Enlarged perivascular spaces in alcohol-related brain damage induced by dyslipidemia.

Perivascular spaces (PVSs) as the anatomical basis of the glymphatic system, are increasingly recognized as potential imaging biomarkers of neurological conditions. However, it is not clear whether enlarged PVSs are associated with alcohol-related brain damage (ARBD). We aimed to investigate the effect of long-term alcohol exposure on dyslipidemia and the glymphatic system in ARBD. We found that patients with ARBD exhibited significantly enlargement of PVSs in the frontal cortex and basal ganglia, as well as a notable increased levels of total cholesterol (TC) and triglycerides (TG). The anatomical changes of the glymphatic drainage system mentioned above were positively associated with TC and TG. To further explore whether enlarged PVSs affects the function of the glymphatic system in ARBD, we constructed long alcohol exposure and high fat diet mice models. The mouse model of long alcohol exposure exhibited increased levels of TC and TG, enlarged PVSs, the loss of aquaporin-4 polarity caused by reactive astrocytes and impaired glymphatic drainage function which ultimately caused cognitive deficits, in a similar way as high fat diet leading to impairment in glymphatic drainage. Our study highlights the contribution of dyslipidemia due to long-term alcohol abuse in the impairment of the glymphatic drainage system.

The nucleoside analog 4'-fluorouridine suppresses the replication of multiple enteroviruses by targeting 3D polymerase.

Human enteroviruses are the major pathogens causing hand-foot-and-mouth disease in infants and young children throughout the world, and infection with enterovirus is also associated with severe complications, such as aseptic meningitis and myocarditis. However, there are no antiviral drugs available to treat enteroviruses infection at present. In this study, we found that 4'-fluorouridine (4'-FlU), a nucleoside analog with low cytotoxicity, exhibited broad-spectrum activity against infections of multiple enteroviruses with EC50 values at low micromolar levels, including coxsackievirus A10 (CV-A10), CV-A16, CV-A6, CV-A7, CV-B3, enterovirus A71 (EV-A71), EV-A89, EV-D68, and echovirus 6. With further investigation, the results indicated that 4'-FlU directly interacted with the RNA-dependent RNA polymerase of enterovirus, the 3D pol, and impaired the polymerase activity of 3D pol, hence inhibiting viral RNA synthesis and significantly suppressing viral replication. Our findings suggest that 4'-FlU could be promisingly developed as a broad-spectrum direct-acting antiviral agent for anti-enteroviruses therapy.

Renal dysfunction in AQP4 NMOSD and MS; a potential predictor of relapse and prognosis.

OBJECTIVE: This study aimed to explore the association between kidney function and the risk of relapse as well as prognosis in patients with aquaporin-4 (AQP4)-immunoglobulin G (IgG)-seropositive neuromyelitis optica spectrum disorder (NMOSD). METHODS: We focused on patients experiencing their first onset of AQP4-IgG-seropositive NMOSD. Data on demographics, disease characteristics, and kidney function were collected, with the primary assessment utilizing the estimated glomerular filtration rate (eGFR). Associations between eGFR and relapse risk were examined using multivariate Cox proportional hazards regression models. Additionally, logistic regression models were employed to evaluate the impact of eGFR on clinical prognosis. RESULTS: Our analysis revealed glomerular hyperfiltration and impaired urine concentrating ability in patients with AQP4-IgG-seropositive NMOSD. Multivariate Cox proportional hazards regression demonstrated a positive correlation between eGFR and the risk of relapse. Logistic regression analysis further identified higher eGFR as an independent predictor of disease relapse and prognosis in AQP4-IgG-seropositive NMOSD patients. CONCLUSIONS: The eGFR of patients with AQP4-IgG-seropositive NMOSD emerges as a potential diagnostic biomarker for this condition, indicating its significance in predicting both relapse risk and clinical prognosis.

Research Hotspots and Trends of Social Robot Interaction Design: A Bibliometric Analysis.

