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Abstract Background Acute glaucoma, characterized by a sudden elevation in intraocular pressure (IOP) and retinal ganglion cells (RGCs) death, is a major cause of irreversible blindness worldwide that lacks approved effective therapies, validated treatment targets and clear molecular mechanisms. We sought to explore the potential molecular mechanisms underlying the causal link between high IOP and glaucomatous RGCs death. Methods A murine retinal ischemia/ reperfusion (RIR) model and an in vitro oxygen and glucose deprivation/reoxygenation (OGDR) model were used to investigate the pathogenic mechanisms of acute glaucoma. Results Our findings reveal a novel mechanism of microglia-induced pyroptosis-mediated RGCs death associated with glaucomatous vision loss. Genetic deletion of gasdermin D (GSDMD), the effector of pyroptosis, markedly ameliorated the RGCs death and retinal tissue damage in acute glaucoma. Moreover, GSDMD cleavage of microglial cells was dependent on caspase-8 (CASP8)-hypoxia-inducible factor-1α (HIF-1α) signaling. Mechanistically, the newly identified nucleotide-binding leucine-rich repeat-containing receptor (NLR) family pyrin domain-containing 12 (NLRP12) collaborated with NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing protein 4 (NLRC4) downstream of the CASP8-HIF-1α axis, to elicit pyroptotic processes and interleukin-1β (IL-1β) maturation through caspase-1 activation, facilitating pyroptosis and neuroinflammation in acute glaucoma. Interestingly, processing of IL-1β in turn magnified the CASP8-HIF-1α-NLRP12/NLRP3/NLRC4-pyroptosis circuit to accelerate inflammatory cascades. Conclusions These data not only indicate that the collaborative effects of NLRP12, NLRP3 and NLRC4 on pyroptosis are responsible for RGCs death, but also shed novel mechanistic insights into microglial pyroptosis, paving novel therapeutic avenues for the treatment of glaucoma-induced irreversible vision loss through simultaneously targeting of pyroptosis.

Abstract. Background:. Hepatitis C virus (HCV) genotype 3, particularly subtype 3b, is increasing in prevalence and distribution in China. This study evaluated the prevalence, regional distribution, clinical characteristics, host factors, treatment outcomes, and disease progression of patients with HCV genotype 3 in China. Methods:. A 5-year follow-up was preceded by a cross-sectional study. Treatment choices were at the discretion of treating physicians. Estimated infection time to overall-disease-progression (defined by ≥1 of: newly diagnosed cirrhosis; cirrhosis at baseline, Child-Turcotte-Pugh score increased 2 points or more; progression from compensated cirrhosis to decompensated cirrhosis; hepatocellular carcinoma; liver transplantation; or death) was calculated using the Kaplan-Meier method. Cox regression analyses were conducted to evaluate the risk factors for disease progression. Results:. The cross-sectional study enrolled 997 patients, including 91 with HCV genotype 3 infection. Among them, subtype 3b (57.1%) was more dominant than subtype 3a (38.5%). Five hundred and twelve patients were included into the follow-up phase. Among patients analyzed for estimated infection time to overall-disease-progression, 52/304 (17.1%) patients with HCV genotype 1 and 4/41 (9.8%) with HCV genotype 3 (4/26 with genotype 3b, 0/13 with genotype 3a, and 0/2 with undefined subtype of genotype 3) experienced overall-disease-progression. Patients with HCV genotype 3 were younger than those with genotype 1 (mean age: 39.5 ± 8.7 vs. 46.9 ± 13.6 years) and demonstrated more rapid disease progression (mean estimated infection time to overall-disease-progression 27.1 vs. 35.6 years). Conclusions:. HCV genotype 3, specifically subtype 3b, is associated with more rapid progression of liver disease. Further analysis to compare HCV subtype 3a and 3b is needed in high prevalence regions. Trial registration:. NCT01293279, https://clinicaltrials.gov/ct2/show/NCT01293279; NCT01594554, https://clinicaltrials.gov/ct2/show/NCT01594554.

The objective of this study was to evaluate the clinical effectiveness of surgical reconstruction of aortic valve using autologous pericardium, and the hemodynamic impact of matching the circumferential direction of the trimmed leaflet to inherent fiber orientation of the pericardium during surgery. A patient specific aortic valve model was built based on CTA data. The reconstructive surgery was carried out on the model following normal operating procedures. FSI simulation was performed to analyze the hemodynamic characteristics among the diseased model, normal model and three operative models with different misaligned angles between the circumferential direction of the substitute and inherent fiber orientation. The differences of EOA, velocity distribution, stress and strain on leaflets, and the valve deformation between the five models were compared and analyzed. The results showed that reconstructive surgery helps enlarge EOA, reduce abnormity of leaflet motion and blood ejection compared to diseased model. There was no significant difference between operative models with different misaligned angles in terms of leaflet motion and flow pattern, but as the misaligned angle increased, greater strain and deformation were observed on leaflets during the diastolic period. The present study demonstrated the instant clinical effectiveness of the reconstructive surgery of aortic valve by the improvement of EOA and flow pattern, and suggested that during the operation it may be unnecessary to match the circumferential direction of the substitute to inherent fiber orientation of the pericardium since the hemodynamic characteristics were insensitive to the fiber alignment, but the strain and deformation increment on the substitutes during diastolic period still raised concern about their durability.

Constituitively active CRISPR systems have the risk of adverse off-target effects. Here the authors use chemical masking and activation of gRNA to control activity.

Tiller number (TN) is an important agronomic trait affecting gramineous crop yield. To understand the static and dynamic information of quantitative trait locus (QTLs) controlling TN of Agropyron Gaertn., both the unconditional and conditional quantitative trait loci (QTL) mapping of TN were conducted using a cross-pollinated (CP) hybrid population with a total of 113 plant lines from the cross between Agropyron cristatum (L.) Gaertn. Z1842 and Allium mongolicum Keng Z2098, based on the phenotypic data of TN at five developmental stages [i.e., recovering stage (RS), jointing stage (JS), heading stage (HS), flowering stage (FS), and maturity stage (MS)] in 4 years (i.e., 2017, 2018, 2020, and 2021) and the genetic map constructed of 1,023 single-nucleotide polymorphism (SNP) markers. Thirty-seven QTLs controlling TN were detected using two analysis methods in 4 years, which were distributed in six linkage groups. Each QTL explained 2.96–31.11% of the phenotypic variation, with a logarithum of odds (LOD) value of 2.51–13.95. Nine of these loci detected both unconditional and conditional QTLs. Twelve unconditional major QTLs and sixteen conditional major QTLs were detected. Three relatively major stable conditional QTLs, namely, cQTN1-3, cQTN1-5, and cQTN4-1, were expressed in 2020 and 2021. Meantime, two pairs of major QTLs cQTN1-5 and qTN1-4 and also cQTN2-4 and qTN2-3 were located at the same interval but in different years. Except for qTN2-2 and qTN3-5/cQTN3-5, other thirty-four QTLs were first detected in this study. This study provides a better interpretation of genetic factors that selectively control tiller at different developmental stages and a reference for molecular marker-assisted selection in the related plant improvement.

