Expression of a viral ecdysteroid UDP-glucosyltransferase enhanced the insecticidal activity of the insect pathogenic fungus Beauveria bassiana.

BACKGROUND: Entomopathogenic fungi, such as Beauveria bassiana, hold promise as biological control agents against insect pests. However, the efficacy of these fungi can be hindered by insect immune responses. One strategy to enhance fungal virulence is to manipulate host immune by targeting key regulatory molecules like 20-hydroxyecdysone (20E). RESULTS: In this study, we engineered B. bassiana strains to constitutively express the enzyme ecdysteroid UDP-glucosyltransferase (EGT), which inactivates 20E, a crucial insect molting hormone. The engineered strain Bb::EGT-1 exhibited robust expression of EGT, leading to a significant reduction in insect 20E levels upon infection. Moreover, infection with Bb::EGT-1 resulted in accelerated larval mortality. Immune responses analysis revealed repression of insect immune response genes and decreased phenoloxidase (PO) activity in larvae infected with Bb::EGT-1. Microbiome analysis indicated alterations in bacterial composition within infected insects, with increased abundance observed during infection with Bb::EGT-1. Additionally, the presence of bacteria hindered hyphal emergence from insect cadavers, suggesting a role for microbial competition in fungal dissemination. CONCLUSIONS: Constitutive expression of EGT in B. bassiana enhances fungal virulence by reducing insect 20E levels, suppressing immune responses, and altering the insect microbiome. These findings highlighted the potential of engineered fungi as effective biocontrol agents against insect pests and provide insights into the complex interactions between entomopathogenic fungi, their hosts, and associated microbes. © 2024 Society of Chemical Industry.

MCT1-mediated transport of valeric acid promotes porcine preimplantation embryo development by improving mitochondrial function and inhibiting the autophagic AMPK-ULK1 pathway.

Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. During in vitro culture, many stressful conditions can affect embryo quality and viability, leading to adverse clinical outcomes such as abortion and congenital abnormalities. In this study, we found that valeric acid (VA) increased the mitochondrial membrane potential and ATP content, decreased the level of reactive oxygen species that the mitochondria generate, and thus improved mitochondrial function during early embryonic development in pigs. VA decreased expression of the autophagy-related factors LC3B and BECLIN1. Interestingly, VA inhibited expression of autophagy-associated phosphorylation-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylation-UNC-51-like autophagy-activated kinase 1 (p-ULK1, Ser555), and ATG13, which reduced apoptosis. Short-chain fatty acids (SCFAs) can signal through G-protein-coupled receptors on the cell membrane or enter the cell directly through transporters. We further show that the monocarboxylate transporter 1 (MCT1) was necessary for the effects of VA on embryo quality, which provides a new molecular perspective of the pathway by which SCFAs affect embryos. Importantly, VA significantly inhibited the AMPK-ULK1 autophagic signaling pathway through MCT1, decreased apoptosis, increased expression of embryonic pluripotency genes, and improved embryo quality.

Synergistic Effects of Chemotherapy and Phototherapy on Ovarian Cancer Using Follicle-Stimulating Hormone Receptor-Mediated Liposomes Co-Loaded with SN38 and IR820.

