Chemical constituents from the endophytic fungus Aspergillus sp. S3 of Hibiscus tiliaceus.

A new sterol, aspersterol E (1), a newly discovered alkaloid, asperginine A (2), and five known compounds (3-7) were obtained from the endophytic fungus Aspergillus sp. S3 of Hibiscus tiliaceus Linn. The compounds were extracted from their fermentation products using silica gel, ODS C18, and semi-preparative HPLC. The structure of each compound was determined through spectroscopic analysis. All the obtained compounds (1-7) were evaluated for their cytotoxic activity against the mouse pre-gastric cancer cell line MFC by using the MTT assay. The IC50 values of compounds 1, 2, 3, and 5 were found to be 153.43 µM, 61.25 µM, 73.19 µM, and 181.69 µM respectively.

Post-activation Performance Enhancement of Countermovement Jump after Drop Jump versus Squat Jump Exercises in Elite Rhythmic Gymnasts.

Drop jump (DJ) and squat jump (SJ) exercises are commonly used in rhythmic gymnastics training. However, the acute effects of DJ and SJ on countermovement jump (CMJ) performance have not been investigated. This study aimed to verify the post-activation performance enhancement (PAPE) responses induced by DJ and SJ with optimal power load and evaluate the relationship between peak PAPE effects and strength levels. Twenty female rhythmic gymnasts completed the following exercises in a randomized order on three separate days: 6 repetitions of DJs; 6 repetitions of SJs with optimal power load; and no exercise (control condition). Jump height was assessed before (baseline) and at 30 seconds and 3, 6, and 9 minutes after each exercise. DJs significantly improved jump height by 0.8 cm (effect size (ES) = 0.25; P = 0.003) at 30 seconds post-exercise compared with baseline. Jump height significantly decreased by -0.14 cm (ES = -0.61; P = 0.021) at 9 minutes after the control condition. SJs significantly improved jump height by 1.02 cm (ES = 0.36; P = 0.005) at 9 minutes post-exercise compared to the control condition. Jump height and relative back squat one-repetition maximum were positively related after performing DJs (r = 0.63; P = 0.003) and SJs (r = 0.64; P = 0.002). DJ and SJ exercises effectively improved countermovement jump height. DJ improved jump height early, while SJ produced greater potentiation effects later. Athletes with a higher strength level benefited the most from these exercises.

Mechanistic analysis of thermal stability in a novel thermophilic polygalacturonase MlPG28B derived from the marine fungus Mucor lusitanicus.

In this study, heterologous MlPG28B expression was obtained by cloning the Mucor lusitanicus gene screened from a marine environment. The enzyme activity of MlPG28B was maximum at 60 °C, 30 % of the enzyme activity was retained after incubation at 100 °C for 30 min, and enzyme activity was still present after 60 min incubation, one of the best thermostable polygalacturonases characterized until now. The high-purity oligosaccharide standards (DP2-DP7) were prepared with polygalacturonic acid as a substrate. Kinetic parameters showed that MlPG28B at the optimum temperature has a low Km value (3055 ± 1104 mg/L), indicating high substrate affinity. Sequence alignment analysis inferred key residues Cys276, Cys284, Lys107, and Gln237 for MlPG28B thermal stability. Molecular docking and molecular dynamics simulation results indicated that MlPG28B has flexible T1 and T3 loops conducive to substrate recognition, binding, and catalysis and forms a hydrogen bond to the substrate by a highly conserved residue Asn161 in the active-site cleft. Based on site-directed mutation results, the five residues are key in determining MlPG28B thermal stability. Therefore, MlPG28B is a promising candidate for industrial enzymes in feed preparation.

Visible-Light-Induced Metal- and Photosensitizer-Free C(sp3)-H Phosphorylation of 3,4-Dihydroquinoxalin-2(1H)-ones with Diphenylphosphine Oxide.

Herein, we report a direct phosphorylation of the C(sp3)-H bond of 3,4-dihydroquinoxalin-2(1H)-ones using oxygen as a green oxidant under visible light at room temperature. This transformation was readily accomplished in the absence of metal and photosensitizer to construct new C(sp3)-P bonds and provide a series of phosphonylated dihydroquinoxalin-2-ones in good to excellent yields. This approach opens straightforward and environmentally friendly access to 3-phosphoryl quinoxalin-2-ones derivatives.

