PRDX1 Interfering Peptide Disrupts Amino Acids 70-90 of PRDX1 to Inhibit the TLR4/NF-κB Signaling Pathway and Attenuate Neuroinflammation and Ischemic Brain Injury.

Ischemic stroke ranks among the leading causes of death and disability in humans and is accompanied by motor and cognitive impairment. However, the precise mechanisms underlying injury after stroke and effective treatment strategies require further investigation. Peroxiredoxin-1 (PRDX1) triggers an extensive inflammatory cascade that plays a pivotal role in the pathology of ischemic stroke, resulting in severe brain damage from activated microglia. In the present study, we used molecular dynamics simulation and nuclear magnetic resonance to detect the interaction between PRDX1 and a specific interfering peptide. We used behavioral, morphological, and molecular experimental methods to demonstrate the effect of PRDX1-peptide on cerebral ischemia-reperfusion (I/R) in mice and to investigate the related mechanism. We found that PRDX1-peptide bound specifically to PRDX1 and improved motor and cognitive functions in I/R mice. In addition, pretreatment with PRDX1-peptide reduced the infarct area and decreased the number of apoptotic cells in the penumbra. Furthermore, PRDX1-peptide inhibited microglial activation and downregulated proinflammatory cytokines including IL-1ß, IL-6, and TNF-α through inhibition of the TLR4/NF-κB signaling pathway, thereby attenuating ischemic brain injury. Our findings clarify the precise mechanism underlying PRDX1-induced inflammation after ischemic stroke and suggest that the PRDX1-peptide can significantly alleviate the postischemic inflammatory response by interfering with PRDX1 amino acids 70-90 and thereby inhibiting the TLR4/NF-κB signaling pathway. Our study provides a theoretical basis for a new therapeutic strategy to treat ischemic stroke.

Moderators of treatment effect of non-steroidal anti-inflammatory drugs for patients with (sub) acute low back pain: Protocol for a systematic review with individual participant data meta-analysis.

A Cochrane review found that non-steroidal anti-inflammatory drugs (NSAIDs) are slightly more effective than placebo on acute and subacute low back pain (LBP) outcomes (pain intensity, disability, and global improvement). Our objectives are: (1) to assess the overall treatment effect of NSAIDs in adults with acute and subacute LBP; (2) to identify the moderation of baseline patients' characteristics on treatment effect. We will conduct a systematic search of RCTs on effectiveness of NSAIDs compared with placebo in adults with non-chronic LBP in Medline ALL, Embase, Cochrane Central Register of Controlled Trials*. We will screen the records after January 2020, and include eligible RCTs before January 2020 screened by the Cochrane review mentioned above. Our primary outcomes are pain intensity, disability, and health-related quality of life, secondary outcomes are adverse events. Our IPD dataset will consist of the information on each eligible trial characteristics and included variables according to a predefined coding scheme. We will assess risk-of-bias of included RCTs with the Cochrane Risk Of Bias (RoB)-2 assessment tool. We will perform power calculations with closed-form solutions and prioritize a one-stage approach for IPD-MA. For reporting the results, we will adhere to the PRISMA-IPD statement.

Concentrated biogas slurry and biogas residue can improve the yield and quality of pepper.

The organic fertilizer (biogas slurry and biogas residues) was produced by the self-developed integrated device of "Pressure swirl / inclined plate sedimentation separation pretreatment (P/I) combined with ultrafiltration / reverse osmosis two stages membrane separation (UF/RO)". The paper focuses on the effect of concentrated biogas slurry and biogas residue produced by this technology on the yield and quality (vitamin C, soluble sugar, protein and nitrate content) of pepper as organic fertilizer compared with chemical fertilizer. The concentrated biogas slurry and biogas residue separated by this technology contained active substances such as N, P, K, trace elements and humic acids with stable composition and potential for good fertilization efficiency. The experiment of seed soaking for pepper sprouting confirmed the best effect of seed soaking with a concentration of 80% biogas slurry. Compared with chemical fertilizer treatment, the application of concentrated biogas slurry and biogas residue can improve the yield and quality of pepper, which is related to the nutrient elements in concentrated digestate. Meanwhile, the results of pepper cultivation trials show that the base fertilizer treatment of biogas residue is best with 2000kg/667m2 and foliar spraying of 75% biogas slurry. The results strongly demonstrate the great potential of the concentrated biogas slurry and biogas residue produced by the self-developed digestate concentration technology for pepper cultivation.

