Activation of RIG-I signaling in the early stage of Paragonimus proliferus infection causes lung injury via type I immune response in rat.

Paragonimiasis is a common zoonotic parasitic disease. The retinoic acid-inducible gene I (RIG-I) signaling is very important for the host to recognize invading pathogens (especially viruses and bacteria). However, the role of RIG-I signaling in the early stages of P. proliferus infection remains unclear. Therefore, in this study, Sprague-Dawley (SD) rat models with lung damage caused by P. proliferus were established. Experimental methods including Enzyme-linked Immuno Sorbent Assay (ELISA), real-time fluorescent quantitative polymerase chain reaction (PCR), western blotting, and hematoxylin and eosin (HE) staining were used to explore the mechanisms of lung injury caused by P. proliferus. As a result, the expression of the mRNA and proteins of RIG-I signal-related key target molecules, including RIG-I, tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6), interferon regulatory Factor 7 (IRF7), IPS-1, and downstream C-X-C chemokine ligand 10 (CXCL10), were significantly up-regulated immediately after infection, peaked at 3 or 7 days, and showed a downward trend on after 14 days. The levels of pro-inflammatory cytokines interleukin-1 (IL-1), interferon (IFN)-α, -ß, and -γ, which represent type 1 immune response, gradually increased and reached a peak by 14 days, which was consistent with the changes in the degree of inflammatory damage observed under HE staining of lung tissues. In conclusion, RIG-I signaling is activated in the early stage (before 14 days) of P. proliferus infection, it is inferred that the lung injury of the host may be related to the activation of RIG-I like signaling to induce type I immune response.

Downregulation of circular RNA ETS1 promotes SLE activity and inhibits Treg cell differentiation through miR-1205/FoxP3 molecular axis.

PURPOSE: This study aimed to explore the mechanism by which systemic lupus erythematosus (SLE) activity is promoted through Treg inhibition from the perspective of ceRNA. METHODS: qRT-PCR was used to detect the expressions of circETS1, miR-1205, and FoxP3 in clinical SLE patient samples. Overexpression of circETS1and miR-1205, along with knockdown of miR-1205 and FoxP3 were conducted in CD4+ T cells, while the proliferation of helper T cell 17 (Th17) and regulatory T cell (Treg) was detected. Arescue assay was performed to verify the molecular mechanism of circETS1/miR-1205/Foxp3 mRNA axis in regulating CD4+ T cell differentiation. In the in vivo experiment, the expression of miR-1205 in SLE mice was intervened, and renal function, inflammatory factors, and serum complement were measured. Additionally, Treg/Th17 cell ratio was detected by flow cytometry. RESULTS: In SLE patients, Treg cells were found to decrease, while Th17 cells increased. Transfection with circETS1 overexpression led to CD4+ T cells differentiating into Treg cells, causing an imbalance in the Th17/Treg ratio. Transfection of miR-1205 mimic and si-FoxP3 could reverse the effect of circETS1 overexpression. Moreover, inhibiting the expression of miR-1205 showed therapeutic effects on SLE mice. CONCLUSION: circETS1 inhibits Treg via the miR-1205/FoxP3 axis, thereby promoting SLE activity, which may become a new target for SLE treatment.

Detection and complete genome sequence analysis of human adenovirus in children with acute diarrhea in Yunnan, China, 2015-2021.