(1) Background: Social robot interaction design is crucial for determining user acceptance and experience. However, few studies have systematically discussed the current focus and future research directions of social robot interaction design from a bibliometric perspective. Therefore, we conducted this study in order to identify the latest research progress and evolution trajectory of research hotspots in social robot interaction design over the last decade. (2) Methods: We conducted a comprehensive review based on 2416 papers related to social robot interaction design obtained from the Web of Science (WOS) database. Our review utilized bibliometric techniques and integrated VOSviewer and CiteSpace to construct a knowledge map. (3) Conclusions: The current research hotspots of social robot interaction design mainly focus on #1 the study of human-robot relationships in social robots, #2 research on the emotional design of social robots, #3 research on social robots for children's psychotherapy, #4 research on companion robots for elderly rehabilitation, and #5 research on educational social robots. The reference co-citation analysis identifies the classic literature that forms the basis of the current research, which provides theoretical guidance and methods for the current research. Finally, we discuss several future research directions and challenges in this field.

Escherichia coli triggers α-synuclein pathology in the LRRK2 transgenic mouse model of PD.

Alpha-synuclein (α-syn) pathology is the hallmark of Parkinson's disease (PD). The leucine-rich repeat kinase 2 (LRRK2) gene is a major-effect risk gene for sporadic PD (sPD). However, what environmental factors may trigger the formation of α-syn pathology in carriers of LRRK2 risk variants are still unknown. Here, we report that a markedly increased abundance of Escherichia coli (E. coli) in the intestinal microbiota was detected in LRRK2 risk variant(R1628P or G2385R) carriers with sPD compared with carriers without sPD. Animal experiments showed that E. coli administration triggered pathological α-syn accumulation in the colon and spread to the brain via the gut-brain axis in Lrrk2 R1628P mice, due to the co-occurrence of Lrrk2 variant-induced inhibition of α-syn autophagic degradation and increased phosphorylation of α-syn caused by curli in E. coli-derived extracellular vesicles. Fecal microbiota transplantation (FMT) effectively ameliorated motor deficits and α-syn pathology in Lrrk2 R1628P mice. Our findings elaborate on the mechanism that E. coli triggers α-syn pathology in Lrrk2 R1628P mice, and highlight a novel gene-environment interaction pattern in LRRK2 risk variants. Even more importantly, the findings reveal the interplay between the specific risk gene and the matched environmental factors triggers the initiation of α-syn pathology in sPD.

Cognitive Impairment in Chronic Kidney Disease Is Associated with Glymphatic System Dysfunction.

Introduction: This study was designed to explore the associations between impaired cognition in chronic kidney disease (CKD) patients and the dysfunction of the glymphatic system. Method: Data were obtained from 77 CKD patients and 50 age-matched healthy control individuals from the First Affiliated Hospital of Zhengzhou University. CKD patients were stratified into with and without impaired cognitive function. T2-weighted magnetic resonance imaging results were used to assess area ratios for the perivascular space and ventricles in participants, while the Montreal Cognitive Assessment and the Mini-Mental State Examination were employed to measure cognitive function. Correlations between the perivascular space or ventricle area ratios and cognitive impairment were assessed in CKD patients. Results: Significant increases in the burden of enlarged perivascular spaces in the frontal cortex and basal ganglia were observed in CKD patients with cognitive impairment relative to those without such impairment, with a concomitant increase in analyzed ventricle area ratios. Enlarged perivascular spaces in the frontal cortex, basal ganglia and increased area ratios of lateral ventricles and 4th ventricle exhibited relatively high sensitivity and specificity as means of differing between the CKD patients with and without cognitive impairment. Conclusion: These results indicate that the burden of enlarged perivascular spaces in the frontal cortex and basal ganglia and increases in ventricle area ratio values may offer utility as biomarkers that can aid in detection of even mild cognitive decline in individuals with CKD. The dysfunction of the glymphatic system may play a key role in the pathogenesis of CKD-related cognitive impairment.

