A clinical and computed tomography-based nomogram to predict the outcome in patients with anterior circulation large vessel occlusion after endovascular mechanical thrombectomy.

PURPOSE: To explore the positive predictors of the clinical outcome in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (ACLVO) after endovascular mechanical thrombectomy (EMT) at a 90-day follow-up, and to establish a nomogram model to predict the clinical outcome. MATERIALS AND METHODS: AIS patients with ACLVO detected by multimodal Computed Tomography imaging who underwent EMT were collected. Patients were divided into the favorable and the unfavorable groups according to the 90-day modified Rankin Scale (mRS) score. Univariate and multivariate analyses were performed to investigate predictors of the favorable outcome (mRS of 0-2). A nomogram model for predicting the clinical outcome after EMT was drawn, and the receiver operating characteristic (ROC) curve was used to evaluate its predictive value. RESULTS: Totally 105 patients including 65 patients in the favorable group and 40 in the unfavorable group were enrolled. Multivariate logistic regression analysis showed that admission National Institute of Health Stroke scale (NIHSS) score [0.858 (95% CI 0.778-0.947)], ACLVO at M2 [20.023 (95% CI 2.204-181.907)] and infarct core (IC) volume [0.943 (95% CI 0.917-0.969)] was positively correlated with favorable outcome. The accuracy of the nomogram model in predicting the outcome was 0.923 (95% CI 0.870-0.976), with a cutoff value of 119.6 points. The area under the ROC curve was 0.848 (95% CI 0.780-0.917; sensitivity, 79.7%; specificity, 90.0%). CONCLUSION: A low Admission NIHSS score, ACLVO at M2, and a small IC volume were positive predictors for favorable outcome. The nomogram model may well predict the outcome in AIS patients with ACLVO after EMT.

NIR-Triggered Thermosensitive Nanoreactors for Dual-Guard Mechanism-Mediated Precise and Controllable Cancer Chemo-Phototherapy.

Thermosensitive nanoparticles can be activated by externally applying heat, either through laser irradiation or magnetic fields, to trigger the release of drug payloads. This controlled release mechanism ensures that drugs are specifically released at the tumor site, maximizing their effectiveness while minimizing systemic toxicity and adverse effects. However, its efficacy is limited by the low concentration of drugs at action sites, which is caused by no specific target to tumor sties. Herein, hyaluronic acid (HA), a gooey, slippery substance with CD44-targeting ability, was conjugated with a thermosensitive polymer poly(acrylamide-co-acrylonitrile) to produce tumor-targeting and thermosensitive polymeric nanocarrier (HA-P) with an upper critical solution temperature (UCST) at 45 °C, which further coloaded chemo-drug doxorubicin (DOX) and photosensitizer Indocyanine green (ICG) to prepare thermosensitive nanoreactors HA-P/DOX&ICG. With photosensitizer ICG acting as the "temperature control element", HA-P/DOX&ICG nanoparticles can respond to temperature changes when receiving near-infrared irradiation and realize subsequent structure depolymerization for burst drug release when the ambient temperature was above 45 °C, achieving programmable and on-demand drug release for effective antitumor therapy. Tumor inhibition rate increased from 61.8 to 95.9% after laser irradiation. Furthermore, the prepared HA-P/DOX&ICG nanoparticles possess imaging properties, with ICG acting as a probe, enabling real-time monitoring of drug distribution and therapeutic response, facilitating precise treatment evaluation. These results provide enlightenment for the design of active tumor targeting and NIR-triggered programmable and on-demand drug release of thermosensitive nanoreactors for tumor therapy.

Entrectinib inhibits NLRP3 inflammasome and inflammatory diseases by directly targeting NEK7.

Excessive inflammation caused by abnormal activation of the NLRP3 inflammasome contributes to the pathogenesis of multiple human diseases, but clinical drugs targeting the NLRP3 inflammasome are still not available. In this study, we identify entrectinib (ENB), a US Food and Drug Administration (FDA)-approved anti-cancer agent, as a target inhibitor of the NLRP3 inflammasome to treat related diseases. ENB specifically blocks NLRP3 without affecting activation of other inflammasomes. Furthermore, we demonstrate that ENB directly binds to arginine 121 (R121) of NEK7 and blocks the interaction between NEK7 and NLRP3, thereby inhibiting inflammasome assembly and activation. In vivo studies show that ENB has a significant ameliorative effect on mouse models of NLRP3 inflammasome-related diseases, including lipopolysaccharide (LPS)-induced systemic inflammation, monosodium urate (MSU)-induced peritonitis, and high-fat diet (HFD)-induced type 2 diabetes (T2D). These data show that ENB is a targeted inhibitor of NEK7 with strong anti-NLRP3 inflammasome activity, making it a potential candidate drug for the treatment of inflammasome-related diseases.