The aims of this study were to determine the distribution and prevalence of gastroenteritis caused by human adenovirus (HAdV) in children in Yunnan province, China, in 2015-2021 and to identify preventive measures that can be taken to reduce morbidity and mortality in children.HAdV is a significant agent of diarrhea in children, but limited data are available regarding the epidemiology and genetic diversity of HAdV in children with diarrhea in Yunnan province, China. A total of 1754 fecal samples were subjected to real-time RT-PCR to detect and quantify HAdV. Positive samples were further analyzed using next-generation sequencing (NGS), and epidemiological data were analyzed as well.1754 patients with diarrhea were enrolled, of which 1041 were male and 713 were female (M:F ratio: 1.46). Seventy-two stool samples out of 1754 (4.10%) were positive for HAdV. The detection rates of all age groups varied from 2.50-4.78%. The highest incidence of HAdV was observed in children under 2 years of age, especially in children 12-24 months-old. From 2015-2021, the annual detection rate ranged from 1.62-12.26%. HAdV was detected throughout the year, but with marked seasonality. Children were most likely to be positive for HAdV in June and November. We detected HAdV in 15.53% (16/103) of samples collected in June and in 8.19% (14/171) of those collected in November. The entire viral genome was successfully sequenced for 13 of the 72 HAdV-positive samples, and 76.92% (10/13) of these were classified as genotype F41 and 23.08% (3/13) were classified as genotype C2.ConclusionsIn Yunnan province, children of all ages are susceptible to HAdV infection, but there has been marked variation in the yearly prevalence. The highest rate of HAdV detection was in June, followed by November. Priority should be given to disease prevention over the development of targeted antiviral therapies, and effective vaccines for preventing HAdV diarrhea are needed. It is also important to establish a surveillance system to collect relevant clinical and epidemiological data quickly in order to assess the potential risk of HAdV infection in children and to identify epidemic strains for the development of effective vaccines.

Chitosan-polyvinyl alcohol-diatomite hydrogel removes methylene blue from water.

Dye pollution in the aquatic environment can harm ecosystems and human health. Here, we developed a new green adsorbent by applying an improved drying process. Diatomite was embedded in a network structure formed between chitosan and polyvinyl alcohol without using any crosslinking agent to prepare chitosan-polyvinyl alcohol-diatomite hydrogel beads through alkali solidification. The beads were tested for removing a cationic dye (methylene blue (MB)) from water. The structure of the adsorbent beads was analysed using scanning electron microscopy, energy-dispersive spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy. The adsorption capacity was investigated, and the results indicated excellent MB adsorption properties. The adsorbents had a rough surface and high swelling capacity of 66.9 g/g. The maximum MB adsorption capacity was 414.70 mg/g, and the adsorption followed the Freundlich isothermal and quasi-second-order kinetic models. The adsorption was an endothermic spontaneous process governed by both intra-particle and external diffusion processes. The proposed adsorption mechanisms involved hydrogen bonding and electrostatic interactions. These adsorbent beads have considerable application potentials owing to their high adsorption capacity, green composition, and non-polluting nature.

Downregulation of circETS1 disrupts Th17/Treg homeostasis by inhibiting FOXP3 transcription: A new potential biomarker in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an imbalance of T helper 17 (Th17) to regulatory T cells (Tregs). However, the underlying mechanism remains unclear. Increasing evidence suggests that circular RNAs play a crucial role in SLE. Although circETS1 was discovered 30 years ago, detailed exploration of its functions remains limited. In this study, we measured the expression levels of circETS1 in peripheral blood mononuclear cells (PBMCs) and CD4+ T cells of patients with SLE by quantitative polymerase chain reaction. The impact of circETS1 expression on the Th17/Treg balance and underlying mechanism were evaluated using double-luciferase reporter, gain-/loss-of-function, and rescue assays. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic value of circETS1. Both circETS1 and FOXP3 expression were downregulated in the PBMCs and CD4+ T cells of patients with SLE (n = 28) compared with those in the cells of healthy controls (n = 20). Mechanistically, we found that circETS1 can bind directly to the microRNA miR-1205, acting as a sponge to upregulate the transcription of FOXP3, thereby maintaining the Th17/Treg balance. Notably, ROC analysis showed that the expression level of circETS1 in PBMCs had an area under the curve of 0.873 (95% confidence interval: 0.771-0.976; p < .001) for diagnosing SLE, with a sensitivity of 80.00% and a specificity of 89.29%. Finally, we found negative correlations between the level of circETS1 in PBMCs and disease severity (according to the Systemic Lupus Erythematosus Disease Activity Index) in patients with SLE (r = -0.7712, 95% CI: -0.8910 to -0.5509; p < .001). The imbalance in Th17/Treg cells in SLE may be attributed, in part, to the circETS1/miR-1205/FOXP3 pathway. CircETS1 has potential to serve as a valuable biomarker for the diagnosis and evaluation of SLE.

