Coexistence of blaKPC-2 and blaNDM-1 in one IncHI5 plasmid confers transferable carbapenem resistance from a clinical isolate of Klebsiella michiganensis in China.

OBJECTIVES: This study firstly identified an IncHI5 plasmid pK254-KPC_NDM co-carrying two different class carbapenemase genes blaKPC-2 and blaNDM-1 in Klebsiella michiganensis K254. METHODS: The strain K254 was sequenced by high-throughput genome sequencing. A detailed genomic and phenotypic characterization of pK254-KPC_NDM was performed. RESULTS: pK254-KPC_NDM displayed the conserve IncHI5 backbone and carried a resistant accessory region: Tn1696-related transposon Tn7414 containing blaKPC-2 and blaNDM-1. A sequence comparison was applied to a collection of four Tn1696-related transposons (Tn7414-Tn7417) harbouring carbapenemase genes. For all these four transposons, the blaNDM-1 was carried by Tn125 derivatives within three different mobile genetic elements. Tn7414 further acquired another carbapenemase gene, blaKPC-2, because of the integration of the local blaKPC-2 genetic environment from Tn6296, resulting in the high-level carbapenem resistance of K. michiganensis K254. The conjugal transfer and plasmid stability experiments confirmed that pK254-KPC_NDM could be transferred intercellularly and keep the stable vertical inheritance in different bacteria, which would contribute to the further dissemination of multiple carbapenemase genes and enhance the adaption and survival of K. michiganensis under complex and diverse antimicrobial selection pressures. CONCLUSION: This study was the first to report the K. michiganensis isolate coharbouring blaKPC-2 and blaNDM-1 in the Tn1696-related transposon in IncHI5 plasmid. The emergence of novel transposons simultaneously carrying multiple carbapenemase genes might contribute to the further dissemination of high-level carbapenem resistance in the isolates of the hospital settings and pose new challenges for the treatment of nosocomial infection.

The association between glaucoma and all-cause mortality in middle-aged and elderly Chinese people: results from the China Health and Retirement Longitudinal Study.

OBJECTIVES: This population-based, prospective cohort study investigated the association between glaucoma and mortality in older adults. METHODS: Participants aged 45 years or older at baseline (47.9% male) were enrolled in 2011 for the China Health and Retirement Longitudinal Study (CHARLS). All-cause mortality was observed during 7 years of follow-up. The baseline data were collected in the 2011 CHARLS, and participants were followed up for 7 years (until 2018). The risk of all-cause mortality was investigated using Cox proportional-hazards regression with age as the time scale, adjusting for significant risk factors and comorbid conditions. RESULTS: Among the 14,803 participants included, the risk of all-cause death was significantly higher among people with glaucoma than among those without glaucoma, after adjustment for other confounders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.04 to 2.03). In a subgroup analysis based on the mean age of death, among those who were 75 years and older (n=1,231), the risk of all-cause death was significantly higher in patients with glaucoma than in those without glaucoma (HR, 1.89; 95% CI, 1.24 to 1.89). CONCLUSIONS: Participants with glaucoma had a higher risk of all-cause mortality, especially those aged 75 years and above. Our findings revealed potential mechanisms underlying an association between glaucoma and all-cause mortality. They also highlighted the importance of glaucoma management to prevent premature death in middle-aged and older adults.

Genomic analysis of chromosomal cointegrated bla NDM-1-carrying ICE and bla RSA-1-carrying IME from clinical multidrug resistant Aeromonas caviae.

