IGSF8 is an innate immune checkpoint and cancer immunotherapy target.

Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival in vitro or in vivo. It is overexpressed and associated with low antigen presentation, low immune infiltration, and worse clinical outcomes in many tumors. An antibody that blocks IGSF8-NK receptor interaction enhances NK cell killing of malignant cells in vitro and upregulates antigen presentation, NK cell-mediated cytotoxicity, and T cell signaling in vivo. In syngeneic tumor models, anti-IGSF8 alone, or in combination with anti-PD1, inhibits tumor growth. Our results indicate that IGSF8 is an innate immune checkpoint that could be exploited as a therapeutic target.

Stressful life events can predict post-stroke fatigue in patients with ischemic stroke.

OBJECTIVE: To investigate whether stressful life events (SLEs) can predict post-stroke fatigue (PSF) in patients with acute ischemic stroke (AIS). METHODS: This prospective cohort study included data from patients with AIS who were followed up to 2-year interview. PSF was assessed at admission and at 6 (n = 916), 12 (n = 880), and 24 (n = 857) months with the fatigue severity scale (FSS). SLEs were measured with the Social Readjustment Rating Scale questionnaire at 6, 12 and 24 months' interview. RESULTS: A significant dose-response association was found between SLEs and FSS score across all examined time-points: compared with those did not experience SLEs, FSS score was higher for those experiencing SLEs ≥3 at 6 months (ß 0.53, 95% CI 0.28-0.78), 12 months (ß 0.54, 95% CI 0.30-0.78) and 24 months (ß 0.48, 95% CI 0.29-0.68). Longitudinal analyses indicated a significantly positive relationship between the number of SLEs and FSS score (SLEs: ≥3 vs. 0, ß 0.14, 95% CI 0.09-0.19). Moreover, a distinct interaction of follow-up time and SLE numbers on FSS score was observed (p < 0.05), which means elevated exposure to SLEs during follow-up was associated with a lower rate of fatigue decline. A similar association was found in SLE load analysis. CONCLUSION: Patients with severe fatigue were more likely to report increased number of SLEs in the previous 6 months, which could suggest that a non-specific stressful event leads to an extra burden to an already vulnerable psychological system.

Label-free and highly sensitive detection of DNA adenine methylation methyltransferase through cathodic photoelectrochemistry.

In this work, we report the first exploration of cathodic photoelectrochemistry for the determination of the activity of DNA adenine methylation (Dam) methyltransferase (MTase). In this sensing system, potassium ferricyanide (K3[Fe(CN)6]) can greatly stimulate the photocurrent of a CdS quantum dot (QD) sensitized NiO (NiO/CdS) photocathode. After immobilization of the hairpin DNA probe on the electrode surface, its high steric hindrance and the electrostatic repulsion block the access of K3[Fe(CN)6] to the electrode surface, leading to depressed photocurrent of the photocathode. Once the hairpin DNA probe is methylated by Dam MTase, it can be recognized and cleaved by Dpn I, and then further digested by (Exo I), ultimately leading to the removal of the hairpin DNA probe from the electrode surface. This configurational change induces the decrement of steric hindrance/electrostatic repulsion effects and allows the efficient flux of K3[Fe(CN)6] to the photoelectrode for photocurrent stimulation. The cathodic PEC assay is presented in the "turn-on" mode, which can detect Dam MTase in the linear range from 0.04 to 100 U mL-1, with a detection limit as low as 0.028 U mL-1. In principle, the platform presents a promising method for probing various biomolecules that can lead to configuration or charge variations at the electrode surface, which may become a general strategy for versatile targets.

Endovascular treatment of acute ischemic stroke due to anterior circulation large vessel occlusion beyond 6 hours: a real-world study in China.