Evaluation of an identification method for the SARS-CoV-2 Delta variant based on the amplification-refractory mutation system.

The Delta variant of SARS-CoV-2 dominated the COVID-19 pandemic due to its high viral replication capacity and immune evasion, causing massive outbreaks of cases, hospitalizations, and deaths. Currently, variant identification is performed mainly by sequencing. However, the high requirements for equipment and operators as well as its high cost have limited its application in underdeveloped regions. To achieve an economical and rapid method of variant identification suitable for undeveloped areas, we applied an amplification-refractory mutation system (ARMS) based on PCR for the detection of novel coronavirus variants. The results showed that this method could be finished in 90 min and detect as few as 500 copies/mL and not react with SARS-Coronavirus, influenza A H1N1(2009), and other cross-pathogens or be influenced by fresh human blood, α- interferon, and other interfering substances. In a set of double-blind trials, tests of 262 samples obtained from patients confirmed with Delta variant infection revealed that our method was able to accurately identify the Delta variant with high sensitivity and specificity. In conclusion, the ARMS-PCR method applied in Delta variant identification is rapid, sensitive, specific, economical, and suitable for undeveloped areas. In our future study, ARMS-PCR will be further applied in the identification of other variants, such as Omicron.

Identification of integrase inhibitor-related drug resistance mutations in newly diagnosed ART-naïve HIV patients.

BACKGROUND: In China, the recommended treatment regimens for HIV-infected individuals were tenofovir in combination with lamivudine or emtricitabine as NRTIs, efavirenz or rilpivirine as NNRTIs, lopinavir/ritonavir as protease inhibitors, and raltegravir or dolutegravir as INSTIs. The development of drug resistance increases the risk of viral rebound, opportunistic infections, and ultimately treatment failure such that the early detection of resistance is ideal. This study was developed to explore primary drug resistance characteristics and genotypic distributions in newly diagnosed antiretroviral therapy (ART)-naïve HIV-1 patients in Nanjing with the goal of establishing a basis for their individualized treatment in the clinic. METHODS: Samples of serum were collected from newly diagnosed ART-naïve HIV patients from the Second Hospital of Nanjing between May 2021 and May 2022. The HIV-1 integrase (IN), protease (PR), and reverse transcriptase (RT) gene coding sequences were amplified from these samples, sequenced, and assessed for drug resistance-related mutations. RESULTS: Major integrase resistance-related mutations were detected in 4/360 amplified samples, with 5 other patient samples exhibiting accessory resistance mutations. The overall prevalence of PR and RT inhibitor-related transmitted drug resistance mutations (TDRMs) in this patient population was 16.99% (61/359). The most common mutations were non-nucleoside reverse transcriptase inhibitor-related mutations (51/359; 14.21%), followed by those associated with nucleoside reverse transcriptase inhibitors (7/359; 1.95%) and protease inhibitors (7/359; 1.95%). Dual-resistant strains were also observed in a subset of patients. CONCLUSIONS: In summary, this study is the first to have surveyed the prevalence of integrase inhibitor resistance-related mutations and other drug resistance-related mutations among newly diagnosed ART-naïve HIV-positive patients in Nanjing, China. These results highlight the need for further molecular surveillance-based monitoring of the HIV epidemic in Nanjing.

NA-OR: A path optimization method for manipulators via node attraction and obstacle repulsion.

This paper is concerned with the issue of path optimization for manipulators in multi-obstacle environments. Aimed at overcoming the deficiencies of the sampling-based path planning algorithm with high path curvature and low safety margin, a path optimization method, named NA-OR, is proposed for manipulators, where the NA (node attraction) and OR (obstacle repulsion) functions are developed to refine the path by iterations. In the iterations of path optimization, the node attraction function is designed to pull the path nodes toward the center of their neighbor nodes, thereby reducing the path curvature and improving the smoothness. Also, the obstacle repulsion function is developed to push the path nodes out of the potentially unsafe region by generating a repulsive torque on the path nodes, thus improving the safety margin of the motion. By introducing the effect of NA-OR, the optimized path has a significant improvement in path curvature and safety margin compared with the initial path planned by Bi-RRT, which meaningfully enhances the operation ability of manipulators for the applications that give a strong emphasis on security. Experimental results on a 6-DOF manipulator in 4 scenarios demonstrate the effectiveness and superiority of the proposed method in terms of the path cost, safety margin, and path smoothness.