Mobile phone addiction and academic burnout: the mediating role of technology conflict and the protective role of mindfulness.

With the rapid development of Internet technology, more and more college students are facing the threat of mobile phone addiction. However, the relationship and underlying mechanism between mobile phone addiction and academic burnout haven't been explored in depth. This study proves the mediating role of technology conflict and the moderating role of mindfulness in the relation between mobile phone addiction and academic burnout. 752 college students were recruited to complete the questionnaire of mobile phone addiction, technology conflict, mindfulness and academic burnout. Results showed that mobile phone addiction was significantly and positively associated with academic burnout, and this relationship could be mediated by technology conflict. Besides, the direct effect of mobile phone addiction on academic burnout and the indirect effect of technology conflict in this link were moderated by mindfulness. Both these two effects are stronger for college students with lower level of mindfulness. Our findings enrich our understanding of how and when mobile phone addiction was related to academic burnout. Educational professionals and parents should take timely measure to the academic burnout of college students suffering from mobile phone addiction, particularly for those with lower level of mindfulness.

Prognostic Models for Chronic Low Back Pain Outcomes in Primary Care Are at High Risk of Bias and Lack Validation-High-Quality Studies Are Needed: A Systematic Review.

OBJECTIVE: To provide an updated overview of available prognostic models for people with chronic low back pain (LBP) in primary care. DESIGN: Prognosis systematic review LITERATURE SEARCH: We searched for relevant studies on MEDLINE, Embase, Web of Science, and CINAHL databases (up to July 13, 2022), and performed citation tracking in Web of Science. STUDY SELECTION CRITERIA: We included observational (cohort or nested case-control) studies and randomized controlled trials that developed or validated prognostic models for adults with chronic LBP in primary care. The outcomes of interest were physical functioning, pain intensity, and health-related quality of life at any follow-up time-point. DATA SYNTHESIS: Data were extracted using the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS), and the Prediction model Risk of Bias Assessment Tool (PROBAST) tool was used to evaluate the risk of bias of the models. Due to the number of studies retrieved and the heterogeneity, we reported the results descriptively. RESULTS: Ten studies (out of 5593 hits screened) with 34 models met our inclusion criteria, of which six are development studies and four are external validation studies. Five studies reported the area under the curve of the models (ranging from 0.48 to 0.84), whereas no study reported calibration indices. The most promising model is the Örebro Musculoskeletal Pain Screening Questionnaire Short-Form. CONCLUSIONS: Given the high risk of bias and lack of external validation, we cannot recommend that clinicians use prognostic models for patients with chronic LBP in primary care settings. J Orthop Sports Phys Ther 2024;54(5):1-13. Epub 15 February 2024. doi:10.2519/jospt.2024.12081.

Efbemalenograstim alfa not inferior to pegfilgrastim in providing neutrophil support in women with breast cancer undergoing myelotoxic chemotherapy: results of a phase 2 randomized, multicenter, open-label trial.

PURPOSE: Evaluate the safety and efficacy of efbemalenograstim alfa for neutrophil support in breast cancer patients undergoing myelosuppressive chemotherapy in a phase 2, dose-finding, open-label study (NCT01648322, ClinicalTrials.gov, 2012-07-19). METHODS: 232 patients received up to 4 cycles of chemotherapy, 141 patients with docetaxel + cyclophosphamide (TC) and 91 patients with docetaxel + doxorubicin + cyclophosphamide (TAC). Patients were randomized to efbemalenograstim alfa (80, 240, or 320 µg/kg [TC]; 240 or 320 µg/kg [TAC]) or pegfilgrastim (6 mg) on Day 2 of each cycle. RESULTS: Efbemalenograstim alfa was non-inferior to pegfilgrastim in duration of moderate and severe neutropenia (absolute neutrophil count [ANC] < 1.0 × 109/L) in TAC Cycle 1 (mean [SD] of 2.1 [1.58] and 2.1 [1.46] days for 240 µg/kg and 320 µg/kg efbemalenograstim alfa, respectively, and 1.8 [1.28] days for pegfilgrastim), with a difference (95% CI) of 0.3 (-0.4, 1.1) days. ANC nadir occurred between Days 7-8 of TAC Cycle 1, with mean [SD] of 0.68 [1.064], 0.86 [1.407] and 0.78[1.283] × 109/L for 240 µg/kg, 320 µg/kg efbemalenograstim alfa and pegfilgrastim, respectively. Time to ANC recovery post nadir (defined as an ANC > 2.0 × 109/L after the expected ANC nadir) was 2.0-2.4 and 1.9 days for TAC patients treated with efbemalenograstim alfa and pegfilgrastim, respectively. No significant difference was found between any dose of efbemalenograstim alfa and pegfilgrastim in TAC Cycle 1 for incidence of moderate to severe neutropenia (76%-77% of patients) or incidence of severe neutropenia (ANC < 0.5 × 109/L; 63%-72%). Efbemalenograstim alfa exhibited similar safety profile to pegfilgrastim. Febrile neutropenia occurred in 4 (1.8%) patients, 2 patients each for 320 µg/kg efbemalenograstim alfa and pegfilgrastim, with no event considered related to study drug. CONCLUSION: Efbemalenograstim alfa was comparable to pegfilgrastim in efficacy and safety. GOV IDENTIFIER: NCT01648322.

