Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke.

BACKGROUND: Dual antiplatelet treatment has been shown to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke. The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied. METHODS: In 222 hospitals in China, we conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy. Patients were randomly assigned, in a 1:1 ratio, within 72 hours after symptom onset to receive clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 21) or matching clopidogrel placebo plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 90). There was no interaction between this component of the factorial trial design and a second part that compared immediate with delayed statin treatment (not reported here). The primary efficacy outcome was new stroke, and the primary safety outcome was moderate-to-severe bleeding - both assessed within 90 days. RESULTS: A total of 6100 patients were enrolled, with 3050 assigned to each trial group. TIA was the qualifying event for enrollment in 13.1% of the patients. A total of 12.8% of the patients were assigned to a treatment group no more than 24 hours after stroke onset, and 87.2% were assigned after 24 hours and no more than 72 hours after stroke onset. A new stroke occurred in 222 patients (7.3%) in the clopidogrel-aspirin group and in 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.008). Moderate-to-severe bleeding occurred in 27 patients (0.9%) in the clopidogrel-aspirin group and in 13 (0.4%) in the aspirin group (hazard ratio, 2.08; 95% CI, 1.07 to 4.04; P = 0.03). CONCLUSIONS: Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin therapy initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone but was associated with a low but higher risk of moderate-to-severe bleeding. (Funded by the National Natural Science Foundation of China and others; INSPIRES ClinicalTrials.gov number, NCT03635749.).

Comparative study of the removal of sulfate by UASB in light and dark environment.

At present, the application of sewage treatment technologies is restricted by high sulfate concentrations. In the present work, the sulfate removal was biologically treated using an upflow anaerobic sludge blanket (UASB) in the absence/presence of light. First, the start-up of UASB for the sulfate removal was studied in terms of COD degradation, sulfate removal, and effluent pH. Second, the impacts of different operation parameters (i.e., COD/SO42- ratio, temperature and illumination time) on the UASB performance were explored. Third, the properties of sludge derived from the UASB at different time were analyzed. Results show that after 28 days of start-up, the COD removal efficiencies in both the photoreactor and non-photoreactor could reach a range of 85-90% while such reactors could achieve > 90% of sulfate being removed. Besides, higher illumination time could facilitate the removal of pollutants in the photoreactor. To sum up, the present study can provide technical support for the clean removal of sulfate from wastewater using photoreactors.

Thickness-ratio-dependent performances of broadband organic photodiodes based on a tin phthalocyanine/PTCDA heterojunction.

Employing a photosensitive donor/acceptor planar heterojunction (DA-PHJ) with complementary optical absorption as the active layer is one of the key strategies for realizing broad spectral organic photodiodes (BS-OPDs). To achieve superior optoelectronic performance, it is vital to optimize the thickness ratio of the donor layer to acceptor layer (the DA thickness ratio) in addition to the optoelectronic properties of the DA-PHJ materials. In this study, we realized a BS-OPD exploiting tin(II) phthalocyanine (SnPc)/3,4,9,10-perylenete-acarboxylic dianhydride (PTCDA) as the active layer and investigated the effect of the DA thickness ratio on the device performance. The results showed that the DA thickness ratio has a significant impact on the device performance, and an optimized DA thickness ratio of 30:20 was found. Upon the optimization of the DA thickness ratio, improvements of 187% in photoresponsivity and 144% in specific detectivity were achieved on average. Trap-free space-charge-limited photocarrier transport and balanced optical absorption over the wavelength range can be ascribed to the improved performance at the optimized DA thickness ratio. These results establish a solid photophysical foundation for improving the performance of BS-OPDs via thickness ratio optimization.

Co-gasification of rural solid waste and biomass in rural areas: Simulation and plant-scale process.