Water in the Electrical Double Layer of Ionic Liquids on Graphene.

The performance of electrochemical devices using ionic liquids (ILs) as electrolytes can be impaired by water uptake. This work investigates the influence of water on the behavior of hydrophilic and hydrophobic ILs─with ethylsulfate and tris(perfluoroalkyl)trifluorophosphate or bis(trifluoromethyl sulfonyl)imide (TFSI) anions, respectively─on electrified graphene, a promising electrode material. The results show that water uptake slightly reduces the IL electrochemical stability and significantly influences graphene's potential of zero charge, which is justified by the extent of anion depletion from the surface. Experiments confirm the dominant contribution of graphene's quantum capacitance (CQ) to the total interfacial capacitance (Cint) near the PZC, as expected from theory. Combining theory and experiments reveals that the hydrophilic IL efficiently screens surface charge and exhibits the largest double layer capacitance (CIL ∼ 80 µF cm-2), so that CQ governs the charge stored. The hydrophobic ILs are less efficient in charge screening and thus exhibit a smaller capacitance (CIL ∼ 6-9 µF cm-2), which governs Cint already at small potentials. An increase in the total interfacial capacitance is observed at positive voltages for humid TFSI-ILs relative to dry ones, consistent with the presence of a satellite peak. Short-range surface forces reveal the change of the interfacial layering with potential and water uptake owing to reorientation of counterions, counterion binding, co-ion repulsion, and water enrichment. These results are consistent with the charge being mainly stored in a ∼2 nm-thick double layer, which implies that ILs behave as highly concentrated electrolytes. This knowledge will advance the design of IL-graphene-based electrochemical devices.

Epidemiology of Nontuberculous Mycobacteria in Nanjing and MAB_0540 Mutations Associated with Clofazimine Resistance in Mycobacterium abscessus.

Background: Nontuberculous mycobacteria (NTM) are easily misdiagnosed as multidrug-resistant tuberculosis (MDR-TB), and treatment drugs are very limited. The main objective of our study was to evaluate the minimal inhibitory concentration (MIC) in vitro of bedaquiline (BDQ), clofazimine (CFZ), linezolid (LZD), delamanid (DLM), and pretomanid (PA-824) for treatment of M. abscessus and M. intracellulare. Furthermore, we determined whether MAB_1448, MAB_4384, MAB_2299c, MAB_1483, MAB_0540, rplD, rplC, and rrl were related to drug resistance to provide an experimental basis for the use of these five drugs in the treatment of NTM. Methods: We identified sample characteristics of epidemics in 550 patients with suspected NTM infection in Nanjing from 2019 to 2021 using the PCR-reverse spot hybrid method. Furthermore, we evaluated the MIC of BDQ, CFZ, DLM, LZD, and PA-824 against 155 clinical isolates of NTM using the microbroth dilution method. The resistant isolates were sequenced using Sanger sequencing. Results: The top three dominant species of NTM distributed in Nanjing were M. intracellulare, M. avium, and M. abscessus. Notably, the proportion of M. abscessus infections increased. The proportion of M. abscessus increased from 12% in 2019 to 18% in 2021. Demographic analysis showed that female infection rates were substantialy greater than male for M. abscessus (P=0.017, <0.05). Our results demonstrate that NTM are highly sensitive to bedaquiline and clofazimine in vitro. However, delamanid and pretomanid had little effect on M. abscessus and M. intracellulare. In addition, we found 30-41 nucleotide deletion mutations and some novel point mutations in the MAB_0540 gene of M. abscessus that are resistant to clofazimine. Conclusion: Bedaquiline, clofazimine, and linezolid were more successful in vitro treatments against M. abscessus and M. intracellulare. The MAB_0540 mutation may be associated with resistance of M. abscessus to clofazimine.