Loop-Mediated Isothermal Amplification (LAMP): Potential Point-of-Care Testing for Vulvovaginal Candidiasis.

PURPOSE: The aim of this study is to establish a loop-mediated isothermal amplification (LAMP) method for the rapid detection of vulvovaginal candidiasis (VVC). METHODS: We developed and validated a loop-mediated isothermal amplification (LAMP) method for detecting the most common Candida species associated with VVC, including C. albicans, N. glabratus, C. tropicalis, and C. parapsilosis. We evaluated the specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and Kappa value of the LAMP method to detect different Candida species, using the conventional culture method and internal transcribed spacer (ITS) sequencing as gold standards and smear Gram staining and real-time Rolymerase Chain Reaction (PCR) as controls. RESULTS: A total of 202 cases were enrolled, of which 88 were VVC-positive and 114 were negative. Among the 88 positive patients, the fungal culture and ITS sequencing results showed that 67 cases (76.14%) were associated with C. albicans, 13 (14.77%) with N. glabratus, 5 (5.68%) with C. tropicalis, and 3 (3.41%) with other species. Regarding the overall detection rate, the LAMP method presented sensitivity, specificity, PPV, NPV, and Kappa values of 90.91%, 100%, 100%, 93.4%, and 0.919, respectively. Moreover, the LAMP had a specificity of 100% for C. albicans, N. glabratus, and C. tropicalis, with a sensitivity of 94.03%, 100%, and 80%, respectively. Moreover, the microscopy evaluation had the highest sensitivity, while the real-time PCR was less specific for C. albicans than LAMP. In addition, CHROMagar Candida was inferior to LAMP in detecting non-albicans Candida (NAC) species. CONCLUSIONS: Based on the cost-effective, rapid, and inexpensive characteristics of LAMP, coupled with the high sensitivity and specificity of our VVC-associated Candida detection method, we provided a possibility for the point-of-care testing (POCT) of VVC, especially in developing countries and some laboratories with limited resources.

Lightweight, Flexible, and Covalent-Bonding Phenolic Fabric Reinforced Phenolic Ablator for Thermal Insulation and Conformal Infrared Stealth.

Fiber-reinforced phenolic resin aerogel (FRPRA) composite materials are seductive candidates for high-temperature thermal protection owing to their low density, excellent thermostability, and thermal insulation. However, the intrinsic stiffness restricts their further application for high efficiency. We report a homogeneous and chemical bonding strategy for fabricating lightweight and flexible FRPRA with good ablative thermal insulation performance. The compressible (cyclic strain of 60%) and bendable (cyclic strain of 30%) abilities as well as the structural stability during ablation all benefit from the compatibility between the phenolic resin aerogel matrix and the phenolic fiber reinforcement. Additionally, low bulk density and thermal conductivity of 0.20 g cm-3 and 0.043 W m-1 K-1, respectively, endow the composite with efficient thermal insulation capability. With an 8 mm-thick coupon, the temperature of 200 °C can be decreased to 70.6 °C and the temperature around 1200 °C can be camouflaged to 78 °C through combining with the Al panel. The material also enables a conformal stealth of 600 °C based on its bendability. Hence, the composite has potential in applications of both static and dynamic thermal insulation.

A microfluidic-chip-based system with loop-mediated isothermal amplification for rapid and parallel detection of Trichomonas vaginalis and human papillomavirus.