We have developed an ovarian cancer-targeted drug delivery system based on a follicle-stimulating hormone receptor (FSHR) peptide. The lipophilic chemotherapeutic drug SN38 and the photosensitizer IR820 were loaded into the phospholipid bilayer of liposomes. The combination of chemotherapy and phototherapy has become a promising strategy to improve the therapeutic effect of chemotherapy drugs on solid tumors. IR820 can be used for photodynamic therapy (PDT), effectively converting near-infrared light (NIR) into heat and producing reactive oxygen species (ROS), causing damage to intracellular components and leading to cell death. In addition, PDT generates heat in near-infrared, thereby enhancing the sensitivity of tumors to chemotherapy drugs. FSH liposomes loaded with SN38 and IR820 (SN38/IR820-Lipo@FSH) were prepared using thin-film hydration-sonication. FSH peptide binding was analyzed using 1H NMR spectrum and Maldi-Tof. The average size and zeta potential of SN38/IR820-Lipo@FSH were 105.1 ± 1.15 nm (PDI: 0.204 ± 0.03) and -27.8 ± 0.42 mV, respectively. The encapsulation efficiency of SN38 and IR820 in SN38/IR820-Lipo@FSH liposomes were 90.2% and 91.5%, respectively, and their release was slow in vitro. FSH significantly increased the uptake of liposomes, inhibited cell proliferation, and induced apoptosis in A2780 cells. Moreover, SN38/IR820-Lipo@FSH exhibited better tumor-targeting ability and anti-ovarian cancer activity in vivo when compared with non-targeted SN38/IR820-Lipo. The combination of chemotherapy and photodynamic treatment based on an FSH peptide-targeted delivery system may be an effective approach to treating ovarian cancer.

Impact of thermal ultrasound on enzyme inactivation and flavor improvement of sea cucumber hydrolysates.

In this study, the effects of the thermal ultrasonic enzyme inactivation process on flavor enhancement in sea cucumber hydrolysates (SCHs) and its impact on the inactivation of neutral proteases (NPs) were investigated. The body wall of the sea cucumber was enzymatically hydrolyzed with NPs. On the one hand, the structure of NPs subjected to different enzyme inactivation methods was analyzed using ζ-potential, particle size, and Fourier transform infrared (FT-IR) spectroscopy. On the other hand, the microstructure and flavor changes of SCHs were examined through scanning electron microscopy, E-nose, and gas chromatography-ion mobility spectrometry (GC-IMS). The results indicated that thermal ultrasound treatment at 60 °C could greatly affect the structure of NPs, thereby achieving enzyme inactivation. Furthermore, this treatment generated more pleasant flavor compounds, such as pentanal and (E)-2-nonenal. Hence, thermal ultrasound treatment could serve as an alternative process to traditional heat inactivation of enzymes for improving the flavor of SCHs.

Assessment of sedation by automated pupillometry in critically ill patients: a prospective observational study.

BACKGROUND: Quantitative measurement of pupil change has not been assessed against the Richmond Agitation and Sedation Scale (RASS) and spectral edge frequency (SEF) during sedation. The aim of this study was to evaluate pupillometry against these measures in sedated critically ill adult patients. METHODS: In ventilated and sedated patients, pupillary variables were measured by automated pupillometry at each RASS level from -5 to 0 after discontinuation of hypnotics, while processed electroencephalogram variables were displayed continuously and SEF was recorded at each RASS level. Correlations were made between percentage pupillary light reflex (%PLR) and RASS, and between %PLR and SEF. The ability of %PLR to differentiate light sedation (RASS ≥-2), moderate (RASS =-3), and deep sedation (RASS ≤-4) was assessed by areas under receiver operating characteristic (ROC) curves. RESULTS: A total of 163 paired measurements were recorded in 38 patients. With decreasing sedation depth, median %PLR increased progressively from 20% (interquartile range 17-25%) to 36% (interquartile range 33-40%) (P<0.001). Strong correlations were found between %PLR and RASS (Rho=0.635) and between %PLR and SEF (R=0.641). Area under the curve (AUC) of 0.87 with a %PLR threshold of 28% differentiated moderate/light sedation from deep sedation with sensitivity of 83% and specificity of 83%. An AUC of 0.82 with a threshold of 31% distinguished light sedation from moderate/deep sedation with a sensitivity of 81% and a specificity of 75%. CONCLUSIONS: Quantitative assessment of %PLR correlates with other indicators of sedation depth in critically ill patients.

Deep Learning Imaging Reconstruction Algorithm for Carotid Dual Energy CT Angiography: Opportunistic Evaluation of Cervical Intervertebral Discs-A Preliminary Study.