Introduction: The objective of this study is to thoroughly analyze the detailed genomic characteristics of clinical strain 211703 of Aeromonas caviae, which co-carrying bla RSA-1 and bla NDM-1 genes. 211703 was isolated from the patient's cerebrospinal fluid drainage sample in a Chinese tertiary hospital. Methods: Carbapenemase NDM was detected by the immunocolloidal gold technique. The MIC values were determined by VITEK2. The whole genome sequence of 211703 was analyzed using phylogenetics, genomic comparison, and extensive dissection. Results: This study revealed that 211703 only contained a single 4.78 Mb chromosome (61.8% GC content), and no plasmids were discovered in 211703. 15 different types of resistant genes were detected in the genome of 211703, including bla RSA-1 harbored on integrative and mobilizable element (IME) Tn7413a, and bla NDM-1 harbored on integrative and conjugative element (ICE). The ICE and IME were all carried on the chromosome of 211703 (c211703). Detailed comparison of related IMEs/ICEs showed that they shared similar conserved backbone regions, respectively. Comprehensive annotation revealed that bla RSA-1 was carried by the gene cassette of a novel integron In2148 on Tn7413a, and bla NDM-1 was captured by an insertion sequence ISCR14-like on the ICE of 211703. We speculated that mobile genetic elements (MGEs) such as ICE and IME facilitated the spread of resistance genes such as bla RSA-1 and bla NDM-1. Discussion: In conclusion, this study provides an overall understanding of the genomic characterization of clinically isolated A. caviae 211703, and an in-depth discussion of multiple acquisition methods of drug resistance genes in Aeromonas. To the best of our knowledge, this is the first report of A. caviae carrying bla RSA-1 even both bla RSA-1 and bla NDM-1, and this is the first bacterium carrying bla RSA-1 isolated from the clinical setting.

Bifidobacterium promotes retinal ganglion cell survival by regulating the balance of retinal glial cells.

INTRODUCTION: Optic nerve injury is a leading cause of irreversible blindness worldwide. The retinal ganglion cells (RGCs) and their axons cannot be regenerated once damaged. Therefore, reducing RGC damage is crucial to prevent blindness. Accordingly, we aimed to investigate the potential influence of the gut microbiota on RGC survival, as well as the associated action mechanisms. METHODS: We evaluated the effects of microbiota, specifically Bifidobacterium, on RGC. Optic nerve crush (ONC) was used as a model of optic nerve injury. Vancomycin and Bifidobacterium were orally administered to specific pathogen-free (SPF) mice. RESULTS: Bifidobacterium promoted RGC survival and optic nerve regeneration. The administration of Bifidobacterium inhibited microglia activation but promoted Müller cell activation, which was accompanied by the downregulation of inflammatory cytokines and upregulation of neurotrophic factors and retinal ERK/Fos signaling pathway activation. CONCLUSIONS: Our study demonstrates that Bifidobacterium-induced changes in intestinal flora promote RGC survival. The protective effect of Bifidobacterium on RGC can be attributed to the inhibition of microglia activation and promotion of Müller cell activation and the secondary regulation of inflammatory and neurotrophic factors.

Progression of Polypoidal Lesions Associated with Exudative Recurrence in Polypoidal Choroidal Vasculopathy.

PURPOSE: To investigate the characteristics of the branching vascular network (BVN) and polypoidal lesions in polypoidal choroidal vasculopathy (PCV) to determine near-term indicators that may predict exudative recurrence. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with PCV receiving anti-vascular endothelial growth factor (VEGF) monotherapy or anti-VEGF plus photodynamic therapy were followed for at least 1 year using swept-source OCT angiography (SS-OCTA) imaging. METHODS: Patients were divided into 2 groups based on whether exudative recurrence occurred during follow-up. Multiple parameters were collected and compared between the 2 groups, such as age, gender, visual acuity, number of polypoidal lesions, lesion area at the first SS-OCTA visit, and total lesion area change from the first SS-OCTA visit to the last SS-OCTA visit. To evaluate the association between SS-OCTA imaging-based risk factors and the exudative recurrences, imaging features associated with PCV such as BVN growth and polypoidal lesion progression (enlargement, new appearance, and reappearance) at each follow-up visit were analyzed. The time intervals from the nonexudative visit with lesion progression to the corresponding exudative recurrence visit were documented to explore their association with exudative recurrences. Cox regression and logistic regression analyses were used. MAIN OUTCOME MEASURES: Association between BVN growth and polypoidal lesion progression with exudative recurrence. RESULTS: Thirty-one eyes of 31 patients (61% men) were included. Sixteen eyes had no recurrence of exudation, and 15 eyes had recurrence during follow-up. The average follow-up duration was 20.55 ± 6.86 months (range, 12-36 months). Overall, the recurrence group had worse best-corrected visual acuity (P = 0.019) and a greater increase in lesion area (P = 0.010). Logistical regression analysis showed that polypoidal lesion progression, including new appearance, enlargement, and reappearance of polypoidal lesions, was associated with exudative recurrences within 3 months (odds ratio, 26.67, 95% confidence interval, 3.77-188.54, P = 0.001). CONCLUSIONS: Growth of nonexudative BVN and progression of polypoidal lesions were found to be lesion characteristics associated with exudative recurrences, and progression of polypoidal lesions might serve as a stand-alone indicator for the near-term onset of exudation. In PCV, more frequent follow-up visits are recommended when polypoidal lesions show progression.