Cervical cancer is a significant global health issue primarily caused by high-risk types of human papillomavirus (HPV). Recent studies have reported an association between Trichomonas vaginalis (T. vaginalis) infections and HPV infections, highlighting the importance of simultaneously detecting these pathogens for effective cervical cancer risk management. However, current methods for detecting both T. vaginalis and HPV are limited. In this study, we present a novel approach using a microfluidic-chip-based system with loop-mediated isothermal amplification (LAMP) for the rapid and parallel detection of T. vaginalis, HPV16, HPV18, and HPV52 in a reagent-efficient and user-friendly manner. Compared to conventional LAMP assays in tubes, our system exhibits enhanced sensitivity with values of 2.43 × 101, 3.00 × 102, 3.57 × 101, and 3.60 × 102 copies per reaction for T. vaginalis, HPV16, HPV18, and HPV52, respectively. Additionally, we validated the performance of our chip by testing 47 clinical samples, yielding results consistent with the diagnostic methods used by the hospital. Therefore, our system not only offers a promising solution for concurrent diagnosis of T. vaginalis and HPV infections, particularly in resource-limited areas, due to its cost-effectiveness, ease of use, and rapid and accurate detection performance, but can also contribute to future research on the co-infection of these two pathogens. Moreover, the system possesses the capability to simultaneously detect up to 22 different types of pathogens, making it applicable across a wide range of domains such as diagnostics, food safety, and water monitoring.

Synthesis and properties of novel type I photosensitizer polycyclic amide.

Herein, we have designed and synthesized a novel type-I photosensitizer (PhPA) via Rh-catalyzed oxidative cyclization of diacetoxyterephthalamide with alkynes. The photoelectric properties, photosensitivity and photodegradation process of PhPA have been systematically investigated. The remarkable fluorescence quenching effect (ΦPL < 0.01) of PhPA suggests that the intersystem crossing from the singlet excited state to the reactive triplet state is enhanced by the enlarged conjugated backbone. Additionally, the ability of superoxide radical (O2-˙) generation was confirmed by electron paramagnetic resonance spectroscopy. Finally, the mechanism of PhPA photo-oxidative degradation via the structure of two metabolites is proposed.

Enhanced brain delivery of hypoxia-sensitive liposomes by hydroxyurea for rescue therapy of hyperacute ischemic stroke.

Ischemic stroke is characterized by high morbidity, disability, and mortality. Unfortunately, the only FDA-approved pharmacological thrombolytic, alteplase, has a narrow therapeutic window of only 4.5 h. Other drugs like neuroprotective agents have not been clinically used because of their low efficacy. To improve the efficacy of neuroprotective agents and the effectiveness of rescue therapies for hyperacute ischemic stroke, we investigated and verified the variation trends of the blood-brain barrier (BBB) permeability and regional cerebral blood flow over 24 h in rats that had ischemic strokes. Hypoperfusion and the biphasic increase of BBB permeability are still the main limiting factors for lesion-specific drug distribution and drug brain penetration. Herein, the nitric oxide donor hydroxyurea (HYD) was reported to downregulate the expression of tight junction proteins and upregulate intracellular nitric oxide content in the brain microvascular endothelial cells subjected to oxygen-glucose deprivation, which was shown to facilitate the transport of liposomes across  brain endothelial monolayer in an in vitro model. HYD also increased the BBB permeability and promoted microcirculation in the hyperacute phase of stroke. The neutrophil-like cell-membrane-fusogenic hypoxia-sensitive liposomes exhibited excellent performance in targeting the inflamed brain microvascular endothelial cells, enhancing cell association, and promoting rapid hypoxic-responsive release in the hypoxic microenvironment. Overall, the combined HYD and hypoxia-sensitive liposome dosing regimen effectively decreased the cerebral infarction volume and relieved neurological dysfunction in rats that had ischemic strokes; these therapies were involved in the anti-oxidative stress effect and the neurotrophic effect mediated by macrophage migration inhibitory factor.

An Integrated and Multi-Target Nucleic Acid Isothermal Analysis System for Rapid Diagnosis of Vulvovaginal Candidiasis.

Rapid identification of Candida species is significant for the diagnosis of vulvovaginal candidiasis (VVC). An integrated and multi-target system for the rapid, high-specificity, and high-sensitivity detection of four Candida species was developed. The system consists of a rapid sample processing cassette and a rapid nucleic acid analysis device. The cassette could process the Candida species to release nucleic acids in 15 min. The released nucleic acids were analyzed by the device as fast as within 30 min, using the loop-mediated isothermal amplification method. The four Candida species could be simultaneously identified, with each reaction using only 1.41 µL of reaction mixture, which was low cost. The RPT (rapid sample processing and testing) system could detect the four Candida species with high sensitivity (<2 CFU/reaction) and high specificity. The system also processed and analyzed 32 clinical samples, giving the results with high clinical sensitivity and specificity. Hence, the system was a significant and effective platform for the diagnosis of VVC. Furthermore, the period of validity of the reagents and chips used in the system was >90 days, and the system could also be used for the detection of bacteria.