BackgroundTranscatheter mitral valve-in-valve (TMVIV) procedure with aortic transcatheter heart valves has recently become a less invasive alternative for patients with mitral bioprosthetic dysfunction. This study reports the initial experience of TMVIV implantation using the J-Valve System (JieCheng Medical Technology Corporation Ltd., Suzhou, China).MethodsA retrospective observational multicenter study was conducted to evaluate the short-term outcomes of TMVIV. In total, 26 consecutive patients with symptomatic bioprosthetic failure at eight hospitals underwent TMVIV using the J-Valve System between May 2019 and June 2021. Procedural results and clinical outcomes were analyzed using the Mitral Valve Academic Research Consortium criteria.ResultsThe mean age was 75.3 ± 7.1 years and 69.2% of patients were female. The mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 12.3 ± 8.3%. The technical success rate was 96.2%. Nine of the 26 patients (34.6%) were implanted with a J-Valve of a size equal to the internal diameters of the deteriorated prostheses. At the 30-day and 1-year follow-ups, all-cause mortality was 3.8 and 16.0% and the stroke rates were 0 and 12.0%, respectively. Device-related mortality was 0% and the mean mitral valve gradient was 6.4 ± 2.7 mm Hg. No patient experienced device embolization, left ventricular outflow tract obstruction, or mitral valve reintervention. Postprocedural mitral regurgitation was none or trace in all the patients. All the patients were in the New York Heart Association (NYHA) class ≤ II at the last follow-up.Conclusion:Transcatheter implantation of the J-Valve System in high-risk patients with mitral bioprosthetic dysfunction was found to be a reasonable alternative and associated with good short-term outcomes.

Subepithelial platelet-derived growth factor receptor alpha (PDGFRα)+ cells found in the colonic mucosal tissue come in close contact with epithelial cells, immune cells, neurons, capillaries, and lymphatic networks. Mucosal subepithelial PDGFRα+ cells (MuPαC) are important regulators in various intestinal diseases including fibrosis and inflammation. However, the transcriptome of MuPαC has not yet been elucidated. Using Pdgfra-eGFP mice and flow cytometry, we isolated colonic MuPαC and obtained their transcriptome data. In analyzing the transcriptome, we identified three novel, and selectively expressed, markers (Adamdec1, Fin1, and Col6a4) found in MuPαC. In addition, we identified a unique set of MuPαC-enriched genetic signatures including groups of growth factors, transcription factors, gap junction proteins, extracellular proteins, receptors, cytokines, protein kinases, phosphatases, and peptidases. These selective groups of genetic signatures are linked to the unique cellular identity and function of MuPαC. Furthermore, we have added this MuPαC transcriptome data to our Smooth Muscle Genome Browser that contains the transcriptome data of jejunal and colonic smooth muscle cells (SMC), interstitial cells of Cajal (ICC), and smooth muscle resident PDGFRα+ cells: (https://med.unr.edu/physio/transcriptome). This online resource provides a comprehensive reference of all currently known genetic transcripts expressed in primary MuPαC in the colon along with smooth muscle resident PDGFRα cells, SMC, and ICC in the murine colon and jejunum.

ObjectiveThe present study explored whether pyroptosis is involved in the injury process of PC12 cells induced by glucocorticoid (GC) and the regulatory relationship between endoplasmic reticulum stress (ERS) and pyrolysis.MethodsLDH leakage of PC12 cells was detected by LDH assay. The number of dead cells was detected by SYTOX green nucleic acid staining. The levels of IL-1β and IL-18 in the supernatants was detected by ELSIA assay. The expression levels of glucose regulated protein 78 (GRP78), cleaved gasdermin D-NT (cleaved-GSDMD-NT), NLR-pyrin domain-containing 3 (NLRP3) and cleaved-caspase-1 were observed by immunofluorescence staining and western blot.ResultsThe LDH assay revealed that GC exposure significantly increased the release of LDH. The results of SYTOX green acid staining showed that GC exposure significantly increased the number of SYTOX green acid-positive cells. The ELSIA assay revealed that GC exposure significantly increased the levels of IL-1β and IL-18 in the supernatants. The results of immunofluorescence staining and western blot showed that GC exposure significantly increased the expression of GRP78, cleaved-GSDMD-NT, NLRP3 and cleaved caspase-1. Treatment with the ERS inhibitor tauroursodeoxycholate (TUDCA) and siRNA GSDMD attenuated related damage and downregulated the expression of the abovementioned proteins.ConclusionThe present study clearly demonstrated that GC exposure can induce GSDMD-dependent pyrolysis, and ERS is involved in the above damage process.

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is an organophosphorus flame retardant that has been utilized in recent years as a primary replacement for polybrominated diphenyl ethers (PBDEs) in a wide variety of fire-sensitive applications. However, the impact of TDCPP on the immune system has not been fully determined. As the largest secondary immune organ in the body, the spleen is considered to be an important study endpoint for determining immune defects in the body. The aim of this study is to investigate the effect of TDCPP toxicity on the spleen and its possible molecular mechanisms. In this study, for 28 consecutive days, TDCPP was administered intragastrically (i.g), and we assessed the general condition of mice by evaluating their 24 h water and food intake. Pathological changes in spleen tissues were also evaluated at the end of the 28-day exposure. To measure the TDCPP-induced inflammatory response in the spleen and its consequences, the expression of the critical players in the NF-κB pathway and mitochondrial apoptosis were detected. Lastly, RNA-seq was performed to identify the crucial signaling pathways of TDCPP-induced splenic injury. The results showed that TDCPP intragastric exposure triggered an inflammatory response in the spleen, likely through activating the NF-κB/IFN-γ/TNF-α/IL-1β pathway. TDCPP also led to mitochondrial-related apoptosis in the spleen. Further RNA-seq analysis suggested that the TDCPP-mediated immunosuppressive effect is associated with the inhibition of chemokines and the expression of their receptor genes in the cytokine–cytokine receptor interaction pathway, including four genes of the CC subfamily, four genes of the CXC subfamily, and one gene of the C subfamily. Taken together, the present study identifies the sub-chronic splenic toxicity of TDCPP and provides insights on the potential mechanisms of TDCPP-induced splenic injury and immune suppression.

The linear eigenmode characterizations and the nonlinear turbulence energy spreading of the drift waves in a tokamak plasma with strong pedestal gradient are numerically investigated based on an electromagnetic Landau fluid model. By the linear eigenmode analysis, it is found that the dominant instability in the low β regime is the ion-temperature-gradient (ITG ^c ) mode and the electron drift wave instability (eDWI ^p ) in the core and edge region with strong density gradient, respectively. Multiple eigenstates of the eDWI ^p with different peak locations in the poloidal direction can be obtained by the eigenvalue problem solver. The dominant one is the high order eDWI ^p corresponding to the unconventional ballooning mode structure with multiple peaks in the poloidal position, in contrast to the conventional modes that peak at the outboard mid-plane, and has been verified through initial value simulation. In the high β regime, the dominant eigenmodes in the core and edge region are the conventional and unconventional kinetic ballooning modes respectively. In the nonlinear simulation, an inward turbulence spreading phenomenon during the quasi-saturation phase of the edge turbulence is clearly observed. The inward speed of the turbulence energy front in the high β regime is much faster than that in the low β regime. It is interestingly found that the speed of the turbulence energy front increases with the increase of the plasma β in the low β regime, while it is almost unchanged in the high β regime. It is identified that the turbulence spreading in the low and high β regimes are determined by the nonlinear dynamics and the linear toroidal coupling respectively.