Defect Detection of Pipeline Inner Surface Based on Coaxial Digital Image Correlation with Hypercentric Lens.

A coaxial dual-camera digital image correlation system using a hypercentric lens was proposed to determine the defect position in the inner wall of a pipeline under loads. Compared with the traditional dual-camera system, this system ensures that both cameras can capture a 360-degree panoramic image in the same position. Herein, the imaging principle of the system was introduced in detail. In addition, the effectiveness and accuracy of the proposed method were verified through verification and application experiments.

Emergence of Extensively Drug-Resistant ST170 Citrobacter portucalensis with Plasmids pK218-KPC, pK218-NDM, and pK218-SHV from a Tertiary Hospital, China.

The objective of this study is to characterize the molecular mechanism of a clinical carbapenem-resistant Citrobacter portucalensis strain K218, which coproduces KPC and NDM carbapenemases. K218 was isolated from a patient's blood sample in a Chinese tertiary hospital. Carbapenemases were detected by the immunocolloidal gold technique. The MIC values were determined by VITEK2. Whole-genome sequencing was performed on K218 and sequence data were analyzed using phylogenetics and extensive genomic comparison. This study reveals that K218 contains a single 5.08 Mb chromosome (51.8% GC content) and four plasmids, pK218-KPC (106 Kb), pK218-NDM (111 Kb), pK218-SHV (191 Kb), and pK218-NR (5 Kb). Twenty-nine types of antibiotic resistance genes were carried on K218, including blaKPC-2 harbored on pK218-KPC and blaNDM-1 harbored on pK218-NDM. Detailed comparison of related plasmids of pK218-KPC, pK218-NDM, and pK218-SHV showed that they shared similar conserved backbone regions, respectively. Comprehensive annotation revealed large accessory modules were recombined on the genome of K218. Further analysis speculated that mobile genetic elements bearing abundant resistance genes facilitated the formation of these accessory modules. In conclusion, this study provides an in-depth understanding of the genomic characterization of K218, an extensively drug-resistant C. portucalensis strain coproducing NDM and KPC carbapenemase. To the best of our knowledge, this is the first report of C. portucalensis strain coharboring blaKPC-2 and blaNDM-1 from the clinical setting. IMPORTANCE This is the first report of extensively drug-resistant C. portucalensis harboring both blaKPC-2 and blaNDM-1. This study will not only extend the understanding of the structural dissection of plasmids and chromosomes carried in C. portucalensis, but also expand knowledge of the genetic environment of the blaKPC-2 and blaNDM-1 genes. blaKPC-2 and blaNDM-1 genes have been suggested to facilitate the propagation and persistence of their host bacteria under different antimicrobial selection pressures. Large accessory regions carrying blaKPC-2 and blaNDM-1 genes have become hot spots for transposition and integration, and their structural variation and evolution should receive attention. The multidrug-resistant plasmids pK218-KPC, pK218-NDM, and pK218-SHV with several multidrug resistance regions and the chromosome cK218 with two novel transposons Tn7410 and Tn7411 contribute to the formation of extensively drug-resistant C. portucalensis.

Epidemiology of Klebsiella michiganensis Carrying Multidrug-Resistant IncHI5 Plasmids in the Southeast Coastal Area of China.