BACKGROUND: We aimed to assess the safety and efficacy of endovascular treatment (EVT) in patients with anterior circulation emergent large vessel occlusion (ELVO) beyond 6 h from symptom onset in a real-world cohort of patients in China. METHODS: We retrospectively examined 305 patients with anterior circulation ELVO treated with EVT. Patients were divided into two groups: treated with known onset within 6 h (n = 238) and beyond 6 h (n = 67). Multivariable logistic regression and ordinal shift analyses were used to evaluate the associations between onset-to-groin puncture time and safety and efficacy outcomes. RESULTS: Treatment beyond 6 h was not associated with symptomatic intracranial hemorrhage within 48 h (sICH; odds ratio [OR] 2.03, 95% confidence interval [CI] 0.48-8.57, p = 0.334), in-hospital mortality (OR 1.95, 95% CI 0.48-7.91, p = 0.348), successful recanalization (modified Thrombolysis in Cerebral Infarction score 2b or 3; OR 0.73, 95% CI 0.31-1.73, p = 0.470), favorable functional outcome (modified Rankin Scale score 0-2; OR 0.55, 95% CI 0.25-1.23, p = 0.145), and functional improvement (modified Rankin Scale shift by 1-point decrease; common OR 0.80, 95%CI 0.45-1.42, p = 0.450) at 3 months compared with treatment within 6 h. Futher interaction analysis showed that stroke etiology did not modify the associations between onset-to-groin puncture time and outcomes (p > 0.05). CONCLUSIONS: In this real-world study, after careful assessment, EVT beyond 6 h from known stroke onset was safe, effective and had comparable short-term outcomes to EVT within 6 h.

Clinical significance of stroke nurse in patients with acute ischemic stroke receiving intravenous thrombolysis.

BACKGROUND: Reports have proven that shorter door-to-needle time (DTN time) indicates better outcomes in AIS patients received intravenous thrombolysis. Efforts have been made by hospitals and centers to minimize DTN time in many ways including introducing a stroke nurse. However, there are few studies to discuss the specific effect of stroke nurse on patients' prognosis. This study aimed to compare consecutive AIS patients before and after the intervention to analyze the effect of stroke nurse on clinical outcome of AIS patients. METHODS: In this retrospective study, we observed 1003 patients from November 2016 to December 2020 dividing in two groups, collected and analyzed AIS patients' medical history, clinical assessment information, important timelines, 90 mRS score, etc. Comparative analysis and mediation analysis were also used in this study. RESULTS: A total of 418 patients was included in this study, and 199 patients were enrolled in the stroke nurse group and 219 was in the preintervention group. Baseline characteristics of patients showed no significant difference except there seems more patients with previous ischemic stroke history in the group of stroke nurse. (p = 0.008). The median DTN time significantly decreased in the stroke nurse group (25 min versus 36 min, p < 0.001) and multivariate logistic regression analysis showed the 90-day mRS clinical outcome significantly improved in the stroke nurse group (p = 0.001). Mediation analysis indicated the reduction of DTN time plays a partial role on the 90 days mRS score and the stroke nurse has some direct effect on the improvement of clinical outcome (p = 0.006). CONCLUSIONS: The introduction of stroke nurse is beneficial to clinical outcome of AIS patients and can be use of reference in other hospitals or centers.

Biotransformation of ginsenoside Rc to Rd by endophytic bacterium Bacillus sp. G9y isolated from Panax quinquefolius.

To isolate endophytic bacterium with the ability to specifically convert ginsenoside Rc from Panax quinquefolius. An endophytic bacterium G9y was isolated from Panax quinquefolius and indentified as Bacillus sp. based on 16s rDNA gene sequence. Ginsenoside Rc was effectively converted to Rd by G9y, which was confirmed by thin-layer chromatography and high performance liquid chromatography (HPLC) analysis. The biotransformation conditions were further optimized as follows: inoculum amount 5%, converting temperature 45 °C, medium beef extract peptone broth at pH of 7, and the time of Rc addition was 4 h after bacterium G9y growth, under which ginsenoside Rc was completely converted to Rd by bacterium G9y within 25 h after inoculation. A strain of G9y with the ability to convert ginsenoside Rc into Rd was screened from endophytic bacteria isolated from P. quinquefolius. The results provide a new microbial resource for preparing ginsenoside Rd via biotransformation, and explore a pathway for Rc utilization, which has great potential application value.