Pre-trained transformer language models (LMs) on large unlabeled corpus have produced state-of-the-art results in natural language processing, organic molecule design, and protein sequence generation. However, no such models have been applied to learn the composition patterns for the generative design of material compositions. Here we train a series of seven modern transformer models (GPT, GPT-2, GPT-Neo, GPT-J, BLMM, BART, and RoBERTa) for materials design using the expanded formulas of the ICSD, OQMD, and Materials Projects databases. Six different datasets with/out non-charge-neutral or EB samples are used to benchmark the generative design performances and uncover the biases of modern transformer models for the generative design of materials compositions. Our experiments show that the materials transformers based on causal LMs can generate chemically valid material compositions with as high as 97.61% to be charge neutral and 91.22% to be electronegativity balanced, which has more than six times higher enrichment compared to the baseline pseudo-random sampling algorithm. Our LMs also demonstrate high generation novelty and their potential in new materials discovery is proved by their capability to recover the leave-out materials. We also find that the properties of the generated compositions can be tailored by training the models with selected training sets such as high-bandgap samples. Our experiments also show that different models each have their own preference in terms of the properties of the generated samples and their running time complexity varies a lot. We have applied our materials transformers to discover a set of new materials as validated using density functional theory calculations. All our trained materials transformer models and code can be accessed freely at http://www.github.com/usccolumbia/MTransformer .

Abstract Between June 9–11, 2019, the International Conference on Intelligent Biology and Medicine (ICIBM 2019) was held in Columbus, Ohio, USA. The conference included 12 scientific sessions, five tutorials or workshops, one poster session, four keynote talks and four eminent scholar talks that covered a wide range of topics in bioinformatics, medical informatics, systems biology and intelligent computing. Here, we describe 13 high quality research articles selected for publishing in BMC Bioinformatics.

Several drugs in development for nonalcoholic fatty liver disease (NAFLD) aim to decrease the amount of fat in the liver. We compared quantity and quality of fat in subcutaneous, visceral and muscle compartments, liver fibrosis, and prevalence of metabolic abnormalities between Chinese patients with moderate/severe hepatic steatosis versus those with mild hepatic steatosis. NAFLD patients were prospectively recruited from Peking University People's Hospital in Beijing, China. All patients had baseline body composition measurements using computed tomography and analytic morphomics, clinical evaluation, labs and Fibroscan® controlled attenuation parameter and liver stiffness measurement. Moderate/severe hepatic steatosis was defined as computed tomography liver attenuation of 40 Hounsfield units or less. Calorie intake and physical activity were based on self‐report. A total of 160 NAFLD patients were included (46% men, median age 47 years): 50% had normal body mass index (BMI), 24% were diabetic, and 56% had metabolic syndrome (MS). Fifty‐three (33%) had moderate/severe steatosis, of whom 19 (35.8%) had normal BMI, and the rest had mild steatosis. Patients who had moderate/severe steatosis had significantly higher BMI, waist circumference, aminotransferases, controlled attenuation parameter, liver stiffness measurement, and prevalence of MS compared to those with mild steatosis. They also had larger visceral fat area, subcutaneous fat area, and low density dorsal muscle area. In addition, their calorie intake was higher and time spent on recreation activities was shorter. Conclusion: NAFLD patients with moderate/severe steatosis, including those with normal BMI, had higher prevalence of MS and more fat in visceral, subcutaneous, and muscle compartments than those with mild steatosis. They also had more advanced liver disease. Strategies to decrease hepatic fat may benefit both liver and metabolic diseases.

China’s urbanization process is accompanied by land use and cover change (LUCC), influencing variations of air pollutants at multiple spatial scales. Monitoring the spatiotemporal variations of air pollutants and their relationship with land cover (LC) is vital for understanding the mechanisms of land-air interaction and guiding environmental management. In this study, both statistical and geo-statistical analysis is used to investigate the relationship between spatiotemporal variations of air pollutants and LC composition in the vicinity of China’s three major urban agglomerations (UAs), including Jing-Jin-Ji (JJJ), Yangtze River Delta Region (YRD), and Guangdong-Hong Kong-Macau Greater Bay Area (GBA). Results show that the spatial variations of six criteria air pollutants intra-region are large, even greater than inter-region and inter-season differences. Partial correlation analysis shows that although the impervious surface is the main driving force in elevating air pollution on a local scale, cropland is more important in elevating air pollutant levels at a regional scale. Besides that, the relationship between air pollutant levels and LC demonstrates varied seasonal and regional characteristics for different air pollutants. Our analysis provides a comprehensive understanding of the relationship between air pollutant levels and LC composition, emphasizing the impact of LC at different spatial scales.

Polymyxin B (PMB) exert bactericidal effects on the cell wall of Gram-negative bacteria, leading to changes in the permeability of the cytoplasmic membrane and resulting in cell death, which is sensitive to the multi-resistant Gram-negative bacteria. However, the severe toxicity and adverse side effects largely hamper the clinical application of PMB. Although the molecular pathology of PMB neurotoxicity has been adequately studied at the cellular and molecular level. However, the impact of PMB on the physiological states of central nervous system in vivo may be quite different from that in vitro, which need to be further studied. Therefore, in the current study, the biocompatible ultra-uniform Fe3O4 nanoparticles were employed for noninvasively in vivo visualizing the potential impairment of PMB to the central nervous system. Systematic studies clearly reveal that the prepared Fe3O4 nanoparticles can serve as an appropriate magnetic resonance contrast agent with high transverse relaxivity and outstanding biosafety, which thus enables the following in vivo susceptibility-weighted imaging (SWI) studies on the PMB-treated mice models. As a result, it is first found that the blood-brain barrier (BBB) of mice may be impaired by successive PMB administration, displaying by the discrete punctate SWI signals distributed asymmetrically across brain regions in brain parenchyma. This result may pave a noninvasive approach for in-depth studies of PMB medication strategy, monitoring the BBB changes during PMB treatment, and even assessing the risk after PMB successive medication in multidrug-resistant Gram-negative bacterial infected patients from the perspective of medical imaging.

Congenital cataract is one of the leading causes of blindness in children worldwide. About one-third of congenital cataracts are caused by genetic defects. LSS, which encodes lanosterol synthase, is a causal gene for congenital cataracts. LSS is critical in preventing abnormal protein aggregation of various cataract-causing mutant crystallins; however, its roles in lens development remain largely unknown. In our study, we generated a mouse model harboring Lss G589S mutation, which is homologous to cataract-causing G588S mutation in human LSS. LssG589S/G589S mice exhibited neonatal lethality at postal day 0 (P0), whereas these mice showed severe opacity in eye lens. Also, we found that cataract was formed at E17.5 after we examined the opacity of embryonic lens from E13.5 to E18.5. Moreover, disrupted lens differentiation occurred at E14.5 prior to formation of the opacity of eye lens, shown as delayed differentiation of lens secondary fiber and disordered lens fiber organization. In addition, RNA-seq analysis indicated that cholesterol synthesis signaling pathways were significantly downregulated. Overall, our findings provide clear evidence that a mouse model harboring a homozygous Lss G589S mutation can recapitulate human congenital cataract. Our study points out that LSS functions as a critical determinant of lens development, which will contribute to better understanding LSS defects in cataractogenesis and developing therapies for cataracts.