Purpose: This study aimed to explore the genomic characterization of multidrug-resistant IncHI5-carrying Klebsiella michiganensis strains and detailed genomic dissection of the IncHI5 plasmids. Materials and Methods: Through whole-genome sequencing, the IncHI5 plasmid pK92-qnrS was obtained from a single clinical K. michiganensis isolate K92. All complete genomes of K. michiganensis strains from the Genome database of NCBI were collected and used to construct a maximum likelihood (ML) phylogenetic tree. The epidemiology and geographic distribution of all the K. michiganensis strains were conducted. An extensive comparison of the seven IncHI5 plasmids of K. michiganensis (one from this study, six from GenBank) was applied. Results: This study revealed that all K. michiganensis strains carrying IncHI5 plasmids from different clonal groups were located in the southeast coastal area of China. The backbone regions of IncHI5 plasmids were composed of replicon (repHI5B and repFIB), partition (parABC), and conjugal transfer (tra1/tra2). The main accessory resistant regions of IncHI5 could be divided into two categories, Tn1696-related region and Tn6535-related region. These seven IncHI5 plasmids carried multiple drug-resistance genes which were all mediated by the mobile genetic elements (MGEs). Conclusion: Data presented here help to provide an overall in-depth understanding of epidemiology and geographic distribution of IncHI5-carrying K. michiganensis and the structure and evolutionary history of IncHI5 plasmids.

Glaucoma Characterization by Machine Learning of Tear Metabolic Fingerprinting.

Glaucoma is a common optic neuropathy disease affecting over 76 million people. Both timely diagnosis and progression monitoring are critical but challenging. Conventional characterization of glaucoma needs a combination of methods, calling for tedious procedures and experienced doctors. Herein, a platform through machine learning of tear metabolic fingerprinting (TMF) using nanoparticle enhanced laser desorption-ionization mass spectrometry is built. Direct TMF is obtained noninvasively, with fast speed and high reproducibility, using trace tear samples (down to 10 nL). Consequently, glaucoma patients are screened against healthy controls with the area under the curve (AUC) of 0.866, through machine learning of TMF. Further, primary open-angle glaucoma (POAG) is differentiated from primary angle-closure glaucoma (PACG) and an early-stage POAG is identified. Finally, a biomarker panel of six metabolites for glaucoma characterization (including screening, subtyping, and early diagnosis) with AUC of 0.827-0.891 is constructed, showing related metabolic pathways. The work will provide insights into eye diseases not limited to glaucoma.

Association of Microvasculature and Macular Sensitivity in Idiopathic Macular Epiretinal Membrane: Using OCT Angiography and Microperimetry.

Purpose: To investigate the correlation between retinal capillary structure and macular function in patients with idiopathic epiretinal membrane (iERM) by using optical coherence tomography angiography (OCTA) and microperimetry. Methods: This retrospective and observational study included 30 idiopathic ERM eyes of 30 consecutive patients. OCTA was performed to evaluate macular microvasculature including the superficial capillary plexus, deep capillary plexus, and foveal avascular zone. Best corrected visual acuity (BCVA) and microperimetry were measured at baseline and 3 months after surgery. Associations between macular microvasculature and visual function were assessed. Results: Visual function including BCVA and macular sensitivity improved significantly at 3 months post-operatively (p < 0.001). At baseline, BCVA was positively correlated with foveal or parafoveal sensitivities and negatively correlated with central foveal thickness (p < 0.05). Pre-operative foveal sensitivity was significantly correlated with the vessel density of foveal or parafoveal superficial capillary plexus (p < 0.05). A multiple regression model revealed that pre-operative vessel density of foveal deep capillary plexus was an independent positive prognostic factor for post-operative BCVA (B = -0.020 ± 0.006, p = 0.006) and macular sensitivity (B = 0.200 ± 0.081, p = 0.027). Conclusion: Integrated evaluation of iERM by using OCTA and microperimetry shows an association between microvasculature and macular sensitivity. Pre-operative vessel density of foveal deep capillary plexus assessed by OCTA may be a potentially valuable prognostic factor for iERM surgery.

Geographic variations in idiopathic epiretinal membranes in China.

BACKGROUND: Idiopathic epiretinal membranes (ERMs) often cause metamorphopsia and the progressive loss of central visual function, which seriously affect quality of life. We aimed to map the distribution pattern of idiopathic ERMs in China and to examine the factors affecting the surgical choices of multicenter surgeons. METHODS: A national ophthalmologist-oriented questionnaire was administered, applied with a multistage probability sampling method. Data of essential characteristics, including age, professional title, residence, and perioperative and postoperative care, were gathered. All the data are expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The histogram and choropleth map were generated by Excel 2016. RESULTS: In total, 1,137 (85.2%) valid responses were returned with maximized response and completion rates. The study showed that monthly admission numbers, and preoperative and postoperative care varied significantly across different regions in China. Generally, the monthly patient admission numbers were lower in the Western region than the Eastern region. However, patients in the Eastern region had longer preoperative waiting periods and shorter hospital stays. CONCLUSIONS: The epidemiology of idiopathic ERMs varied significantly across different regions in China. The distribution pattern of ERM in China and the overview of the factors affecting the surgery approaches of multicenter surgeons were shown. The findings of this study will contribute to the formulation of medical policies, and provide insights into the healthcare environments across China.