Co-gasification technology is considered to be one of the most potential technologies for solid waste treatment, and the co-gasification treatment of rural solid waste (RSW) and biomass can effectively promote waste reduction and resource utilization. In the present study, the co-gasification of RSW and biomass in an updraft fixed bed gasifier was simulated using the Aspen Plus software, where the simulation results were validated via plant-scale experiments. In this scenario, the impacts of biomass source (i.e., rice husk, rice straw, tree bark and corn straw), co-gasification ratio (CGR) (0-40%) and air equivalence ratio (AER) (0.30-0.55) on the performance of the fixed-bed were investigated. Results showed that Aspen Plus could describe the plant-scale co-gasification process well. Besides, the tree bark-RSW system had the highest heat conversion efficiency of 6.00 MJ/kg the simulation temperature of the gasification layer increased greatly from 485 to 913 °C when the AER increased from 0.40 to 0.55. In addition, the co-gasification of RSW and tree bark could achieve the highest efficiency at the AER of 0.45 and CGR of 20% w, in which the gasification temperature reached 799 °C with the gasification efficiency of 57.17%. This study explored the use of co-gasification of RSW and biomass in rural areas by simulation and plant-scale processes, which promotes the commercial application of co-gasification technology and contributes to sustainable waste management in rural areas.

Dense, Three-Dimensional, Highly Absorbent, Graphene Oxide Aerogel Coating on ZnCo2O4/ZnO Particles Exerts a Synergistic Catalytic Effect for Ammonium Perchlorate Thermal Decomposition.

As a new type of carbon material, graphene oxide aerogel (GA) is widely used in catalysis due to its porous structure, high-efficiency adsorption, and superb conductivity. In this study, GA was prepared into a dense coating layer surrounding ZnCo2O4/ZnO particles to form a composite GA-ZnCo2O4/ZnO by means of a hydrothermal, blast drying, and vacuum-freeze-drying approach applied to catalyze the thermal decomposition of ammonium perchlorate (AP). The physicochemical properties of the obtained GA-ZnCo2O4/ZnO were characterized by different analytical methods. Scanning electron microscopy (SEM) analysis exhibited that GA is coated on the surface of ZnCo2O4/ZnO, forming a dense layer. Brunner Emmet Teller (BET) measurement results show that GA-ZnCo2O4/ZnO has a smooth macropore distribution curve and a larger specific surface area. Moreover, The catalytic effect investigation on AP with GA-ZnCo2O4/ZnO: the high temperature decomposition (HTD) peak temperature of AP in the presence of 5 wt % GA-ZnCo2O4/ZnO was reduced from 441 to 294 °C, and the exotherm of AP was expanded from 205 to 1275 J/g at a heating rate of 15 °C/min. Through the calculation, GA-ZnCo2O4/ZnO makes the activation energy and Gibbs free energy of the AP pyrolysis lower so that the reaction is easier to occur. Thermogravimetric-mass (TG-MS) spectrometry revealed that during thermal decomposition of AP, GA-ZnCo2O4/ZnO leveraged the synergistic catalysis of ZnCo2O4/ZnO and GA that boosted the flow of electrons from ClO4- to O2 and increased the absorption of the gas product to accelerate the AP pyrolysis. These results provided a facile strategy to prepare GA-based composite catalysts with extraordinary application prospects in the domain of solid propellants.

Listeria adhesion protein-expressing bioengineered probiotics prevent fetoplacental transmission of Listeria monocytogenes in a pregnant Guinea pig model.

Pregnancy is a high-risk factor for foodborne pathogen Listeria monocytogenes (Lm), which causes abortion, premature birth, or stillbirth. The primary route of Lm transmission is oral hence intestinal epithelial barrier crossing is a prerequisite for systemic spread. Intestinal barrier crossing, in part, is attributed to the interaction of Listeria adhesion protein (LAP) with its cognate receptor, Hsp60. In a recent study, we showed that oral-dosing of bioengineered Lactobacillus caseiprobiotic (BLP) expressing the LAP protected nonpregnant mice from lethal infection; however, its ability to prevent listeriosis during pregnancy is not known. Therefore, we investigated whether BLP could prevent fetoplacental transmission of Lm in a pregnant guinea pig model. After 14 consecutive days on probiotic (~109 CFU/ml in drinking water), pregnant guinea pigs (gestational days 24-28) were orally challenged with Lm (9 × 108-2.5 × 109 CFU/animal) and were euthanized 72 h post-infection. Maternal mesenteric lymph node (MLN), liver, spleen, lungs, blood, and placenta, and fetal liver were analyzed for the presence/absence of Lm. All tissues/organs from Lm-challenged naïve dams and fetuses were Lm positive. Similar tissue distribution was also seen in guinea pigs that received wild-type Lactobacillus casei (LbcWT). Remarkably, Lm was absent in the maternal blood, kidney, lungs, and placenta, and fetal liver from the BLP-fed group even though the Lm was present in the maternal liver, spleen, and MLN. BLP feeding also suppressed Lm-induced inflammatory response in mothers. These data highlight the potential for the prevention of fetoplacental transmission of Lm by LAP-expressing BLP during pregnancy.

