Acute ischemic stroke in tuberculous meningitis.

Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.

Development of a novel Eu2+ activated oxonitridosilicate cyan phosphor for enhancing the color quality of a violet-chip-based white LED.

Cyan phosphors are urgently needed to fill the cyan gap and improve the spectral continuity of white light-emitting diodes (LEDs) to cater to the high demand for high-quality lighting. Here, a series of new Eu2+-activated La3Si6.5Al1.5N9.5O5.5 (LSANO) cyan phosphors were prepared, and their luminescence properties and color centers were analyzed through fluorescence spectral measurements from 7 K to 475 K. At 300 K, the photoluminescence excitation (PLE) spectrum monitored at 483 nm presents a broadband of 200-460 nm with a peak at 398 nm, matching well with commercial violet LED chips. When excited by 398 nm violet light, the photoluminescence emission (PL) spectrum of LSANO:0.01Eu2+ exhibits a cyan emission band at about 483 nm. At 7 K, the emission spectrum clearly shows an asymmetric emission band and the emission peak wavelength changes from 483 nm (300 K) to 500 nm (7 K), indicating that there are two possible color centers in the LSANO:Eu2+ phosphor. Moreover, the maximum emission value can be adjusted from 480 to 499 nm by adjusting the doping content of Eu2+. Finally, a violet-chip-based white LED with the optimized color quality of Ra = 91.4, Rf = 90.1, and Rg = 93.6 was fabricated by adding the prepared cyan phosphor, verifying the potential application of the prepared cyan phosphor LSANO:Eu2+ in high-quality white LEDs.

Effects of home-based exercise interventions on post-stroke depression: A systematic review and network meta-analysis.

BACKGROUND: Post-stroke depression (PSD) is a common and persistent mental disorder that negatively impacts stroke outcomes. Exercise-based interventions have been shown to be an effective non-pharmacological treatment for improving depression in patients with mild stroke, but no reviews have yet synthesized the effects of home-based exercise on PSD. OBJECTIVE: The purpose of this systematic review and network meta-analysis was to synthesize the available evidence to compare the effectiveness of different types of home-based exercise programs on PSD and identify the optimal home-based exercise modality to inform clinical decision-making for the treatment of PSD. METHODS: PubMed, Embase, the Cochrane Library, CINAHL, and PsycINFO were systematically searched from their inception dates to March 7, 2023. We searched for randomized controlled trials (RCTs) of home-based exercise for PSD in adults aged 18 years and older. Only scores of depression retrieved directly post-treatment were included as the primary endpoint for the analysis. Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB-2) was used to assess the quality of included studies. We conducted traditional pairwise meta-analysis for direct comparisons using Review Manager 5.4.1, followed by network meta-analysis using Stata 15.1 for both the network evidence plot and analysis. The surface under the cumulative ranking curve (SUCRA) was used to estimate the intervention hierarchy. The protocol was registered with PROSPERO under registration number CRD42022363784. RESULTS: A total of 517 participants from nine RCTs were included. Based on the ranking probabilities, mind-body exercise was the most effective way in improving PSD (SUCRA: 90.4 %, Hedges' g: -0.59, 95 % confidence interval [CI]: -1.16 to -0.02), followed by flexibility/neuro-motor skills training (SUCRA: 42.9 %, Hedges' g: -0.10, 95 % CI: -0.70 to 0.49), and aerobic exercise (SUCRA: 39.3 %, Hedges' g: -0.07, 95 % CI: -0.81 to 0.67). We performed a subgroup analysis of mind-body exercise. In mind-body exercise interventions, Tai Chi was the most effective way to improve PSD (SUCRA: 99.4 %, Hedges' g: -0.94, 95 % CI: -1.28 to -0.61). CONCLUSIONS: Our network meta-analysis that provides evidence with very low certainty indicates potential benefits of home-based exercise for alleviating PSD, with mind-body exercises, notably Tai Chi, showing promise as an effective treatment. However, further rigorous studies are needed to solidify these findings. Specifically, multicenter RCTs comparing specific exercises to no intervention are crucial, assessing not only efficacy but also dose, reach, fidelity, and long-term effects for real-world optimization.

Efficient All-Perovskite Tandem Solar Cells with Low-Optical-Loss Carbazolyl Interconnecting Layers.