How to update esophageal masses imaging using literature review (MRI and CT features).

MRI offers new opportunities for detailed visualization of the different layers of the esophageal wall, as well as early detection and accurate characterization of esophageal lesions. Staging of esophageal tumors including extramural extent of disease, and status of the adjacent organ can also be performed by MRI with higher accuracy compared to other imaging modalities including CT and esophageal endoscopy. Although MDCT appears to be the primary imaging modality that is indicated for preoperative staging of esophageal cancer to assess tumor resectability, MDCT is considered less accurate in T staging. This review aims to update radiologists about emerging imaging techniques and the imaging features of various esophageal masses, emphasizing the imaging features that differentiate between esophageal masses, demonstrating the critical role of MRI in esophageal masses. CRITICAL RELEVANCE STATEMENT: MRI features may help differentiate mucosal high-grade neoplasia from early invasive squamous cell cancer of the esophagus, also esophageal GISTs from leiomyomas, and esophageal malignant melanoma has typical MR features. KEY POINTS: MRI can accurately visualize different layers of the esophagus potentially has a role in T staging. MR may accurately delineate esophageal fistulae, especially small mediastinal fistulae. MRI features of various esophageal masses are helpful in the differentiation.

Nickel foam-loaded Co-MOF@TiO2/MoS2 as electrode materials for dual-function devices for glucose detection and hydrogen evolution.

Dual-functional nanomaterial electrodes have the capability to satisfy the requirements for both sweat analysis and the hydrogen evolution reaction (HER), thereby enabling the integration of electrochemical sensing and hydrogen production. In this study, ZIF-67 cubes are synthesized on nickel foam (NF), while TiO2 is obtained through an annealing process. Subsequently, the ZIF-67@TiO2/MoS2 nanocomposite is fabricated on nickel foam via a hydrothermal method. This composite material exhibits exceptional photocatalytic properties and is also suitable for the detection of glucose in sweat. The glucose detection range spans from 10 nM to 10 mM with a sensitivity of 7.24 µA mM-1 cm-2 for a signal-to-noise ratio of 3 and a detection limit of 0.43 µM. Moreover, when utilized as a hydrogen evolution electrode, this material demonstrates a current density of 10 mA cm-2 at an overpotential of 118 mV, with a Tafel slope of 73 mV/dec. The synthesis process is both straightforward and economical. This research introduces a novel concept for the design of multifunctional chemical sensors.

IL-20 is produced by CD3γδ T cells and induced in the mucosal tissues of grass carp during infection with Aeromonas hydrophila.

Interleukin (IL) 20 is a multifunctional cytokine and plays a vital role in regulating autoimmune diseases, inflammation, and immune responses. IL-20 homologs have been described in fish. However, due to the lack of antibodies, cellular sources and immunological functions of fish IL-20 in response to infections have not been fully characterized. In this study, a monoclonal antibody (mAb) was generated against the recombinant grass carp (Ctenopharyngodon idella) IL-20 protein and characterized by immunoblotting, immunofluorescent microscopy and flow cytometry. It was shown that the IL-20 mAb specifically recognized recombinant IL-20 proteins expressed in the E. coli cells and HEK293 cells. Using confocal microscopy, the IL-20+ cells were identified in the head kidney, gills and intestine of grass carp, and induced after infection with Aeromonas hydrophila. Moreover, the IL-20 protein was found to be secreted mainly by CD3γδ T cells which were located predominantly in the gill filaments and intestinal mucosa. Taken together, our results suggest that IL-20 producing T cells are required for the mucosal immunity against bacterial infection in fish.

A cytokine-like factor 1 homolog acts as a macrophage chemoattractant in grass carp.