Thus, the aim of this study is to evaluate the performance of deep learning imaging reconstruction (DLIR) algorithm in different image sets derived from carotid dual-energy computed tomography angiography (DECTA) for evaluating cervical intervertebral discs (IVDs) and compare them with those reconstructed using adaptive statistical iterative reconstruction-Veo (ASiR-V). Forty-two patients who underwent carotid DECTA were included in this retrospective analysis. Three types of image sets (70 keV, water-iodine, and water-calcium) were reconstructed using 50% ASiR-V and DLIR at medium and high levels (DLIR-M and DLIR-H). The diagnostic acceptability and conspicuity of IVDs were assessed using a 5-point scale. Hounsfield Units (HU) and water concentration (WC) values of the IVDs; standard deviation (SD); and coefficient of variation (CV) were calculated. Measurement parameters of the 50% ASIR-V, DLIR-M, and DLIR-H groups were compared. The DLIR-H group showed higher scores for diagnostic acceptability and conspicuity, as well as lower SD values for HU and WC than the ASiR-V and DLIR-M groups for the 70 keV and water-iodine image sets (all p < .001). However, there was no significant difference in scores and SD among the three groups for the water-calcium image set (all p > .005). The water-calcium image set showed better diagnostic accuracy for evaluating IVDs compared to the other image sets. The inter-rater agreement using ASiR-V, DLIR-M, and DLIR-H was good for the 70 keV image set, excellent for the water-iodine and water-calcium image sets. DLIR improved the visualization of IVDs in the 70 keV and water-iodine image sets. However, its improvement on color-coded water-calcium image set was limited.

Disease burden of COPD attributable to PM2.5 in China, Japan and South Korea from 1990 to 2019: a comparative study based on Global Burden of Disease Study 2019.

OBJECTIVE: We hope to reveal the changing trends of chronic obstructive pulmonary disease (COPD) burden attributable to particulate matter pollution (PM2.5) and its age, period and cohort effects in China, Japan and Korea. DESIGN: We analysed the trend of COPD disease burden attributable to PM2.5 from 1990 to 2019 based on the latest Global Burden of Disease Database (GBD 2019) using JoinPoint model and analysed the effect of age, period and cohort on COPD burden attributable to PM2.5 in China, Japan and Korea from 1990 to 2019 using age-period-cohort model (model). SETTING: GBD data from 1990 to 2019. PARTICIPANTS: Data were publicly available and individuals were not involved. MAIN OUTCOMES: Outcomes included the age standardised mortality rate (ASMR), the age-standardised disability-adjusted life year (DALY), average annual per cent change (AAPC), net drift, local drift, longitudinal age curves, period (cohort) rate ratios, age (period, cohort) bias coefficient. RESULTS: From 1990 to 2019, the ASMR of COPD attributable to PM2.5 in China (AAPC=-5.862), Japan (AAPC=-1.715) and Korea (AAPC=-1.831) showed a downward trend. The age-standardised DALY of COPD attributable to PM2.5 in China (AAPC=-5.821), Japan (AAPC=-1.39) and Korea (AAPC=-1.239) showed a downward trend. Mortality of COPD attributable to PM2.5 increased slowly with age in Korea and Japan. Mortality of COPD attributable to PM2.5 in China decreased after rising (95% CI: 404.66 to 466.01). Mortality of COPD attributable to PM2.5 decreased over time in China and Korea, while it increased in Japan from 2015 to 2019. In China and Japan, mortality of COPD attributable to PM2.5 was approximately lower the later the birth, while in Korea it decreased after an increase (95% CI: 2.13 to 2.40) in the 1900-1910. CONCLUSIONS: Most COPD burden attributable to PM2.5 is on the decline; COPD mortality attributable to PM2.5 both increased with age and decreased with time and cohort. Countries with high burden should develop targeted measures to control PM2.5.

An Oxidoreductase-like Protein is Required for Verticillium dahliae Infection and Participates in the Metabolism of Host Plant Defensive Compounds.