Intercalated doxorubicin acting as stimulator of PbS photocathode for probing DNA-protein interactions.

Label-free and turn-on DNA-binding protein detection based on the doxorubicin (Dox)-intercalated DNA as a signal stimulator in cathodic photoelectrochemistry is reported. The double-stranded DNA (dsDNA) acted as the matrix accommodating the intercalative Dox and allowed its effective photoelectrochemical (PEC) communication with the PbS quantum dots (QDs) for realizing cathodic photocurrent readout. In the presence of the target of the vascular endothelial growth factor (VEGF), the dsDNA was prevented from being digested by the exonuclease III (Exo III), allowing the anchor of Dox to perform as activation stimuli of the photocurrent. The VEGF can be detected in the linear range from 1.5 pM to 100 nM, with an impressively low detection limit of 0.49 pM. This study hints the prospect of DNA intercalated architectures as innovative signaling transduction elements for wide and versatile cathodic PEC bioassays. Effective signaling molecules that are conducive to probe-related cathodic PEC bioassays using DNA as the recognition or signification elements are scarce but very demanding. Herein, the doxorubicin intercalated in duplex DNA functions as an efficient signal stimulator of PbS-consisted photocathode, and thus hints the versatility of the strategy for various targets through cathodic photoelectrochemistry.

Vanillin derivative VND3207 activates DNA-PKcs conferring protection against radiation-induced intestinal epithelial cells injury in vitro and in vivo.

Vanillin is a natural compound endowed with antioxidant and anti-mutagenic properties. We previously identified the vanillin derivative VND3207 with strong radio-protective and antioxidant effects and found that VND3207 confers survival benefit and protection against radiation-induced intestinal injury (RIII) in mice. We also observed that VND3207 treatment enhanced the expression level of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) in human lymphoblastoid cells with or without γ-irradiation. DNA-PKcs is a critical component of DNA double strand break repair pathway and also regulates mitotic progression by stabilizing spindle formation and preventing mitotic catastrophe in response to DNA damage. In the present study, we found that VND3207 protected intestinal epithelial cells in vitro against ionizing radiation by promoting cell proliferation and inhibiting cell apoptosis. In addition, VND3207 promoted DNA-PKcs activity by increasing autophosphorylation at S2056 site. Consistent with this, VND3207 significantly decreased the number of γH2AX foci and mitotic catastrophe after radiation. DNA-PKcs deficiency abolished these VND3207 radio-protective effects, indicating that DNA-PKcs activation is essential for VND3207 activity. In conclusion, VND3207 promoted intestinal repair following radiation injury by regulating the DNA-PKcs pathway.

Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most commonly observed in children. Alantolactone (ALT) has been reported to exhibit anti-tumor activity in different types of cancer. The aim of the present study was to investigate the anti-tumor activity and molecular mechanism of ALT in ALL. METHODS: ALL cell lines were treated with 1, 5 and 10 µM ALT, and cell viability was assessed using an MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were used to measure cell apoptosis and autophagy. Additionally, western blot analysis was used to detect expression of apoptosis and autophagy related proteins. Finally, the effects of ALT on tumor growth were assessed in a BV173 xenograft nude mouse model. RESULTS: ALT inhibited the proliferation of ALL cells in a dose-dependent manner. Additionally, it was demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and reduced tumor growth in vivo through upregulating the expression of adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, the autophagy activator rapamycin, attenuated the pro-apoptotic effects of ALT on BV173 and NALM6 cell lines. Overexpression of AP2M1 decreased the expression of Beclin1 and the LC3-II/LC3-1 ratio, and increased p62 expression. Knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C, and decreased bcl-2 expression. CONCLUSIONS: The present study demonstrated that ALT exerts anti-tumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, highlighting a potential therapeutic strategy for treatment of ALL.