Cytokine-like factor 1 (CYTL1) is a small cytokine and has diverse biological functions in mammals. However, whether CYTL1 exists in lower vertebrates is not clear. In this study, we identified cytl homologs in fish and characterized the immune functions in a teleost species, grass carp (Ctenopharyngodon idella). Fish CYTL1 homologs share conserved molecular features with their mammalian counterparts, including 6 cysteine residues in the mature peptide, genomic organization and synteny. Gene expression analysis revealed that cytl1 was constitutively expressed in tissues of grass carp, with the highest expression detected in the heart. Upon infection with Aeromonas hydrophila (A. hydrophila), cytl1 was downregulated in the hindgut, head kidney, skin, and spleen. In the primary head kidney leukocytes (HKLs), stimulation with inactivated A. hydrophila, LPS, poly(I:C), IL-22, IFN-a or IFN-γrel resulted in downregulation of cytl1 expression. Recombinant grass carp CYTL1 protein produced in the HEK293-F cells was potent to induce il-10 expression, but had little effect on the expression of il-1ß and il-6. In vivo experiments revealed that CYTL1 was effective to recruit macrophages to the muscle injected with cytl expression plasmids. Taken together, our results indicate that CYTL1 is a potent chemokine for recruitment of macrophages in fish.

AHNAK2 Promotes the Progression of Pancreatic Ductal Adenocarcinoma by Maintaining the Stability of c-MET.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant and rapidly progresses. The overall response rate of PDAC to current treatment methods is still unsatisfactory. Thus, identifying novel targets and clarifying the underlying mechanisms associated with PDAC progression may potentially offer additional treatment strategies. AHNAK2 is aberrantly expressed in a variety of tumors and exerts pro-tumorigenic effects. However, the biological role of AHNAK2 in PDAC remains poorly understood. Methods: The expression of AHNAK2 in PDAC and paired non-tumor tissues was detected by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). Lentivirus knockdown was performed to investigate the impact of AHNAK2 on the biological function of pancreatic cancer cells. The subcutaneous cell-derived xenograft (CDX) model and the KPC spontaneous mouse model with AHNAK2 silencing were used to observe the effects of AHNAK2 on tumor growth and prognosis. The expression of c-MET at protein level in response to HGF treatment was assessed using western blot. Results: Our results demonstrated that AHNAK2 was highly expressed in PDAC clinical samples and associated with poor prognosis. Knockdown of AHNAK2 significantly inhibited the proliferation, migration, and invasion of pancreatic cancer cells. AHNAK2 knockdown or knockout resulted in tumor growth suppression and prolonged survival in mice with PDAC. In addition, AHNAK2 and c-MET expression levels showed a significant positive correlation at the post-transcriptional level. Mechanistically, AHNAK2 promoted tumor progression by preventing c-MET degradation and persistently activating the HGF/c-MET signaling pathway. Conclusion: Overall, our study revealed that AHNAK2 plays an important role in PDAC progression by modulating the c-MET signaling pathway, and targeting AHNAK2 may be an effective therapeutic strategy for PDAC.

Analysis of tissue tropism of GCRV-II infection in grass carp using a VP35 monoclonal antibody.

Grass carp, one of the major freshwater aquaculture species in China, is susceptible to grass carp reovirus (GCRV). GCRV is a non-enveloped RNA virus and has a double-layered capsid, causing hemorrhagic disease and high mortalities in infected fish. However, the tropism of GCRV infection has not been investigated. In this study, monoclonal antibodies against recombinant VP35 protein were generated in mice and characterized. The antibodies exhibited specific binding to the N terminal region (1-155 aa) of the recombinant VP35 protein expressed in the HEK293 cells, and native VP35 protein in the GCRV-II infected CIK cells. Immunofluorescent staining revealed that viruses aggregated in the cytoplasm of infected cells. In vivo challenge experiments showed that high levels of GCRV-II viruses were present in the gills, intestine, spleen and liver, indicating that they are the major sites for virus infection. Our study showed that the VP35 antibodies generated in this study exhibited high specificity, and are valuable for the development of diagnostic tools for GCRV-II infection.

Therapeutic Implications of Phenolic Acids for Ameliorating Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder, and its complex etiology makes prevention and treatment challenging. Research on new drugs and treatment strategies is currently a focal point. Phenolic acids are widely present in plant-based diets and have demonstrated the potential to alleviate colitis due to their powerful antioxidant and anti-inflammatory properties. In this review, we provide an overview of the structures and main dietary sources of phenolic acids, encompassing benzoic acid and cinnamic acid. Additionally, we explore the potential of phenolic acids as a nutritional therapy for preventing and treating IBD. In animal and cell experiments, phenolic acids effectively alleviate IBD induced by drug exposure or genetic defects. The mechanisms include improving intestinal mucosal barrier function, reducing oxidative stress, inhibiting excessive activation of the immune response, and regulating the balance of the intestinal microbiota. Our observation points towards the need for additional basic and clinical investigations on phenolic acids and their derivatives as potential novel therapeutic agents for IBD.