Verticillium dahliae, a notorious phytopathogenic fungus, is responsible for vascular wilt diseases in numerous crops. Uncovering the molecular mechanisms underlying pathogenicity is crucial for controlling V. dahliae. Herein, we characterized a putative oxidoreductase-like protein (VdOrlp) from V. dahliae that contains a functional signal peptide. While the expression of VdOrlp was low in artificial media, it significantly increased during host infection. Deletion of VdOrlp had minimal effects on the growth and development of V. dahliae but severely impaired its pathogenicity. Metabolomic analysis revealed significant changes in organic heterocyclic compounds and phenylpropane compounds in cotton plants infected with ΔVdOrlp and V991. Furthermore, VdOrlp expression was induced by lignin, and its deletion affected the metabolism of host lignin and phenolic acids. In conclusion, our results demonstrated that VdOrlp plays an important role in the metabolism of plant phenylpropyl lignin and organic heterocyclic compounds and is required for fungal pathogenicity in V. dahliae.

Epidural ropivacaine versus bupivacaine for cesarean sections: a system review and meta-analysis.

INTRODUCTION: It is still no consensus on the use of ropivacaine or bupivacaine in epidural anesthesia for cesarean section (CS), because their anesthetic potency and relative complications remains controversial. This system review and meta-analysis aimed to compare the efficacy of epidural ropivacaine and bupivacaine for elective CSs and investigate relative complications for parturients and neonates. METHODS: We searched PubMed, MEDLINE, Embase, Cochrane Library, Science-Direct, and Google Scholar to June 30, 2023 for randomized controlled trials (RCTs), which compared epidural ropivacaine with bupivacaine for elective CSs. The success rate of epidural anesthesia (EA) was primary outcome. The secondary outcomes included onset times of sensory block, maternal side effects, neonatal Apgar scores and umbilical artery pH. RESULTS: We analyzed 8 RCTs with 532 parturients. 0.75% ropivacaine is associated with a shorter onset time of sensory block than 0.5% bupivacaine (SMD = -0.43, 95% CI: -0.70 to -0.17; p = .001). 0.5% ropivacaine resulted in a reduced nausea than 0.5% bupivacaine (RR = 0.49, 95% CI: 0.28 to 0.83; p = .008). In addition, there were no significant difference between ropivacaine and bupivacaine groups in terms of success rate of epidural anesthesia, maternal side effects (hypotension, bradycardia, shivering), and neonatal Apgar scores and umbilical artery pH. CONCLUSIONS: The findings suggest that there were no significant difference between epidural ropivacaine and bupivacaine for elective CSs in terms of the success rate (85.9% vs. 83.5), maternal side effects (hypotension, bradycardia, shivering), and neonatal Apgar scores and umbilical artery pH. But compared with 0.5% bupivacaine, epidural 0.75% ropivacaine was mildly effective for reducing onset time of sensory block and 0.5% ropivacaine reduced the incidence of maternal nausea.

Bbhox2 is a key regulator for conidiation and virulence in Beauveria bassiana.

Beauveria bassiana, a well-known filamentous biocontrol fungus, is the main pathogen of numerous field and forest pests. To explore the potential factors involved in the fungal pathogenicity, Bbhox2, an important and conserved functional transcription factor containing homeodomain was carried out by functional analysis. Homologous recombination was used to disrupt the Bbhox2 gene in B.bassiana. The conidia yield of the deletant fungal strain was significantly reduced. The conidial germination was faster, and stress tolerance to Congo red and high osmotic agents were decreased compared with that in the wildtype. Additionally, ΔBbhox2 showed a dramatic reduction in virulence no matter in topical inoculations or in intra-hemolymph injections against Galleria mellonella larvae, which is likely due to the failure of appressorium formation and the defect in producing hyphal body. These results indicate that the Bbhox2 gene markedly contributes to conidiation and pathogenicity in B. bassiana.

Long-term tadalafil once daily in Chinese men with erectile dysfunction: a 2-year final analysis of a post-marketing, multicenter, randomized, open-label trial.