The Impact of Diabetes Mellitus on Patient-Reported Outcomes of Chronic Low Back Pain with Modic Changes at One Year: A Prospective Cohort Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: Diabetes mellitus (DM) is associated with unfavourable patient-reported outcomes after spine surgery. Chronic low back pain (CLBP) with Modic Changes (MCs) in the lumbar vertebrae, as observed on MRI, forms a specific subgroup. This study aims to investigate the potential influence of DM on CLBP with MCs. METHODS: This study involved 259 patients with CLBP accompanied MCs. We recorded the patient-reported outcomes (visual analogue scale (VAS), Oswestry Disability Index (ODI), and Roland-Morris Disability Questionnaire (RMDQ)) at baseline, 3, 6, and 12 months. Multivariable linear regression analyses were performed to determine predictors of patient-reported outcomes. RESULTS: 103 patients had DM. Patients with DM exhibited higher VAS (P < .05), ODI (P < .001), and RMDQ (P < .001) scores at 3, 6, and 12 months, while patients without DM experienced more significant improvements in the scores over time (P < .001). Patients with DM reported longer durations of physical exercise (P = .007). Additionally, patients without DM had a significantly higher patient satisfaction index (P < .001) and a lower prevalence of hypertension (P < .001). Notably, significant differences were observed in the distribution of MCs of lumbar vertebrae (P = .034) and Pfirrmann grades of intervertebral disc degeneration between two groups (P < .001). CONCLUSION: Patients with DM demonstrated poorer patient-reported outcomes compared to those without DM in 1-year. DM emerged as an independent predictor of adverse patient-reported outcomes. It can be utilized to enhance the management and treatment of CLBP in patients with MCs.

A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection.

Infection with coxsackievirus A10 (CV-A10) can cause hand-foot-mouth disease and is also associated with severe complications, including viral pneumonia, aseptic and viral meningitis. Coxsackievirus infection may also play a role in the pathogenesis of acute myocardial infarction and in the increased risk of type 1 diabetes mellitus in adults. However, there are no approved vaccines or direct antiviral agents available to prevention or treatment of coxsackievirus infection. Here, we reported that GC376 potently inhibited CV-A10 infection in different cell lines without cytotoxicity, significantly suppressed production of viral proteins, and strongly reduced the yields of infectious progeny virions. Further study indicated that GC376, as viral 3C protease inhibitor, had the potential to restrain the cleavage of the viral polyprotein into individually functional proteins, thus suppressed the replication of CV-A10. Furthermore, the drug exhibited antiviral activity against coxsackieviruses of various serotypes including CV-A6, CV-A7 and CV-A16, suggesting that GC376 is a broad-spectrum anti-coxsackievirus inhibitor and the 3C protease is a promising target for developing anti-coxsackievirus agents.

Fooling Examples: Another Intriguing Property of Neural Networks.

Neural networks have been proven to be vulnerable to adversarial examples; these are examples that can be recognized by both humans and neural networks, although neural networks give incorrect predictions. As an intriguing property of neural networks, adversarial examples pose a serious threat to the secure application of neural networks. In this article, we present another intriguing property of neural networks: the fact that well-trained models believe some examples to be recognizable objects (often with high confidence), while humans cannot recognize such examples. We refer to these as "fooling examples". Specifically, we take inspiration from the construction of adversarial examples and develop an iterative method for generating fooling examples. The experimental results show that fooling examples can not only be easily generated, with a success rate of nearly 100% in the white-box scenario, but also exhibit strong transferability across different models in the black-box scenario. Tests on the Google Cloud Vision API show that fooling examples can also be recognized by real-world computer vision systems. Our findings reveal a new cognitive deficit of neural networks, and we hope that these potential security threats will be addressed in future neural network applications.

Effects of Hermetia illucens larvae meal on the Pacific white shrimp (Litopenaeus vannamei) revealed by innate immunity and 16S rRNA gene sequencing analysis.