Role of pyroptosis in the pathogenesis and treatment of diseases.

Programmed cell death (PCD) is regarded as a pathological form of cell death with an intracellular program mediated, which plays a pivotal role in maintaining homeostasis and embryonic development. Pyroptosis is a new paradigm of PCD, which has received increasing attention due to its close association with immunity and disease. Pyroptosis is a form of inflammatory cell death mediated by gasdermin that promotes the release of proinflammatory cytokines and contents induced by inflammasome activation. Recently, increasing evidence in studies shows that pyroptosis has a crucial role in inflammatory conditions like cardiovascular diseases (CVDs), cancer, neurological diseases (NDs), and metabolic diseases (MDs), suggesting that targeting cell death is a potential intervention for the treatment of these inflammatory diseases. Based on this, the review aims to identify the molecular mechanisms and signaling pathways related to pyroptosis activation and summarizes the current insights into the complicated relationship between pyroptosis and multiple human inflammatory diseases (CVDs, cancer, NDs, and MDs). We also discuss a promising novel strategy and method for treating these inflammatory diseases by targeting pyroptosis and focus on the pyroptosis pathway application in clinics.

Tendon-regulating and bone-setting manipulation promotes the recovery of synovial inflammation in rabbits with knee osteoarthritis via the TLR4-MyD88-NF-κB signaling pathway.

Background: The aim of this study was to clarify the mechanism of tendon-regulating and bone-setting manipulation in the treatment of knee osteoarthritis (KOA). Methods: A total of 30 adult healthy specific pathogen-free (SPF) New Zealand white rabbits (male; weight 2.0-2.5 kg) were selected and divided into a normal control (NC) group, KOA group, and KOA + manual treatment (MT) group. Each group comprised 10 rabbits. A KOA model was established using the modified Hulth method in the KOA and KOA + MT groups. The 3 groups were fed under the same conditions for 8 weeks. The Lequesne index for KOA was used to evaluate the behavioral status of the model rabbits; hematoxylin and eosin (HE) staining was employed to observe the pathological morphology of the tibial plateau and medial femoral condyle cartilage; the Mankin scoring scale was used to evaluate the cartilage morphology of the model rabbits; Western blot was used to detect the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor κB (NF-κB) proteins in the synovial tissue of the model rabbits; the contents of interleukin (IL)-1ß, IL-6, and, tumor necrosis alpha (TNF-α) in the synovial fluid of the model rabbits were determined using the enzyme-linked immunosorbent assay (ELISA) method. Results: Compared with those in the NC group, Lequesne index score, Mankin score of cartilage tissue, protein expression, and content of inflammatory factors were significantly increased in the KOA and KOA + MT groups (P<0.05), and these values were significantly higher in the KOA group. Microscopy showed that the cartilage tissue of the experimental rabbits in the KOA and KOA + MT groups was significantly degenerated. Compared with those in the KOA group, the Lequesne index score, Mankin score, protein expression, and inflammatory factor content of the model rabbits in the KOA + MT group were significantly reduced (P<0.05), and microscopy showed that cartilage tissue degeneration of the experimental rabbits in the KOA + MT group was significantly improved. Conclusions: Tendon-regulating and bone-setting manipulation can significantly improve the activity state and motor function of KOA model rabbits and significantly inhibit the expression of the TLR4-MyD88-NF-κB signaling pathway in synovial tissue, thereby reducing knee joint synovial inflammation and delaying the occurrence and development of KOA.

Machine Learning System for Lung Neoplasms Distinguished Based on Scleral Data.

Lung cancer remains the most commonly diagnosed cancer and the leading cause of death from cancer. Recent research shows that the human eye can provide useful information about one's health status, but few studies have revealed that the eye's features are associated with the risk of cancer. The aims of this paper are to explore the association between scleral features and lung neoplasms and develop a non-invasive artificial intelligence (AI) method for detecting lung neoplasms based on scleral images. A novel instrument was specially developed to take the reflection-free scleral images. Then, various algorithms and different strategies were applied to find the most effective deep learning algorithm. Ultimately, the detection method based on scleral images and the multi-instance learning (MIL) model was developed to predict benign or malignant lung neoplasms. From March 2017 to January 2019, 3923 subjects were recruited for the experiment. Using the pathological diagnosis of bronchoscopy as the gold standard, 95 participants were enrolled to take scleral image screens, and 950 scleral images were fed to AI analysis. Our non-invasive AI method had an AUC of 0.897 ± 0.041(95% CI), a sensitivity of 0.836 ± 0.048 (95% CI), and a specificity of 0.828 ± 0.095 (95% CI) for distinguishing between benign and malignant lung nodules. This study suggested that scleral features such as blood vessels may be associated with lung cancer, and the non-invasive AI method based on scleral images can assist in lung neoplasm detection. This technique may hold promise for evaluating the risk of lung cancer in an asymptomatic population in areas with a shortage of medical resources and as a cost-effective adjunctive tool for LDCT screening at hospitals.