Extended-field coverage hyperspectral camera based on a single-pixel technique.

A spectral single-pixel imaging system facilitates effective image compression, but the imaging region is limited by its single detector. This paper presents a hyperspectral camera that allows extended-field coverage to be collected by one detector. Compressive data of a large field of view is achieved by our highly sensitive detection camera, which can be extended to near-infrared or infrared spectral monitoring. We acquire a hyperspectral datacube of 256×256 spatial pixels and 3 nm spectral resolution at a sampling rate of 25%. Finally, we apply our camera to monitoring fruit freshness nondestructively by differentiating a banana's ripeness over time.

Strong population structure of Schizopygopsis chengi and the origin of S. chengi baoxingensis revealed by mtDNA and microsatellite markers.

The Tibetan Plateau underwent dramatic geological and climatic changes, which had important implications for genetic divergence and population dynamics of freshwater fish populations. Fluctuations of the ecogeographical environment and major hydrographic formations might have promoted the formation of new subspecies or species. In order to understand the impact of plateau uplift on freshwater fish evolutionary history, we estimated the genetic diversity and population structure in two subspecies of Schizopygopsis chengi (S. c. chengi and S. c. baoxingensis) in upper Yangtze River in Tibetan Plateau area using mitochondrial DNA control region and eight microsatellite markers, which suggested that there was a close genetic relationship. S. chengi showed some significant genetic structure that did not correlate with geographic distance. Bayesian assignment tests indicated that S. chengi samples in the study could be divided into four populations: upstream population, midstream population, tributary population and S. c. baoxingensis population. S. c. chengi and S. c. baoxingensis showed significant genetic divergence. However, phylogenetic analysis, population structure analysis and historical gene flow estimation suggested that there was close genetic relationship between S. c. baoxingensis and the Dawei population which belongs to populations of S. c. chengi. The time that Dawei population suffered from a bottleneck and S. c. baoxingensis underwent population expansion was congruent with the last glacial period on the Tibetan Plateau. The results confirmed the hypothesis that the Dawei River and Baoxing River were once connected, and the Dawei and Baoxing populations originated from a single population, but were isolated into separate populations because of crustal movements and the Baoxing population evolved as S. c. baoxingensis.

The Application of PBM Therapy in Patients Subjected to Oral GVHD: A Review.

Background: Oral graft-versus-host disease (GVHD) is characterized by mucosal lesions, salivary gland dysfunction etc., accompanied by pain and oral dysfunction. The efficacy of photobiomodulation (PBM) in managing pain and inflammation has been demonstrated. PBM has been applied in oral GVHD and is regarded as a potent adjunctive therapy. Objective: To review the application of PBM for oral GVHD and summarize its biological mechanisms and recommended parameters. Materials and Methods: The article provides an overview of the therapeutic effects of PBM in oral GVHD cases. It analyzes the biological mechanisms from different aspects and explores the potential prospects of PBM, and appropriate parameters and frequency for GVHD are recommended. Conclusions: The efficacy of PBM in oral GVHD has been demonstrated through symptom alleviation and function improvement. It is recommended as an adjuvant therapy for oral GVHD. However, further research is required to explore optimal devices, parameters, and potential complications associated with using PBM in oral GVHD.

Protocol to reveal the binding partner of secreted housekeeping enzymes in Listeria monocytogenes via in silico prediction to in vivo validation.

