Metabolic signatures of tear extracellular vesicles caused by herpes simplex keratitis.

PURPOSE: Herpes simplex keratitis (HSK), caused by type 1 herpes simplex virus (HSV) reactivation, is a severe infectious disease that leads to vision loss. HSV can trigger metabolic reprogramming in the host cell and change the extracellular vesicles (EV) cargos; however, little is known about the EV metabolic signatures during ocular HSV infection. Here, we aimed to depict the EV-associated metabolic landscape in HSK patients' tears. METHODS: We collected 82 samples from 41 participants with unilateral HSK (contralateral unaffected tears were set as negative control), including subtype cohorts of 13 epithelial, 20 stromal, and 8 endothelial HSK. We isolated tear EVs via our previously established platform and conducted metabolic analysis using LC-MS/MS. The metabolic signatures for recognizing HSK and subtypes were assessed through differential analysis and machine learning algorithms. RESULTS: Hypopsia and increased extracellular CD63 levels were observed in affected eyes. We identified 339 metabolites based on sEVs isolated from tears. Differential analysis revealed alterations in energy and amino acid metabolism, as well as the infectious microenvironment. Furthermore, we observed dysregulated metabolite such as methyldopa, which is associated with inappropriate neovascularization and corneal sensation loss, contributing to the HSK severity particularly in the stromal subtype. Moreover, machine learning classification also suggested a set of EV metabolic signatures that have potential for pan-keratitis detection. CONCLUSIONS: Our findings demonstrate that tear EV metabolites can serve as valuable indicators for comprehending the underlying pathological mechanisms. This knowledge is expected to facilitate the development of liquid biopsy means and therapeutic target discovery.

Efficacy and safety of 1565-nm nonablative fractional laser combined with mucopolysaccharide polysulfate cream for erythematous acne scars.

PURPOSE: To evaluate the efficacy and safety of 1565-nm nonablative fractional laser (NAFL) combined with mucopolysaccharide polysulfate (MPS) cream in the treatment of erythematous acne scars. METHODS: A total of 28 subjects with erythematous acne scars from June 2021 to April 2022 were enrolled. One side of each subject's face was randomly assigned to be treated with 1565-nm NAFL (at 2 sessions with four-week intervals) combined with MPS cream (twice daily) for 8 weeks, and the other side with 1565-nm NAFL combined with placebo cream. CBS® images and parameters, dermoscopic images and the quantitative data processed by ImageJ software, and quantitative global scarring grading system (GSS) score were obtained at baseline and after treatment. Subjects' satisfaction assessment was performed after treatment. Adverse events were recorded during treatment. RESULTS: In CBS® parameters, the red area, red area concentration, and smoothness were improved more significantly on the 1565-nm NAFL combined with MPS cream side than on the 1565-nm NAFL combined with placebo cream side after treatment (p = 0.015, p = 0.013, and p = 0.021). For dermoscopy, both scar area and scar redness achieved a significantly greater percentage of improvement on the side of 1565-nm NAFL combined with MPS cream than the side of 1565-nm NAFL combined with placebo cream after treatment (p = 0.005 and p = 0.041). The reduction of quantitative GSS score and Subjects' satisfaction assessment were similarly superior on the 1565-nm NAFL combined with MPS cream side. Temporary erythema was experienced by all subjects after each 1565-nm NAFL treatment. No subject reported intolerance or allergy to the cream during follow-up. CONCLUSIONS: The combined application of 1565-nm NAFL and MPS cream could be an effective and safe treatment for erythematous acne scars. ImageJ software enables quantitative evaluation of dermoscopic images of acne scars.

Efficient precise integration of large DNA sequences with 3'-overhang dsDNA donors using CRISPR/Cas9.