Miniaturized microfluidic-based nucleic acid analyzer to identify new biomarkers of biopsy lung cancer samples for subtyping.

Identifying new biomarkers is necessary and important to diagnose and treat malignant lung cancer. However, existing protein marker detection methods usually require complex operation steps, leading to a lag time for diagnosis. Herein, we developed a rapid, minimally invasive, and convenient nucleic acid biomarker recognition method, which enabled the combined specific detection of 11 lung cancer typing markers in a microliter reaction system after only one sampling. The primers for the combined specific detection of 11 lung cancer typing markers were designed and screened, and the microfluidic chip for parallel detection of the multiple markers was designed and developed. Furthermore, a miniaturized microfluidic-based analyzer was also constructed. By developing a microfluidic chip and a miniaturized nucleic acid analyzer, we enabled the detection of the mRNA expression levels of multiple biomarkers in rice-sized tissue samples. The miniaturized nucleic acid analyzer could detect ≥10 copies of nucleic acids. The cell volume of the typing reaction on the microfluidic chip was only 0.94 µL, less than 1/25 of that of the conventional 25-µL Eppendorf tube PCR method, which significantly reduced the testing cost and significantly simplified the analysis of multiple biomarkers in parallel. With a simple injection operation and reverse transcription loop-mediated isothermal amplification (RT-LAMP), real-time detection of 11 lung cancer nucleic acid biomarkers was performed within 45 min. Given these compelling features, 86 clinical samples were tested using the miniaturized nucleic acid analyzer and classified according to the cutoff values of the 11 biomarkers. Furthermore, multi-biomarker analysis was conducted by a machine learning model to classify different subtypes of lung cancer, with an average area under the curve (AUC) of 0.934. This method shows great potential for the identification of new nucleic acid biomarkers and the accurate diagnosis of lung cancer.

Assessment of causal associations between handgrip strength and cardiovascular diseases: A two sample mendelian randomization study.

Background: Several observational studies have identified that handgrip strength was inversely associated with cardiovascular diseases (CVDs). Nevertheless, causality remains controversial. We conducted Mendelian randomization (MR) analysis to examine whether handgrip strength and risk of CVDs are causally associated. Methods: We identified 160 independent single nucleotide polymorphisms (SNPs) for right-hand grip strength and 136 independent SNPs for left-hand grip strength at the genome-wide significant threshold (P < 5 × 10-8) from UK Biobank participants and evaluated these in relation to risk of CVDs. MR estimates was calculated using the inverse-variance weighted (IVW) method and multiple sensitivity analysis was further conducted. Results: Genetical liability to handgrip strength was significantly associated with coronary artery disease (CAD) and myocardial infarction (MI), but not stroke, hypertension, or heart failure. Additionally, there was significant association between right-hand grip strength and atrial fibrillation (OR, 0.967; 95% CI, 0.950-0.984; p = 0.000222), however, suggestive significance was found between left-hand grip strength and atrial fibrillation (OR, 0.977; 95% CI, 0.957-0.998; p = 0.033). Results were similar in several sensitivity analysis. Conclusion: Our study provides support at the genetic level that handgrip strength is negatively associated with the risk of CAD, MI, and atrial fibrillation. Specific handgrip strength interventions on CVDs warrant exploration as potential CVDs prevention measures.

Virucidal and biodegradable specialty cellulose nonwovens as personal protective equipment against COVID-19 pandemic.