TAT-W61 peptide attenuates neuronal injury through blocking the binding of S100b to the V-domain of Rage during ischemic stroke.

Ischemic stroke is a devastative nervous system disease associated with high mortality and morbidity rates. Unfortunately, no clinically effective neuroprotective drugs are available now. In ischemic stroke, S100 calcium-binding protein b (S100b) binds to receptor for advanced glycation end products (Rage), leading to the neurological injury. Therefore, disruption of the interaction between S100B and Rage can rescue neuronal cells. Here, we designed a peptide, termed TAT-W61, derived from the V domain of Rage which can recognize S100b. Intriguingly, TAT-W61 can reduce the inflammatory caused by ischemic stroke through the direct binding to S100b. The further investigation demonstrated that TAT-W61 can improve pathological infarct volume and reduce the apoptotic rate. Particularly, TAT-W61 significantly improved the learning ability, memory, and motor dysfunction of the mouse in the ischemic stroke model. Our study provides a mechanistic insight into the abnormal expression of S100b and Rage in ischemic stroke and yields an invaluable candidate for the development of drugs in tackling ischemic stroke. KEY MESSAGES: S100b expression is higher in ischemic stroke, in association with a high expression of many genes, especially of Rage. S100b is directly bound to the V-domain of Rage. Blocking the binding of S100b to Rage improves the injury after ischemic stroke.

Establishment of prediction models to predict survival among patients with cervical cancer based on socioeconomic factors: a retrospective cohort study based on the SEER Database.

OBJECTIVE: To construct and validate predictive models based on socioeconomic factors for predicting overall survival (OS) in cervical cancer and compare them with the American Joint Council on Cancer (AJCC) staging system. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: We extracted data from 5954 patients who were diagnosed with cervical cancer between 2007 and 2011 from the Surveillance, Epidemiology, and End Results Database. This database holds data related to cancer incidence from 18 population-based cancer registries in the USA. OUTCOME MEASURES: 1-year and 5-year OS. RESULTS: Of the total 5954 patients, 5820 patients had 1-year mortality and 5460 patients had 5-year mortality. Lower local education level [Hazard ratios (HR): 1.15, 95% confidence interval (CI): 1.04 to 1.27, p= 0.005] and being widowed (HR 1.28, 95% CI 1.06 to 1.55, p=0.009) were associated with a worse OS for patients with cervical cancer. Having insurance (HR 0.75, 95% CI 0.62 to 0.90, p=0.002), earning a local median annual income of ≥US$56 270 (HR 0.83, 95% CI 0.75 to 0.92, p<0.001) and being married (HR 0.79, 95% CI 0.69 to 0.89, p<0.001) were related to better OS in patients with cervical cancer. The predictive models based on socioeconomic factors and the AJCC staging system had a favourable performance for predicting OS in cervical cancer compared with the AJCC staging system alone. CONCLUSION: Our proposed predictive models exhibit superior predictive performance, which may highlight the potential clinical application of incorporating socioeconomic factors in predicting OS in cervical cancer.

Insulin-like growth factor-1 and retinopathy of prematurity: A systemic review and meta-analysis.