Objectives: To evaluate the 2-year clinical safety and hemodynamic outcomes of the Cingular bovine pericardial bioprosthesis.Methods: A prospective, multicenter, single-arm trial was conducted in patients who required aortic or mitral valve replacement. From March 2016 to October 2017, 197 patients were implanted with the Cingular bovine pericardial valve at five sites in China. The clinical outcomes and hemodynamic performance were assessed through a 2-year follow-up. Clinical safety events were reviewed by an independent clinical events committee, and echocardiographic data were assessed by an independent core laboratory.Results: The mean age was 66.9 ± 4.9 years. The 2-year survival rate was 96.4%. A complete 2-year clinical follow-up was achieved in 189 of 190 survivors. No case of structural valve deterioration, major perivalvular leak, prosthetic valve endocarditis, or valve-related reoperation was seen. For the aortic valve, the mean pressure gradient observed was 12.5 ± 4.0 mm Hg, and the effective orifice area (EOA) was 2.0 ± 0.3 cm2. For the smaller size aortic valves, 19 mm and 21 mm, respective mean EOA values of 1.7 ± 0.2 cm2 and 1.8 ± 0.2 cm2 were found. The values for mean pressure gradient and mean EOA for mitral bioprostheses were 4.0 ± 1.4 mm Hg and 2.2 ± 0.3 cm2, respectively. There was no significant change between 1-year and 2-year hemodynamic performance.Conclusions: The Cingular bovine pericardial valve showed favorable clinical safety and hemodynamic outcomes over a 2-year follow-up. Further follow-up is required to validate the long-term durability.

Uveitis is a sight-threatening intraocular inflammation, and the exact pathogenesis of uveitis is not yet clear. Recent studies, including multiple genome-wide association studies (GWASs), have identified genetic variations associated with the onset and progression of different types of uveitis, such as Vogt–Koyanagi–Harada (VKH) disease and Behcet’s disease (BD). However, epigenetic regulation has been shown to play key roles in the immunoregulation of uveitis, and epigenetic therapies are promising treatments for intraocular inflammation. In this review, we summarize recent advances in identifying epigenetic programs that cooperate with the physiology of intraocular immune responses and the pathology of intraocular inflammation. These attempts to understand the epigenetic mechanisms of uveitis may provide hope for the future development of epigenetic therapies for these devastating intraocular inflammatory conditions.

Background: Dyslipidemia is one of the modifiable risk factors for cardiovascular diseases (CVD). Identifying subjects with lipid abnormality facilitates preventative interventions.Objectives: To evaluate the effects of lipid indices on the risks of ischemic stroke (IS), coronary heart disease (CHD), CVD, all-cause death, and CVD death.Methods: The cohort study of 4,128 subjects started in May 2009 and followed up to July 2020. Restricted cubic spline (RCS) regression analysis was used to explore the dose-response relationship between lipid indices with outcomes. Cox proportional hazard regression analysis was used to estimate the association with a hazard ratio (HR) and 95% CI.Results: RCS analysis showed that there were significant linear associations of TG with IS, non-high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (ApoB), and total cholesterol (TC)/HDL-C ratio with all-cause death, non-HDL-C and RC with CVD death, and significant non-linear associations of ApoB with IS and CVD, TC, LDL-C, ApoAI, and TC/HDL-C ratio with CHD, and TC with all-cause death (all P 185 mg/dl (vs. 155–184 mg/dl), and ApoB 2.1 g/l (vs. 1.6–2.1 g/l) and TG

Background: Dry eye disease (DED) is a multifactorial inflammatory disease of the ocular surface. It is hypothesized that dysbiosis of the conjunctival microbiota contributes to the development of DED. However, species-level compositions of the conjunctival microbiota in DED and the potential dysbiosis involving microorganisms other than bacteria remain largely uncharacterized.Methods: We collected conjunctival impression samples from a cohort of 95 individuals, including 47 patients with DED and 48 healthy subjects. We examined the conjunctival microbiota of these samples using shotgun metagenomic sequencing and analyzed microbial dysbiosis in DED at the species level.Results: The conjunctival microbiota in DED exhibited a decreased α-diversity and an increased inter-individual variation. The α-diversity of female patients with DED was higher than that of male patients. Despite a decreased prevalence in DED, 23 microbial species were identified to show abnormally high abundance in DED samples positive for the species. Among these species, a fungal species Malassezia globosa was enriched female patients. In addition, distinct patterns of associations with disease status were observed for different species of the same genus. For DED subtypes, Staphylococcus aureus and S. capitis were associated with meibomian gland dysfunction (MGD), whereas S. hominis was enriched in patients solely with aqueous tear deficiency (ATD). The microbiota of patients with a mixed type of diagnosis was more similar to MGD patients than ATD patients.Conclusion: We demonstrated that the conjunctival microbiota dysbiosis in DED is characterized by significant heterogeneity. Microbial signatures may offer novel insights into the complicated etiology of DED and potentially promote the development of personalized treatment for DED in the future.

As the most common heavy metal pollutant, hexavalent chromium [Cr(VI)] has caused serious environmental pollution and health damage. Although the toxic effect of Cr(VI) has been widely studied, and oxidative stress has been confirmed to be the main mechanism of its cytotoxicity, the toxicity of Cr(VI) to human immune system remains to be elucidated. Neutrophil extracellular traps (NETs) participate in the innate immune response, and the release of NETs is considered to be the most important part of the extracellular killing mechanism. We demonstrated in this study that Cr(VI) inhibited the formation of NETs in rat peripheral blood and induced neutrophils apoptosis by inhibiting the AMP-activated protein kinase (AMPK) signaling pathway. Cr(VI)-induced inhibition of NETs was accompanied by down-regulated myeloperoxidase (MPO)/Histones-3 (H3) protein expressions and decreased NETs-associated intracellular and extracellular DNA levels in the neutrophils. Metformin (Met), as an AMPK activator, triggered autophagy and thus alleviated the inhibitory effect of Cr(VI) on NETs. At the same time, Met can reduce the intracellular reactive oxygen species (ROS) level by activating the AMPK/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway, thus alleviating Cr(VI)-induced neutrophils apoptosis. In conclusion, this study elucidated the mechanism of Cr(VI)-induced neutrophils toxicity and the role of AMPK as a key regulatory signal, which could provide valuable experimental basis for the prevention and treatment of related diseases in Cr(VI)-exposed populations.

Recent advances have identified significant associations between the composition and function of the gut microbiota and various disorders in organ systems other than the digestive tract. Utilizing next-generation sequencing and multiomics approaches, the microbial community that possibly impacts ocular disease has been identified. This review provides an overview of the literature on approaches to microbiota analysis and the roles of commensal microbes in ophthalmic diseases, including autoimmune uveitis, age-related macular degeneration, glaucoma, and other ocular disorders. In addition, this review discusses the hypothesis of the “gut-eye axis” and evaluates the therapeutic potential of targeting commensal microbiota to alleviate ocular inflammation.