The larvae of the black soldier fly, Hermetia illucens, are now attracting attention and becoming promising sources for aquafeed ingredient due to the nutritious substance. However, the introduction of a novel ingredient into the recipe may have unpredictable effects on the innate immune function and gut bacteria composition of crustaceans. Therefore, the present study aimed to evaluate how dietary black soldier fly larvae meal (BSFLM) affected the antioxidant ability, innate immunity and gut microbiome of shrimp (Litopenaeus vannamei) fed with a practical diet, including the gene expression of Toll and immunodeficiency (IMD) pathways. Six experimental diets were formulated by replacing gradient levels of fish meal (0 %, 10 %, 20 %, 30 %, 40 % and 50 %) based on a commercial shrimp diet. Four replicates of shrimp were fed different diets three times daily for 60 days. Growth performance linearly decreased with increasing BSFLM inclusion. Results of antioxidative enzyme activities and gene expression suggested that low dietary BSFLM levels activated the antioxidant capacity of shrimp, while dietary BSFLM levels up to 100 g/kg may induce oxidative stress and inhibit glutathione peroxidase activity. Although traf6, toll1, dorsal and relish were significantly upregulated in different BSFLM groups, the expression of tak1 was significantly downregulated in groups containing BSFLM, implying the immune susceptibility may be weakened. Gut flora analysis indicated dietary BSFLM altered both beneficial and opportunistic pathogenic bacterial abundance, with low levels of dietary BSFLM increased the abundance of bacteria that may contribute to carbohydrate utilization, while high levels of dietary BSFLM may cause intestinal disease and low intestinal immune response. To conclude, 60-80 g/kg of dietary BSFLM showed no adverse effects on the growth, antioxidant capacity and gut flora of shrimp, which was the adequate level in shrimp diet. While 100 g/kg dietary BSFLM may induce oxidative stress and potentially weaken the innate immunity of shrimp.

Evaluation of Phytosterols as an Alternative to Cholesterol in Practical Diets on Growth and Nonspecific Immunity of Litopenaeus vannamei.

This study is aimed at evaluating the effectiveness of phytosterols as an alternative to cholesterol in practical diets of Pacific white shrimp Litopenaeus vannamei from the perspective of growth and nonspecific immunity. Five diets were formulated to contain different sterol sources and levels. Two diets were supplemented with 1 g/kg cholesterol (LC (low cholesterol)) or phytosterol (LP (low phytosterol)). Other three experimental diets were supplemented with 2 g/kg cholesterol (HC (high cholesterol)), 2 g/kg phytosterol (HP (high phytosterol)), or mixed sterol source (CP, 1 g/kg cholesterol + 1 g/kg phytosterol), respectively. A total of 750 healthy and uniform-sized shrimp (0.52 ± 0.008 g) were randomly distributed into 5 groups with 3 replicates and fed with the five experimental diets for 60 days. Results showed that the growth performance of shrimp was influenced by the sterol levels and supplementation with 2 g/kg sterol level facilitated the growth of shrimp. The inclusion of phytosterol has a cholesterol-lowering effect on shrimp, as evidenced by a reduction in hemolymph cholesterol and triglyceride contents in the HP group. Besides, supplementation with 2 g/kg phytosterol or mixed sterol sources had positive effects on the hemolymph superoxide dismutase, phenol oxidase, and lysozyme as well as hepatopancreas alkaline phosphatase activities, demonstrating that the nonspecific immunity and antioxidative capacity were improved. In conclusion, phytosterols could be an appropriate alternative to partially replace dietary cholesterol in shrimp feeds. This study preliminarily revealed the effects of different sterol sources and levels on the growth and nonspecific immunity of shrimp and provided a basis for further exploration of the mechanism of phytosterol.

Microbiota-ear-brain interaction is associated with generalized anxiety disorder through activation of inflammatory cytokine responses.

Introduction: Generalized anxiety disorder (GAD) is one of the most enduring anxiety disorders, being associated with increased systemic inflammation. However, the trigger and mechanisms underlying the activation of inflammatory cytokine responses in GAD remain poorly understood. Materials and methods: We characterized the ear canal microbiome in GAD patients through 16S rRNA gene sequencing and metagenomic sequencing and identified the serum inflammatory markers in GAD patients. Spearman correlations were applied to test the relationship between the microbiota changes and systemic inflammation. Results: Our findings showed the higher microbial diversity, accompanied with the significantly increased abundance of Proteobacteria, and decreased abundance of Firmicutes in the ear canal of GAD participants compared to that of the age- and sex-matched healthy controls (HC). Metagenomic sequencing showed that Pseudomonas aeruginosa were significantly increased at species-level in GAD patients. Furthermore, we observed the relative abundance of Pseudomonas aeruginosa was positively associated with elevated systemic inflammatory markers and the severity of disease, suggesting that these ear canal microbiota alterations might be correlated with GAD by activating the inflammatory response. Conclusions: These findings indicate that microbiota-ear-brain interaction via upregulating inflammatory reaction involve in the development of GAD, as well as suggest that ear canal bacterial communities may be a target for therapeutic intervention.