Combining wide-band gap (WBG) and narrow-band gap (NBG) perovskites with interconnecting layers (ICLs) to construct monolithic all-perovskite tandem solar cell is an effective way to achieve high power conversion efficiency (PCE). However, optical losses from ICLs need to be further reduced to leverage the full potential of all-perovskite tandem solar cells. Here, metal oxide nanocrystal layers anchored with carbazolyl hole-selective-molecules (CHs), which exhibit much lower optical loss, is employed to replace poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT : PSS) as the hole transporting layers (HTLs) in lead-tin (Pb-Sn) perovskite sub-cells and ICLs in all-perovskite tandem solar cells. Optically transparent indium tin oxide nanocrystals (ITO NCs) layers are employed to enhance anchoring of CHs, while a mixture of two CHs is adopted to tune the surface energy-levels of ITO NCs. The optimized mixed Pb-Sn NBG perovskite solar cells demonstrate a high PCE of 23.2 %, with a high short-circuit current density (Jsc ) of 33.5 mA cm-2 . A high PCE of 28.1 % is further obtained in all-perovskite tandem solar cells, with the highest Jsc of 16.7 mA cm-2 to date. Encapsulated tandem solar cells maintain 90 % of their reference point after 500 h of operation at the maximum power point (MPP) under 1-Sun illumination.

The dynamics of deltamethrin resistance evolution in Aedes albopictus has an impact on fitness and dengue virus type-2 vectorial capacity.

BACKGROUND: Worldwide invasion and expansion of Aedes albopictus, an important vector of dengue, chikungunya, and Zika viruses, has become a serious concern in global public health. Chemical insecticides are the primary means currently available to control the mosquito populations. However, long-term and large-scale use of insecticides has selected for resistance in the mosquito that is accompanied by a genetic load that impacts fitness. RESULTS: A number of laboratory strains representing different resistance mechanisms were isolated and identified from laboratory-derived, deltamethrin-resistant Ae. albopictus recovered in previous work. Resistance levels and fitness costs of the strains were evaluated and compared to characterize the evolution of the resistance genotypes and phenotypes. The heterozygous F1534S mutation (1534F/S) in the voltage gated sodium channel (vgsc) gene product (VGSC), first detected in early stages of resistance evolution, not only confers high-level resistance, but also produces no significant fitness costs, leading to the rapid spread of resistance in the population. This is followed by the increase in frequency of homozygous F1534S (1534S/S) mosquitoes that have significant fitness disadvantages, prompting the emergence of an unlinked I1532T mutation with fewer side effects and a mating advantage better adapted to the selection and reproductive pressures imposed in the experiments. Metabolic resistance with no significant fitness cost and mediating a high-tolerance resistance phenotype may play a dominant role in the subsequent evolution of resistance. The different resistant strains had similar vector competence for dengue virus type-2 (DENV-2). Furthermore, a comparative analysis of vectorial capacity revealed that increased survival due to deltamethrin resistance balanced the negative fitness cost effects and contributed to the risk of dengue virus (DENV) transmission by resistant populations. The progressive evolution of resistance results in mosquitoes with both target-site insensitivity and metabolic resistance with lower fitness costs, which further leads to resistant populations with both high resistance levels and vectorial capacity. CONCLUSIONS: This study reveals a possible mechanism for the evolution of deltamethrin resistance in Aedes albopictus. These findings will help guide practical strategies for insecticide use, resistance management and the prevention and control of mosquito-borne disease.

Moving adsorption belt system for continuous bioproduct recovery utilizing composite fibrous adsorbents.

A continuous protein recovery and purification system based on the true moving bed concept is presented. A novel adsorbent material, in the form of an elastic and robust woven fabric, served as a moving belt following the general designs observed in known belt conveyors. The composite fibrous material that forms the said woven fabric showed high protein binding capacity, reaching a static binding capacity equal to 107.3 mg/g, as determined via isotherm experiments. Moreover, testing the same cation exchange fibrous material in a packed bed format resulted in excellent dynamic binding capacity values (54.5 mg/g) even when operating at high flow rates (480 cm/h). In a subsequent step, a benchtop prototype was designed, constructed, and tested. Results indicated that the moving belt system could recover a model protein (hen egg white lysozyme) with a productivity up to 0.5 mg/cm2/h. Likewise, a monoclonal antibody was directly recovered from unclarified CHO_K1 cell line culture with high purity, as judged by SDS-PAGE, high purification factor (5.8), and in a single step, confirming the suitability and selectivity of the purification procedure.

