Risk factors of disease activity and renal damage in patients with systemic lupus erythematosus.

PURPOSE: To evaluate the clinical features of patients with Systemic Lupus Erythematosus (SLE) and explore the risk factors of disease activity and renal damage. METHODS: A retrospective study involving 194 patients were performed. Patients were divided into lupus nephritis (LN) group (63.40%) and non-LN group (36.60%), different disease activity group, and different renal function group according to the clinical data. Multivariate logistic regression analysis showed that albumin (ALB), uric acid (UC), total cholesterol (TC), and anti-dsDNA antibodies were the influencing factors of LN in patients with SLE (P < 0.05); ALB, UC, and complement 3(C3) were the influencing factors of lupus disease activity (P < 0.05); UC, C3, and hemoglobin (HB) were the influencing factors of abnormal renal function in SLE patients. RESULTS: The results of the ROC curve showed that ALB, UA, and TC had certain predictive value for combined LN in patients with SLE, and the predictive value of ALB was greater than that of TC (P < 0.05); ALB, UA, and C3 being predictors of the activity of patients with SLE; BUN, UA, and HB all had certain predictive value for the abnormal renal function in patients with LN. SLE patients have the high incidence of renal impairment. CONCLUSION: The results of this study suggest that patients with SLE should regularly monitor the levels of ALB, UA, TC, C3, and HB, as well as pay attention to the intervention of hyperlipidemia and hyperuricemia in patients with SLE to better control disease progression.

Correlation between the serum FABP4, ANGPTL3, and ANGPTL4 levels and coronary artery disease.

BACKGROUND: Lipid metabolism related factors, such as angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like 4 (ANGPTL4), fatty acid-binding protein 4 (FABP4) are newly discovered factors that can affect coronary artery disease (CAD). In this study, we aimed to investigate the relationship between CAD and these lipid metabolism factors. HYPOTHESIS: ANGPTL3, ANGPTL4, and FABP4 may provide a new method for the control of CAD risk factors and the prevention and treatment of CAD. METHODS: We enrolled 284 consecutive inpatients with suspected CAD and divided them into CAD and non-CAD groups based on the coronary angiography results. Serum ANGPTL3, ANGPTL4, FABP4, and tumor necrosis factor-α (TNF-α) levels were estimated using the enzyme-linked immunosorbent assay. Multivariate logistic regression was used to assess the risk factors for CAD. The receiver operating characteristic curve was used to determine the cutoff and diagnostic values. RESULTS: The serum TNF-α, FABP4, ANGPTL3, and ANGPTL4 values showed a significant difference between the CAD and non-CAD groups (p < .05). After adjusting for confounding factors, the FABP4, ANGPTL3, and ANGPTL4 levels were independently associated with CAD (p < .05). The ANGPTL3 expression level was an independent risk factor for CAD in patients with hypertension, but not in those without hypertension. The ANGPTL3 > 67.53 ng/mL, ANGPTL4 > 29.95 ng/mL, and FABP4 > 1421.25 ng/L combination had the highest diagnostic value for CAD. CONCLUSION: ANGPTL3, ANGPTL4, and FABP4 were identified as independent risk factors for CAD and have valuable clinical implications for the diagnosis and treatment of CAD.

Parkinson's disease kinase LRRK2 coordinates a cell-intrinsic itaconate-dependent defence pathway against intracellular Salmonella.

Cell-intrinsic defences constitute the first line of defence against intracellular pathogens. The guanosine triphosphatase RAB32 orchestrates one such defence response against the bacterial pathogen Salmonella, through delivery of antimicrobial itaconate. Here we show that the Parkinson's disease-associated leucine-rich repeat kinase 2 (LRRK2) orchestrates this defence response by scaffolding a complex between RAB32 and aconitate decarboxylase 1, which synthesizes itaconate from mitochondrial precursors. Itaconate delivery to Salmonella-containing vacuoles was impaired and Salmonella replication increased in LRRK2-deficient cells. Loss of LRRK2 also restored virulence of a Salmonella mutant defective in neutralizing this RAB32-dependent host defence pathway in mice. Cryo-electron tomography revealed tether formation between Salmonella-containing vacuoles and host mitochondria upon Salmonella infection, which was significantly impaired in LRRK2-deficient cells. This positions LRRK2 centrally within a host defence mechanism, which may have favoured selection of a common familial Parkinson's disease mutant allele in the human population.