Analysis of the Endophytic Bacteria Community Structure and Function of Panax notoginseng Based on High-Throughput Sequencing.

Panax notoginseng has long been used as a Chinese herb with high medicinal value. The endophytic bacteria in this medicinal plant have multiple biological functions. High-throughput sequencing is a rapidly evolving technique that helps profile the endophytic bacterial community structure of medicinal plants. However, few studies on the endophytic bacteria in P. notoginseng, particularly in dry P. notoginseng roots as a raw medicinal material, have been conducted. In this study, fresh P. notoginseng and dry P. notoginseng were analysed using high-throughput sequencing on an Illumina MiSeq platform to explore the diversity and functions of the endophytic bacteria in different parts of P. notoginseng. The results showed that a total of 201 operational taxonomic units were obtained from fresh P. notoginseng and dry P. notoginseng. The dominant phyla in the fresh and dry P. notoginseng were Proteobacteria (85.9%) and Firmicutes (99.9%), respectively, whereas the dominant genera in these samples were Enterobacter (84.4%) and Bacillus (99.6%), respectively. Fresh P. notoginseng exhibited a higher degree of endophytic bacterial diversity than dry P. notoginseng, but functional prediction of metabolism indicated that the relative abundance of the metabolic function of terpenoids and polyketides synthesis in the dry sample was higher than that in the fresh sample. Our study indicates significant differences in the diversity and metabolic function of the endophytic bacteria between fresh and dry P. notoginseng, providing useful information for the exploitation and utilization of endophytic bacteria resources from P. notoginseng.

A GWAS-supported variant interacting with diabetes predicts risk of atherothrombotic stroke in Han Chinese population.

BACKGROUND: A recent genome-wide association study has identified that rs4376531 variant conferred risk of atherothrombotic stroke (AS) in a Japanese population. This study was to explore the association in Han Chinese population. METHODS: A total of 1036 cases and 643 healthy controls were enrolled. We genotyped rs4376531 variant with SNPscan. Multivariate logistic regression analysis was used to determine the association of genetic variation with risk of AS. Interaction analysis was examined by SNPStats web tool. RESULTS: After adjusting for gender, age, body mass index (BMI), hypertension, diabetes and smoking, compared with CC genotype, we observed that GC and GG/GC genotypes were associated with a significantly decreased risk of AS (OR = 0.76, 95% CI = 0.58-0.99 and OR = 0.76, 95% CI = 0.58-0.98, respectively). The decreased risk was more obvious among subgroups with high BMI (OR = 0.63, 95% CI = 0.45-0.88), no hypertension (OR = 0.66, 95% CI = 0.46-0.94), diabetes (OR = 0.33, 95% CI = 0.17-0.64), and smoking (OR = 0.65, 95% CI = 0.44-0.95) in the dominant model (GG/GC vs CC). Interaction analysis also revealed that compared with non-diabetic patients with CC genotype, diabetic patients with CC genotype had a 4.48-fold (OR = 4.48; 95% CI = 2.98-6.72) increased risk of AS. CONCLUSION: Our data suggested that GC and GG/GC of rs4376531 contributed to a decreased risk of AS while CC genotype, interacting with diabetes, increased the stroke risk in Han Chinese population.

p53-inducible gene 3 promotes cell migration and invasion by activating the FAK/Src pathway in lung adenocarcinoma.