The long-term safety and effectiveness of once-daily tadalafil is crucial, but limited data are available in Chinese patients with erectile dysfunction (ED). In this post-marketing, multicenter, randomized, open-label trial with 2-year follow-up, 635 ED cases were randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months, of whom 580 continued once-daily tadalafil 5 mg for 21 months. Treatment-emergent adverse events in the 12-month and 24-month period were similar, with the most common being viral upper respiratory tract infection, upper respiratory tract infection, and headache. Significant improvement from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) score was detected at month 12 (least squares mean [LSM] change: 7.9, 95% confidence interval [CI]: 7.5-8.4, P < 0.001) and was maintained to month 24 (LSM change: 8.6, 95% CI: 8.1-9.0, P < 0.001). The proportions of patients regaining normal erectile function (IIEF-EF score ≥26) were 43.7% and 48.0% at months 12 and 24, respectively. Global Assessment Questionnaire results showed improved erection function in 97.5% of patients and improved ability to engage in sexual activity in 95.9% of patients at month 12; these values were 96.1% and 95.0% at month 24, respectively. The quality of sexual life score based on the Sexual Life Quality Questionnaire (SLQQ) was increased by 52.2% at month 12 and by 55.3% at month 24 (both P < 0.001). The treatment satisfaction score determined by SLQQ (mean ± standard deviation) was 62.4 ± 21.0 at month 12 versus 65.9 ± 20.2 at month 24. Two-year daily application of tadalafil 5 mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

Comprehensive repair of the alveolar cleft using cortical and cancellous bone layers: A retrospective study.

To retrospectively review the clinical effect of comprehensive treatment of alveolar cleft (CTAC) using the mandible as the bone source. Patients with alveolar clefts who met the inclusion criteria were subjected to a CTAC protocol that included the following: (1) preoperative orthodontic treatment for creating good soft-tissue conditions; (2) 'area-like grafting' with subperiosteal osteogenic chin bone instead of cartilaginous osteogenic iliac bone; (3) simulation of normal bone anatomy via a sandwich-like bone graft consisting of 'cortical bone + cancellous bone + cortical bone'; and (4) strong internal fixation to ensure initial bone block stability. At 6 months postoperatively, the titanium plate was removed and cone-beam computed tomography was performed to evaluate the surgical results. A total of 54 patients underwent treatment with the CTAC protocol. The average age at the initial operation was 10.3 ± 2.1 years, and the average hospital stay was 2.8 ± 0.6 days. At 6 months postoperatively, 49 patients (90.7%) showed good clinical results. The transplanted bone block formed a 'cortical bone + cancellous bone + cortical bone' structure similar to that of the normal jawbone. A mature bone bridge formed, and the impacted permanent teeth continued to erupt and enter the bone graft area. CTAC is a comprehensive restorative solution for alveolar cleft repair that integrates multiple concepts, including orthodontics, embryology, anatomy, and improvements to surgical methods. The method is easy to perform, causes little surgical trauma, and shows a stable success rate, and is thus worth promoting.

Cyclophosphamide reduces gene transcriptional activity and embryo in vitro development by inhibiting NF-κB expression through decreasing AcH4K12.

Cyclophosphamide (CTX), a widely used chemotherapeutic agent for cancer treatment, has been associated with long-term toxicity and detrimental effects on oocytes and ovaries, resulting in female reproductive dysfunction. This study aimed to investigate the potential impact of CTX on in vitro maturation (IVM) injury of porcine oocytes and subsequent embryonic development, as well as its effects on epigenetic modification and gene activation during early embryonic development. The results demonstrated that CTX treatment caused aberrant spindle structure and mitochondrial dysfunction during oocyte maturation, inducing DNA damage and early apoptosis, which consequently disrupted meiotic maturation. Indeed, CTX significantly reduced the in vitro developmental capacity of porcine embryos, and induced DNA damage and apoptosis in in vitro fertilization (IVF) blastocysts. Importantly, CTX induced abnormal histone modification of AcH4K12 in early porcine embryos. Moreover, addition of LBH589 before zygotic genome activation (ZGA) effectively increased AcH4K12 levels and restored the protein expression of NF-κB, which can effectively enhance the in vitro developmental potential of IVF embryos. The DNA damage and apoptosis induced by CTX compromised the quality of the blastocysts, which were recovered by supplementation with LBH589. This restoration was accompanied by down-regulation of BAX mRNA expression and up-regulation of BCL2, POU5F1, SOX2 and SOD1 mRNA expression. These findings indicated that CTX caused abnormal histone modification of AcH4K12 in early porcine embryos and reduced the protein expression of NF-κB, a key regulator of early embryo development, which may block subsequent ZGA processes.