Research progress of implantation materials and its biological evaluation.

With the development of modern material science, life science and medical science, implantation materials are widely employed in clinical fields. In recent years, these materials have also evolved from inert supports or functional substitutes to bioactive materials able to trigger or promote the regenerative potential of tissues. Reasonable biological evaluation of implantation materials is the premise to make sure their safe application in clinical practice. With the continual development of implantation materials and the emergence of new implantation materials, new challenges to biological evaluation have been presented. In this paper, the research progress of implantation materials, the progress of biological evaluation methods, and also the characteristics of biocompatibility evaluation for novel implantation materials, like animal-derived implantation materials, nerve contact implantation materials, nanomaterials and tissue-engineered medical products were reviewed in order to provide references for the rational biological evaluation of implantable materials.

Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed -1 ribosomal frameshifting.

Many positive-strand RNA viruses, including all known coronaviruses, employ programmed -1 ribosomal frameshifting (-1 PRF) to regulate the translation of polycistronic viral RNAs. However, only a few host factors have been shown to regulate -1 PRF. Through a genome-wide CRISPR-Cas9 knockout screen, we have identified host factors that either suppress or enhance severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -1 PRF. Among them, eukaryotic translation initiation factor 2A (eIF2A) specifically and directly enhances -1 PRF independent of changes in initiation. Consistent with the crucial role of efficient -1 PRF in transcriptase/replicase expression, loss of eIF2A reduces SARS-CoV-2 replication in cells. Furthermore, transcriptome-wide analysis shows that eIF2A preferentially binds CG-rich RNA motifs, including a region within 18S ribosomal RNA near the contacts between the SARS-CoV-2 frameshift-stimulatory element (FSE) and the ribosome. Thus, our results indicate a role for eIF2A in modulating the translation of specific RNAs independent of its role during initiation.

Application of systemic inflammation indices and lipid metabolism-related factors in coronary artery disease.

OBJECTIVE: We aimed to investigate the relationship between coronary artery disease (CAD) and systemic inflammation indices and lipid metabolism-related factors and subsequently, discuss the clinical application of these factors in CAD. METHODS: We enrolled 284 consecutive inpatients with suspected CAD and divided them into a CAD group and a non-CAD group according to coronary angiography results. Serum levels of angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like protein 4 (ANGPTL4), fatty acid-binding protein 4 (FABP4), and tumor necrosis factor-α (TNF-α) levels were assessed using the ELISA and the systemic inflammation indices were calculated. Multivariate logistic regression was used to assess the risk factors of CAD. The receiver operating characteristic curve was used to determine the cutoff and diagnostic values. RESULTS: The neutrophil-to-high density lipoprotein cholesterol ratio (5.04 vs. 3.47), neutrophil-to-lymphocyte ratio (3.25 vs. 2.45), monocyte-to-high density lipoprotein cholesterol ratio (MHR) (0.46 vs. 0.36), monocyte-to-lymphocyte ratio (0.31 vs. 0.26), systemic immune-inflammation index (SII) (696.00 vs. 544.82), serum TNF-α (398.15 ng/l vs. 350.65 ng/l), FABP4 (1644.00 ng/l vs. 1553.00 ng/l), ANGPTL3 (57.60 ng/ml vs. 52.85 ng/ml), and ANGPTL4 (37.35 ng/ml vs. 35.20 ng/ml) values showed a significant difference between the CAD and non-CAD groups ( P  < 0.05). After adjusting for confounding factors, the following values were obtained: ANGPTL3 > 67.53 ng/ml [odds ratio (OR) = 8.108, 95% confidence interval (CI) (1.022-65.620)]; ANGPTL4 > 29.95 ng/ml [OR = 5.599, 95% CI (1.809-17.334)]; MHR > 0.47 [OR = 4.872, 95% CI (1.715-13.835)]; SII > 589.12 [OR = 5.131, 95% CI (1.995-13.200)]. These factors were found to be independently associated with CAD ( P  < 0.05). Diabetes combined with MHR > 0.47, SII > 589.12, TNF-α >285.60 ng/l, ANGPTL3 > 67.53 ng/ml, and ANGPTL4 > 29.95 ng/l had the highest diagnostic value for CAD [area under the curve: 0.921, 95% CI, (0.881-0.960), Sensitivity: 88.9%, Specificity: 82.2%, P  < 0.001]. CONCLUSION: MHR > 0.47, SII > 589.12, TNF-α >285.60 ng/l, ANGPTL3 > 67.53 ng/ml, and ANGPTL4 > 29.95 ng/l were identified as independent CAD risk factors and have valuable clinical implications in the diagnosis and treatment of CAD.