Preparation and Characterization of a Janus Membrane with an "Integrated" Structure and Adjustable Hydrophilic Layer Thickness.

Oil-water emulsions are types of wastewater that are difficult to treat. A polyvinylidene fluoride hydrophobic matrix membrane was modified using a hydrophilic polymer, poly(vinylpyrrolidone-vinyltriethoxysilane), to form a representative Janus membrane with asymmetric wettability. The performance parameters of the modified membrane, such as the morphological structure, the chemical composition, the wettability, the hydrophilic layer thickness, and the porosity, were characterized. The results showed that the hydrolysis, migration, and thermal crosslinking of the hydrophilic polymer in the hydrophobic matrix membrane contributed to an effective hydrophilic layer on the surface. Thus, a Janus membrane with unchanged membrane porosity, a hydrophilic layer with controllable thickness, and hydrophilic/hydrophobic layer "structural integration" was successfully prepared. The Janus membrane was used for the switchable separation of oil-water emulsions. The separation flux of the oil-in-water emulsions on the hydrophilic surface was 22.88 L·m-2·h-1 with a separation efficiency of up to 93.35%. The hydrophobic surface exhibited a separation flux of 17.45 L·m-2·h-1 with a separation efficiency of 91.47% for the water-in-oil emulsions. Compared to the lower flux and separation efficiency of purely hydrophobic and hydrophilic membranes, the Janus membrane exhibited better separation and purification effects for both oil-water emulsions.

Identification of a circRNA-miRNA-mRNA network to explore the effects of circRNAs on renal injury in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. At present, the mechanism of non-coding RNA in renal injury in SLE patients is still unclear. A total of 64 DEcircRNAs, 75 DEmiRNAs, and 249 DEmRNAs were identified. We integrated 10 circRNAs, 10 miRNAs, and 88 target mRNAs into a circRNA-miRNA-mRNA network and obtained 9 hub genes (circ-0000006, miR-766-3p, miR-409-3p, miR-339-3p, miR-331-3p, miR-140-3p, miR-186-5p, miR-149-5p, PSME3). The ROC curve results showed that the diagnostic efficiency of 6 hub miRNA was higher than that of has_circ_0000006 and PSEME3. SsGSEA analysis revealed immune cell composition in SLE and control renal tissues, including 3 types of immune cells up-regulated (gamma delta T cell, effector memory CD4 T cell, central memory CD8 T cell) and 4 types down-regulated (memory B cell, mast cell, macrophage, immature dendritic cell, eosinophil) in SLE patients. In addition, PSME3 was negatively correlated with 3 up-regulated immune cells and positively correlated with 4 down-regulated immune cells in SLE patients. Our study provides a deeper understanding of the circRNA-related competing endogenous RNA regulatory mechanism in the renal injury of systemic lupus erythematosus.

Constructing a Hierarchical Hydrophilic Crosslink Network on the Surface of a Polyvinylidene Fluoride Membrane for Efficient Oil/Water Emulsion Separation.

Oil/water mixtures from industrial and domestic wastewater adversely affect the environment and human beings. In this context, the development of a facile and improved separation method is crucial. Herein, dopamine was used as a bioadhesive to bind tea polyphenol (TP) onto the surface of a polyvinylidene fluoride (PVDF) membrane to form the first hydrophilic polymer network. Sodium periodate (NaIO4) is considered an oxidising agent for triggering self-polymerisation and can be used to introduce hydrophilic groups via surface manipulation to form the second hydrophilic network. In contrast to the individual polydopamine (PDA) and TP/NaIO4 composite coatings for a hydrophobic PVDF microfiltration membrane, a combination of PDA, TP, and NaIO4 has achieved the most facile treatment process for transforming the hydrophobic membrane into the hydrophilic state. The hierarchical superhydrophilic network structure with a simultaneous underwater superoleophobic membrane exhibited excellent performance in separating various oil-in-water emulsions, with a high water flux (1530 L.m-2 h-1.bar) and improved rejection (98%). The water contact angle of the modified membrane was 0° in 1 s. Moreover, the steady polyphenol coating was applied onto the surface, which endowed the membrane with an adequate antifouling and recovery capability and a robust durability against immersion in an acid, alkali, or salt solution. This facile scale-up method depends on in situ plant-inspired chemistry and has remarkable potential for practical applications.