Effect of rehabilitation therapy combined with neuromuscular electrical stimulation on cognitive dysfunction and activities of daily life in stroke patients.

OBJECTIVE: To determine the effects of rehabilitation therapy combined with neuromuscular electrical stimulation (NES) on cognitive dysfunction and ability to perform activities of daily living (ADLs) of stroke patients. METHODS: The clinical data of 100 stroke patients treated in the Second Affiliated Hospital of Soochow University from February 2019 to August 2021 were retrospectively analyzed. According to the therapeutic regimen, the patients given rehabilitation therapy combined with NES were assigned to a study group (n=52) and those given rehabilitation therapy alone were assigned to a control group (n=48). The treatment efficacy in the two groups was evaluated, and the levels of plasma cortisol (Cor) and neuropeptide Y (NPY), neurological function, motor function, balance ability, swallowing function, cognitive function, negative emotions, and quality of life (QoL) after therapy were evaluated. The maximum amplitude of surface electromyography (sEMG) and swallowing time were compared between the two groups. RESULTS: The study group yielded significantly better efficacy than the control group (P<0.05). Before therapy, there were no significant differences between the two groups in Cor and NPY levels, neurological function, motor function, balance ability, swallowing function, cognitive function, sEMG, swallowing time or negative emotions (P>0.05). After therapy, the above all indices all greatly improved, with more notso in the study group. In addition, after therapy, the study group had significantly better QoL indexes than the control group. CONCLUSION: Rehabilitation therapy combined with NES is effective in treating stroke. It can substantially ameliorate the cognitive dysfunction, prognosis and QoL in patients.

[Clinical analysis of endoscopic esophageal dilation for the treatment of corrosive esophageal strictures in children]. / å† é•œä¸‹é£Ÿç®¡æ‰©å¼ æ²»ç–—å„¿ç«¥è èš€æ€§é£Ÿç®¡ç‹­çª„çš„ä¸´åºŠåˆ†æž.

OBJECTIVES: To investigate the clinical application of endoscopic esophageal dilation in the treatment of corrosive esophageal strictures in children. METHODS: A retrospective analysis was performed on the clinical data of 15 children with corrosive esophageal strictures who underwent endoscopic esophageal dilation in Children's Hospital, Zhejiang University School of Medicine. The clinical features, treatment modality of endoscopic esophageal dilation, number of dilations, complications, and prognosis were reviewed. RESULTS: A total of 96 esophageal dilations were performed in the 15 children with corrosive esophageal strictures, with a median of 6 dilations per child. Among them, 9 children (60%) underwent 6 or more dilations. The children with a stricture length of >3 cm had a significantly higher number of dilations than those with a stricture length of ≤3 cm (P<0.05). The children with strictures in a single segment had a significantly better treatment outcome than those with strictures in multiple segments (P=0.005). No complication was observed during all sessions of dilation. The overall effective rate (including significant improvement and improvement) of endoscopic esophageal dilation treatment was 87%, with 2 cases of failure. CONCLUSIONS: Endoscopic esophageal dilation is an effective and relatively safe treatment method for corrosive esophageal strictures in children, and children with strictures in a single segment tend to have a better treatment outcome than those with strictures in multiple segments.