Natamycin-Loaded Ethyl Cellulose/PVP Films Developed by Microfluidic Spinning for Active Packaging.

The preparation of active packaging loaded with antimicrobial, antioxidant, and other functional agents has become a hot topic for food preservation in recent years. In this field, active fiber films based on spinning methods have attracted the interest of researchers owing to their high specific surface area, high porosity, high loading capacity, and good controlled release capacity. In the present work, neatly arranged ethyl cellulose (EC)/polyvinyl-pyrrolidone (PVP) fibrous films loaded with natamycin as an antimicrobial agent were prepared by microfluidic spinning. The encapsulation efficiency of natamycin was more than 90% in each group and the loading increased with increasing natamycin content. According to the characterization results of the natamycin-loaded EC/PVP fibrous films, hydrogen bonding was formed between natamycin and EC and PVP in the fibrous films. Meanwhile, the water contact angle of the fibrous films was increased, suggesting the improved hydrophobicity of the films. In the in vitro bacterial inhibition experiments, the active fiber films loaded with natamycin showed good antimicrobial activity, which could significantly inhibit the growth of gray mold. In conclusion, N-EC/PVP fibrous films with antimicrobial activity prepared by microfluidic spinning showed good potential in the field of active packaging.

Establishment of a Predictive Model for Poor Prognosis of Incomplete Revascularization in Patients with Coronary Heart Disease and Multivessel Disease.

OBJECTIVE: To establish a predictive model for poor prognosis after incomplete revascularization (ICR) in patients with multivessel coronary artery disease (MVD). METHODS: Clinical data of 757 patients with MVD and ICR after percutaneous coronary intervention (PCI) in the Affiliated Hospital of Chengde Medical University from January 2020 to August 2021 were retrospectively collected. The least absolute shrinkage and selection operator regression method was used to screen variables, and multivariate logistic regression was used to establish a predictive model. An independent cohort was used to validate the model. The C-statistic was used to verify and evaluate the discriminative ability of the model; the calibration curve was drawn, and the decision curve analysis (DCA) was performed to evaluate the calibration degree, the clinical net benefit, and the practicability of the model. RESULTS: The predictive factors included female, age, unconjugated bilirubin, uric acid, low-density lipoprotein, hyperglycemia, total occlusion, and severe tortuosity lesion on coronary angiography. The C-statistic of the training and validation sets were 0.628 and 0.745, respectively. The statistical value of the Hosmer-Lemeshow test for the calibration curve of the training and validation sets were 5.27(P = 0.873) and 6.27 (P = 0.792), respectively. DCA showed that the model was clinically applicable when the predicted probability value of major adverse cardiovascular events(MACEs) ranged from 0.07 to 0.68. CONCLUSIONS: We established a predictive model for poor prognosis after ICR in patients with MVD. The predictive and calibration ability and the clinical net benefit of the predictive model were good, indicating that it can be used as an effective tool for the early prediction of poor prognosis after ICR in patients with MVD.