The prevalence of retinopathy of prematurity (ROP) is rapidly increasing worldwide. Many researchers have explored the relationship between insulin-like growth factor-1 (IGF-1) and ROP; however, the results are controversial. This meta-analysis evaluates the correlation between IGF-1 and ROP systematically. We searched for PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, SinoMed, ClinicalTrials.gov, and 3 Chinese databases up to June 2022. Then, the meta-regression and subgroup analysis were carried out. Twelve articles with 912 neonates were included in this meta-analysis. The results revealed that 4 of 7 covariates account for significant heterogeneity: location, measurement method of IGF-1 levels, collection time of blood sample, and the severity of ROP. The pooled analysis showed that low IGF-1 levels could serve as a risk factor associated with the development and severity of ROP. Serum IGF-1 monitoring in preterm infants after birth will be helpful in the diagnosis and treatment of ROP, and the reference value of IGF-1 should be standardized according to the measurement of IGF-1 and the region, as well as the postmenstrual age of prematurity.

The influence of comorbidities on outcomes for older people with back pain: BACE-D cohort study.

BACKGROUND: Comorbidities are common in older people with back pain but little is known about the influence of comorbidities on outcomes. OBJECTIVES: To explore the influence of the most prevalent comorbidities, and the number of comorbidities, on short (at 3 months) and long-term (at 12 months) outcomes of back pain in older people. METHODS: We analyzed data from the 'Back Complaints in the Elders' Dutch study cohort (BACE-D) and included participants aged >55 years. We used the modified Self-Administered Comorbidities Questionnaire (SCQ), the Numeric Rating Scale (NRS) and the Roland-Morris Disability Questionnaire (RMDQ) to assess the number of comorbidities, pain intensity and back-related physical functioning, respectively. We conducted separate linear regression models to analyze the association between comorbidities and outcomes including potential confounders of age, sex, body mass index, smoking and alcoholic drinking status, back pain history, and baseline NRS and RMDQ scores. RESULTS: Our study included 669 participants with a mean age of 66.5 (SD 7.7) years of whom 394 were female. More comorbidities were positively associated with higher pain intensity (3-month regression coefficient (ß) =0.27, 95% CI 0.14-0.39; 12-month ß = 0.31, 95% CI 0.17-0.45) and worse physical functioning (3-month ß = 0.54, 95% CI 0.31-0.77; 12-month ß = 0.64, 95% CI 0.37-0.92). Four of the 5 commonest comorbidities were musculoskeletal problems. Older participants with musculoskeletal comorbidities had higher pain intensity (3-month ß = 0.89 95% CI 0.41-1.37; 12-month ß = 1.17, 95% CI 0.65-1.69), and worse physical functioning (3-month ß = 1.61, 95% CI 0.71-2.52; 12-month ß = 1.85, 95% CI 0.82-2.89, P-value < 0.001) compared to participants without musculoskeletal comorbidities. CONCLUSIONS: More comorbidities are associated with worse back pain outcomes in older adults. Participants with musculoskeletal comorbidities had worse back pain outcomes than those without.

Rethinking the potential and necessity of drug delivery systems in neovascular age-related macular degeneration therapy.

Age-related macular degeneration (AMD) is the predominant threat to human vision and ultimately results in blindness. With the increase in the aging population, it has become a more crucial issue to human health. AMD is a multifactorial disease with the unique feature of uncontrollable angiogenesis during initiation and progression. Although increasing evidence indicates that AMD is largely hereditary, the predominant efficient treatment is antiangiogenesis, which mainly involves VEGF and HIF-α as therapeutic targets. The repeated administration of this treatment over the long term, generally through intravitreal injection, has called for the introduction of long-term drug delivery systems, which are expected to be achieved by biomaterials. However, the clinical results of the port delivery system indicate that the optimization of medical devices toward prolonging the activities of therapeutic biologics in AMD therapy seems more promising. These results indicate that we should rethink the possibility and potential of biomaterials as drug delivery systems in achieving long-term, sustained inhibition of angiogenesis in AMD therapy. In this review, the etiology, categorization, risk factors, pathogenesis, and current clinical treatments of AMD are briefly introduced. Next, the development status of long-term drug delivery systems is discussed, and the drawbacks and shortages of these systems are emphasized. By comprehensively considering the pathological aspect and the recent application of drug delivery systems in AMD therapy, we hope to find a better solution for the further development of long-term therapeutic strategies for AMD.

Research Progress of Organic Field-Effect Transistor Based Chemical Sensors.