Efficacy of faecal microbiota transplantation in patients with progressive supranuclear palsy-Richardson's syndrome: a phase 2, single centre, randomised clinical trial.

Background: Faecal microbiota transplantation (FMT) has demonstrated efficacy in treating gastrointestinal (GI) diseases, such as Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). GI dysfunction is a frequent and occasionally dominating symptom of progressive supranuclear palsy-Richardson's syndrome (PSP-RS). However, it is not known whether FMT has clinical efficacy for PSP-RS. Methods: This 36-week, randomised, placebo-controlled, parallel-group, phase 2 clinical trial was performed at a university tertiary referral hospital in China. From August 15 2021 to December 31 2021, a total of 68 newly diagnosed patients with PSP-RS (male 40 [59%], female 28 [41%]) who had never received any antiparkinsonian medications were enrolled and randomly assigned to receive either healthy donor FMT (n = 34, FMT group) or a mixture of 0.9% saline and food colouring (E150c) as sham transplantation (n = 34, placebo group) through transendoscopic enteral tubing (TET). Two days after oral antibiotics, participants received 1 week of transplantation. After an interval of 4 weeks, retransplantation was performed. Then, the last transplantation was given after another interval of 4 weeks, and the participants were followed up for 24 weeks (week 36). Clinicaltrials.gov identifier: ChiCTR-2100045397. Findings: Among 68 patients who were randomised (mean age, 67.2 (SD 5.1); 40 [59%] were male, 28 [41%] were female), 63 participants completed the trial. Efficacy analyses were performed on the intention-to-treat (ITT) analysis set. At week 16, the mean PSP Rating Scale (PSPRS) scores (the primary outcome) improved from 40.1 (SD 7.6) to 36.9 (SD 5.9) in the FMT group, whereas the scores changed from 40.1 (SD 6.9) to 41.7 (SD 6.2) in the placebo group, for a treatment benefit of 4.3 (95% CI, 3.2-5.4) (P < 0.0001). After 3-cycle intervention, symptoms of constipation, depression, and anxiety (the secondary outcome) improved significantly at week 16 in the FMT group compared with the placebo group, the majority of which were maintained at the 24-week follow-up (week 36). Interpretation: Our findings suggest that, compared with placebo, FMT treatment significantly improved motor and nonmotor symptoms in patients with PSP-RS, as well as reduced intestinal inflammation and enhanced the intestinal barrier by regulating the intestinal microbiota composition. Funding: The National Natural Science Foundation of China (No. 82122022, 82171248, 81873791, and 82230084), Natural Science Foundation of Henan Province for Excellent Young Scholars (no. 202300410357), and Henan Province Young and Middle-Aged Health Science and Technology Innovation Talent Project (YXKC2020033).

Mutations in ARHGEF15 cause autosomal dominant hereditary cerebral small vessel disease and osteoporotic fracture.

Cerebral small vessel disease (CSVD) is a prominent cause of ischemic and hemorrhagic stroke and a leading cause of vascular dementia, affecting small penetrating vessels of the brain. Despite current advances in genetic susceptibility studies, challenges remain in defining the causative genes and the underlying pathophysiological mechanisms. Here, we reported that the ARHGEF15 gene was a causal gene linked to autosomal dominant inherited CSVD. We identified one heterozygous nonsynonymous mutation of the ARHGEF15 gene that cosegregated completely in two families with CSVD, and a heterozygous nonsynonymous mutation and a stop-gain mutation in two individuals with sporadic CSVD, respectively. Intriguingly, clinical imaging and pathological findings displayed severe osteoporosis and even osteoporotic fractures in all the ARHGEF15 mutation carriers. In vitro experiments indicated that ARHGEF15 mutations resulted in RhoA/ROCK2 inactivation-induced F-actin cytoskeleton disorganization in vascular smooth muscle cells and endothelial cells and osteoblast dysfunction by inhibiting the Wnt/ß-catenin signaling pathway in osteoblast cells. Furthermore, Arhgef15-e(V368M)1 transgenic mice developed CSVD-like pathological and behavioral phenotypes, accompanied by severe osteoporosis. Taken together, our findings provide strong evidence that loss-of-function mutations of the ARHGEF15 gene cause CSVD accompanied by osteoporotic fracture.