Signaling and functions of interleukin-33 in immune regulation and diseases.

Interleukin-33 (IL-33) which belongs to the interleukin-1 (IL-1) family is an alarmin cytokine with critical roles in tissue homeostasis, pathogenic infection, inflammation, allergy and type 2 immunity. IL-33 transmits signals through its receptor IL-33R (also called ST2) which is expressed on the surface of T helper 2 (Th2) cells and group 2 innate lymphoid cells (ILC2s), thus inducing transcription of Th2-associated cytokine genes and host defense against pathogens. Moreover, the IL-33/IL-33R axis is also involved in development of multiple types of immune-related diseases. In this review, we focus on current progress on IL-33-trigggered signaling events, the important functions of IL-33/IL-33R axis in health and diseases as well as the promising therapeutic implications of these findings.

[Spermic Toxicity Test of Medical Devices for Human Assisted Reproductive Technology].

In order to provide a thorough summary and analysis over sperm toxicity evaluation of medical devices for human in vitro assisted reproductive technology, as well as to forecast its future direction, currently available test methods and evaluation indicators related to human sperm were elaborated here. Furthermore, their weakness and risk points were analyzed and possible ways for further improvement were also provided.

RNA demethylation increases the yield and biomass of rice and potato plants in field trials.

RNA N6-methyladenosine (m6A) modifications are essential in plants. Here, we show that transgenic expression of the human RNA demethylase FTO in rice caused a more than threefold increase in grain yield under greenhouse conditions. In field trials, transgenic expression of FTO in rice and potato caused ~50% increases in yield and biomass. We demonstrate that the presence of FTO stimulates root meristem cell proliferation and tiller bud formation and promotes photosynthetic efficiency and drought tolerance but has no effect on mature cell size, shoot meristem cell proliferation, root diameter, plant height or ploidy. FTO mediates substantial m6A demethylation (around 7% of demethylation in poly(A) RNA and around 35% decrease of m6A in non-ribosomal nuclear RNA) in plant RNA, inducing chromatin openness and transcriptional activation. Therefore, modulation of plant RNA m6A methylation is a promising strategy to dramatically improve plant growth and crop yield.

Calprotectin and Neutrophil Gelatinase-Associated Lipocalin As Biomarkers of Acute Kidney Injury in Acute Coronary Syndrome.

BACKGROUND: Acute kidney injury (AKI) is increasingly being seen in patients with acute coronary syndromes (ACS) and it is associated with higher short-term and long-term morbidity and mortality. Therefore, it is of paramount importance to identify those ACS patients at risk for the development of AKI. The objective of this study was to evaluate two different plasma biomarkers calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) in early detecting the development of AKI in ACS patients. METHODS: 172 ACS patients admitted to the Coronary Care Unit in Yantai Yuhuangding Hospital were prospectively enrolled. Their blood samples were obtained on admission and subjected to enzyme-linked immunosorbent assay to determine the levels of novel biomarkers. The clinical data and biomarkers were recorded and analyzed. RESULTS: In this study, 23 (13.4%) patients had a diagnosis of AKI. Statistical analysis demonstrated that in ACS patients with AKI, the following two biomarkers were significantly higher than these without AKI: plasma calprotectin (5942.26 ± 1955.88 ng/mL vs. 3210.29 ± 1833.60 ng/mL, p < 0.001) and plasma NGAL (164.91 ± 43.63 ng/mL vs. 122.48 ± 27.33 ng/mL, p < 0.001). Plasma calprotectin and NGAL could discriminate the development of AKI respectively with an area under the ROC curve (AUC) of 0.864 and 0.850. A combination of the two plasma biomarkers calprotectin and NGAL could early discriminate AKI in ACS patients with an AUC of 0.898. CONCLUSIONS: This study demonstrated a promising panel of plasma calprotectin and NGAL as early diagnostic biomarkers for AKI in ACS patients.