Predictors and prognosis of early neurological outcomes on patients with Vertebrobasilar artery occlusion undergoing endovascular treatment.

BACKGROUND: This research explored the factors influencing early neurological outcomes (ENO) in patients who had vertebrobasilar artery occlusion (VBAO) and received endovascular treatment (EVT), as well as examining the causal influence of ENO on the prognosis of VBAO patients. METHODS: A retrospective review was carried out on patients from 65 Chinese stroke centers, all within 24 hours of the estimated occlusion time. ENO includes early neurological improvement (ENI) and early neurological deterioration (END), defined as a decrease or an increase of at least 4 points in NIHSS score between baseline and 24 hours after EVT. Death within 24 hours after EVT also consider as END. END was further divided into explainable END and unexplainable END (unEND). Independent predictors of ENO and the association between ENO and outcomes in patients with VBAO were determined using center-adjusted analyses. The study developed a multivariate logistic regression model to examine the comparative risk of unEND versus explainable END on the clinical outcomes in VBAO patients. RESULTS: A total of 2257 patients were included. Glasgow Coma Scale (GCS) (OR 1.16, 95% CI 1.03-1.30) and successful reperfusion (OR 1.15, 95% CI 1.02-1.30) were associated with ENI. Baseline NIHSS (OR 0.60, 95% CI 0.53-0.68), successful reperfusion (OR 0.79, 95% CI 0.71-0.89) and puncture to reperfusion time (OR 1.17, 95% CI 1.03-1.33) were associated with END. When examining three-month prognostic indexes, both END and ENI were found to be linked to the three-month outcomes, but in opposite directions. A subgroup analysis of END suggested that unexplained END typically demonstrated a more favorable prognosis compared to explained END, although the prognosis remained generally unfavorable. CONCLUSIONS: ENO, whether they manifested as early improvement or deterioration, were linked to the prognosis of VBAO patients undergoing EVT. The outcomes after unEND were more favorable than those following explained END.

Redefining left bundle branch block from high-density electroanatomical mapping.

BACKGROUND: The existing ECG criteria for diagnosing left bundle branch block (LBBB) are insufficient to distinguish between true and false blocks accurately. METHODS: We hypothesized that the notch width of the QRS complex in the lateral leads (I, avL, V5, V6) on the LBBB-like ECG could further confirm the diagnosis of true complete left bundle branch block (t-LBBB). We conducted high-density, three-dimensional electroanatomical mapping in the cardiac chambers of 37 patients scheduled to undergo CRT. These patients' preoperative electrocardiograms met the ACC/AHA/HRS guidelines for the diagnosis of complete LBBB. If the left bundle branch potential could be mapped from the base of the heart to the apex on the left ventricular septum, it was defined as a false complete left bundle branch block (f-LBBB). Otherwise, it was categorized as a t-LBBB. We conducted a comparative analysis between the two groups, considering the clinical characteristics, real-time correspondence between the spread of ventricular electrical excitation and the QRS wave, QRS notch width of the lateral leads (I, avL, V5, V6), and the notch width/left ventricular end-diastolic diameter (Nw/LVd) ratio. We performed the ROC correlation analysis of Nw/LVd and t-LBBB to determine the sensitivity and specificity for diagnostic authenticity. RESULTS: Twenty-five patients were included in the t-LBBB group, while 12 patients were assigned to the f-LBBB group. Within the t-LBBB group, the first peak of the QRS notch correlated with the depolarization of the right ventricle and septum, the trough corresponded to the depolarization of the left ventricle across the left ventricle, and the second peak aligned with the depolarization of the left ventricular free wall. In contrast, within the f-LBBB group, the first peak coincided with the depolarization of the right ventricle and a majority of the left ventricle, the second peak occurred due to the depolarization of the latest, locally-activated myocardium in the left ventricle, and the trough was a result of delayed activation of the left ventricle that did not align with the usual peak timing. The QRS notch width (45.2 ± 12.3 ms vs. 52.5 ± 9.2 ms, P < 0.05) and the Nw/LVd ratio (0.65 ± 0.19 ms/mm vs. 0.81 ± 0.17 ms/mm, P < 0.05) were compared between the two groups. After conducting the ROC correlation analysis, a sensitivity of 56% and a specificity of 91.7% for diagnosing t-LBBB using Nw/LVd were obtained. CONCLUSION: By utilizing the current diagnostic criteria for LBBB, an increased Nw/LVd value can enhance the effectiveness of diagnosing LBBB.