CRISPR/Cas9 genome-editing tools have tremendously boosted our capability of manipulating the eukaryotic genomes in biomedical research and innovative biotechnologies. However, the current approaches that allow precise integration of gene-sized large DNA fragments generally suffer from low efficiency and high cost. Herein, we developed a versatile and efficient approach, termed LOCK (Long dsDNA with 3'-Overhangs mediated CRISPR Knock-in), by utilizing specially designed 3'-overhang double-stranded DNA (odsDNA) donors harboring 50-nt homology arm. The length of the 3'-overhangs of odsDNA is specified by the five consecutive phosphorothioate modifications. Compared with existing methods, LOCK allows highly efficient targeted insertion of kilobase-sized DNA fragments into the mammalian genomes with low cost and low off-target effects, yielding >fivefold higher knock-in frequencies than conventional homologous recombination-based approaches. This newly designed LOCK approach based on homology-directed repair is a powerful tool suitable for gene-sized fragment integration that is urgently needed for genetic engineering, gene therapies, and synthetic biology.

Detection of skin thickness and density in healthy Chinese people by using high-frequency ultrasound.

OBJECTIVES: Due to a recent development of high-frequency ultrasound (HFUS) systems, it is easier to realize high-resolution in vivo imaging of the biological tissues. The object of this study was to map the thickness and echo density of skin layers in healthy Chinese people and assess the influence of gender, age, and region on it. METHODS: A total of 189 volunteers (85 male, 104 female) with age range of 22-75-year old (mean age of 41.2-year old) were enrolled. The thickness and density of the epidermis and dermis layer were detected by high-frequency (22 or 75 MHz) ultrasonography at 13 different anatomical sites, including the forehead, cheeks, flexor and extensor forearms, flexor and extensor upper arms, inner and outer legs, inner and outer thighs, back, and abdomen. RESULTS: The thickness and density of epidermis/dermis between different anatomical sites were statistically significant (p < 0.05). The epidermis thickness of the face and trunk were less than that of the limbs, whereas the thicknesses of the dermis were on the contrary. The density of the epidermis/dermis of the face and trunk were less than that of the limbs. The thickness of dermis in most of the sites were higher in male than in female, and the density of epidermis and dermis in most of the sites were less in men than in women. The thicknesses/densities of dermis were lower in older age group in almost all sites, whereas only several sites reached statistical. The difference between the north and south regions showed the environment also influenced the thickness and density of the skin. CONCLUSION: HFUS provides a simple noninvasive method for evaluating the skin thickness and echo-density, which, reflecting intradermal structure, exhibit systematic regional variation. With the establishment of Chinese phenotypic database of skin thickness and density, it will be helpful for the skin disease assessment, skin surgery, and cosmetology technology.

A nomogram based on clinicopathological and ultrasound characteristics to predict central neck lymph node metastases in papillary thyroid cancer.

Purpose: Papillary thyroid cancer (PTC) has grown rapidly in prevalence over the past few decades, and central neck lymph node metastasis (CNLNM) is associated with poor prognoses. However, whether to carry out preventive central neck lymph node dissection (CNLND) is still controversial. We aimed to construct a prediction model of CNLNM to facilitate making clinical surgical regimens. Methods: A total of 691 patients with PTC between November 2018 and December 2021 were included in our study. Univariate and multivariate analyses were performed on basic information and clinicopathological characteristics, as well as ultrasound characteristics (American College of Radiology (ACR) scores). The prediction model was constructed and performed using a nomogram, and then discriminability, calibrations, and clinical applicability were evaluated. Results: Five variables, namely, male, age >55 years, clinical lymph node positivity, tumor size ≥1 cm, and ACR scores ≥6, were independent predictors of CNLNM in the multivariate analysis, which were eventually included to construct a nomogram model. The area under the curve (AUC) of the model was 0.717, demonstrating great discriminability. A calibration curve was developed to validate the calibration of the present model by bootstrap resampling, which indicated that the predicted and actual values were in good agreement and had no differentiation from the ideal model. The decision curve analysis (DCA) indicated that the prediction model has good clinical applicability. Conclusions: Our non-invasive prediction model combines ACR scores with clinicopathological features presented through nomogram and has shown good performance and application prospects for the prediction of CNLNM in PTCs.