Blocking podoplanin inhibits platelet activation and decreases cancer-associated venous thrombosis.

BACKGROUND: Patients with cancer are at a high risk of venous thromboembolism (VTE), studies have shown that high expression of podoplanin (PDPN) in tumors is associated with increased risk of VTE. METHODS: Two human malignant cell lines (NCI-H226 and C8161) expressing high levels of PDPN were selected to explore the role of platelet in cancer-associated venous thrombosis in vitro and in vivo. Immunohistochemical staining using anti-PDPN antibody was performed in the pulmonary carcinoma patients. RESULTS: Both NCI-H226 and C8161 cells expressing high PDPN triggered platelet activation via CLEC-2 in vitro, which was abrogated by an anti-PDPN antibody SZ-168. Furthermore, the in vivo study revealed that injection of CHO-PDPN or C8161 in two mouse model of venous thrombosis activated platelets, increased platelet counts and enhanced thrombosis. More importantly, PDPN-enhanced thrombosis was reduced in mice treated with SZ168. A total of 63.3% tumor specimens stained positive for PDPN. High PDPN expression was associated with an increased risk of VTE and poor prognosis. CONCLUSIONS: PDPN expression in tumors induced platelet activation and was related to a high risk of VTE via platelet activation. SZ168 inhibited PDPN-induced platelet activation in vitro and decreased the incidence of VTE in mice.

The Detection of Plasma Soluble Podoplanin of Patients with Breast Cancer and Its Clinical Signification.

BACKGROUND: Podoplanin (PDPN) is a type-1 membrane sialoglycoprotein that is expressed in many cancer tumors including breast cancer; nonetheless, its roles in tumor occurrence, development, and metastasis are unclear. In this study, we aimed to investigate the clinical significance of plasma soluble PDPN (sPDPN) levels in patients with breast cancer and its significance in the diagnosis and metastasis. MATERIALS AND METHODS: Blood samples from healthy controls (CTL), patients with fibroadenomas of breast (FOB), and breast cancer (pathological type: invasive ductal carcinoma, IDC) were collected. sPDPN levels in the plasma of CTL and patients with FOB and IDC were measured by the ELISA. RESULTS: The plasma sPDPN levels in IDC patients (159 cases, 22.59±3.70 ng/mL) were higher than those in FOB patients (50 cases, 8.29±1.09 ng/mL; P<0.05) and CTL (100 cases, 1.21±0.12 ng/mL; P<0.0001). The sPDPN levels in patients at stage III and stage IV (30.08±4.66 ng/mL) were higher than in patients at stage I and stage II (11.84±1.12 ng/mL; P=0.005). The sPDPN levels in patients with high-moderate and moderate differentiation (17.50±3.02 ng/mL) were lower than those in patients with moderately low and low differentiation (35.73±4.26 ng/mL; P=0.026). The sPDPN levels in patients with metastasis (30.60±4.27 ng/mL) were much higher than those in patients without metastasis (13.02±1.30 ng/mL; P=0.017). CONCLUSION: Plasma sPDPN may be used as a new marker for the determination of the clinical stage, differentiation degree, and metastasis status of breast cancer.

Recent Advancements in the Loading and Modification of Therapeutic Exosomes.

Exosomes have a rapid development of bio-nanoparticles for drug delivery and confluent advances in next-generation diagnostics, monitoring the progression of several diseases, and accurate guidance for therapy. Based on their prominent stability, cargo-carriage properties, stable circulating capability, and favorable safety profile, exosomes have great potential to regulate cellular communication by carrying variable cargoes into specific site. However, the specific loading strategies and modification methods for engineered exosomes to enhance the targeting ability are unclear. The clinical application of exosomes is still limited. In this review, we discuss both original and modified exosomes for loading specific therapeutic molecules (proteins, nucleic acids, and small molecules) and the design strategies used to target specific cells. This review can be used as a reference for further loading and modification strategies as well as for the therapeutic applications of exosomes.