A DBHS family member regulates male determination in the filariasis vector Armigeres subalbatus.

The initial signals governing sex determination vary widely among insects. Here we show that Armigeres subalbatus M factor (AsuMf), a male-specific duplication of an autosomal gene of the Drosophila behaviour/human splicing (DBHS) gene family, is the potential primary signal for sex determination in the human filariasis vector mosquito, Ar. subalbatus. Our results show that AsuMf satisfies two fundamental requirements of an M factor: male-specific expression and early embryonic expression. Ablations of AsuMf result in a shift from male- to female-specific splicing of doublesex and fruitless, leading to feminization of males both in morphology and general transcription profile. These data support the conclusion that AsuMf is essential for male development in Ar. subalbatus and reveal a male-determining factor that is derived from duplication and subsequent neofunctionalization of a member of the conserved DBHS family.

Construction and characterization of a synthesized herpes simplex virus H129-Syn-G2.

Herpes simplex virus type 1 (HSV-1) causes lifelong infections worldwide, and currently there is no efficient cure or vaccine. HSV-1-derived tools, such as neuronal circuit tracers and oncolytic viruses, have been used extensively; however, further genetic engineering of HSV-1 is hindered by its complex genome structure. In the present study, we designed and constructed a synthetic platform for HSV-1 based on H129-G4. The complete genome was constructed from 10 fragments through 3 rounds of synthesis using transformation-associated recombination (TAR) in yeast, and was named H129-Syn-G2. The H129-Syn-G2 genome contained two copies of the gfp gene and was transfected into cells to rescue the virus. According to growth curve assay and electron microscopy results, the synthetic viruses exhibited more optimized growth properties and similar morphogenesis compared to the parental virus. This synthetic platform will facilitate further manipulation of the HSV-1 genome for the development of neuronal circuit tracers, oncolytic viruses, and vaccines.

Mobile APP-assisted family physician program for improving blood pressure outcome in hypertensive patients.

BACKGROUND: This study was aimed to examine the effectiveness of App-assisted self-care in a Beijing community based on intelligent family physician-optimised collaborative model (IFOCM) program.  METHODS: We conducted a survey of 12,050 hypertensive patients between Jan 2014 and Dec 2021. Generalized linear model was used to analyze the covariates that associated with blood pressure (BP) control. Decision tree and random forest algorithm was used to extract the important factors of BP outcome. RESULTS: The study included 5937 patients, mean age 66.2 ± 10.8, with hypertension in the baseline; 3108(52.4) were female. The community management resulted in mean systolic BP and diastolic BP reductions of 4.6 mmHg and 3.8 mmHg at follow-up. There were 3661 (61.6%) hypertension patients with BP control, increasing from 55.0% in 2014 to 75.0% in 2021. After adjusted for covariates, antihypertensive medication adherence, diabetes, and APP-assisted self-care were common predictors associated with BP control in GLM model and machine learning algorithm. CONCLUSION: Community management based on IFOCM program significantly improved BP control in hypertensive patients. APP-assisted self-care would be beneficial for the management of chronic disease.

A Simple Federated Learning-Based Scheme for Security Enhancement Over Internet of Medical Things.

Nowadays, Federated Learning (FL) over Internet of Medical Things (IoMT) devices has become a current research hotspot. As a new architecture, FL can well protect the data privacy of IoMT devices, but the security of neural network model transmission can not be guaranteed. On the other hand, the sizes of current popular neural network models are usually relatively extensive, and how to deploy them on the IoMT devices has become a challenge. One promising approach to these problems is to reduce the network scale by quantizing the parameters of the neural networks, which can greatly improve the security of data transmission and reduce the transmission cost. In the previous literature, the fixed-point quantizer with stochastic rounding has been shown to have better performance than other quantization methods. However, how to design such quantizer to achieve the minimum square quantization error is still unknown. In addition, how to apply this quantizer in the FL framework also needs investigation. To address these questions, in this paper, we propose FedMSQE - Federated Learning with Minimum Square Quantization Error, that achieves the smallest quantization error for each individual client in the FL setting. Through numerical experiments in both single-node and FL scenarios, we prove that our proposed algorithm can achieve higher accuracy and lower quantization error than other quantization methods.