The gut microbiota of silkworm are altered by antibiotic exposure.

In recent years, antibiotics have frequently been detected in soil, lakes, and rivers. Antibiotic residues in the environment may alter microbial structure and cause bacterial resistance, but their effect on interactions among host microbiota is still poorly understood. To investigate this issue, here we used silkworm (Bombyx mori) fed on antibiotic-treated mulberry leaf as a model to explore the effects of antibiotic exposure on gut bacteria and fungi. We observed that elimination of fungi significantly reduced bacterial richness and diversity in silkworm intestine after exposure to the antifungal amphotericin B, while the elimination of bacteria dramatically increased the richness and diversity of fungi after exposure to the antibacterial ampicillin-streptomycin. Thus, antibiotic-treated mulberry leaf significantly altered the community structure of microbiota in the gut of silkworm. Clearance of gut bacteria enhanced the correlation between gut fungi and leaf-derived fungi, while clearance of gut fungi promoted abnormal proliferation of gut bacteria. These data provide a simple model to explore the comprehensive effect of diet-derived bacteria, fungi, and antibiotics on gut microbiota.

Summarization and comparison of dermoscopic features on different subtypes of rosacea.

BACKGROUND: The dermoscopic features of rosacea have already been reported. However, the current findings are incomplete, and little is known about phymatous rosacea. Hence, this study aimed to summarize and compare the dermoscopic features and patterns of three rosacea subtypes (erythematotelangiectatic [ETR], papulopustular [PPR], and phymatous [PHR]) in the Chinese Han population and to evaluate whether these features differ with patients' genders, ages, and durations. METHODS: Dermoscopic images of 87 rosacea patients were collected in non-polarized and polarized dermoscopy contact modes at 20-fold magnification. Dermoscopic features, including vessels, scales, follicular findings, and other structures, were summarized and evaluated. RESULTS: The reticular linear vessels and red diffuse structureless areas of ETR were distinctive. For PPR, red diffuse structureless areas, reticular linear vessels, yellow scales, follicular plugs, and follicular pustules were typical dermoscopic criteria. The common dermoscopic features of PHR were: orange diffuse structureless areas, linear vessels with branches, perifollicular white color, orange focal structureless areas, and white lines. The following features statistically differed among the three rosacea subtypes: reticular linear vessels ( P  < 0.001), unspecific linear vessels ( P  = 0.005), linear vessels with branches ( P  < 0.001), yellow scales ( P  = 0.001), follicular plugs ( P  < 0.001), perifollicular white color ( P  < 0.001), red diffuse structureless areas ( P  = 0.022), orange diffuse structureless areas ( P  < 0.001), red focal structureless areas ( P  = 0.002), orange focal structureless areas ( P  = 0.003), white lines ( P  < 0.001), follicular pustules ( P  < 0.001), and black vellus hairs ( P  < 0.001). CONCLUSIONS: The dermoscopic patterns of ETR are red diffuse structureless areas and reticular linear vessels. For PPR, the pattern comprehends combinations of red diffuse structureless areas, reticular linear vessels, yellow scales, follicular plugs, and follicular pustules. Meanwhile, PHR is characterized by remarkable orange diffuse structureless areas, linear vessels with branches, perifollicular white color, orange focal structureless areas, and white lines.

Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study.

OBJECTIVE: Genome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis. METHODS: We built gene expression predictive models in blood B cells, CD4+ and CD8+ T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches. RESULTS: TWAS identified 171 genes for SLE (p<1.0×10-5); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association between CD83 and SLE (p<7.7×10-8). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5×10-9) around CD83. For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect on ACAP1, and that presence of the SLE risk allele decreased ACAP1 expression. CONCLUSIONS: Cell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

How fluorescent labels affect the kinetics of the toehold-mediated DNA strand displacement reaction.