Due to their high sensitivity and selectivity, chemical sensors have gained significant attention in various fields, including drug security, environmental testing, food safety, and biological medicine. Among them, organic field-effect transistor (OFET) based chemical sensors have emerged as a promising alternative to traditional sensors, exhibiting several advantages such as multi-parameter detection, room temperature operation, miniaturization, flexibility, and portability. This review paper presents recent research progress on OFET-based chemical sensors, highlighting the enhancement of sensor performance, including sensitivity, selectivity, stability, etc. The main improvement programs are improving the internal and external structures of the device, as well as the organic semiconductor layer and dielectric structure. Finally, an outlook on the prospects and challenges of OFET-based chemical sensors is presented.

Flexible solar cells based on foldable silicon wafers with blunted edges.

Flexible solar cells have a lot of market potential for application in photovoltaics integrated into buildings and wearable electronics because they are lightweight, shockproof and self-powered. Silicon solar cells have been successfully used in large power plants. However, despite the efforts made for more than 50 years, there has been no notable progress in the development of flexible silicon solar cells because of their rigidity1-4. Here we provide a strategy for fabricating large-scale, foldable silicon wafers and manufacturing flexible solar cells. A textured crystalline silicon wafer always starts to crack at the sharp channels between surface pyramids in the marginal region of the wafer. This fact enabled us to improve the flexibility of silicon wafers by blunting the pyramidal structure in the marginal regions. This edge-blunting technique enables commercial production of large-scale (>240 cm2), high-efficiency (>24%) silicon solar cells that can be rolled similarly to a sheet of paper. The cells retain 100% of their power conversion efficiency after 1,000 side-to-side bending cycles. After being assembled into large (>10,000 cm2) flexible modules, these cells retain 99.62% of their power after thermal cycling between -70 °C and 85 °C for 120 h. Furthermore, they retain 96.03% of their power after 20 min of exposure to air flow when attached to a soft gasbag, which models wind blowing during a violent storm.

Directional Activated Exciton Highway via Fractal Electric Field Modulation for Ultrasensitive Carbon Nanotube-Based Sensors.

The electrical vapor sensor based on carbon nanotubes (CNTs) has attracted wide attention due to its excellent conductivity, stable interfacial structure, and low dimensional quantum effects. However, the conductivity and contact interface activity were still limited by the random distribution of coated CNTs, which led to limited performance. We developed a new strategy to unify the CNT directions with image fractal designing of the electrode system. In such a system, directional aligned CNTs were gained under a well-modulated electric field, leading to microscale CNT exciton highways and molecule-scale host-guest site activation. The carrier mobility of the aligned CNT device is 20-fold higher than that of the random network CNT device. With excellent electrical properties, such modulated CNT devices based on fractal electrodes behave as an ultrasensitive vapor sensor for methylphenethylamine, a mimic of illicit drug methamphetamine. The detection limit reached as low as 0.998 ppq, 6 orders of magnitude sensitive than the reported 5 ppb record based on interdigital electrodes with random distributed CNTs. Since the device is easily fabricated in wafer-level and compatible with the CMOS process, such a fractal design strategy for aligned CNT preparation will be widely applied in a variety of wafer-level electrical functional devices.

Knockdown of LINC00511 enhances radiosensitivity of lung adenocarcinoma via regulating miR-497-5p/SMAD3.

As the most common histological subtype of primary lung cancer, lung adenocarcinoma (LUAD) causes enormous cancer deaths worldwide. Radiotherapy has been frequently used in LUAD cases, and radiosensitivity is vital for LUAD therapy. This research sought to explore the genetic factors affecting radiosensitivity in LUAD and inner mechanisms. LINC00511, miR-497-5p, and SMAD3 expression in LUAD cells were detected via qRT-PCR and western blot. CCK-8 assays, colony formation, and flow cytometry assays were employed to explore the cell viability, apoptosis, and radiosensitivity in PC-9 and A549 cells. The targeting relationship between LINC00511, miR-497-5p, and SMAD3 was verified by dual luciferase reporter assay. Furthermore, xenograft experiments were performed for the in vivo verification. In conclusion, LINC00511 was overexpressed in LUAD cells, which downregulated downstream miR-497-5p expression and mediately led to SMAD3 activation. LINC00511 downregulation suppressed cell viability while enhanced apoptosis rate in LUAD cells. Also, LINC00511 and SMAD3 were overexpressed, while miR-497-5p was downregulated in LUAD cells exposed to 4Gy irradiation treatment. Moreover, LINC00511 inhibition could block SMAD3 expression and promoted the radiosensitivity both in vitro and in vivo. These findings uncover LINC00511 knockdown promoted miR-497-5p expression and subsequently led to lower SMAD3 level, which enhanced radiosensitivity in LUAD cells. LINC00511/miR-497-5p/SMAD3 axis could be of considerable potential to enhance radiosensitivity in LUAD.