Estimating international trade status of countries from global liner shipping networks.

Maritime shipping is a backbone of international trade and, thus, the world economy. Cargo-loaded vessels travel from one country's port to another via an underlying port-to-port transport network, contributing to international trade values of countries en route. We hypothesize that ports that involve trans-shipment activities serve as a third-party broker to mediate trade between two foreign countries and contribute to the corresponding country's status in international trade. We test this hypothesis using a port-level dataset of global liner shipping services. We propose two indices that quantify the importance of countries in the global liner shipping network and show that they explain a large amount of variation in individual countries' international trade values and related measures. These results support a long-standing view in maritime economics, which has yet to be directly tested, that countries that are strongly integrated into the global maritime transportation network have enhanced access to global markets and trade opportunities.

Laser Capture Microdissection-Based RNA Microsequencing Reveals Optic Nerve Crush-Related Early mRNA Alterations in Retinal Ganglion Cell Layer.

Purpose: To establish a method of laser capture microdissection (LCM) and RNA microsequencing for exploring optic nerve crush (ONC)-related early mRNA alterations in retinal ganglion cell (RGC) layer. Methods: An LCM protocol was developed using retinal tissue sections to obtain high-quality RNA for microsequencing. Cells in the RGC layer were collected by laser pressure catapulting (LPC) using a PALM Zeiss UV LCM system. The effect of section thickness and slide type on tissue capture success and RNA yield and the integrity after LCM were evaluated. The optimal LCM protocol was used to explore ONC-related early mRNA alterations in the RGC layer. Candidate genes were validated by real-time polymerase chain reaction of the RGC layer tissue dissected by "cut and LPC" using the same LCM system. Results: We successfully established an optimal LCM protocol using 30-µm-thick retinal tissue sections mounted on glass slides and laser pressure catapulting (LPC) to collect cells in the RGC layer and to obtain high-quality RNA for microsequencing. On the basis of our protocol, we identified 8744 differentially expressed genes that were involved in ONC-related early mRNA alterations in the RGC layer. Candidate genes included Atf3, Lgals3, LOC102551701, Plaur, Tmem140, and Maml1. Conclusions: The LCM-based single-cell RNA sequencing allowed a new sight into the early mRNA changes of RGCs highlighting new molecules associated to ONC. Translational Relevance: This technique will be helpful for more accurate transcriptome analysis of clinical pathological samples of ophthalmology and provide important reference for the discovery of new pathological diagnosis indicators and drug development targets.

Plasma lipid levels and risk of primary open angle glaucoma: a genetic study using Mendelian randomization.

BACKGROUND: The causal effects of plasma lipid concentrations and the risk of primary open angle glaucoma (POAG) are still unclear. Thus, the purpose of this study was to identify, applying a two-sample Mendelian randomization (MR) analysis, whether plasma lipid concentrations are causally associated with the risk of POAG. METHODS: Two-sample MR analysis of data from a genome-wide association study (GWAS) was performed to investigate the causal role of plasma lipid levels and POAG. A total of 185 independent single-nucleotide polymorphisms (SNPs) associated with plasma lipid levels were selected as instrumental variables (IVs). The SNPs were obtained from a meta-analysis of GWAS based on 188,577 European-ancestry individuals for MR analyses. Association with POAG for the SNPs was obtained from a GWAS conducted among the United Kingdom (UK) Biobank study participants with a total of 463,010 European-ancestry individuals. Four MR methods (inverse variance weighted [IVW], weighted mode, weighted median, and MR-Egger regression) were applied to obtain the overall causal estimate for multiple, instrumental SNPs. RESULTS: Using the IVW analysis method, no evidence was found to support a causal association between plasma LDL-C level and POAG risk (ß = - 0.00026; 95% CI = -0.00062, 0.00011; P = 0.165) with no significant heterogeneity among SNPs. The overall causal estimate between plasma LDL-C level and POAG was consistent using the other three MR methods. Using the four MR methods, no evidence of an association between plasma HDL-C (ß = 0.00023; 95% CI = -0.00015, 0.00061; P = 0.238; IVW method) or TG levels (ß = - 0.00028; 95% CI = -0.00071, 0.00015; P = 0.206; IVW method) and POAG risk was found. Sensitivity analyses did not reveal any sign of directional pleiotropy. CONCLUSIONS: The present study did not find any evidence for a causal association between plasma lipid levels and POAG risk. Further research is needed to elucidate the potential biological mechanisms to provide a reasonable interpretation for these results.