Gait strategies for individuals with knee osteoarthritis when transitioning between floor and stair walking.

Objective: Individuals with knee osteoarthritis are at higher risk for falls during transitions between floor and stair walking due to their reduced lower extremity function. However, the adjust gait characteristics of knee osteoarthritis subjects for dealing with stair transitions have not been explored. We aimed to investigate gait strategies in individuals with knee osteoarthritis compared to age-matched individuals without knee OA during the transition between walking on floor and stairs. Method: Gait of 30 individuals with knee osteoarthritis and 30 individuals without knee osteoarthritis during floor-to-stair and stair-to-floor walking transitions were accessed using a 3D motion capture system. Foot-tread clearance, and angles of lower extremity joints and trunk at Foot-tread clearance timepoint were analyzed by using biomechanical software (Visual 3D). Results: Compared with asymptomatic control group, the knee osteoarthritis group demonstrated no difference in vertical Foot-tread clearance and horizontal Foot-tread clearance during stair transitions. However, ankle dorsiflexion (p = 0.01) decreased, hip flexion (p = 0.02) and trunk lateral tilt (p = 0.02) increased in knee osteoarthritis group during the stair ascent transition. Moreover, trunk lateral tilt to the support side (p = 0.003) and pelvic rotation (p = 0.03) increased, while hip abduction of the swing leg (p = 0.03) decreased during the stair descent transition in individuals with knee osteoarthritis. Conclusion: Increased trunk lateral tilt and altered angle of hip may be a strategy utilized by individuals with knee OA to increase the foot clearance ability and compensate for the disease-related loss of lower extremity strength, range of motion, and balance. However, compensatory manifestations, such as the increased lateral tilt of the trunk and movement of the gravity center may enhance the risk of falls and result in more abnormal knee joint loading.

Shot-noise-limited photon-counting precoding scheme for MIMO ultraviolet communication in atmospheric turbulence.

Photon counting is a promising solution to detecting low-power optical signals for ultraviolet (UV) communications in the forthcoming sixth-generation (6G) network. Different from the conventional additive white Gaussian noise (AWGN) model, the discrete signal-dependent Poisson shot noise poses challenges to the signal processing of photon-counting systems. In this paper, a joint design of precoder and equalizer is proposed for photon-counting multiple-input multiple-output (PhC-MIMO) UV systems. To circumvent the impasse arising from the signal-dependent shot noise, we propose an alternating optimization algorithm based on the minimum mean squared error (MMSE) criterion. The algorithm decomposes the joint design into convex subproblems solved in an alternating manner, and guarantees at least a stationary point solution. Numerical results corroborate that the proposed system exhibits robustness to turbulence fading and offers high throughput while mitigating the adverse effect of background radiation noise. Specifically, the 32 × 8 system can achieve a bit error rate (BER) of 10-5 at the signal energy of -154.0 dBJ per bit under strong Gamma-Gamma turbulence with the scintillation index (S.I.) of 3.

Impaired glymphatic drainage underlying obstructive sleep apnea is associated with cognitive dysfunction.

Obstructive sleep apnea (OSA) is highly prevalent but easily undiagnosed and is an independent risk factor for cognitive impairment. However, it remains unclear how OSA is linked to cognitive impairment. In the present study, we found the correlation between morphological changes of perivascular spaces (PVSs) and cognitive impairment in OSA patients. Moreover, we developed a novel set of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) methods to evaluate the fluid dynamics of glymphatic drainage system. We found that the inflow and outflow parameters of the glymphatic drainage system in patients with OSA were obviously changed, indicating impairment of glymphatic drainage due to excessive perfusion accompanied with deficient drainage in OSA patients. Moreover, parameters of the outflow were associated with the degree of cognitive impairment, as well as the hypoxia level. In addition, continuous positive airway pressure (CPAP) enhances performance of the glymphatic drainage system after 1 month treatment in OSA patients. We proposed that ventilation improvement might be a new strategy to ameliorate the impaired drainage of glymphatic drainage system due to OSA-induced chronic intermittent hypoxia, and consequently improved the cognitive decline.