Mitochondria have beneficial effects on cells by producing ATP and contributing to various biosynthetic procedures. On the other hand, dysfunctional mitochondria have detrimental effects on cells by inducing cellular damage, inflammation, and causing apoptosis in response to various stimuli. Therefore, a series of mitochondrial quality control pathways are required for the physiological state of cells to be maintained. Recent research has provided solid evidence to support that mitochondria are ejected from cells for transcellular degradation or transferred to other cells as metabolic support or regulatory messengers. In this review, we summarize the current understanding of the regulation of mitochondrial transmigration across the plasma membranes and discuss the functional significance of this unexpected phenomenon, with an additional focus on the impact on the pathogenesis of cardiovascular diseases. We also provide some perspective concerning the unrevealed mechanisms underlying mitochondrial ejection as well as existing problems and challenges concerning the therapeutic application of mitochondrial ejection.

Conventional luminescent solar concentrators (LSCs) lack the ability of dynamic modulation, energy saving, and privacy protection. In this work, a thermoresponsive laminated LSC was created and further used as a “smart” window (SW). The laminated LSC “smart” window (LSC-SW) was prepared by introducing carbon quantum dots (CQDs) into the sandwiched LSCs filled with aqueous thermosensitive polymer (PNIPAm) solution. To realize better compatibility, two types of fluorescent materials, hydrophilic CQDs (blue and green emitting CQDs), had been synthesized. The LSC-SW showed a good dynamic response to the ambient temperature and solar irradiation, which can be switched between transparent (32 °C). Besides, the optimal LSC-SW had high transmittance (>80%) at the transparent state and low transmittance (ηopt of 7.49%), energy saving.

The antibody repertoire is a critical component of the adaptive immune system and is believed to reflect an individual’s immune history and current immune status. Delineating the antibody repertoire has advanced our understanding of humoral immunity, facilitated antibody discovery, and showed great potential for improving the diagnosis and treatment of disease. However, no tool to date has effectively integrated big Rep-seq data and prior knowledge of functional antibodies to elucidate the remarkably diverse antibody repertoire. We developed a Rep-seq dataset Analysis Platform with an Integrated antibody Database (RAPID; https://rapid.zzhlab.org/), a free and web-based tool that allows researchers to process and analyse Rep-seq datasets. RAPID consolidates 521 WHO-recognized therapeutic antibodies, 88,059 antigen- or disease-specific antibodies, and 306 million clones extracted from 2,449 human IGH Rep-seq datasets generated from individuals with 29 different health conditions. RAPID also integrates a standardized Rep-seq dataset analysis pipeline to enable users to upload and analyse their datasets. In the process, users can also select set of existing repertoires for comparison. RAPID automatically annotates clones based on integrated therapeutic and known antibodies, and users can easily query antibodies or repertoires based on sequence or optional keywords. With its powerful analysis functions and rich set of antibody and antibody repertoire information, RAPID will benefit researchers in adaptive immune studies.

The bicuspid aortic valve (BAV) is a congenital malformation of the aortic valve with a variety of structural features. The current research on BAV mainly focuses on the systolic phase, while ignoring the diastolic hemodynamic characteristics and valve mechanics. The purpose of this study is to compare the differences in hemodynamics and mechanical properties of BAV with different phenotypes throughout the cardiac cycle by means of numerical simulation. Based on physiological anatomy, we established an idealized tricuspid aortic valve (TAV) model and six phenotypes of BAV models (including Type 0 a–p, Type 0 lat, Type 1 L–R, Type 1 N-L, Type 1 R-N, and Type 2), and simulated the dynamic changes of the aortic valve during the cardiac cycle using the fluid–structure interaction method. The morphology of the leaflets, hemodynamic parameters, flow patterns, and strain were analyzed. Compared with TAV, the cardiac output and effective orifice area of different BAV phenotypes decreased certain degree, along with the peak velocity and mean pressure difference increased both. Among all BAV models, Type 2 exhibited the worst hemodynamic performance. During the systole, obvious asymmetric flow field was observed in BAV aorta, which was related to the orientation of BAV. Higher strain was generated in diastole for BAV models. The findings of this study suggests specific differences in the hemodynamic characteristics and valve mechanics of different BAV phenotypes, including different severity of stenosis, flow patterns, and leaflet strain, which may be critical for prediction of other subsequent aortic diseases and differential treatment strategy for certain BAV phenotype.

Purpose: Accurate prediction of the progression to severe stroke in initially diagnosed nonsevere patients with acute–subacute anterior circulation nonlacuna ischemic infarction (ASACNLII) is important in making clinical decision. This study aimed to apply a machine learning method to predict if the initially diagnosed nonsevere patients with ASACNLII would progress to severe stroke by using diffusion-weighted images and clinical information on admission.Methods: This retrospective study enrolled 344 patients with ASACNLII from June 2017 to August 2020 on admission, and 108 cases progressed to severe stroke during hospitalization within 3–21 days. The entire data were randomized into a training set (n = 271) and an independent test set (n = 73). A U-Net neural network was employed for automatic segmentation and volume measurement of the ischemic lesions. Predictive models were developed and used for evaluating the progression to severe stroke using different feature sets (the volume data, the clinical data, and the combination) and machine learning methods (random forest, support vector machine, and logistic regression).Results: The U-Net showed high correlation with manual segmentation in terms of Dice coefficient of 0.806 and R2 value of the volume measurements of 0.960 in the test set. The random forest classifier of the volume + clinical combination achieved the best area under the receiver operating characteristic curve of 0.8358 (95% CI 0.7321–0.9269), and the accuracy, sensitivity, and specificity were 0.7780 (0.7397–0.7945), 0.7695 (0.6102–0.9074), and 0.8686 (0.6923–1.0), respectively. The Shapley additive explanation diagram showed the volume variable as the most important predictor.Conclusion: The U-Net was fully automatic and showed a high correlation with manual segmentation. An integrated approach combining clinical variables and stroke lesion volumes that were derived from the advanced machine learning algorithms had high accuracy in predicting the progression to severe stroke in ASACNLII patients.

Resistance to the tyrosine kinase inhibitor Sorafenib, which is the standard treatment for advanced hepatocellular carcinoma, is a major clinical challenge. Here, the authors show that phosphoglycerate dehydrogenase, a key enzyme in the serine synthesis pathway, drives sorafenib resistance.

Abstract Background Synonymous mutations do not change amino acids but do sometimes change the tRNAs (anticodons) that decode a particular codon. An isoaccepting codon is a synonymous codon that shares the same tRNA. If a mutated codon could base pair with the same anticodon as the original, the mutation is termed an isoaccepting mutation. An interesting but less-studied type of codon bias is codon co-occurrence bias. There is a trend to cluster the isoaccepting codons in the genome. The proposed advantage of codon co-occurrence bias is that the tRNA released from the ribosome E site could be quickly recharged and subsequently decode the following isoaccepting codons. This advantage would enhance translation efficiency. In plant species, whether there are signals of positive selection on isoaccepting mutations in the codon co-occurred regions has not been studied. Results We termed polymorphic mutations in coding regions using publicly available RNA-seq data in maize (Zea mays). Next, we classified all synonymous mutations into three categories according to the context, i.e., the relationship between the focal codon and the previous codon, as follows: isoaccepting, nonisoaccepting and nonsynonymous. We observed higher fractions of isoaccepting mutations in the isoaccepting context. If we looked at the minor allele frequency (MAF) spectrum, the isoaccepting mutations have a higher MAF in the isoaccepting context than that in other regions, and accordingly, the nonisoaccepting mutations have a higher MAF in the nonisoaccepting context. Conclusion Our results indicate that in regions with codon co-occurrence bias, natural selection maintains this pattern by suppressing the nonisoaccepting mutations. However, if the consecutive codons are nonisoaccepting, mutations tend to switch these codons to become isoaccepting. Our study demonstrates that the codon co-occurrence bias in the maize genome is selectively maintained by natural selection and that the advantage of this trend could potentially be the rapid recharging and reuse of tRNAs to increase translation efficiency.