Numerous interacting protein partners exist without recognized interactive domains, necessitating a standardized methodology to decipher more in-depth interaction profiles. Here, we present a protocol to reveal the binding partner of a secreted housekeeping enzyme, alcohol acetaldehyde dehydrogenase (Listeria adhesion protein), in Listeria monocytogenes through in silico modeling and in vivo experiments. We describe steps for target protein modeling, biophysical profiling, ClusPro docking optimization, protein variant modeling, and docking comparison. We then provide detailed procedures for in vitro and in vivo protein binding validation. For complete details on the use and execution of this protocol, please refer to Liu et al.1.

Electroenzymatic tandem catalysis for the conversion of nitrate into ammonia.

A porous silver nanostructure-supported ionic liquid-modified chloroperoxidase nanohybrid was successfully used in electroenzymatic tandem catalysis to achieve an efficient, mild, and stable approach for the conversion of nitrate into ammonia.

Pangenome characterization and analysis of the NAC gene family reveals genes for Sclerotinia sclerotiorum resistance in sunflower (Helianthus annuus).

BACKGROUND: Sunflower (Helianthus annuus) is one of the most important economic crops in oilseed production worldwide. The different cultivars exhibit variability in their resistance genes. The NAC transcription factor (TF) family plays diverse roles in plant development and stress responses. With the completion of the H. annuus genome sequence, the entire complement of genes coding for NACs has been identified. However, the reference genome of a single individual cannot cover all the genetic information of the species. RESULTS: Considering only a single reference genome to study gene families will miss many meaningful genes. A pangenome-wide survey and characterization of the NAC genes in sunflower species were conducted. In total, 139 HaNAC genes are identified, of which 114 are core and 25 are variable. Phylogenetic analysis of sunflower NAC proteins categorizes these proteins into 16 subgroups. 138 HaNACs are randomly distributed on 17 chromosomes. SNP-based haplotype analysis shows haplotype diversity of the HaNAC genes in wild accessions is richer than in landraces and modern cultivars. Ten HaNAC genes in the basal stalk rot (BSR) resistance quantitative trait loci (QTL) are found. A total of 26 HaNAC genes are differentially expressed in response to Sclerotinia head rot (SHR). A total of 137 HaNAC genes are annotated in Gene Ontology (GO) and are classified into 24 functional groups. GO functional enrichment analysis reveals that HaNAC genes are involved in various functions of the biological process. CONCLUSIONS: We identified NAC genes in H. annuus (HaNAC) on a pangenome-wide scale and analyzed S. sclerotiorum resistance-related NACs. This study provided a theoretical basis for further genomic improvement targeting resistance-related NAC genes in sunflowers.

Clinical efficacy of photodynamic therapy of oral potentially malignant disorder.

OBJECTIVE: To investigate the clinical efficacy of aminovalerate hydrochloride photodynamic therapy (PDT) for oral potentially malignant disorder (OPMD),oral leukoplakia (OLK), along with identifying the influencing factors.Additionally, the study aims to detect the rates of recurrence and malignancy after PDT. METHOD: 60 patients with OPMD who received PDT at our hospital from 2006 to 2021 were included in this study. Relevant patient medical data were collected and analyzed using SAS 9.4 software.The Mann-Whitney U test was used to retrospectively analyze the factors influencing clinical efficacy, as well as recurrence rate and malignant transformation rate (MTR) after treatment. RESULT: Among the 60 OPMD patients receiving PDT, complete remission in 13 (21.67 %), partial remission in 39 (65.00 %), and no remission in eight (13.33 %), resulting in an overall effective rate of 86.67 %.Fifteen patients experienced relapse, leading to a recurrence rate of 25.00 %. Among these relapses,11 patients occurred within one year after treatment, corresponding to an 18.33 % recurrence rate during that period. Moreover, nine patients developed malignant transformation (MT), resulting in an MTR of 15.00 %. Out of these patients, six individuals developed MT within one year after treatment, resulting in a one-year MTR of 10.00 %. CONCLUSION: The study findings indicate that PDT shows promising clinical efficacy in the treatment of OPMD, with relatively limited and tolerable postoperative adverse reactions. However, there remains a certain rate of recurrence and malignancy after treatment. Therefore, close attention should be paid to postoperative monitoring, regular follow-up, and further expansion of the sample size to observe its long-term efficacy.

Multifunctional Ultrathin Metasurface with a Low Radar Cross Section and Variable Infrared Emissivity.