Successful Rescue of Synthetic AcMNPV with a ~17 kb Deletion in the C1 Region of the Genome.

Baculoviruses have been widely used as expression vectors. However, numerous genes in the baculoviral genome are non-essential for cellular infection and protein expression, making the optimisation of baculovirus expression vectors possible. We used a synthetic biological method to reduce the number of genes in a partial region of the autograph californica multiple nucleopolyhedrovirus (AcMNPV), the most widely used baculovirus expression vector. The C1 region of the AcMNPV is 46.4 kb and is subdivided into B1, B2, and B3 fragments. We first designed modified B1, B2, and B3 fragments by deleting the non-essential genes, and then synthesised complete viral genomes containing either individual modified B fragments or joint modified B fragments through transformation-related recombination in yeast. The synthetic genomes were then transfected into Sf9 cells to rescue the progeny viruses and test their infectivity. The design-build-test cycle was repeated until the ultimately rescued virus could produce progeny viruses efficiently. Finally, AcMNPV-Syn-mC1-1.1 by deleting approximately 17.2 kb, including 20 ORFs, in the C1 region, was obtained. This is essential to the synthesis of a minimal AcMNPV genome that can generate infectious progeny viruses and can be further used to optimise the foundation of baculovirus expression vectors.

Prevalence and prognostic significance of malnutrition risk in patients with pulmonary tuberculosis: A hospital-based cohort study.

Background: The prevalence and prognostic significance of malnutrition risk remain unclear in Chinese patients with pulmonary tuberculosis. Therefore, we aimed to investigate the malnutrition risk in Chinese patients and explore the relationship between malnutrition risk and follow-up outcomes. Methods: We conducted a hospital-based cohort study from January 2020 to December 2020. Malnutrition risks were evaluated using nutritional scales, including the Nutritional Risk Screening 2002 (NRS-2002), the controlling nutritional status score (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index (PNI). The primary outcome was all-cause mortality at a one-year follow-up. Malnutrition risk was calculated, and the relationship between malnutrition and follow-up outcomes was analyzed. We assessed the performance of malnutrition risks to predict clinical outcomes in prognostic models. Results: A total of 1,075 patients were included. According to NRS-2002, CONUT, GNRI, and PNI, 818 (76.09%), 954 (88.74%), 682 (63.44%), and 364 (33.86%) patients were at risk of malnutrition, respectively. Before 1-year follow-up, a total of 99 patients (9.2%) had died. After adjustment for risk factors, the association between severe malnutrition in CONUT (HR = 4.78, 95% CI: 1.14-20.11, P = 0.033), GNRI (HR = 3.53, 95% CI: 1.70-7.34, P = 0.001), or PNI (HR = 2.94, 95% CI: 1.76-4.88, P < 0.001) and death before 1-year follow-up remained significant. The addition of the nutritional scales to prognostic models improved death prediction, as validated by the integrated discrimination index (all P-values of <0.05). Conclusion: Malnutrition in patients with pulmonary tuberculosis was associated with an increased risk of all-cause death in the long-term follow-up. Our findings provided evidence for the use of admission nutrition screening in patients with pulmonary tuberculosis.

Biohybrid Magnetic Microrobots for Tumor Assassination and Active Tissue Regeneration.

Magnetic microrobots have attracted increasing research interest for diverse biomedical applications, such as targeted therapy and tissue regeneration. However, multifunctional microrobots with complex morphology at the microscale are urgently needed to be fabricated, actively controlled, and functionalized. In this study, the chrysanthemum pollen-derived biohybrid magnetic microrobots (CDBMRs) with spiny protrusion, hollow cavity, and porous surface structure were proposed for tumor assassination and active tissue regeneration. By exquisitely designing the sequential treatment process, CDBMRs were fabricated and the innate morphology of pollen templates was well preserved. Under magnetic field, CDBMR exhibited various individual and collective behaviors. CDBMRs were utilized for synergetic tumor treatment by the combination of magnetically controlled physical assassination and active drug delivery. Meanwhile, CDBMRs showed excellent ability for active cell delivery and tissue regeneration, which was further proved by enhanced osteogenesis ability. By making full use of the natural morphology of pollen grains, the biohybrid microrobots presented a promising strategy for effective tumor therapeutics and tissue regeneration.