The p53-inducible gene 3 (PIG3) is one of the p53-induced genes at the onset of apoptosis, which plays an important role in cell apoptosis and DNA damage response. Our previous study reported an oncogenic role of PIG3 associated with tumor progression and metastasis in non-small cell lung cancer (NSCLC). In this study, we further analyzed PIG3 mRNA expression in 504 lung adenocarcinoma (LUAD) and 501 lung squamous cell carcinoma (LUSC) tissues from The Cancer Genome Atlas database and we found that PIG3 expression was significantly higher in LUAD with lymph node metastasis than those without, while no difference was observed between samples with and without lymph node metastasis in LUSC. Gain and loss of function experiments were performed to confirm the metastatic role of PIG3 in vitro and to explore the mechanism involved in its oncogenic role in NSCLC metastasis. The results showed that PIG3 knockdown significantly inhibited the migration and invasion ability of NSCLC cells, and decreased paxillin, phospho-focal adhesion kinase (FAK) and phospho-Src kinase expression, while its overexpression resulted in the opposite effects. Blocking FAK with its inhibitor reverses PIG3 overexpression-induced cell motility in NSCLC cells, indicating that PIG3 increased cell metastasis through the FAK/Src/paxillin pathway. Furthermore, PIG3 silencing sensitized NSCLC cells to FAK inhibitor. In conclusion, our data revealed a role for PIG3 in inducing LUAD metastasis, and its role as a new FAK regulator, suggesting that it could be considered as a novel prognostic biomarker or therapeutic target in the treatment of LUAD metastasis.

The vanillin derivative 6-bromine-5-hydroxy-4-methoxybenzaldehyde induces aberrant mitotic progression and enhances radio-sensitivity accompanying suppression the expression of PLK1 in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the most common form of esophageal cancer in China. Since chemotherapy is the standard clinical intervention for advanced ESCC, the development of highly effective and minimal/non-toxic drugs is essential to improve the clinical outcome and prognosis of the patients. A novel derivative of vanillin, 6-bromine-5-hydroxy-4-methoxybenzaldehyde (BVAN08), has been recently reported to activate different cell death pathways in cancer cells. In this study, we demonstrate that BVAN08 exhibits a potent anti-proliferation effect on ESCC cells (TE-1 and ECA-109) by inhibiting the expression of PLK1, an important mitotic kinase. Consistent with this, BVAN08 induces mitotic arrest and chromosomal misalignment in ESCC cells. The disruption of microtubule nucleation around centrosomes is also observed in BVAN08 treated ESCC cells. Furthermore, BVAN08 enhances radio-sensitivity of ESCC cells by prolonging DNA damage repair. These findings underscore the potential value of BVAN08 in cancer therapeutics and demonstrate the underlying mechanism by which BVAN08 induces mitotic catastrophe and enhances radio-sensitivity in ESCC cells.

A Study of GWAS-Supported Variants of rs9943582 in a Chinese Han Population with Ischemic Stroke: No Associations with Disease Onset and Clinical Outcomes.

BACKGROUND: The variant rs9943582 of APLNR (apelin receptor) was identified by a large-scale study to be associated with an increased risk of ischemic stroke in a Japanese population. We conducted this study to investigate the association between the variant and age of onset and clinical outcomes of ischemic stroke in a Chinese population. METHODS: Improved multiple ligase detection reaction was used to genotype the variant. We compared the mean age at ischemic stroke onset with one-way ANOVA. The Kaplan-Meier method, log-rank test, and Cox proportional hazards regression models were performed to analyze the association between the variant and clinical outcomes (recurrence and death). RESULTS: A total of 916 ischemic stroke patients were recruited for the study. For age at ischemic stroke onset, no significant association was identified with the variant in any genetic model. In addition, the variant was not strongly associated with recurrence and death risk of ischemic stroke, as shown by the results. CONCLUSIONS: The findings indicated that the variant rs9943582 was not associated with age at onset and clinical outcomes of ischemic stroke. However, evidence from well-designed studies with larger and in different ethnic populations are warranted to further explore the effects of APLNR on the ischemic stroke onset and clinical outcomes.

Target mediated bioreaction to engineer surface vacancy effect on Bi2O2S nanosheets for photoelectrochemical detection of FEN1.