Background: Whether achieving sustained virological response (SVR) in patients with hepatitis C attains complete elimination of hepatitis C virus (HCV) is unknown, because occult HCV infection (OCI), defined as the detection of HCV-RNA in hepatocytes or peripheral blood mononuclear cells (PBMC) in absence of serum HCV-RNA, may occur. We thus investigated the prevalence and clinical relevance of OCI. Methods: Subjects from three hospitals who had achieved serum HCV clearance, including 60 of Direct-acting antiviral agents (DAAs) induced SVR, 50 of pegylated interferon plus ribavirin (PR) induced SVR, and 30 of spontaneous resolution, were subjected to detect HCV-RNA in liver by robust RNAscope assay and PBMC by qPCR. Paired liver biopsies at baseline and at SVR24 were analyzed. Results: OCI was detected in 16 of 140 subjects (11.4%), with 15.0% in DAA-based group, 10.0% in PR group and 6.7% in spontaneously resolved group. In DAA-based subgroups, the incidence of OCI was gradually increased in group of solely DAA(s) therapy, combining DAA and PR therapy and combining DAA and ribavirin therapy. OCI is more frequent in patients with genotype 3. No correlation between baseline viral load, interleukin-28B genotype, baseline transaminases, post-SVR transaminases and OCI were found. However, OCI was significantly linked with severity of fibrosis and active inflammation at post-SVR, even considering basal fibrosis status. In addition, both the magnitude and the frequency of fibrosis regression were lower in patients with OCI than in those without OCI. In the multivariate analysis, PR therapy was identified an independent negative prognostic factor for both hepatic inflammation (P = .022) and fibrosis regression (P = .015). Importantly, we found HCV relapse in one of the OCI patients at 48 weeks after the end of PR treatment. Conclusions: HCV-RNA can persist in hepatocytes and/or PBMC in a certain of patients who achieved spontaneous or treatment-induced HCV RNA clearance from serum and associated with persistent histological abnormality. Our findings provide new insights into cure of HCV and could influence the following-up scenario after SVR. Keywords: Occult hepatitis C, Direct-acting antiviral agents, RNAscope assay, Liver fibrosis, Hepatic pathology

Abstract. Background:. Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC. Methods:. RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development. Results:. RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P

Abstract Background Pegylated interferon (PEG-IFN) alfa-2b is recommended for chronic hepatitis B (CHB). We aimed to investigate the sustainability of off-treatment responses among Chinese HBeAg-positive CHB patients treated with PEG-IFN alfa-2b from a randomized trial. Methods Eligible Chinese patients (n = 322) were followed up by one visit after a median of 6 years (LTFU) following their participation in a randomized trial evaluating the efficacy of three PEG-IFN alfa-2b dosing regimens (1.0 or 1.5 μg/kg/wk. 24 weeks or 1.5 μg/kg/wk. 48 weeks). Primary endpoints at the LTFU were sustained SR and CR (SR/CR at the end of original study [EOS] and at the LTFU). SR was defined as HBeAg loss and seroconversion to anti-HBe and CR as HBeAg loss and seroconversion to anti-HBe and HBV-DNA

Abstract Background Nonsynonymous mutations change the protein sequences and are frequently subjected to natural selection. The same goes for nonsense mutations that introduce pre-mature stop codons into CDSs (coding sequences). Synonymous mutations, however, are intuitively thought to be functionally silent and evolutionarily neutral. Now researchers know that the optimized synonymous codon usage is advantageous in the speedy mRNA translation process. With the advent of NGS technique, the explosion of NGS data generated from the tumor tissues help researchers identify driver mutations in cancer-related genes, but relatively less attention is paid to the SNP data in healthy human populations when studying cancer. Methods Here, we analyzed the publically available human SNPs. We classified these SNPs according to their functional and evolutionary categories. By simply dividing the human genes into cancer-related genes and other genes, we compared the features of nonsynonymous, synonymous and nonsense mutations in these two gene sets from multiple aspects. Results We provided lines of evidence that the nonsynonymous, synonymous and nonsense mutations in cancer-related genes undergo stronger purifying selection when compared to the expected pattern in other genes. The lower nonsynonymous to synonymous ratio observed in cancer-related genes suggests the suppression of amino acid substitutions in these genes. The synonymous SNPs, after excluding those in splicing regions, exhibit preferred changes in codon usage and higher codon frequencies in cancer-related genes compared to other genes, indicating the constraint exerted on these mutations. Nonsense mutations are less frequent and located closer to stop codons in cancer-related genes than in other genes, which putatively minimize their deleterious effects. Conclusion Our study demonstrated the evolutionary constraint on mutations in CDS of cancer-related genes without the requirement of data from cancer tissues or patients. Our work provides novel perspectives on interpreting the constraint on mutations in cancer-related genes. We reveal extra constraint on synonymous mutations in cancer-related genes which is related to codon usage bias and is in addition to the splicing effect.

Abstract. Background:. Alcohol consumption has been observed to be a contributing factor in liver damage. However, very few studies have tried to decipher the correlation between patients with liver disease and alcohol consumption. Therefore, this study was planned to determine the prevalence of alcohol consumption among patients with liver disease, and to evaluate the risk factors, liver diseases, and chronic medical conditions associated with alcohol drinking. Methods:. A cross-sectional study was conducted among patients with liver disease in 30 provinces, autonomous regions, and municipalities across China. All participants answered the questionnaire, which led to the calculation of Alcohol Use Disorders Inventory Test (AUDIT) score for each patient. Based on this score, low-risk drinkers, hazardous drinkers, and harmful drinkers were defined as having AUDIT score of

Incubation experiments using a typical cornfield soil in the Wujiang River watershed, SW China, were conducted to examine the impacts of soil moisture and fertilizer on N2O emissions and production mechanisms. According to the local fertilizer type, we added NH4NO3 (N) and glucose (C) during incubation to simulate fertilizer application in the cornfield soil. The results showed that an increase in soil moisture and fertilizer significantly stimulated N2O emissions in cornfield soil in the karst area, and it varied with soil moisture. The highest N2O emission fluxes were observed in the treatment with nitrogen and carbon addition at 70% water-filled pore space (WFPS), reaching 6.6 mg kg−1 h−1, which was 22,310, 124.9, and 1.4 times higher than those at 5%, 40%, and 110% WFPS, respectively. The variations of nitrogen species indicated that the production of extremely high N2O at 70% WFPS was dominated by nitrifier denitrification and denitrification, and N2O was the primary form of soil nitrogen loss when soil moisture was >70% WFPS. This study provides a database for estimating N2O emissions in cropland soil in the karst area, and further helped to promote proper soil nitrogen assessment and management of agricultural land of the karst watersheds.