Agronomic, physiological and transcriptional characteristics provide insights into fatty acid biosynthesis in yellowhorn (Xanthoceras sorbifolium Bunge) during fruit ripening.

Yellowhorn (Xanthoceras sorbifolium Bunge) is an oil-bearing tree species in northern China. In this study, we used yellowhorn from Heilongjiang to analyze the morphological and physiological changes of fruit development and conducted transcriptome sequencing. The results showed that the fruit experienced relatively slow growth from fertilization to DAF20 (20 days after flowering). From DAF40 to DAF60, the fruit entered an accelerated development stage, with a rapid increase in both transverse and longitudinal diameters, and the kernel contour developed completely at DAF40. From DAF60 to DAF80, the transverse and vertical diameters of the fruit developed slowly, and the overall measures remained stable until maturity. The soluble sugar, starch, and anthocyanin content gradually accumulated until reaching a peak at DAF80 and then rapidly decreased. RNA-seq analysis revealed differentially expressed genes (DEGs) in the seed coat and kernel, implying that seed components have different metabolite accumulation mechanisms. During the stages of seed kernel development, k-means clustering separated the DEGs into eight sub-classes, indicating gene expression shifts during the fruit ripening process. In subclass 8, the fatty acid biosynthesis pathway was enriched, suggesting that this class was responsible for lipid accumulation in the kernel. WGCNA revealed ten tissue-specific modules for the 12 samples among 20 modules. We identified 54 fatty acid biosynthesis pathway genes across the genome, of which 14 was quantified and confirmed by RT-qPCR. Most genes in the plastid synthesis stage showed high expression during the DAF40-DAF60 period, while genes in the endoplasmic reticulum synthesis stage showed diverse expression patterns. EVM0012847 (KCS) and EVM0002968 (HCD) showed similar high expression in the early stages and low expression in the late stages. EVM0022385 (HCD) exhibited decreased expression from DAF40 to DAF60 and then increased from DAF60 to DAF100. EVM0000575 (KCS) was increasingly expressed from DAF40 to DAF60 and then decreased from DAF60 to DAF100. Finally, we identified transcription factors (TFs) (HB-other, bHLH and ARF) that were predicted to bind to fatty acid biosynthesis pathway genes with significant correlations. These results are conducive to promoting the transcriptional regulation of lipid metabolism and the genetic improvement in terms of high lipid content of yellowhorn.

The MRI radiomics signature can predict the pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma.

OBJECTIVES: To investigate the MRI radiomics signatures in predicting pathologic response among patients with locally advanced esophageal squamous cell carcinoma (ESCC), who received neoadjuvant chemotherapy (NACT). METHODS: Patients who underwent NACT from March 2015 to October 2019 were prospectively included. Each patient underwent esophageal MR scanning within one week before NACT and within 2-3 weeks after completion of NACT, prior to surgery. Radiomics features extracted from T2-TSE-BLADE were randomly split into the training and validation sets at a ratio of 7:3. According to the progressive tumor regression grade (TRG), patients were stratified into two groups: good responders (GR, TRG 0 + 1) and poor responders (non-GR, TRG 2 + 3). We constructed the Pre/Post-NACT model (Pre/Post-model) and the Delta-NACT model (Delta-model). Kruskal-Wallis was used to select features, logistic regression was used to develop the final model. RESULTS: A total of 108 ESCC patients were included, and 3/2/4 out of 107 radiomics features were selected for constructing the Pre/Post/Delta-model, respectively. The selected radiomics features were statistically different between GR and non-GR groups. The highest area under the curve (AUC) was for the Delta-model, which reached 0.851 in the training set and 0.831 in the validation set. Among the three models, Pre-model showed the poorest performance in the training and validation sets (AUC, 0.466 and 0.596), and the Post-model showed better performance than the Pre-model in the training and validation sets (AUC, 0.753 and 0.781). CONCLUSIONS: MRI-based radiomics models can predict the pathological response after NACT in ESCC patients, with the Delta-model exhibiting optimal predictive efficacy. CLINICAL RELEVANCE STATEMENT: MRI radiomics features could be used as a useful tool for predicting the efficacy of neoadjuvant chemotherapy in esophageal carcinoma patients, especially in selecting responders among those patients who may be candidates to benefit from neoadjuvant chemotherapy. KEY POINTS: • The MRI radiomics features based on T2WI-TSE-BLADE could potentially predict the pathologic response to NACT among ESCC patients. • The Delta-model exhibited the best predictive ability for pathologic response, followed by the Post-model, which similarly had better predictive ability, while the Pre-model performed less well in predicting TRG.