Photoelectrochemistry represents a promising technique for bioanalysis, though its application for the detection of Flap endonuclease 1 (FEN1) has not been tapped. Herein, this work reports the exploration of creating oxygen vacancies (Ov) in situ onto the surface of Bi2O2S nanosheets via the attachment of dopamine (DA), which underlies a new anodic PEC sensing strategy for FEN1 detection in label-free, immobilization-free and high-throughput modes. In connection to the target-mediated rolling circle amplification (RCA) reaction for modulating the release of the DA aptamer to capture DA, the detection system showed good performance toward FEN1 analysis with a linear detection range of 0.001-10 U/mL and a detection limit of 1.4 × 10-4 U/mL (S/N = 3). This work features the bioreaction engineered surface vacancy effect of Bi2O2S nanosheets as a PEC sensing strategy, which allows a simple, easy to perform, sensitive and selective method for the detection of FEN1. This sensing strategy might have wide applications in versatile bioasssays, considering the diversity of a variety of biological reactions may produce the DA aptamer.

Thioredoxin Reductase-Mediated Reaction Evokes In Situ Surface Polarization Effect on BiOIO3: Toward a New Sensing Strategy for Cathodic Photoelectrochemistry.

We have witnessed the fast progress of cathodic photoelectrochemistry over the past decades, though its signal transduction tactic still lacks diversity. Exploring new sensing strategies for cathodic photoelectrochemistry is extremely demanding yet hugely challenging. This article puts forward a unique idea to incorporate an enzymatic reaction-invoked surface polarization effect (SPE) on the surface of BiOIO3 to implement an innovative cathodic photoelectrochemical (PEC) bioanalysis. Specifically, the thioredoxin reductase (TrxR)-mediated reaction produced the polar glutathione (GSH), which spontaneously coordinated to the surface of BiOIO3 and induced SPE by forming a polarized electric field, resulting in improved electron (e-) and hole (h+) pair separation efficiency and an enhanced photocurrent output. Correlating this phenomenon with the detection of TrxR exhibited a high performance in terms of sensitivity and selectivity, achieving a linear range of 0.007-0.5 µM and a low detection limit of 2.0 nM (S/N = 3). This study brings refreshing inspiration for the cathodic PEC signal transduction tactic through enzyme-mediated in situ reaction to introduce SPE, which enriches the diversity of available signaling molecules. Moreover, this study unveils the potential of in situ generated SPE for extended and futuristic applications.

Alleviate environmental concerns with biochar as a container substrate: a review.

Peat moss has desirable properties as a container substrate, however, harvesting it from peatland for greenhouse/nursery production use has disturbed peatland ecosystem and caused numerous environmental concerns. More recently, many nations have taken actions to reduce or ban peat moss production to reach the carbon neutral goal and address the environmental concerns. Also, the overuse of fertilizers and pesticides with peat moss in greenhouse/nursery production adds extra environmental and economic issues. Thus, it is urgent to find a peat moss replacement as a container substrate for greenhouse/nursery production. Biochar, a carbon-rich material with porous structure produced by the thermo-chemical decomposition of biomass in an oxygen-limited or oxygen-depleted atmosphere, has drawn researchers' attention for the past two decades. Using biochar to replace peat moss as a container substrate for greenhouse/nursery production could provide environmental and economic benefits. Biochar could be derived from various feedstocks that are regenerated faster than peat moss, and biochar possesses price advantages over peat moss when local feedstock is available. Certain types of biochar can provide nutrients, accelerate nutrient adsorption, and suppress certain pathogens, which end up with reduced fertilizer and pesticide usage and leaching. However, among the 36,474 publications on biochar, 1,457 focused on using biochar as a container substrate, and only 68 were used to replace peat moss as a container substrate component. This study provides a review for the environmental and economic concerns associated with peat moss and discussed using biochar as a peat moss alternative to alleviate these concerns.

The Potential of Gut Microbiota in Prediction of Stroke-Associated Pneumonia.