At the start of the COVID-19 pandemic, there was an increase in the use of antibiotics for the treatment of community-acquired respiratory tract infection (CA-ARI) in patients admitted for suspected or confirmed COVID-19, raising concerns for misuse. These antibiotics are not under the usual purview of the antimicrobial stewardship unit (ASU). Serum procalcitonin, a biomarker to distinguish viral from bacterial infections, can be used to guide antibiotic recommendations in suspected lower respiratory tract infection. We modified our stewardship approach, and used a procalcitonin-guided strategy to identify “high yield” interventions for audits in patients admitted with CA-ARI. With this approach, there was an increase in the proportion of patients with antibiotics discontinued within 4 days (16.5% vs. 34.9%, p < 0.001), and the overall duration of antibiotic therapy was significantly shorter [7 (6–8) vs. 6 (3–8) days, p < 0.001]. There was a significant decrease in patients with intravenous-to-oral switch of antibiotics to “complete the course” (45.3% vs. 34.4%, p < 0.05). Of the patients who had antibiotics discontinued, none were restarted on antibiotics within 48 h, and there was no-30-day readmission or 30-day mortality attributed to respiratory infection. This study illustrates the importance of the antimicrobial stewardship during the pandemic and the need for ASU to remain attuned to prescriber’s practices, and adapt accordingly to address antibiotic misuse to curb antimicrobial resistance.

Comprehensive eigenmode characterizations of ion-temperature-gradient (ITG) instabilities in slab geometries with different magnetic shear profiles are investigated using an eigenvalue method. The results in the uniform magnetic shear configuration are verified via the Hamaguchi–Horton theory [S. Hamaguchi and W. Horton, Phys. Fluids B 2, 1833 (1990)]. However, it is interestingly found that the linear growth rate and mode frequency change non-monotonically as the magnetic shear at the half simulation domain s(x < x0) changes continuously from the positive value to the negative value. There are multiple peaks in the dependence curve of the linear growth rate on s(x < x0) in the weak magnetic shear regime. The variation of magnetic shear, which can produce an additional potential well to excite instability, is identified to play an important role in the maximization of the growth rate of slab ITG modes. In the configuration with a moderate separation between two potential wells, multiple ITG modes with higher radial wave numbers l become unstable simultaneously. While |s(x < x0)| is weak compared to the local magnetic shear s(x = x0) at the center mode rational surface, asymmetric structures of low-order eigenmodes are obtained and high-order eigenmodes tend to be localized between two potential wells. Additionally, as the separation between two rational surfaces in the negative shear configuration further decreases, the high-order-l eigenmode would be stabilized. The mode structures of the low-order-l unstable eigenmode are present between two rational surfaces.

Nitrous oxide (N2O), an important greenhouse gas, is emitted from landfill reservoirs, especially in the working face, where nitrification and denitrification occur under different O2 concentrations. In order to explore the effects of O2 concentration on N2O emissions and production pathways, the production of N2O from simulated fresh waste landfilling under 0%, 5%, 10%, and 21% (vol/vol) O2 concentrations were examined, and 15N isotopes were used as tracers to determine the contributions of nitrification (NF), heterotrophic denitrification (HD), and nitrification-coupled denitrification (NCD) to N2O production over a 72-h incubation period. Equal amounts of total nitrogen consumption occurred for all studied O2 concentration and the simulated waste tended to release more N2O under 0% and 21% O2. Heterotrophic denitrification was the main source of N2O release at the studied oxygen concentrations, contributing 90.51%, 69.04%, 80.75%, and 57.51% of N2O under O2 concentrations of 0%, 5%, 10%, and 21%, respectively. Only denitrification was observed in the simulated fresh waste when the oxygen concentration of the bulk atmosphere was 0%. The nitrate reductase (nirS)-encoding denitrifiers in the simulated landfill were also studied and significant differences were observed in the richness and diversity of the denitrifying community at different taxonomic levels. It was determined that optimising the O2 content is a crucial factor in N2O production that may allow greenhouse gas emissions and N turnover during landfill aeration to be minimised.

Background: Patients with type 2 diabetes mellitus (T2DM) are prone to ocular surface infections. We therefore characterized the conjunctival microbiome of T2DM patients and the influence of topical levofloxacin to investigate whether a dysbiosis is associated with this phenomenon.Methods: Conjunctival microbiome of 79 T2DM patients and 113 non-diabetic controls was profiled using the 16S rDNA sequencing approach. Furthermore, 21 T2DM and 14 non-diabetic patients who underwent cataract surgeries were followed up perioperatively and the influence of pre- and post-operative levofloxacin on the conjunctival microbiome was further investigated prospectively and compared longitudinally.Results: The α-diversity of the conjunctival microbiota was significantly higher in T2DM patients than in controls (P < 0.05). Significant differences in both composition and function of the conjunctival microbiome were identified on the ocular surface of T2DM patients as compared to non-diabetic controls. Particularly, phylum Bacteroidetes and Fusobacteria, genus Pseudomonas, Haemophilus, and Empedobacter were enriched, while genus Streptococcus was reduced on the T2DM ocular surface. Microbial genes functioning of bacterial chemotaxis was elevated in the conjunctival microbiome of T2DM patients. Furthermore, compared to the initial status, several genera including Staphylococcus were more abundant in the conjunctival microbiome of T2DM patients after 3-days use of preoperative levofloxacin topically, while no genus was more abundant in the non-diabetic follow-up group. No difference was observed between initial status and 7 days after ceasing all postoperative medications in both diabetic and non-diabetic follow-up groups.Conclusions: The conjunctival microbiome of T2DM patients was more complex and may respond differently to topical antibiotics.

Background: Grade 2+ residual mitral regurgitation (MR 2+) is associated with the recurrence of MR and a lower survival rate in interventional mitral valve (MV) edge-to-edge (EE) repair. We sought to determine the MV anatomic factors affecting residual MR 2+ during interventional EE repair with the ValveClamp system in patients with degenerative MR (DMR).Methods: In this multicenter study, 62 patients with significant (grade 3+ to 4+) DMR underwent ValveClamp implantation across eight centers from July 2018 to December 2019. Patient clinical, anatomical, and procedural characteristics were prospectively collected and retrospectively analyzed.Results: A single clamp was implanted in 59 patients, and two clamps were implanted in three patients. Residual MR 2+ was found in 14 patients (22.6%) immediately after the ValveClamp procedure. Patients with residual MR 2+ showed significantly larger preoperative tenting sizes and annular dimensions than the residual MR ≤1+ group. Multivariate analysis identified tenting volume as the major determinant of residual MR 2+ after ValveClamp procedures (odds ratio, 1.410 per 0.1-mL/m2 increase; 95% confidence interval, 1.167–1.705; P < 0.001). Receiver operating characteristic curves identified a tenting volume index ≥0.82 mL/m2 as the optimal cutoff point to predict residual MR 2+ (area under curve, 0.84). Patients with a tenting volume index ≥0.82 mL/m2 were more likely to develop recurrent 3+ MR or undergo MV surgery during short-term follow-up (P < 0.001).Conclusions: Preoperative assessment of the tenting volume index will help to predict intraoperative residual MR 2+ in patients with DMR receiving EE-based interventional repair. Improvements in the interventional strategy are warranted for sustained MR reduction in patients with DMR with unfavorable anatomy.