Case report: A 9-year systematic treatment failure of a pulmonary tuberculosis patient.

Objective: To explore the reasons of failure in a case of pulmonary tuberculosis (PTB) after 9 years systematic treatment. Methods: We extracted the patients' treatment history, drug susceptibility testing (DST), Computed tomography (CT) images, and sequenced the isolated strains by whole gene sequencing (WGS). Results: Although most results of the phenotypical DSTs were consistent with the genotype DST, the occurrence of gene resistance to amikacin (AMK), capreomycin (CAP), moxifloxacin (MFX) was earlier than the phenotypical DST. Based on the continuously reversed results of phenotypical DSTs, CT images in different stages and WGS, it can be confirmed that the patient was infected with two different strains of Mycobacterium tuberculosis (M.TB). Moreover, severe cavities may be another factor leading to treatment failure. Conclusion: Given the suggestive effect of genotype DST is earlier than the phenotypical DST, so genotype DST can play a better guiding role in patients with MDR-TB. Additionally, for patients who have not been cured for a long time, medication should be more cautious and the role of WGS in drug resistance surveillance should be fully utilized.

Armigeres subalbatus is a potential vector for Zika virus but not dengue virus.

BACKGROUND: Zika virus (ZIKV) and dengue virus (DENV) are closely related flaviviruses primarily transmitted by Aedes mosquitoes. Armigeres subalbatus is an emerging and widely distributed mosquito, and ZIKV has been detected and isolated from it. However, it is not clear whether Ar. subalbatus could be a vector for ZIKV and DENV or not. In this study, we investigated the infection and transmission of Ar. subalbatus to ZIKV and DENV. METHODS: A line of Ar. subalbatus was isolated from Guangdong, China, and further identified by the mitochondrial cytochrome oxidase subunit 1 (COI) gene. The adults of Ar. subalbatus were fed with blood meal containing ZIKV or DENV-2. At 4, 7, 10, 14, and 21 days post-inoculation (dpi), the infections of ZIKV or DENV-2 in the midguts, ovaries and salivary glands were detected and quantified by RT-PCR and RT-qPCR. To assess the transmissibility, suckling mice were exposed to bites of ZIKV-infected mosquitoes, and ZIKV was detected in brain tissue by RT-qPCR and plaque assays. Furthermore, the larvae of Ar. subalbatus were reared in artificial urine containing ZIKV or DENV-2. The infection rates and viral titers of larvae and adults were analyzed by RT-PCR and RT-qPCR, and the viral distribution in larval tissues was observed by immunohistochemistry. Chi-square test and one-way ANOVA analysis were used for assessing the infection rate and viral titer in varied tissues and different time points, respectively. RESULTS: Following oral inoculation, ZIKV but not DENV-2 could be detected in Ar. subalbatus midguts at 4 dpi, ovaries at 7 dpi and salivary glands at 10 dpi. The highest infection rate (IR) of ZIKV was 27.8% in midgut at 7 dpi, 9.7% in ovary and 5.6% in salivary gland at 21 dpi. Eight days after being bitten by ZIKV-positive mosquitoes, ZIKV was detected in three brain tissues out of four suckling mice exposed to bites. ZIKV could be detected in the larvae reared in artificial urine contained ZIKV at a high concentration of 105 pfu/ml and various tissues of adults with a low infection rate (0.70-1.35%). ZIKV could be observed in anal papillae and midgut of larvae at 4 dpi under laboratory conditions. CONCLUSIONS: ZIKV but not DENV-2 can infect Ar. subalbatus by blood meal and artificial urine, and the infected mosquitoes can transmit ZIKV to suckling mice by bite. From these findings, we can conclude that the Ar. subalbatus isolated from Guangdong province, China, is a potential vector for ZIKV and should therefore be considered in vector control programs to prevent and control of Zika virus disease.

Megaporous monolithic adsorbents for bioproduct recovery as prepared on the basis of nonwoven fabrics.