BACKGROUND: Stroke-associated pneumonia (SAP) is a common stroke complication, and the changes in the gut microbiota composition may play a role. Our study aimed to evaluate the predictive ability of gut microbiota for SAP. METHODS: Acute ischemic stroke patients were prospectively enrolled and divided into two groups based on the presence or absence of SAP. The composition of gut microbiota was characterized by the 16S RNA Miseq sequencing. The gut microbiota that differed significantly between groups were incorporated into the conventional risk scores, the Acute Ischemic Stroke-Associated Pneumonia Score (AIS-APS), and the Age, Atrial fibrillation, Dysphagia, Sex, Stroke Severity Score (A2DS2). The predictive performances were assessed in terms of the area under the curve (AUC), the Net Reclassification Improvement (NRI), and the Integrated Discrimination Improvement (IDI) indices. RESULTS: A total of 135 patients were enrolled, of whom 43 had SAP (31%). The short-chain fatty acids (SCFAs)-producing bacteria, such as Bacteroides, Fusicatenibacter, and Butyricicoccus, were decreased in the SAP group. The integrated models showed better predictive ability for SAP (AUC = 0.813, NRI = 0.333, p = 0.052, IDI = 0.038, p = 0.018, for AIS-APS; AUC = 0.816, NRI = 0.575, p < 0.001, IDI = 0.043, p = 0.007, for A2DS2) in comparison to the differential genera (AUC = 0.699) and each predictive score (AUCAISAPS = 0.777; AUCA2DS2 = 0.777). CONCLUSIONS: The lower abundance of SCFAs-producing gut microbiota after acute ischemic stroke was associated with SAP and may play a role in SAP prediction.

Trap remediation of CuBi2O4 nanopolyhedra via surface self-coordination by H2O2: an innovative signaling mode for cathodic photoelectrochemical bioassay.

This work conveys a new philosophy of surface self-coordination mediated trap remediation for innovative cathodic photoelectrochemical (PEC) signal transduction. Initially, the surface trap states of CuBi2O4 nanopolyhedra resulting from dangling bonds can function as charge carrier recombination centers, which suppress the carrier separation efficiency and result in a low photocurrent output. Particularly, hydrogen peroxide (H2O2) spontaneously interacts with the uncoordinated Cu(II) on the surface of CuBi2O4, enabling efficient elimination of dangling bonds and remedy of trap states, thereby outputting intensified photocurrent readout. Exemplified by Flap endonuclease 1 (FEN1) as a model target, a tetrahedron DNA (THD)-based strand displacement amplification (SDA) was introduced to manipulate the formation of hemin impregnated G-quadruplex (G-quadruplex/hemin) DNAzyme and the resultant catalytic reduction for H2O2. In addition, a highly efficient and ultra-sensitive PEC sensing platform was achieved for FEN1 detection with a wide linear range from 1.0 fM to 100.0 pM and a detection limit of 0.3 fM (S/N = 3). This work not only establishes a new idea of cathodic PEC signal transduction, but also offers an efficient biosensing platform for FEN1.

Catechol exerts an in situ surface oxygen vacancy effect on BiOI: an innovative signal transduction mode for cathodic photoelectrochemistry.

Cathodic photoelectrochemistry, a research hotspot in state-of-art bioassays, is generally circumscribed by its monotonous signal transduction tactic of photoinduced electron transfer (PET) mechanism, which significantly narrows the scope of its applications. In this study, we reveal the surface oxygen vacancy (VO) formation elicited by the spontaneous coordination of catechol (CA) onto the surface of BiOI nanoplates for the innovative operation of the cathodic PEC signal transduction tactic. The in situ-generated VO functions as a carrier separation center to efficiently promote photocurrent generation. Taking tyrosinase (TYR) and Escherichia coli O157:H7 (E. coli O157:H7) as model targets, the established signal transduction tactic was validated as efficient and sensitive for the detection of the two targets with linear ranges from 1.0 × 10-4 to 1.0 U mL-1 and 5.0 to 1.0 × 106 CFU mL-1, respectively. Low-detection limits of 1.0 × 10-4 U mL-1 and 3.0 CFU mL-1 were achieved for TYR and E. coli O157:H7, respectively. This study opens up a new perspective of in situ generated surface VO on semiconductors, which underlies an innovative PEC signal transduction mechanism with convincing analytical performance. Hopefully, it might encourage more explorations of new methodologies for introducing surface vacancies with exquisite applications.