The Salmonella effector protein SopD targets Rab8 to positively and negatively modulate the inflammatory response.

The food-borne bacterial pathogen Salmonella Typhimurium uses a type III protein secretion system to deliver multiple proteins into host cells. These secreted effectors modulate the functions of host cells and activate specific signalling cascades that result in the production of pro-inflammatory cytokines and intestinal inflammation. Some of the Salmonella-encoded effectors counteract this inflammatory response and help to preserve host homeostasis. Here, we demonstrate that the Salmonella effector protein SopD, which is required for pathogenesis, functions to both activate and inhibit the inflammatory response by targeting the Rab8 GTPase, which is a negative regulator of inflammation. We show that SopD has GTPase-activating protein activity for Rab8 and, therefore, inhibits this GTPase and stimulates inflammation. We also show that SopD activates Rab8 by displacing it from its cognate guanosine dissociation inhibitor, resulting in the stimulation of a signalling cascade that suppresses inflammation. We solved the crystal structure of SopD in association with Rab8 to a resolution of 2.3 Å, which reveals a unique contact interface that underlies these complex interactions. These findings show the remarkable evolution of a bacterial effector protein to exert both agonistic and antagonistic activities towards the same host cellular target to modulate the inflammatory response.

Hydrogenation of Citral to Citronellal Catalyzed by Waste Fluid Catalytic Cracking Catalyst Supported Nickel.

In this paper, a waste fluid catalytic cracking (FCC) catalyst is used as a carrier to prepare a supported non-noble metal nickel catalyst (Ni/wFCC), which is applied to the selective hydrogenation of citral to citronellal. X-ray powder diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy were used to analyze the structural characteristics of the Ni-loaded sample. The catalyst after loading Ni still maintained a good zeolite structure, and the surface impurities were reduced. The effect of reaction conditions on the Ni/wFCC-catalyzed hydrogenation of citral to citronellal was investigated, and the optimal reaction conditions were obtained as follows: a Ni loading of 20 wt %, a catalyst amount of 5.6%, a hydrogenation temperature of 180 °C, a hydrogenation time of 90 min, and a hydrogenation pressure of 3.0 MPa. Under these conditions, the conversion of citral and selectivity of citronellal were 98.5 and 86.6%, respectively, indicating that the Ni/wFCC catalyst had strong catalytic activity and selectivity. This research provided new ideas for the recycling of waste FCC catalysts and industrial synthesis of citronellal.

CD276 (B7H3) improve cancer stem cells formation in cervical carcinoma cell lines.

BACKGROUND: Cancer stem cells (CSCs) have been considered as a potential therapeutic target for cervical carcinoma. CD 276 is a well-known immune check point molecular, but its relationship with cervical CSCs was still unclear. METHODS: HeLa cell lines were obtained as cervical carcinoma in vitro model. HeLa cell Sphere formation culture was performed and CD276, OCT4 and SOX2 expression were determined by RT-qPCR. Transiently transfection and siRNA interference were used to modify CD276 expression. HeLa cell colony has been counted and cell proliferation was assessed by MTT assay. The relationship between CD276 and chemotherapy resistance of HeLa cell were evaluated by cisplatin treatment. Additionally, the mice model of xenograft tumor was established and CD276's function was evaluated in vivo. RESULTS: Here, we demonstrate that the expression of CD276 is positively correlated with the amount of sphere-forming cells in HeLa cell lines. Overexpression of CD276 causes the inhibition of HeLa cells' sphere formation, colony formation and cell viability. Meanwhile, the downregulation of CD276 leads to the other way. We also demonstrate that CD276 contributes to the chemotherapy resistance in the cell line. Furthermore, we verify the CD276's function on HeLa xenotransplantation mice model. CONCLUSIONS: These results suggest that CD276 elevates the self-renewal capacity of HeLa CSCs.