While many studies have focused on identifying the association between meteorological factors and the activity of COVID-19, we argue that the contribution of meteorological factors to a reduction of the risk of COVID-19 was minimal when the effects of control measures were taken into account. In this study, we assessed how much variability in COVID-19 activity is attributable to city-level socio-demographic characteristics, meteorological factors, and the control measures imposed. We obtained the daily incidence of COVID-19, city-level characteristics, and meteorological data from a total of 102 cities situated in 27 provinces/municipalities outside Hubei province in China from 1 January 2020 to 8 March 2020, which largely covers almost the first wave of the epidemic. Generalized linear mixed effect models were employed to examine the variance in the incidence of COVID-19 explained by different combinations of variables. According to the results, including the control measure effects in a model substantially raised the explained variance to 45%, which increased by >40% compared to the null model that did not include any covariates. On top of that, including temperature and relative humidity in the model could only result in < 1% increase in the explained variance even though the meteorological factors showed a statistically significant association with the incidence rate of COVID-19. In conclusion, we showed that very limited variability of the COVID-19 incidence was attributable to meteorological factors. Instead, the control measures could explain a larger proportion of variance.

Prestasi organisasi bergantung sepenuhnya kepada prestasi kerja yang ditonjolkan oleh pekerja. Kegagalan organisasi untuk mengekalkan prestasi kerja yang baik membawa kepada masalah isu kadar pusing ganti pekerja yang tinggi yang seterusnya menjejaskan produktiviti syarikat dan ekonomi negara. Objektif kajian ini adalah untuk mengenal pasti faktor-faktor yang mempengaruhi prestasi kerja dalam kalangan penjawat awam dan swasta di kawasan sekitar Lembah Klang. Data primer diperoleh melalui soal selidik dengan sejumlah 139 responden yang terlibat dalam kajian ini. Analisis faktor digunakan untuk menganalisis data yang sekadar diperoleh. Hasil kajian mendapati pekerja berpendapat bahawa ketiga-tiga faktor, iaitu motivasi, persekitaran tempat kerja serta latihan dan pembangunan mempengaruhi prestasi kerja. Pihak organisasi perlu mengutamakan keperluan motivasi intrinsik kepada pekerja dan menetapkan matlamat latihan yang dijalankan dengan jelas untuk meningkatkan prestasi kerja.

MitraClip edge-to-edge (E2E) repair system is the only transcatheter device recommended in the current guidelines for treating mitral regurgitation (MR). The percutaneous femoral venous transseptal access of MitraClip requires a complex steerable delivery system and may thus be technically complex to optimally position and deploy the clip onto the mitral valve. A transapical approach for E2E repair has been devised to treat MR for the ease of operation (ValveClamp system, Hanyu Medical Technology, Shanghai). The first-in-human study of ValveClamp has demonstrated its early feasibility and effectiveness for the treatment of patients with degenerative MR. Transesophageal echocardiography (TEE) is the only imaging modality required for intraoperative guidance of ValveClamp implantation. Successful implantation depends on accurate localization and orientation of the clamp and efficient intraoperative communication between the echocardiographer and the intervention team. Thus, the focus of this review is on elaborating how two-dimensional (2D) and three-dimensional (3D) TEE are used in clinical practice to guide ValveClamp implantation and it may facilitate the understanding of simplicity and safety of this novel procedure. We also describe the implementation of several novel advancements in 3D TEE imaging, which improve the confidence of image interpretation for intraoperative guidance and expedite implantation times.

Sektor perladangan kelapa sawit merupakan sektor yang sangat penting dalam industri pertanian dan merupakan penyumbang terpenting kepada ekonomi Malaysia. Namun begitu, isu tenaga buruh di sektor ini sering diperkatakan kerana masih berintensif buruh. Penyertaan golongan belia dalam sektor perladangan kelapa sawit adalah kurang memberangsangkan berbanding sektor lain walaupun sektor ini menawarkan peluang pekerjaan yang lebih luas. Oleh sebab itu, kajian ini bertujuan untuk mengenal pasti golongan belia yang lebih bersedia untuk melibatkan diri dalam sektor perladangan kelapa sawit berdasarkan faktor demografi mereka. Borang soal selidik digunakan bagi mengumpul data daripada responden yang terdiri daripada golongan belia berusia 18 hingga 35 tahun. Seramai 724 orang responden yang telah menjawab soal selidik ini mewakili setiap negeri di Malaysia. Data yang dikumpul dianalisis menggunakan kaedah analisis faktor dan model regresi logistik. Hasil kajian menunjukkan bahawa faktor jantina, bangsa, tempat tinggal, pengalaman, dan penglibatan ahli keluarga dalam sektor perladangan kelapa sawit merupakan faktor yang menyumbang kepada kesediaan belia untuk melibatkan diri dalam sektor tersebut. Faktor gaji, faedah, persekitaran kerja dan keselamatan perlu ditambah baik bagi menarik lagi minat golongan belia untuk melibatkan diri dalam industri pertanian negara khususnya di sektor perladangan kelapa sawit. Abstract The oil palm plantation sector is a very important sector in the agricultural industry and is a major contributor to the Malaysian economy. However, the issue of labour in this sector is often addressed as it is labour-intensive. The participation of youths in the oil palm plantation sector is less favourable than the other sector although it offers greater employment opportunities. Therefore, this study aimed to identify youths who are better prepared to participate in the oil palm plantation sector based on their demographic factors. The questionnaire was used to collect data from respondents in the age range of 18 to 35 years. A total of 724 respondents answered this questionnaire representing each state in Malaysia. The data collected were analysed using the factor analysis method and logistic regression model. The results show that the gender, race, residence, experience and involvement of family members in the oil palm plantation sector are factors contributing to youths’ readiness to participate in the sector. Factors such as salary, benefits, work environment and safety factors need to be improved to attract more youths to participate in the agricultural industry, especially in the oil palm plantation sector. Keywords: Youth, labour force, oil palm, demographic factors, logistic regression

The term ocular microbiota refers to all types of commensal and pathogenic microorganisms present on or in the eye. The ocular surface is continuously exposed to the environment and harbors various commensals. Commensal microbes have been demonstrated to regulate host metabolism, development of immune system, and host defense against pathogen invasion. An unbalanced microbiota could lead to pathogenic microbial overgrowth and cause local or systemic inflammation. The specific antigens that irritate the deleterious immune responses in various inflammatory eye diseases remain obscure, while recent evidence implies a microbial etiology of these illnesses. The purpose of this review is to provide an overview of the literature on ocular microbiota and the role of commensal microbes in several eye diseases. In addition, this review will also discuss the interaction between microbial pathogens and host factors involved in intraocular inflammation, and evaluate therapeutic potential of targeting ocular microbiota to treat intraocular inflammation.

Plane gratings are widely used as dispersion elements in spectral analysis from the infrared to x-ray regions. This study proposes an optical element, consisting of only a reflection focusing and dispersion plane grating (RFPG) designed for a specific wavelength. A raytracing simulation and a visible light experiment were performed to verify the focusing and wavelength dispersion properties of the proposed RFPG. The raytracing simulation result shows that the designed 635 nm RFPG has a spectral resolution (λ/∆λ) of 423 (linear dispersion = 493.8 eV/m) under specific conditions. Additionally, in the visible light experiment, the spectral resolution of 423 (linear dispersion = 493.8 eV/m) and band range of ±25 nm were obtained at the target wavelength of 635 nm. The experimental results indicate that the proposed optical element, RFPG, exhibits focusing and dispersion properties for a designed wavelength. It is a potential tool for the study of x-ray fluorescence, absorption, and advanced x-ray sources, such as laser wakefield Betatron x-ray sources.