Megaporous adsorbents were prepared based on nonwoven polyethylene terephthalate (PET) fabrics and functionalized by covalent modification with polyvinylamine (PVAm) or monotriazinyl-ß-cyclodextrin-substituted polyvinylamine (PVAm-MCT-ß-CD). Mechanical properties of the resulting fabrics were maintained, as judged by tensile strength tests and scanning electron microscopy. Exceptional porosity (≥82%) and preserved hydrodynamic characteristics (Pe ≥ 63) indicated excellent structural stability when packed. The performance of the constructed adsorbents was evaluated with high molecular weight (proteins) and low molecular weight (dyes) model compounds. The static binding capacity (SBC) for bovine serum albumin (BSA) was 79.7 ± 1.3 and 92.9 ± 8.2 mg/g for PVAm-modified and PVAm-MCT-ß-CD-modified fabrics, respectively. The mentioned materials also adsorbed Orange II, an acidic dye (92.4 ± 2.6 and 101.9 ± 2.6 mg/g, respectively), indicating that the hydrophobicity was a prevailing binding mechanism operating at a pH close to isoelectric point. SBC for lysozyme and toluidine blue O (TBO, a basic dye) onto PVAm-MCT-ß-CD functionalized PET was 52.7 ± 5.1 and 73.3 ± 0.6 mg/g, respectively. TBOs have also shown some affinity for PVAm functionalized PET, but this was most likely to be mediated by hydrophobicity. On the other hand, operating at a superficial velocity of 90 cm/h, dynamic binding capacity for BSA was 11.4 ± 3.5 and 2.5 ± 0.6 mg/g indicating the importance of possible aggregation mechanisms during protein binding at equilibrium. Thus, PET-based adsorbents require further functional improvement for chromatography applications. However, the easy-to-construct, scalable nonwoven adsorbents deserve further attention as a potential alternative to packed-bed-chromatography adsorbents.

Profile and Functional Prediction of Plasma Exosome-Derived CircRNAs From Acute Ischemic Stroke Patients.

Stroke is one of the major causes of death and long-term disability, of which acute ischemic stroke (AIS) is the most common type. Although circular RNA (circRNA) expression profiles of AIS patients have been reported to be significantly altered in blood and peripheral blood mononuclear cells, the role of exosome-containing circRNAs after AIS is still unknown. Plasma exosomes from 10 AIS patients and 10 controls were isolated, and through microarray and bioinformatics analysis, the profile and putative function of circRNAs in the plasma exosomes were studied. A total of 198 circRNAs were differentially quantified (|log2 fold change| ≥ 1.00, p < 0.05) between AIS patients and controls. The levels of 12 candidate circRNAs were verified by qRT-PCR, and the quantities of 10 of these circRNAs were consistent with the data of microarray. The functions of host genes of differentially quantified circRNAs, including RNA and protein process, focal adhesion, and leukocyte transendothelial migration, were associated with the development of AIS. As a miRNA sponge, differentially quantified circRNAs had the potential to regulate pathways related to AIS, like PI3K-Akt, AMPK, and chemokine pathways. Of 198 differentially quantified circRNAs, 96 circRNAs possessing a strong translational ability could affect cellular structure and activity, like focal adhesion, tight junction, and endocytosis. Most differentially quantified circRNAs were predicted to bind to EIF4A3 and AGO2-two RNA-binding proteins (RBPs)-and to play a role in AIS. Moreover, four of ten circRNAs with verified levels by qRT-PCR (hsa_circ_0112036, hsa_circ_0066867, hsa_circ_0093708, and hsa_circ_0041685) were predicted to participate in processes of AIS, including PI3K-Akt, AMPK, and chemokine pathways as well as endocytosis, and to be potentially useful as diagnostic biomarkers for AIS. In conclusion, plasma exosome-derived circRNAs were significantly differentially quantified between AIS patients and controls and participated in the occurrence and progression of AIS by sponging miRNA/RBPs or translating into proteins, indicating that circRNAs from plasma exosomes could be crucial molecules in the pathogenesis of AIS and promising candidates as diagnostic biomarkers and therapeutic targets for the condition.

Engineering Pollen-Derived Microstructures to Reveal Material Morpho-Performance Paradigm.