Identification of gene signatures associated with ulcerative colitis and the association with immune infiltrates in colon cancer.

Background: Inflammatory bowel diseases, including ulcerative colitis (UC) and Crohn's disease, are some of the most common inflammatory disorders of the gastrointestinal tract. The dysfunction of the immune system in the intestines is suggested to be the underlying cause of the pathogenesis of UC. However, the mechanisms regulating these dysfunctional immune cells and inflammatory phenotypes are still unclear. Methods: The differential expression analysis on microarray datasets were performed including GSE24287, GSE87466, GSE102133, and GSE107499, including 376 samples. "Gene Ontology" and "Kyoto Encyclopedia of Genes and Genomes" pathway enrichment analyses were conducted to identify the common differentially expressed genes (DEGs) in these datasets and explore their underlying biological mechanisms. Further algorithms like "Cell-type Identification by Estimating Relative Subsets of RNA Transcripts" were used to determine the infiltration status of immune cells in patients with UC. "Cytoscape" and "Gene Set Enrichment Analysis" were used to screen for hub genes and to investigate their biological mechanisms. The Tumor Immune Estimation Resource database was used to study the correlation between hub genes and infiltrating immune cells in patients with UC. A total of three hub genes, CCL3, MMP3, and TIMP1, were identified using Cytoscape. Results: A positive correlation was observed between these hub genes and patients with active UC. These genes served as a biomarker for active UC. Moreover, a decrease in CCL3, MMP3, and TIMP1 expression was observed in the mucosa of the intestine of patients with active UC who responded to Golimumab therapy. In addition, results show a significant positive correlation between CCL3, MMP3, and TIMP1 expression and different immune cell types including dendritic cells, macrophages, CD8+ T cells, and neutrophils in patients with colon cancer. Moreover, CCL3, MMP3, and TIMP1 expression were strongly correlated with different immune cell markers. Conclusion: Study results show the involvement of hub genes like CCL3, MMP3, and TIMP1 in the pathogenesis of UC. These genes could serve as a novel pharmacological regulator of UC. These could be used as a therapeutic target for treating patients with UC and may serve as biomarkers for immune cell infiltration in colon cancer.

Direct Active Site at the Van der Waals Heterostructure Interface with Synthetic Drug Analogue N-Methylphenethylimine Ultrasensitivity.

CNT/organic probe-based chemiresistive sensors suffer from the problem of low sensitivity and poor stability due to the unstable and unfavorable CNT/organic probe interface. A new designing strategy of a one-dimensional van der Waals heterostructure was developed for ultrasensitive vapor sensing. By modifying the perylene diimide molecule at the bay region with phenoxyl and further Boc-NH- phenoxy side chains, a highly stable 1D VDW heterostructure SWCNT-probe molecule system was formed with ultrasensitivity and specificity. Interfacial recognition sites consisting of SWCNT and the probe molecule are responsible for the synergistical and excellent sensing response to MPEA molecules, which was proved by Raman, XPS, and FTIR characterizations together with dynamic simulation. Based on such a sensitive and stable VDW heterostructure system, the measured detection limit reached as low as 3.6 ppt for the synthetic drug analogue N-methylphenethylimine (MPEA) in the vapor phase, and the sensor showed almost no performance degradation even after 10 days. Furthermore, a miniaturized detector was developed for real-time monitoring of drug vapor detection.

Differential Virulence of Aggregatibacter actinomycetemcomitans Serotypes Explained by Exoproteome Heterogeneity.

Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative bacterial pathogen associated with periodontitis and nonoral diseases like rheumatoid arthritis and Alzheimer´s disease. Aa isolates with the serotypes a, b, and c are globally most prevalent. Importantly, isolates displaying these serotypes have different clinical presentations. While serotype b isolates are predominant in severe periodontitis, serotypes a and c are generally encountered in mild periodontitis or healthy individuals. It is currently unknown how these differences are reflected in the overall secretion of virulence factors. Therefore, this study was aimed at a comparative analysis of exoproteomes from different clinical Aa isolates with serotypes a, b, or c by mass spectrometry, and a subsequent correlation of the recorded exoproteome profiles with virulence. Overall, we identified 425 extracellular proteins. Significant differences in the exoproteome composition of isolates with different serotypes were observed in terms of protein identification and abundance. In particular, serotype a isolates presented more extracellular proteins than serotype b or c isolates. These differences are mirrored in their virulence in infection models based on human salivary gland epithelial cells and neutrophils. Remarkably, serotype a isolates displayed stronger adhesive capabilities and induced more lysis of epithelial cells and neutrophils than serotype b or c isolates. Conversely, serotype c isolates showed relatively low leukotoxicity, while provoking NETosis to similar extents as serotype a and b isolates. Altogether, we conclude that the differential virulence presentation by Aa isolates with the dominant serotypes a, b, or c can be explained by their exoproteome heterogeneity. IMPORTANCE Periodontitis is an inflammatory disease that causes progressive destruction of alveolar bone and supporting tissues around the teeth, ultimately resulting in tooth loss. The bacterium Aggregatibacter actinomycetemcomitans (Aa) is a prevalent causative agent of periodontitis, but this oral pathogen is also associated with serious extraoral diseases like rheumatoid arthritis and Alzheimer's disease. Clinical Aa isolates are usually distinguished by serotyping, because of known serotype-specific differences in virulence. Aa with serotype b is associated with aggressive forms of periodontitis, while isolates with serotypes a or c are usually encountered in cases of mild periodontitis or healthy individuals. The molecular basis for these differences in virulence was so far unknown. In the present study, we pinpoint serotype-specific differences in virulence factor production by clinical Aa isolates. We consider these findings important, because they provide new leads for future preventive or therapeutic approaches to fight periodontitis and associated morbidities.

Gastrodin ameliorates the lipopolysaccharide-induced neuroinflammation in mice by downregulating miR-107-3p.

Background: Neuroinflammation plays a pivotal role in the pathogenesis of Central Nervous System (CNS) diseases. The phenolic glucoside gastrodin (GAS), has been known to treat CNS disorders by exerting anti-inflammatory activities. Our aim was to investigate the potential neuroprotective mechanisms of GAS on lipopolysaccharide (LPS)-induced mice. Methods: Male C57BL/6J mice were treated by LPS, before which GAS was adminisrated. The behavior tests such as forced swim test, tail suspension test, and elevated plus maze were performed to evaluate depressive-anxiety-like behaviors. A high-throughput sequencing (HTS) analysis was performed to screen out distinctive miRNAs which were validated using quantitative real-time PCR. Then, miRNA agomir or NC was injected stereotaxically into hippocampus of mice to explore the role of miRNA on GAS in response to LPS. Furthermore, Immunofluorescence and the hematoxylin and eosin (H&E) staining were employed to observe the cellular morphology. The protein levels of pro-inflammatory factors were evaluated by western blot. Finally, the target mRNA of miRNA was predicted using bioinformatics analysis. GO and KEGG enrichment analyses were conducted to clarify the potential function of target protein, which were visualized by bubble charts. Results: The behavioral data showed that mice in the LPS group had obvious depressive-anxiety-like behaviors, and 100 mg/kg GAS could improve these behavioral changes and alleviate the levels of pro-inflammatory cytokines in the hippocampus when mice were exposed to LPS for 6 h. Meanwhile, LPS-induced microglia and astrocyte activation in the CA1, CA2, CA3, and DG regions of the hippocampus were also reversed by GAS. Furthermore, miR-107-3p were screened out and verified for GAS in response to LPS. Importantly, miR-107-3p overexpression negatively abrogated the neuroprotective effects of GAS. Moreover, KPNA1 might be the target molecular of miR-107-3p. KPNA1 might regulate 12 neuroinflammation-related genes, which were mainly involved in cytokine-mediated signaling pathway. Conclusion: These results suggested that GAS might alleviate the LPS-induced neuroinflammation and depressive-anxiety-like behaviors in mice by downregulating miR-107-3p and upregulating the downstream target KPNA1. The indicates miR-107-3p may provide a new strategy for the treatment of CNS diseases.