T-cell lymphopenia is associated with an increased infecting risk in children after cardiopulmonary bypass.

BACKGROUND: children who undergo CPB operations are at an elevated risk of infection due to immunosuppression. This study aims to investigate the association between lymphopenia following CPB and early postoperative infection in children. METHODS: A retrospective analysis including 41 children under 2 years old underwent CPB. Among them, 9 subjects had an early postoperative infection, and 32 subjects were period-matched without infection. Inflammatory cytokines, serum CRP and PCT values were measured in plasma, additionally, circulating total leucocyte and lymphocyte subpopulations were counted. RESULTS: Infected subjects exhibited significantly higher levels of inflammatory cytokines, including IL-6, IL-8, IL-10, IL-1ß and TNF-α, than non-infected subjects after CPB. Additionally, lower absolute number of lymphocyte and their subpopulations CD3+ T cells, CD4+ T-helper cells and CD8+cytotoxic T-cells, were observed in infected subjects. The impairment of T-cells Immune was found to be associated with higher levels of inflammatory cytokines IL-10. The ROC demonstrated that the absolute number of CD3+ T-cells <1934/ul, CD4+ T helper cells <1203/ul and CD8+cytotoxic T-cells <327/ul were associated with early postoperative infection. CONCLUSION: Higher levels of inflammatory cytokines resulted in T-cells lymphopenia after CPB, which significantly increasing the risk of postoperative infection in infants and young children. IMPACT: Infection complications after cardiopulmonary bypass (CPB) in pediatric CHD patients are serious issues, identifing the infection from after CPB remains a challenging. CPB can release numerous inflammatory cytokines associated with T cells lymphopenia, which increases the risk of postoperative infection after surgery. Monitoring T cells lymphopenia maybe more beneficial to predict early postoperative infection than C-reactive protein and procalcitonin.

Efficient Flexible Fabric-Based Top-Emitting Polymer Light-Emitting Devices for Wearable Electronics.

Low-cost fabric-based top-emitting polymer light-emitting devices (Fa-TPLEDs) have aroused increasing attention due to their remarkable potential applications in wearable displays. However, it is still challenging to realize efficient all-solution-processed devices from bottom electrodes to top electrodes with large-scale fabrication. Here, a smooth reflective Ag cathode integrated on fabric by one-step silver mirror reaction and a composite transparent anode of polydimethylsiloxane/silver nanowires/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) via a water-assisted peeling method are presented, both of which possess excellent optoelectrical properties and robust mechanical flexibility. The Fa-TPLEDs are constructed by spin-coating functional layers on the bottom reflective cathodes and laminating the top transparent anodes. The Fa-TPLEDs show a current efficiency of 16.3 cd A-1 , an external quantum efficiency of 4.9% and angle-independent electroluminescence spectra. In addition, the Fa-TPLEDs possess excellent mechanical stability, maintaining a current efficiency of 14.3 cd A-1 after 200 bending cycles at a radius of 4 mm. The results demonstrate that the integration of solution-processed reflective cathodes and transparent anodes sheds light on a new avenue to construct low-cost and efficient fabric-based devices, showing great potential applications in emerging smart flexible/wearable electronics.

Rescue stenting after failure of endovascular thrombectomy for acute vertebrobasilar artery occlusion: data from the PERSIST registry.