Development and Validation of a Resilience Questionnaire for Patients During Stroke Rehabilitation in China.

PURPOSE: The aim of the study was to develop a comprehensive questionnaire for assessing resilience in patients with stroke during rehabilitation and examine the questionnaire's reliability and validity. DESIGN: A four-phased design was used to develop and validate the questionnaire. METHODS: The preliminary items of the Resilience Questionnaire for Stroke Rehabilitation (RQSR) were generated through a literature review and a qualitative study. Twenty experts were consulted for content validation and modification of the questionnaire. A pilot study was conducted with 55 patients with stroke. A total of 510 participants from seven rehabilitation centers or hospitals were subsequently recruited to examine the psychometric properties of the RQSR. RESULTS: The RQSR consists of 35 items within three dimensions. Dimensions include effective rehabilitation training, accessible support system, and appropriate self-regulation. The content validity index of the total questionnaire was .9335. Seven factors were derived through factor analysis, and cumulative contribution rate of variance was 65.455%. Cronbach's alpha of the total questionnaire was .957, with each dimension ranging from .731 to .918, demonstrating high levels of reliability. CONCLUSION: The RQSR has sound reliability and validity and can be used as an appropriate tool for assessing resilience for patients with stroke during rehabilitation to facilitate effective interventions.

In vitro genotoxicity evaluation and metabolic study of residual glutaraldehyde in animal-derived biomaterials.

Glutaraldehyde (GA) is an important additive that is mainly used in animal-derived biomaterials to improve their mechanical and antimicrobial capacities. However, GA chemical toxicity and the metabolic mechanism remain relatively unknown. Therefore, residual GA has always been a major health risk consideration for animal-derived medical devices. In this study, extracts of three bio-patches were tested via the GA determination test and mouse lymphoma assay (MLA). The results showed that dissolved GA was a potential mutagen, which could induce significant cytotoxic and mutagenic effects in mouse lymphoma cells. These toxic reactions were relieved by the S9 metabolic activation (MA) system. Furthermore, we confirmed that GA concentration decreased and glutaric acid was generated during the catalytic process. We revealed GA could be oxidized via cytochrome P450 which was the main metabolic factor of S9. We found that even though GA was possibly responsible for positive reactions of animal-derived biomaterials' biocompatibility evaluation, it may not represent the real situation occurring in human bodies, owing to the presence of various detoxification mechanisms including the S9 system. Overall, in order to achieve a general balance between risk management and practical application, rational decisions based on comprehensive analyses must be considered.

ZCCHC3 modulates TLR3-mediated signaling by promoting recruitment of TRIF to TLR3.

Toll-like receptor 3 (TLR3)-mediated signaling is important for host defense against RNA virus. Upon viral RNA stimulation, toll and interleukin-1 receptor domain-containing adaptor inducing IFN-ß (TRIF) is recruited to TLR3 and then undergoes oligomerization, which is required for the recruitment of downstream molecules to transmit signals. Here, we identified zinc finger CCHC-type containing 3 (ZCCHC3) as a positive regulator of TLR3-mediated signaling. Overexpression of ZCCHC3 promoted transcription of downstream antiviral genes stimulated by the synthetic TLR3 ligand poly(I:C). ZCCHC3-deficiency markedly inhibited TLR3- but not TLR4-mediated induction of type I interferons (IFNs) and proinflammatory cytokines. Zcchc3-/- mice were more resistant to poly(I:C)- but not lipopolysaccharide-induced inflammatory death. Mechanistically, ZCCHC3 promoted recruitment of TRIF to TLR3 after poly(I:C) stimulation. Our findings reveal that ZCCHC3 plays an important role in TLR3-mediated innate immune response by promoting the recruitment of TRIF to TLR3 after ligand stimulation.