End modification of the toehold domain or near to it using fluorophore dyes or quenchers can significantly modulate the kinetics of the toehold-mediated strand displacement reaction (TMSDR) by almost two orders of magnitude. The labels at the end of the signal strand impede the TMSDR, while those at the end of the toehold domain of the substrate strand accelerate the TMSDR kinetics.

Comparison of dermoscopy and reflectance confocal microscopy accuracy for the diagnosis of psoriasis and lichen planus.

BACKGROUND: Dermoscopy and reflectance confocal microscopy (RCM) as noninvasive tools are gaining increasing importance in the diagnosis of inflammatory skin disorders. The purpose of our study was to calculate and compare the diagnostic accuracy of dermoscopy and RCM in common inflammatory skin diseases. MATERIALS AND METHODS: We retrospectively collected clinical, dermoscopic, and RCM images of psoriasis and lichen planuscases from March 2018 to February 2021 in China-Japan Friendship Hospital. There were 10 experts evaluated dermoscopic and RCM images independently. Sensitivity, specificity, positive predict value, and negative predictive value for each and all investigators were calculated. The diagnostic accuracy was also measured by the area under the curve (AUC) for the Receiver Operator Characteristic (ROC) Curves. RESULTS: We collected 82 psoriasis and 47 lichen planus cases. Dermoscopy was more sensitive than RCM in the diagnosis of psoriasis, and overall diagnostic accuracy of dermoscopy was also higher than RCM measured by AUC (0.879 vs. 0.835, p = 0.0001). For lichen planus, RCM had higher sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy than dermoscopy (AUC 0.916 vs. 0.813, p<0.0001). CONCLUSION: Dermoscopy and RCM play a significant role in assisting the diagnosis of psoriasis and lichens planus. These two noninvasive diagnostic tools have their own advantages and disadvantages for the evaluation of different inflammatory skin diseases, and they can be combined in clinical practice to improve the accuracy of the diagnosis of inflammatory skin diseases.

Deficiency of two-pore segment channel 2 contributes to systemic lupus erythematosus via regulation of apoptosis and cell cycle.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq). RESULTS: TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown-TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation. CONCLUSION: TPCN2 might be a potential protective factor against SLE.

Curvature-Mediated Pair Interactions of Soft Nanoparticles Adhered to a Cell Membrane.

The curvature-mediated interactions by cell membranes are crucial in many biological processes. We systematically studied the curvature-mediated wrapping of soft nanoparticles (NPs) by a tensionless membrane and the underlying pair interactions between NPs in determining it. We found that there are three types of wrapping pathways, namely, independence, cooperation, and tubulation. The particle size, adhesion strength, and softness are found to be strongly related with the wrapping mechanism. Reducing the adhesion strength transforms the wrapping pathway from cooperation to independence, while enhancing the NP softness requires a stronger adhesion to achieve the cooperative wrapping. This transformation of the wrapping pathway is controlled by the curvature-mediated interactions between NPs. For either soft or rigid NPs, the pair interactions are repulsive at short-ranged distances between NPs, while at long-ranged distances, a larger adhesion between NPs and a membrane is needed to generate attraction between NPs. Moreover, an enhancement of NP softness weakens the repulsion between NPs. These distinct behaviors of soft NPs are ascribed to the gentler deformation of the membrane at the face-to-face region between NPs due to the flattening and spreading of soft NPs along the membrane, requiring a reduced energy cost for soft NPs to approach each other. Our results provide a mechanistic understanding in detail about the membrane-mediated interactions between NPs and their interactions with cell membranes, which is helpful to understand the curvature-mediated assemblies of adhesive proteins or NPs on membranes, and offer novel possibilities for designing an effective NP-based vehicle for controlled drug delivery.

Procyanidin B2 alleviates liver injury caused by cold stimulation through Sonic hedgehog signalling and autophagy.