INTRODUCTION: Face masks are regarded as effective Personal Protective Equipment (PPE) during the COVID-19 pandemic. However, the dominant polypropylene (PP)-based masks are devoid of antiviral/antibacterial activities and create enormous environmental burdens after disposal. OBJECTIVES: Here we report a facile and potentially scalable method to fabricate biodegradable, breathable, and biocidal cellulose nonwovens (BCNWs) to address both environmental and hygienic problems of commercially available face masks. METHODS: TEMPO-oxidized cellulose nonwovens are rendered antiviral/antibacterial via covalent bonding with disinfecting polyhexamethylene guanidine or neomycin sulfate through carbodiimide coupling chemistry. RESULTS: The obtained results showed that the BCNWs have virucidal rate of >99.14%, bactericidal efficiency of >99.51%, no leaching-out effect, and excellent air permeability of >1111.5 mm s-1. More importantly, the as-prepared BCNWs can inactivate SARS-CoV-2 instantly. CONCLUSIONS: This strategy provides a new platform for the green fabrication of multifunctional cellulose nonwovens as scalable bio-protective layers with superior performance for various PPE in fighting COVID-19 or future pandemics. Additionally, replacing the non-biodegradable non-antimicrobial PP-based masks with the cellulose-based masks can reduce the plastic wastes and lower the greenhouse gas production from the incineration of disposed masks.

Distribution of FFRCT in single obstructive coronary stenosis and predictors for major adverse cardiac events: a propensity score matching study.

BACKGROUND: Fractional flow reserve derived from computed tomography (FFRCT) has been demonstrated to improve identification of lesion-specific ischemia significantly compared with coronary computed tomography angiography (CCTA). It remains unclear whether the distribution of FFRCT values in obstructive stenosis between patients who received percutaneous coronary intervention (PCI) or not in routine clinical practice, as well as its association with clinical outcome. This study aims to reveal the distribution of FFRCT value in patients with single obstructive coronary artery stenosis and explored the independent factors for predicting major adverse cardiac events (MACE). METHODS: This was a retrospective study of adults with non-ST-segment elevation acute coronary syndrome undergoing FFRCT assessment by using CCTA data from January 1, 2016 to December 31, 2020. Propensity score matching (PSM) method was used to account for patient selection bias. The risk factors for predicting MACE were evaluated by a Cox proportional hazards regression analysis. RESULTS: Overall, 655 patients with single obstructive (≥ 50%) stenosis shown on CCTA were enrolled and divided into PCI group (279 cases) and conservative group (376 cases) according to treatment strategy. The PSM cohort analysis demonstrated that the difference in history of unstable angina, Canadian Cardiovascular Society Class (CCSC) and FFRCT between PCI group (188 cases) and conservative group (315 cases) was statistically significant, with all P values < 0.05, while the median follow-up time between them was not statistically significant (24 months vs. 22.5 months, P = 0.912). The incidence of MACE in PCI group and conservative group were 14.9% (28/188) and 23.5% (74/315) respectively, P = 0.020. Multivariate analysis of Cox proportional hazards regression revealed that history of unstable angina (adjusted odds ratio (adjOR), 3.165; 95% confidence interval (CI), 2.087-4.800; P < 0.001), FFRCT ≤ 0.8 (OR, 1.632;95% CI 1.095-2.431; P = 0.016), and PCI therapy (OR 0.481; 95% CI 0.305-0.758) were the independent factors for MACE. CONCLUSIONS: History of unstable angina and FFRCT value of ≤ 0.8 were the independent risk factors for MACE, while PCI therapy was the independent protective factor for MACE.

Role of inflammasomes in HIV-1 infection and treatment.

Although combined antiretroviral therapy (cART) is effective in inhibiting human immunodeficiency virus type 1 (HIV-1) replication, it does not eradicate the virus because small amounts of latent HIV-1 provirus persist in quiescent memory CD4+ T cells. Therefore, strategies for eradicating latent HIV-1 are urgently needed. Recently, several studies have reported that the inflammatory response and lymphocyte death induced by HIV-1 depend on inflammasomes and pyroptosis, suggesting that inflammasomes and pyroptosis have a vital role in HIV-1 infection and contribute to the eradication of latent HIV-1. In this review, we summarize current knowledge of the role of inflammasomes, including NLR family pyrin domain-containing protein 3 (NLRP3), caspase recruitment domain-containing protein 8 (CARD8), interferon-inducible protein 16 (IFI16), NLRP1, NLR family CARD domain-containing 4 (NLRC4), and absent in melanoma 2 (AIM2), in HIV-1 infection and discuss promising therapeutic strategies for HIV-1-associated diseases by targeting inflammasomes.

Rapid, Highly Sensitive, and Label-Free Pathogen Assay System Using a Solid-Phase Self-Interference Recombinase Polymerase Amplification Chip and Hyperspectral Interferometry.