Construction of Machine Learning Models to Predict Changes in Immune Function Using Clinical Monitoring Indices in HIV/AIDS Patients After 9.9-Years of Antiretroviral Therapy in Yunnan, China.

Objective: To investigate trends in clinical monitoring indices in HIV/AIDS patients receiving antiretroviral therapy (ART) at baseline and after treatment in Yunnan Province, China and to provide the basis for guiding clinical treatment to obtain superior clinical outcomes. Methods: A total of 96 HIV/AIDS patients who had started and persisted in highly active ART treatment from September 2009 to September 2019 were selected. Of these, 54 had a CD4 cell count < 200 cells/µl while 42 had a CD4 cell count ≥ 200 cells/µl. Routine blood tests, liver and renal function, and lipid levels were measured before and 3, 6, 9, and 12 months after treatment. Lymphocyte subset counts and viral load were measured once per year, and recorded for analysis and evaluation. Three machine learning models (support vector machine [SVM], random forest [RF], and multi-layer perceptron [MLP]) were constructed that used the clinical indicators above as parameters. Baseline and follow-up results of routine blood and organ function tests were used to analyze and predict CD4+ T cell data after treatment during long-term follow-up. Predictions of the three models were preliminarily evaluated. Results: There were no statistical differences in gender, age, or HIV transmission route in either patient group. Married individuals were substantially more likely to have <200 CD4+ cells/µl. There was a strong positive correlation between ALT and AST (r = 0.587) and a positive correlation between CD4 cell count and platelet count (r = 0.347). Platelet count was negatively correlated with ALT (r = -0.229), AST (r = -0.251), and positively correlated with WBCs (r = 0.280). Compared with the CD4 cell count < 200 cells/µl group, all three machine learning models exhibited a better predictive capability than for patients with a CD4 cell count ≥ 200 cells/µl. Of all indicators, the three models best predicted the CD4/CD8 ratio, with results that were highly consistent. In patients with a CD4 cell count < 200 cells/µl, the SVM model had the best performance for predicting the CD4/CD8 ratio, while the CD4/CD8 ratio was best predicted by the RF model in patients with a CD4 cell count ≥ 200 cells/µl. Conclusion: By the incorporation of clinical indicators in SVM, RF, and MLP machine learning models, the immune function and recuperation of HIV/AIDS patients can be predicted and evaluated, thereby better guiding clinical treatment.

An Analysis of the Correlation Between Clinical Indexes and Pathological Classifications in 202 Patients with Lupus Nephritis.

OBJECTIVE: To investigate the correlation between clinical indexes and pathological classifications in 202 patients with lupus nephritis (LN). METHODS: A total of 202 LN cases were retrospectively analyzed. All these patients met the four diagnostic criteria for systemic lupus erythematosus (SLE) of the American College of Rheumatology revised in 1997. The pathological diagnostic criteria of LN were in accordance with the pathological LN classification revised by the International Society of Nephrology and the Society of Kidney Pathology in 2003. The patients were scored according to the improved SLE Disease Activity Index 2000 (SLEDAI-2K), and their basic data, clinical data, laboratory data, and pathological data were collected. RESULTS: Among the 202 patients, the ratio of male to female was 1:5.73, and type IV was the most common pathological LN classification. There were differences in the urine analysis, hypertension incidence, blood cell analysis, blood lipids, renal function, plasma albumin, immunological indexes, renal pathological score among the different pathological types (P < 0.05). In the early finding of renal function damage of the patients, cystatin C sensitivity was significantly higher than that of serum creatinine and blood urea nitrogen. Multiple linear regression analysis show that there are strong correlations between AI and SLEDAI, 24hU-Pr, serum C3, serum ALB, BUN, creatinine, UA and PLT (P < 0.001); and there are correlations between AI and serum IgM, IgA, C4, TC and LDL-C (P < 0.05). CONCLUSION: There is a clear correlation between pathological classifications and clinical indexes of LN. TRIAL REGISTRATION: Shen-PJ-2018-40, Study on Clinical and Molecular Mechanism of SLE.

Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease.

Dermatomyositis (DM), an inflammatory disorder, is often associated with interstitial lung disease (ILD). However, the underlying mechanism remains unclear. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of differentially expressed genes (DEGs) in patients with dermatomyositis-associated interstitial lung disease (DM-ILD) and healthy controls. A total of 2,018 DEGs were identified between DM-ILD and healthy blood samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that DEGs were mainly involved in immune- and inflammatory-related biological processes and pathways. Disease ontology (DO) enrichment analysis identified 35 candidate key genes involved in both skin and lung diseases. Meanwhile, a total of 886 differentially expressed alternative splicing (AS) events were found between DM-ILD and healthy blood samples. After overlapping DEGs with differential AS genes, the plasminogen activator and urokinase receptor (PLAUR) involved in immune-related biological processes and complement and coagulation cascades was screened and identified as the most important gene associated with DM-ILD. The protein-protein interaction (PPI) network revealed that PLAUR had interactions with multiple candidate key genes. Moreover, we observed that there were significantly more neutrophils and less naive B cells in DM-ILD samples than in healthy samples. And the expression of PLAUR was significantly positively correlated with the abundance of neutrophils. Significant higher abundance of PLAUR in DM-ILD patients than healthy controls was validated by RT-qPCR. In conclusion, we identified PLAUR as an important player in regulating DM-ILD by neutrophil-associated immune response. These findings enrich our understanding, which may benefit DM-ILD patients.

Comparative effectiveness of two methods for inducing osteoarthritis in a novel animal model, the Diannan small-ear pig.

BACKGROUND: Varieties of animals were used to study osteoarthritis pathogenesis. The Diannan small-ear pig, which is native to Yunnan, China, is thought to have an articular anatomy similar to that of humans and is more likely to be a source of pathological tissues than other animals. The aim of this study was to determine whether this animal can serve as a more effective osteoarthritis model and explore the role of SDF-1/CXCR4 signaling pathway in the development of Osteoarthritis in animals. METHODS: Twenty-seven adult pigs were randomly divided into three groups and underwent the Hulth procedure, papain articular injection, and conventional breeding. After 4, 8, and 12 weeks, cartilage tissues from knee joint were extracted for general and histological observation, immunofluorescence, and biochemical analysis. Synovium was taken out for stromal cell-derived factor-1 analysis. RESULTS: Histopathological observation showed obvious cartilage loss in two experimental groups, this cartilage loss was more severe in the chemical groups. Synovial stromal cell-derived factor1 levels increased over time in all groups. mRNA and protein levels of matrix metalloproteinase-3 were much higher in the chemical groups than in the other groups, whereas levels of collagen type II and aggrecan were significantly lower in the chemical groups than in the other groups. Immunofluorescence assays of collagen type II revealed an apparent reduction in this marker in the chemical groups compared with the other groups. CONCLUSIONS: These results indicated that the Diannan small-ear pig can be used as an effective osteoarthritis model. In addition, it is much more convenient and much faster to induce osteoarthritis by intra-articular injection of papain, which is a method worthy of being promoted.

Safe Reinforcement Learning With Stability Guarantee for Motion Planning of Autonomous Vehicles.