The development of stealth devices that are compatible with both infrared (IR) and radar systems remains a significant challenge, as the material properties required for effective IR and radar stealth are often contradictory. In this work, based on an IR electrochromic device (IR-ECD), concepts of metamaterial manipulating electromagnetic waves are applied to develop a multifunctional ultrathin metasurface with a low radar cross section (RCS) and variable infrared emissivity. This paper presents a linear-to-linear polarization conversion metasurface (PCM) designed by hollowing the IR-ECD. In this way, the IR-ECD based on polyaniline (PANI) can also modulate the reflection waves in the microwave band without affecting its features in the infrared region. Thus, the proposed metasurface integrates both microwave stealth and variable infrared emissivity through a single layer. The measured results show that a 10 dB RCS reduction is achieved in the band of 8.46-9.5 GHz, and the infrared emissivity can be adjusted from 0.870 to 0.513 in the infrared stealth band of 8-14 µm. Due to the ultrathin thickness (only 0.081λ0 at 9 GHz), low RCS in the X-band, and variable infrared emissivity, the designed multifunctional stealth metasurface has promising applications on military platforms with various surrounding environments.

GMP affected assembly behaviors of phosphatidylethanolamine monolayers elucidated by multi-resolved SFG-VS and BAM.

The interaction between nucleotide molecules and lipid molecules plays important roles in cell activities, but the molecular mechanism is very elusive. In the present study, a small but noticeable interaction between the negatively charged phosphatidylethanolamine (PE) and Guanosine monophosphate (GMP) molecules was observed from the PE monolayer at the air/water interface. As shown by the sum frequency generation (SFG) spectra and Pi-A isotherm of the PE monolayer, the interaction between the PE and GMP molecules imposes very small changes to the PE molecules. However, the Brewster angle microscopy (BAM) technique revealed that the assembly conformations of PE molecules are significantly changed by the adsorption of GMP molecules. By comparing the SFG spectra of PE monolayers after the adsorption of GMP, guanosine and guanine, it is also shown that the hydrogen bonding effect plays an important role in the nucleotide-PE interactions. These results provide fundamental insight into the structure changes during the nucleotide-lipid interaction, which may shed light on the molecular mechanism of viral infection, DNA drug delivery, and cell membrane curvature control in the brain or neurons.

Combination of facial and nose features of Amur tigers to determine age.

We found that the area of black round or irregular-shaped spots on the tiger's nose increased with age, indicating a positive relationship between age and nose features. We used the deep learning model to train the facial and nose image features to identify the age of Amur tigers, using a combination of classification and prediction methods to achieve age determination with an accuracy of 87.81%.

Pigmentiphaga kullae CHJ604 improved the growth of tobacco by degrading allelochemicals and xenobiotics in continuous cropping obstacles.

Plant autotoxicity is considered to be one of the important causes of continuous cropping obstacles in modern agriculture, which accumulates a lot of allelochemicals and xenobiotics and is difficult to solve effectively. To overcome tobacco continuous obstacles, a strain Pigmentiphaga kullae CHJ604 isolated from the environment can effectively degrade these compounds in this study. CHJ604 strain can degrade 11 types of autotoxicity allelochemicals and xenobiotics (1646.22 µg/kg) accumulated in the soil of ten-years continuous cropping of tobacco. The 11 allelochemicals and xenobiotics significantly reduced Germination Percentage (GP), Germination Index (GI), and Mean Germination Time (MGT) of tobacco seeds, and inhibited the development of leaves, stems, and roots. These negative disturbances can be eliminated by CHJ604 strain. The degradation pathways of 11 allelochemicals and xenobiotics were obtained by whole genome sequence and annotation of CHJ604 strain. The heterologous expression of a terephthalate 1,2-dioxygenase can catalyze 4-hydroxybenzoic acid, 4-hydroxy-3-methoxybenzoic acid, 4-hydroxybenzaldehyde, and 4-hydroxy-3-methoxy-benzaldehyde, respectively. The phthalate 4,5-dioxygenase can catalyze phthalic acid, diisobutyl phthalate, and dibutyl phthalate. These two enzymes are conducive to the simultaneous degradation of multiple allelochemicals and xenobiotics by strain CHJ604. This study provides new insights into the biodegradation of autotoxicity allelochemicals and xenobiotics as it is the first to describe a degrading bacterium of 11 types of allelochemicals and xenobiotics and their great potential in improving tobacco continuous obstacles.

