer cells, particularly CSCs. CD47 functions by activating signal regulatory protein-α (SIRP-α) expressed on macrophages, preventing phagocytosis. However, the role of CD47 in glioma stem cells (GSCs) has been not been thoroughly investigated. Our study therefore examined the expression and function of this protein in glioma cells and GSCs. We found that CD47 was highly expressed on glioma cells, especially GSCs, and that expression associated with worse clinical outcomes. We also found that CD47+ glioma cells possessed stem/progenitor cell-like characteristics and knocking down CD47 expression resulted in a reduction in these characteristics. Treatment with anti-CD47 antibody led to increased phagocytosis of glioma cells and GSCs by macrophages. We next examined the effects of anti-CD47 antibody on glioma cells/GSCs in an immune competent mouse glioma model, revealing significant inhibition of tumor growth and prolonged survival times. Importantly, there were no apparent side effects in the animal model. In summary, we have shown that CD47 is a potentially safe and effective therapeutic target for glioma.

Polycomb group (PcG) proteins regulate the epigenetic status of transcription regulatory states during development. Progression from pluripotency to differentiation requires the sequential activation and repression of different PcG target genes, however, the relationship between early patterning signals, PcG expression, and the development of the central nervous system is still unclear. Using various models of neuronal differentiation, we provide evidence that CBX2 is a negative regulator of neuronal differentiation. Knock-down of CBX2 expression promotes neurite development, while overexpression of CBX2 inhibits neurite development. Further, we found that CBX2 is a direct target gene of miR-124. During neuronal differentiation, CBX2 was decreased while miR-124 was increased. Mechanistically, CBX2 directly interacts with the promoter region of several neuro-associated genes and regulates their expression. We found that the neuron-specific GAP-43 gene could contribute to the stimulating effect on neurite development associated with inhibition of CBX2.

Purpose. To analyze the correlations between the ocular surface signs and symptoms in patients with dry eye. Methods. In this observational study, 176 dry eye patients, including 60 males and 116 females, were enrolled and their dry eye symptoms and ocular signs were observed. Partial correlation analysis was conducted between OSDI score and each ocular surface sign, and the correlations were further discussed in different age groups. Then multiple linear regression analysis was used to further explore the influence of these signs on OSDI score. Results. Our correlation analyses showed that rounding of lid margins, notching of lid margins, vascularity of lid margins, hyperkeratinization, plugging of orifices, main duct dropout, and conjunctival congestion all had a positive correlation with OSDI score, while main duct number (central 1 cm) and BUT had a negative one. Further analysis suggested that these correlations varied in different age groups. Multiple linear regression analysis indicated that main duct number (central 1 cm), rounding of lid margins, and hyperkeratinization significantly affected OSDI score. Conclusions. Close attention should be paid to the morphology and structure of the eyelid margin and the function of meibomian gland in the diagnosis, treatment, and follow-up of dry eye diseases.

In this study, we investigated interactions among microglia (MG), bone marrow mesenchymal stem cells (BMSCs) and neurons in cerebral ischemia and the potential mechanisms using an in vitro oxygen-glucose deprivation (OGD) model. Rat BMSCs were incubated with conditioned medium (CM) from in vitro cultures of OGD-activated rat MG and murine BV2 MG cells. Effects of glial cell-derived neurotrophic factor (GDNF) on rat neuron viability, apoptosis, lactate dehydrogenase (LDH) leakage and mitochondrial membrane potential (MMP) were analyzed in this model. OGD-activated MG promoted GDNF production by BMSCs (P < 0.01). TNFα, but not IL6 or IL1β, promoted GDNF production by BMSCs (P < 0.001). GDNF or CM pre-treated BMSCs elevated neuronal viability and suppressed apoptosis (P < 0.05 or P < 0.01); these effects were inhibited by the RET antibody. GDNF activated MEK/ERK and PI3K/AKT signaling but not JNK/c-JUN. Furthermore, GDNF upregulated B cell lymphoma 2 (BCL2) and heat shock 60 kDa protein 1 (HSP60) levels, suppressed LDH leakage, and promoted MMP. Thus, activated MG produce TNFα to stimulate GDNF production by BMSCs, which prevents and repairs OGD-induced neuronal injury, possibly via regulating MEK/ERK and PI3K/AKT signaling. These findings will facilitate the prevention and treatment of neuronal injury by cerebral ischemia.