The morphologies of micromaterials play a key role in their functionality and efficiency across a broad range of applications, including catalysis, environmental remediation, and drug delivery. However, the relationships between the morphologies and performances of micromaterials still need to be further understood, to guide the rational design of effective morphologies for specific applications. A pollen-derived microstructure library containing multivariate morphological characterization and functional performance data is proposed and constructed here. Systematic multivariate correlation analysis is conducted to extract the key morphological factors influencing the photocatalytic and adsorption efficiencies, to reveal the morpho-performance relationships of pollen-derived microstructures. Subsequently, a chrysanthemum-derived microstructure is selected as a typical candidate; it features a unique morphology suitable for advanced photocatalysis and dynamic environmental remediation. To summarize, the construction of a pollen-derived microstructure library offers a powerful tool for studying the morpho-performance relationships of micromaterials; this can provide significant guidance and inspiration for the rational design of micro/nanomaterials for numerous applications.

Magnetic-controlled dandelion-like nanocatalytic swarm for targeted biofilm elimination.

Infections caused by drug-resistant strains pose a serious threat to human health. Most bacterial infections are related to biofilms. The generation of a bacterial biofilm greatly reduces the antibacterial efficiency of antibiotics and some traditional antibacterial drugs, and it is very important to develop antibacterial drugs to replace antibiotics. Here, encouraged by the promising magnetic control technology of micro/nanorobots, the synergistic antibacterial strategy of a dandelion-like magnetically-controlled multifunctional hierarchical magnetic biomimetic nanozyme, Fe3O4@SiO2@dendritic mesoporous silica@small-Fe3O4 nanoparticles (FSDMSsF NPs), was developed to be effective against bacterial biofilms. FSDMSsF NPs showed great magnetic properties and peroxidase-like activities, and could act as catalytic carriers for the production of hydroxyl radicals that are highly toxic to bacteria in a low-concentration H2O2 environment, killing planktonic bacteria. The antibacterial rate of FSDMSsF NPs reached 99.5% at a concentration of 200 µg mL-1. The synergistic antibacterial mechanisms of the mechanical factor and the chemical factor are further discussed. Under time-varying magnetic swarm control, the antibacterial performance of FSDMSsF NPs against bacteria was significantly improved. On this basis, the elimination effect of FSDMSsF NPs on bacterial biofilms is further discussed. The results showed that FSDMSsF NPs could target and eliminate biofilms through complex channels under the control of magnetic fields. In addition, the system could remove biofilms in occlusions by changing the morphology and movement mode of an FSDMSsF NP swarm under magnetic field control. The current work proposes a facile and physical-chemical synergistic strategy for effective antibacterial therapy. FSDMSsF NPs could effectively kill planktonic bacteria and remove stubborn biofilms through magnetic field guidance, achieving thorough antibacterial efficacy, which has great potential in the treatment of drug-resistant bacterial infections.

Multiloci Manipulation of Baculovirus Genome Reveals the Pivotal Role of Homologous Regions in Viral DNA Replication, Progeny Production, and Enhancing Transcription.

The engineering of viral genomes facilitates both fundamental and applied research on viruses. However, the multiloci manipulation of DNAs of viruses with large DNA genomes, such as baculoviruses, herpesviruses, and poxviruses, is technically challenging, particularly for highly homologous or repetitive sequences. Homologous regions (hrs) have multiple copies in many large DNA viruses and play pivotal roles in the viral life cycle. Here, we used synthetic biology to investigate the fundamental function of baculoviral hrs by conducting multiloci manipulation of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) DNA that contains eight hrs scattered in the genome. Using transformation-associated recombination in yeast, we generated recombinant AcMNPV genomes in which we deleted all hrs or retained a single hr (hr1, hr2, or hr3). Infectious viruses were rescued after transfecting the synthetic viral genomes into host cells, and their replication features were characterized. The results demonstrated that deletion of all hrs severely compromised viral DNA replication and progeny production, whereas retaining only a single hr was essential for efficient viral DNA replication and progeny production. The synthetic virus with hr2 or hr3 showed a growth curve similar to that of the parental virus. Transcriptomic analysis revealed that hr1, hr2, and hr3 could enhance gene transcription within a surrounding region of 14.6 kb, 13.8 kb, and 29.8 kb, respectively. Overall, this study revealed the advantages of synthetic biology in multiloci engineering and functional studies of large DNA viruses. In addition, our findings on hrs will be helpful for the design and improvement of baculovirus-based expression vectors.