BACKGROUND: Among acute vertebrobasilar artery occlusion (VBAO) patients, successful reperfusion is a strong predictor of favorable outcomes. However, failed reperfusion (FR) with endovascular thrombectomy (EVT) in VBAO was observed to occur in 18-50% of cases. We aim to evaluate the safety and efficacy of rescue stenting (RS) for VBAO after failed EVT. METHODS: Patients with VBAO who received EVT were enrolled retrospectively. Propensity score matching was performed as the primary analysis to compare the outcomes between patients with RS and FR. Furthermore, a comparison between using the self-expanding stent (SES) and balloon-mounted stent (BMS) in the RS group was also conducted. The primary and secondary outcomes were defined as a 90-day modified Rankin Scale (mRS) score 0-3, and a 90-day mRS score 0-2, respectively. Safety outcomes included all-cause mortality at 90 days and symptomatic intracranial hemorrhage (sICH). RESULTS: The RS group showed a significantly higher rate of 90-day mRS score 0-3 (46.6% vs 20.7%; adjusted OR (aOR) 5.06, 95% CI 1.88 to 13.59, P=0.001) and a lower rate of 90-day mortality (34.5% vs 55.2%; aOR 0.42, 95% CI 0.23 to 0.90, P=0.026) than the FR group. The rates of 90-day mRS score 0-2 and sICH were not significantly different between the RS group and FR group. There were no differences in all outcomes between SES and BMS groups. CONCLUSIONS: RS appeared to be a safe and effective rescue approach in patients with VBAO who failed EVT, and there was no difference between using SES and BMS.

Tumour-associated macrophages and Schwann cells promote perineural invasion via paracrine loop in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently accompanied by perineural invasion (PNI), which is associated with excruciating neuropathic pain and malignant progression. However, the relationship between PNI and tumour stromal cells has not been clarified. METHODS: The dorsal root ganglia or sciatic nerves nerve model was used to observe the paracrine interaction and the activation effect among Schwann cells, tumour-associated macrophages (TAMs), and pancreatic cancer cells in vitro. Next generation sequencing, enzyme-linked immunosorbent assay and chromatin immunoprecipitation were used to explore the specific paracrine signalling between TAMs and Schwann cells. RESULTS: We demonstrated that more macrophages were expressed around nerves that have been infiltrated by pancreatic cancer cells compared with normal nerves in murine and human PNI specimens. In addition, high expression of CD68 or GFAP is associated with an increased incidence of PNI and indicates a poor 5-year survival rate in patients with PDAC. Mechanistically, tumour-associated macrophages (TAMs) activate Schwann cells via the bFGF/PI3K/Akt/c-myc/GFAP pathway. Schwann cells secrete IL-33 to recruit macrophages into the perineural milieu and facilitate the M2 pro-tumourigenic polarisation of macrophages. CONCLUSIONS: Our study demonstrates that the bFGF/IL-33 positive feedback loop between Schwann cells and TAMs is essential in the process of PNI of PDAC. The bFGF/PI3K/Akt/c-myc/GFAP pathway would open potential avenues for targeted therapy of PDAC.

Domain nucleation kinetics and polarization-texture-dependent electronic properties in two-dimensional α-In2Se3 ferroelectrics.

Two-dimensional (2D) ferroelectric semiconductors, such as α-In2Se3 with switchable spontaneous polarization and superior optoelectronic properties, exhibit large potential for functional device applications. The electric transport properties and device performance of 2D α-In2Se3 are strongly sensitive to the ferroelectric domain structures and polarization textures, but they are rarely explored at the atomic scale. Herein, by a combination of first-principles calculations and a developed domain switching theory, we report the domain nucleation kinetics and polarization-texture dependent electronic properties in α-In2Se3 ferroelectrics. Our calculated results reveal that the reversed domains characterized by armchair boundaries tend to form triangular or stripped shape. The energy barrier for propagating domain boundaries is ∼1.42 eV and can be reduced by loading external electric field, which is responsible for driving the evolution of domain structures. Moreover, the domain switching leads to notable changes in the band gap and carrier spatial distribution of α-In2Se3 monolayer, resulting in higher electric resistance of multi-polarization domain structures than that of single-polarization state. The domain structures of multilayer α-In2Se3 follow a layer-by-layer switching mechanism, which causes the transition of electronic structures from self-doped p-n junctions to type-II semiconductor homojunctions. This study not only provides an in-depth insight into the domain switching mechanisms of α-In2Se3 but also opens up the possibility to tailor their electronic and transport properties.