Development and Validation of a Nomogram to Predict the Risk of Lumbar Disk Reherniation within 2 Years After Percutaneous Endoscopic Lumbar Discectomy.

OBJECTIVE: To develop and validate a nomogram for predicting recurrent lumbar disk herniation (LDH) within 2 years after percutaneous endoscopic lumbar discectomy. METHODS: Information on patients' LDH was collected from 1 medical center between January 2015 and September 2020. The LASSO (least absolute shrinkage and selection operator) method was applied to select the most significant risk factors. A multivariate logistic regression analysis was used to develop a predictive model incorporating the possible factors selected by the LASSO regression model. The discriminant, corrected, and clinically useful prediction models were evaluated using consistency index (C-index), receiver operating characteristic curve, calibration curves, and decision curve analysis. Internal validation of clinical predictive power was also assessed by bootstrap validation. RESULTS: A total of 690 patients with LDH were included in this study. Sixty-three patients experienced recurrence within 2 years whereas 627 experienced no recurrence. The nomogram predictors included age, body mass index, Modic change, Pfirrmann grade, and sagittal range of motion. The model had good discrimination power, with a reliable C-index of 0.868 (95% confidence interval, 0.822-0.913) and interval validation confirmed a higher C-index value of 0.846. The area under the receiver operating characteristic curve was 0.868, indicating a good predictive value. The decision curve analysis indicated that it was clinically feasible to use the predictive recurrence nomogram model. CONCLUSIONS: We developed and validated a new accurate and effective nomogram for predicting recurrent LDH within 2 years after percutaneous endoscopic lumbar discectomy. Age, body mass index, Modic change, Pfirrmann grade, and sagittal range of motion were significant features for predicting rLDH.

A peptide derived from the N-terminal of NS2A for the preparation of ZIKV NS2A recognition polyclonal antibody.

Zika virus non-structural protein NS2A participates in viral replication, organization, and budding, as well as escaping host immunity. NS2A also involved in the induction of microcephaly by ZIKV. However, the above studies were mainly performed through NS2A with a tag due to the lack of available antibodies against NS2A. ZIKV NS2A is a multiplex transmembrane protein, which leads to difficulties in the preparation of its recognition antibodies, thus seriously affecting the study of ZIKV NS2A. In this study, we found that a peptide (GSTDHMDHFSLGVLC) derived from the N-terminal of ZIKV NS2A coupled to KLH induced antibodies recognizing ZIKV NS2A in rabbits. The purified polyclonal antibody recognized ZIKV NS2A in ZIKV-infected cells with high efficiency and specificity, as detected by western blot and immunofluorescence assay. Our study has important implications for the preparation of ZIKV NS2A antibodies and the in-depth study of ZIKV NS2A.

Acriflavine and proflavine hemisulfate as potential antivirals by targeting Mpro.

The evolving SARS-CoV-2 epidemic buffets the world, and the concerted efforts are needed to explore effective drugs. Mpro is an intriguing antiviral target for interfering with viral RNA replication and transcription. In order to get potential anti-SARS-CoV-2 agents, we established an enzymatic assay using a fluorogenic substrate to screen the inhibitors of Mpro. Fortunately, Acriflavine (ACF) and Proflavine Hemisulfate (PRF) with the same acridine scaffold were picked out for their good inhibitory activity against Mpro with IC50 of 5.60 ± 0.29 µM and 2.07 ± 0.01 µM, respectively. Further evaluation of MST assay and enzymatic kinetics experiment in vitro showed that they had a certain affinity to SARS-CoV-2 Mpro and were both non-competitive inhibitors. In addition, they inhibited about 90 % HCoV-OC43 replication in BHK-21 cells at 1 µM. Both compounds showed nano-molar activities against SARS-CoV-2 virus, which were superior to GC376 for anti-HCoV-43, and equivalent to the standard molecule remdesivir. Our study demonstrated that ACF and PRF were inhibitors of Mpro, and ACF has been previously reported as a PLpro inhibitor. Taken together, ACF and PRF might be dual-targeted inhibitors to provide protection against infections of coronaviruses.