Reinforcement learning with safety constraints is promising for autonomous vehicles, of which various failures may result in disastrous losses. In general, a safe policy is trained by constrained optimization algorithms, in which the average constraint return as a function of states and actions should be lower than a predefined bound. However, most existing safe learning-based algorithms capture states via multiple high-precision sensors, which complicates the hardware systems and is power-consuming. This article is focused on safe motion planning with the stability guarantee for autonomous vehicles with limited size and power. To this end, the risk-identification method and the Lyapunov function are integrated with the well-known soft actor-critic (SAC) algorithm. By borrowing the concept of Lyapunov functions in the control theory, the learned policy can theoretically guarantee that the state trajectory always stays in a safe area. A novel risk-sensitive learning-based algorithm with the stability guarantee is proposed to train policies for the motion planning of autonomous vehicles. The learned policy is implemented on a differential drive vehicle in a simulation environment. The experimental results show that the proposed algorithm achieves a higher success rate than the SAC.

Multi-Path Electron Transfer in 1D Double-Shelled Sn@Mo2 C/C Tubes with Enhanced Dielectric Loss for Boosting Microwave Absorption Performance.

1D tubular micro-nano structural materials have been attracting extensive attention in the microwave absorption (MA) field for their anisotropy feature, outstanding impedance matching, and electromagnetic energy loss capability. Herein, unique double-shelled Sn@Mo2 C/C tubes with porous Sn inner layer and 2D Mo2 C/C outer layer are successfully designed and synthesized via a dual-template method. The composites possess favorable MA performance with an effective absorption bandwidth of 6.76 GHz and a maximum reflection loss value of -52.1 dB. Specifically, the rational and appropriate construction of Sn@Mo2 C/C tubes promotes the multi-path electron transfer in the composites to optimize the dielectric constant and consequently to enhance the capacity of electromagnetic wave energy dissipation. Three mechanisms dominate the MA process: i) the conductive loss resulted from the rapid electron transmission due to the novel 1D hollow coaxial multi-shelled structure, especially the metallic Sn inner layer; ii) the polarization loss caused by abundant heterogeneous interfaces of Sn-Mo2 C/C and Mo2 CC from the precise double-shelled structure; iii) the capacitor-like loss by the potential difference between Mo2 C/C nanosheets. This work hereby sheds light on the design of the 1D hierarchical structure and lays out a profound insight into the MA mechanism.

Low CFB expression is independently associated with poor overall and disease-free survival in patients with lung adenocarcinoma.

Complement factor B (CFB) serves a pivotal role in the alternative signaling pathway of the complement system and exerts a key role in the labelling of target particles, resulting from effective clearance of the target. The present study aimed to investigate the association between low expression levels of CFB and the clinical features and survival status of patients with lung adenocarcinoma (LUAD). Patient data were based on RNA-sequencing and clinical data from The Cancer Genome Atlas database. All patients were divided into two groups based on the median expression of CFB. Kaplan-Meier curve and univariate Cox regression analyses were used to investigate the association between CFB and survival status. Gene set enrichment analysis was used to examine the effects of CFB expression on signaling pathway impairment. Furthermore, reverse transcription-quantitative PCR (RT-qPCR) and western blotting were used to verify the relative expression levels of CFB in LUAD tissues. The data revealed that residual tumor classification, Karnofsky performance score and cancer stage were associated with overall survival, and that Karnofsky performance score and stage were associated with disease-free survival. The results demonstrated that high expression levels of CFB were associated with increased patient overall and disease-free survival according to both continuous and categorical models. The results of multivariate analysis identified that high expression levels of CFB were associated with increased overall and disease-free survival according to both the continuous model [hazard ratio (HR), 0.48; 95% confidence interval (95% CI), 0.25-0.93; P=0.029 for overall survival; HR, 0.29; 95% CI, 0.15-0.59; P=0.001 for disease-free survival] and the categorical model (HR, 0.46; 95% CI, 0.22-0.93; P=0.031 for overall survival; HR, 0.25; 95% CI, 0.12-0.55; P=0.001 for disease-free survival) after adjusting for corresponding covariates (residual tumour classification, Karnofsky performance score and stage). Furthermore, the results of both RT-qPCR and western blotting indicated that the relative mRNA and protein expression levels of CFB in lung tumor tissues were downregulated compared with those in adjacent non-tumor tissues. Collectively, the present results suggested that CFB expression was an independent predictor of overall and disease-free survival in patients with LUAD.