Procyanidin B2 (PB2), a naturally occurring flavonoid abundant in a wide range of fruits, has been shown to exert antioxidant, anti-inflammatory and anticancer properties. However, the role of PB2 in the prevention of cold stimulation (CS)-induced liver injury. The present study was undertaken to determine the effects of PB2 on liver injury induced by cold stimulation and its potential molecular mechanisms. The present study results showed that treatment with PB2 significantly reduced CS-induced liver injury by alleviating histopathological changes and serum levels of alanine transaminase and aspartate transaminase. Moreover, treatment with PB2 inhibited secretion of inflammatory cytokines and oxidative stress in cold-stimulated mice. PB2 reduced cold stimulation-induced inflammation by inhibiting TLR4/NF-κB and Txnip/NLRP3 signalling. Treatment with PB2 reduced oxidative stress by activating Nrf-2/Keap1, AMPK/GSK3ß signalling pathways and autophagy. Furthermore, simultaneous application of Shh pathway inhibitor cyclopamine proved that PB2 targets the Hh pathway. More importantly, co-treatment with PB2 and cyclopamine showed better efficacy than monotherapy. In conclusion, our findings provide new evidence that PB2 has protective potential against CS-induced liver injury, which might be closely linked to the inhibition of Shh signalling pathway.

Skin diseases in the Da Qing Diabetes Study: a cross-sectional study.

BACKGROUND: The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM. METHODS: We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated. RESULTS: In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in "disturbances of pigmentation" and "neurological and psychogenic dermatoses". The duration of T2DM also significantly associated with the prevalence of "disturbances of pigmentation" and "neurological and psychogenic dermatoses". Subsequently, the prevalence of "disturbances of pigmentation" was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of "disturbances of pigmentation" was also significant in NGT and T2DM groups (P < 0.01). CONCLUSIONS: There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.

Acute Kidney Injury in Hospitalized Patients Infected with COVID-19 from Wuhan, China: A Retrospective Study.

BACKGROUND: Since the first diagnosed case of infection with the novel coronavirus (SARS-CoV-2), there has been a rapid spread of the disease with an increasing number of cases confirmed every day, as well as a rising death toll. An association has been reported between acute kidney injury (AKI) and mortality in patients infected with SARS-CoV-2. Therefore, our study was conducted to explore possible risk factors of AKI as well as whether AKI was a risk factor for worse outcome, especially mortality among patients with coronavirus disease (COVID-19). METHODS: We included all hospital admissions with confirmed or clinically diagnosed COVID-19 from January 29 to February 25, 2020. We collected demographic and epidemiological information, past medical history, symptoms, laboratory tests, treatments, and outcome data from electronic medical records. A total of 492 patients with diagnosed or clinically diagnosed COVID-19 were included in this study. RESULTS: The prevalence rate of AKI was 7.32%. Among the factors associated with AKI, males versus females (aOR 2.73), chronic kidney disease (aOR 42.2), hypertension (aOR 2.82), increased leucocytes (aOR 6.08), and diuretic use (aOR 7.89) were identified as independent risk factors for AKI among patients infected by SARS-CoV-2. There was a significant difference in hospital fees and death in patients with and without AKI (p < 0.05). The mortality rate in patients with AKI was 63.9%. CONCLUSIONS: AKI was widespread among patients with COVID-19. The risk factors of AKI in COVID-19 patients included sex, chronic kidney disease, hypertension, infection, and diuretic use. AKI may be associated with a worse outcome, especially mortality in COVID-19 patients.

ActivinA activates Notch1-Shh signaling to regulate proliferation in C2C12 skeletal muscle cells.