Recombinase polymerase amplification (RPA) is a useful pathogen identification method. Several label-free detection methods for RPA amplicons have been developed in recent years. However, these methods still lack sensitivity, specificity, efficiency, or simplicity. In this study, we propose a rapid, highly sensitive, and label-free pathogen assay system based on a solid-phase self-interference RPA chip (SiSA-chip) and hyperspectral interferometry. The SiSA-chips amplify and capture RPA amplicons on the chips, rather than irrelevant amplicons such as primer dimers, and the SiSA-chips are then analysed by hyperspectral interferometry. Optical length increases of SiSA-chips are used to demonstrate RPA detection results, with a limit of detection of 1.90 nm. This assay system can detect as few as six copies of the target 18S rRNA gene of Plasmodium falciparum within 20 min, with a good linear relationship between the detection results and the concentration of target genes (R2 = 0.9903). Single nucleotide polymorphism (SNP) genotyping of the dhfr gene of Plasmodium falciparum is also possible using the SiSA-chip, with as little as 1% of mutant gene distinguished from wild-type loci (m/wt). This system offers a high-efficiency (20 min), high-sensitivity (6 copies/reaction), high-specificity (1% m/wt), and low-cost (∼1/50 of fluorescence assays for RPA) diagnosis method for pathogen DNA identification. Therefore, this system is promising for fast identification of pathogens to help diagnose infectious diseases, including SNP genotyping.

A nature-inspired hierarchical branching structure pressure sensor with high sensitivity and wide dynamic range for versatile medical wearables.

Pressure-sensing capability is essential for flexible electronic devices, which require high sensitivity and a wide detection range to simplify the system. However, the template-based pressure sensor is powerless to detect high pressure due to the rapid deformation saturation of microstructures. Herein, we demonstrated that a nature-inspired hierarchical branching (HB) structure can effectively address this problem. Finite element analysis demonstrates that the HB structure permits a step-by-step mobilization of microstructure deformation, resulting in a dramatically improved sensitivity (up to 2 orders of magnitude) when compared with the traditional monolayer structure. Experiments show that the HB structure enables pressure sensors to have a lower elastic modulus (1/3 of that of monolayer sensors), a high sensitivity of 13.1 kPa-1 (almost 14 times higher than the monolayer sensor), and a wide dynamic range (0-800 kPa, the minimum detection pressure is 1.6 Pa). The maximum frequency that the sensor can detect is 250 Hz. The response/recovery time is 0.675/0.55 ms respectively. Given this performance, the HB sensor enables high-resolution detection of the weak radial artery pulse wave characteristics in different states, indicating its potential to noninvasively reveal cardiovascular status and the effectiveness of related interventions, such as exercise and drug intervention. As a proof of concept, we also verified that the HB sensor can serve as a versatile platform to support diverse applications from low to high pressure.

Antiviral/antibacterial biodegradable cellulose nonwovens as environmentally friendly and bioprotective materials with potential to minimize microplastic pollution.

Personal protective equipment (PPE) such as face masks is vital in battling the COVID-19 crisis, but the dominant polypropylene-based PPE are lack of antiviral/antibacterial activities and environmental friendliness, and have hazardous impact on the soil and aquatic ecosystems. The work presented herein focused on developing biodegradable, antiviral, and antibacterial cellulose nonwovens (AVAB-CNWs) as a multi-functional bioprotective layer for better protection against coronavirus SARS-CoV-2 and addressing environmental concerns raised by the piling of COVID-19 related wastes. Both guanidine-based polymer and neomycin sulfate (NEO) were reactive-modified and covalently grafted onto the surface of cellulose nonwovens, thereby conferring outstanding antiviral and antibacterial activities to the nonwovens without deteriorating the microstructure and biodegradability. Through adjusting the grafting amount of active components and selecting appropriate reagents for pretreatment, the antimicrobial activity and hydrophobicity for self-cleaning of the nonwovens can be tuned. More importantly, we demonstrated for the first time that such multi-functional nonwovens are capable of inactivating SARS-CoV-2 instantly, leading to high virucidal activity (> 99.35%), which is unachievable by conventional masks used nowadays. Meanwhile, the robust breathability and biodegradability of AVAB-CNWs were well maintained. The applications of the as-prepared nonwovens as high-performance textile can be readily extended to other areas in the fight against COVID-19.