Photoreceptors Degenerate Through Pyroptosis After Experimental Retinal Detachment.

Purpose: Gasdermin D (GSDMD) is crucial in neuronal pyroptosis. GSDMD-N and GSDMD-C are two subdomains of the protein GSDMD. GSDMD-N is an executor of pyroptosis, and GSDMD-C has an inhibitory effect on pyroptotic cell death. This study evaluated the role of GSDMD in photoreceptor cell pyroptosis caused by retinal detachment (RD). Methods: RD models were established in rats, and GSDMD cleavage was detected by western blotting. The morphology of photoreceptors was assessed by transmission electron microscopy. Some rats were given subretinal injections of recombinant adeno-associated virus 2/8 (rAAV2/8)-GSDMD-C before RD surgery. We documented the expression of caspase-1 and GSDMD-N in retinas by western blot. Levels of IL-1ß, TNF-α, and monocyte chemoattractant protein-1 (MCP-1) were detected by quantitative RT-PCR. The membrane integrity of photoreceptors was evaluated by TOTO-3 iodide staining. Retinal function was measured by electroretinography, and the thickness of the outer nuclear layer was also recorded. We measured the activation of glial fibrillary acidic protein (GFAP), F4/80, and ionized calcium binding adaptor molecule 1 (Iba-1) by immunofluorescence. Results: The cleavage of GSDMD peaked at 1 day after RD. The administration of rAAV2/8-GSDMD-C reduced the pyroptosis and subsequent apoptosis of photoreceptors and preserved the retinal function after RD. Expression of IL-1, TNF-α, and MCP-1 was decreased in the rAAV2/8-GSDMD-C group. In addition, the activation of GFAP, Iba-1, and F4/80 in retinas was alleviated by administering rAAV2/8-GSDMD-C after RD. Conclusions: GSDMD participates in the pyroptosis of photoreceptor after RD. Overexpression of GSDMD-C may block GSDMD cleavage and attenuate photoreceptor degeneration.

Modular gateway-ness connectivity and structural core organization in maritime network science.

Around 80% of global trade by volume is transported by sea, and thus the maritime transportation system is fundamental to the world economy. To better exploit new international shipping routes, we need to understand the current ones and their complex systems association with international trade. We investigate the structure of the global liner shipping network (GLSN), finding it is an economic small-world network with a trade-off between high transportation efficiency and low wiring cost. To enhance understanding of this trade-off, we examine the modular segregation of the GLSN; we study provincial-, connector-hub ports and propose the definition of gateway-hub ports, using three respective structural measures. The gateway-hub structural-core organization seems a salient property of the GLSN, which proves importantly associated to network integration and function in realizing the cargo transportation of international trade. This finding offers new insights into the GLSN's structural organization complexity and its relevance to international trade.

Successful Treatment for Adult Precursor B-Cell Lymphoblastic Lymphoma Involving Central Nervous System Monitored by 18F-Fluorodeoxyglucose PET/CT Imaging.

Precursor B-cell lymphoblastic lymphoma (PBLL) is a rare subtype of non-Hodgkin lymphoma originating from B-cell precursors. PBLL, as a solitary mass lesion affecting the central nervous system without leukemic disease at presentation, is quite uncommon. Here we report a rare PBLL case with Philadelphia chromosome positivity. The 44-year-old male presented a solitary bulky mass primarily involving the left frontotemporal lobes and extended into the infratemporal fossa. Pretreatment PET/CT imaging showed avid 18F-fluorodeoxyglucose (18F-FDG) uptake of the lesion. By aggressive chemotherapy and imatinib maintenance treatment, the patient achieved and remained in complete remission on another two consecutive PET/CT imaging follow-ups.