The myoblast is a precursor cell that rebuilds muscle tissue after trauma in human and animal skeletal muscle tissue. Proliferation of myoblasts is important for skeletal muscle damage repair and is controlled by numerous transcription factors and signals. The regulation of these signaling pathways and their complex interactions are not fully understood. This study aims to determine the physiological functions of Activin A, Notch and Sonic Hedgehog (Shh) signaling in the proliferation of mouse C2C12 myoblasts and to explore their interactions. Activin A facilitated proliferation of C2C12 cells and promoted the conversion of G1 into S phase in cell cycle, whereas addition of the receptor inhibitor SB431542 attenuated the proliferation activity of rActA on C2C12 cells. Activin A also activated Notch and Shh signaling, while blockage of these pathways attenuated the function of Activin A in cell cycle. Inhibition of the Notch signaling by Notch response inhibitor DAPT significantly down-regulated the expression of Shh signaling molecules, whereas exogenous rShh reversed the inhibition of C2C12 cells proliferative activity induced by DAPT, indicating Notch signaling act upstream of the Shh pathway. Furthermore, inhibition of Notch signaling weakened the activation of Activin A-mediated Shh signaling. Taken together, our results provide a novel role of Activin A in regulating the proliferation of C2C12 skeletal muscle cells, which impacts ActivinA-Notch1-Shh signaling pathways.

Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations. METHODS: We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations. RESULTS: We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10-8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=-0.242) and non-albumin protein (rg=0.238). CONCLUSION: This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

Correlation between laboratory parameters on admission and outcome of COVID-19 in maintenance hemodialysis patients.

PURPOSE: This present study aims to investigate the relationship between laboratory parameters on admission and prognosis of coronavirus disease 2019 (COVID-19) in maintenance hemodialysis patients, as well as providing a theoretical basis for clinical evaluation of prognosis and corresponding intervention measures. METHODS: Retrospective analysis was performed on the clinical data of 47 maintenance hemodialysis patients who infected with COVID-19 and admitted to our hospital. According to their clinical outcome, these patients were divided into a survival group (n = 38) and a fatality group (n = 9). Information on the general condition and laboratory parameters of the patients were collected. Laboratory parameters were compared between different groups. The area under the curve (AUC) was used to evaluate the prognosis of COVID-19 in maintenance hemodialysis patients. RESULTS: Statistically significant differences were observed in age, white blood cell count, neutrophil count, albumin, C-reactive protein (CRP), procalcitonin, and lactate dehydrogenase (LDH) on admission (P < 0.05). Receiver operating characteristic (ROC) curve analysis showed that the values of AUC of CRP, neutrophil count, LDH, white blood cell count, albumin, and procalcitonin were 0.895, 0.813, 0.758, 0.757, 0.743, and 0.728, respectively. CONCLUSIONS: Laboratory parameters including CRP, neutrophil count, LDH, white blood cell count, albumin, and procalcitonin were predictive on the prognosis of maintenance hemodialysis patients with COVID-19. Among them, CRP was the strongest single predictive laboratory indicator.

Starch bio-template synthesis of W-doped CeO2 catalyst for selective catalytic reduction of NOx with NH3: influence of ignition temperature.

A novel tungsten-doped CeO2 catalyst was fabricated via the sweet potato starch bio-template spread self-combustion (SSC) method to secure a high NH3-SCR activity. The study focuses on the influence of ignition temperature on the physical structure and redox properties of the synthesized catalyst and the catalytic performance of NOx reduction with NH3. These were quantitatively examined by conducting TG-DSC measurements of the starch gel, XRD analysis for the crystallites, SEM and TEM assessments for the morphology of the catalyst, XPS and H2-TPR measurements for the distribution of cerium and tungsten, and NH3-TPD assessments for the acidity of the catalyst. It is found that the ignition temperature shows an important role in the interaction of cerium and tungsten species, and the optimal ignition temperature is 500 °C. The increase of ignition temperature from 150 °C is beneficial to the interactions of species in the catalyst, depresses the formation of WO3, and refines the cubic CeO2 crystallite. The sample ignited at 500 °C shows the biggest BET surface area, the highest surface concentration of Ce species and molar ratio of Ce3+/(Ce3++Ce4+), and the most abundant surface Brønsted acid sites, which are the possible reasons for the superiority of the NH3-SCR activity. With a high GHSV of 200,000 mL (g h)-1 and the optimal ignition temperature, Ce4W2Oz-500 can achieve a steadily high NOx reduction of 80% or more at a lowered reduction temperature in the range of 250~500 °C.