The genetic status and rescue measure for a geographically isolated population of Amur tigers.

The Amur tiger is currently confronted with challenges of anthropogenic development, leading to its population becoming fragmented into two geographically isolated groups: smaller and larger ones. Small and isolated populations frequently face a greater extinction risk, yet the small tiger population's genetic status and survival potential have not been assessed. Here, a total of 210 samples of suspected Amur tiger feces were collected from this small population, and the genetic background and population survival potentials were assessed by using 14 microsatellite loci. Our results demonstrated that the mean number of alleles in all loci was 3.7 and expected heterozygosity was 0.6, indicating a comparatively lower level of population genetic diversity compared to previously reported studies on other subspecies. The genetic estimates of effective population size (Ne) and the Ne/N ratio were merely 7.6 and 0.152, respectively, representing lower values in comparison to the Amur tiger population in Sikhote-Alin (the larger group). However, multiple methods have indicated the possibility of genetic divergence within our isolated population under study. Meanwhile, the maximum kinship recorded was 0.441, and the mean inbreeding coefficient stood at 0.0868, both of which are higher than those observed in other endangered species, such as the African lion and the grey wolf. Additionally, we have identified a significant risk of future extinction if the lethal equivalents were to reach 6.26, which is higher than that of other large carnivores. Further, our simulation results indicated that an increase in the number of breeding females would enhance the prospects of this population. In summary, our findings provide a critical theoretical basis for further bailout strategies concerning Amur tigers.

Listeria adhesion protein orchestrates caveolae-mediated apical junctional remodeling of epithelial barrier for Listeria monocytogenes translocation.

The cellular junctional architecture remodeling by Listeria adhesion protein-heat shock protein 60 (LAP-Hsp60) interaction for Listeria monocytogenes (Lm) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate that Lm crosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (lap- or ΔinlA) or double (lap-ΔinlA) mutant strains show significant defects. LAP promotes Lm translocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA facilitates Lm translocation at cells displaying apical E-cadherin during cell extrusion and mucus expulsion from goblet cells. LAP hijacks caveolar endocytosis to traffic integral junctional proteins to the early and recycling endosomes. Pharmacological inhibition in a cell line and genetic knockout of caveolin-1 in mice prevents LAP-induced intestinal permeability, junctional endocytosis, and Lm translocation. Furthermore, LAP-Hsp60-dependent tight junction remodeling is also necessary for InlA access to E-cadherin for Lm intestinal barrier crossing in InlA-permissive hosts. IMPORTANCE: Listeria monocytogenes (Lm) is a foodborne pathogen with high mortality (20%-30%) and hospitalization rates (94%), particularly affecting vulnerable groups such as pregnant women, fetuses, newborns, seniors, and immunocompromised individuals. Invasive listeriosis involves Lm's internalin (InlA) protein binding to E-cadherin to breach the intestinal barrier. However, non-functional InlA variants have been identified in Lm isolates, suggesting InlA-independent pathways for translocation. Our study reveals that Listeria adhesion protein (LAP) and InlA cooperatively assist Lm entry into the gut lamina propria in a gerbil model, mimicking human listeriosis in early infection stages. LAP triggers caveolin-1-mediated endocytosis of critical junctional proteins, transporting them to early and recycling endosomes, facilitating Lm passage through enterocytes. Furthermore, LAP-Hsp60-mediated junctional protein endocytosis precedes InlA's interaction with basolateral E-cadherin, emphasizing LAP and InlA's cooperation in enhancing Lm intestinal translocation. This understanding is vital in combating the severe consequences of Lm infection, including sepsis, meningitis, encephalitis, and brain abscess.

Immediate- or Delayed-Intensive Statin in Acute Cerebral Ischemia: The INSPIRES Randomized Clinical Trial.

Importance: Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis. Objective: To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed. Interventions: Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90). Main Outcomes and Measures: The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome. Results: A total of 11 431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively. Conclusions and Relevance: Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.