Nomogram Based on Dual-Layer Spectral Detector CTA Parameter for the Prediction of Infarct Core in Patients with Acute Ischemic Stroke.

(1) Background: Acute ischemic stroke (AIS) is time-sensitive. The accurate identification of the infarct core and penumbra areas in AIS patients is an important basis for formulating treatment plans, and is the key to dual-layer spectral detector computed tomography angiography (DLCTA), a safer and more accurate diagnostic method for AIS that will replace computed tomography perfusion (CTP) in the future. Thus, this study aimed to investigate the value of DLCTA in differentiating infarct core from penumbra in patients with AIS to establish a nomogram combined with spectral computed tomography (CT) parameters for predicting the infarct core and performing multi-angle evaluation. (2) Methods: Data for 102 patients with AIS were retrospectively collected. All patients underwent DLCTA and CTP. The patients were divided into the non-infarct core group and the infarct core group, using CTP as the reference. Multivariate logistic regression analysis was used to screen predictors related to the infarct core and establish a nomogram model. The receiver operating characteristic (ROC) curve, the calibration curve, and decision curve analysis (DCA) were used to evaluate the predictive efficacy, accuracy, and clinical practicability of the model, respectively. (3) Results: Multivariate logistic analysis identified three independent predictors: iodine density (OR: 0.022, 95% CI: 0.003-0.170, p < 0.001), hypertension (OR: 7.179, 95% CI: 1.766-29.186, p = 0.006), and triglycerides (OR: 0.255, 95% CI: 0.109-0.594, p = 0.002). The AUC-ROC of the nomogram was 0.913. Calibration was good. Decision curve analysis was clinically useful. (4) Conclusions: The spectral CT parameters, specifically iodine density values, effectively differentiate between the infarct core and penumbra areas in patients with AIS. The nomogram, based on iodine density values, showed strong predictive power, discrimination, and clinical utility to accurately predict infarct core in AIS patients.

A longitudinal single-cell atlas of treatment response in pediatric AML.

Pediatric acute myeloid leukemia (pAML) is characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains understudied in pediatric patients. We used single-cell RNA sequencing and single-cell ATAC sequencing to profile 28 patients representing different pAML subtypes at diagnosis, remission and relapse. At diagnosis, cellular composition differed between genetic subgroups. Upon relapse, cellular hierarchies transitioned toward a more primitive state regardless of subtype. Primitive cells in the relapsed tumor were distinct compared to cells at diagnosis, with under-representation of myeloid transcriptional programs and over-representation of other lineage programs. In some patients, this was accompanied by the appearance of a B-lymphoid-like hierarchy. Our data thus reveal the emergence of apparent subtype-specific plasticity upon treatment and inform on potentially targetable processes.

Integrated FET sensing microsystem for specific detection of pancreatic cancer exosomal miRNA10b.

Tumor-derived exosome (TD-Ex) serves as a crucial early diagnostic biomarker of pancreatic cancer (PC). However, accurate identification of TD-Ex from PC is still a challenging work. In this paper, a detection microsystem that integrates magnetic separation and FET biosensor is developed, which is capable of selectively separating TD-Ex of PC from the plasma and detecting exosomal miRNA10b in a sensitive and specific manner. The magnetic beads were functionalized with dual antibody (GPC-1 antibody and EpCAM antibody), enabling selective recognition and capture of PC-derived exosomes. On the other hand, a peptide nucleic acid (PNA)- functionalized reduced graphene oxide field-effect transistor (RGO FET) biosensor was subsequently utilized to detect the exosomal miRNA10b, which is highly expressed in PC- derived exosomes. This system could achieve a low detection limit down to 78 fM, and selectively identify miRNA10b from single-base mismatched miRNA. In addition, 40 clinical plasma samples were tested with this microsystem, and the results indicate that it could effectively distinguish PC patients from healthy individuals. The assay combines specific capture and enrichment of PC-derived exosomes with sensitive and selective detection of exosomal miRNA, showing its potential to be used as an effective scheme for PC early diagnosis.

HIF-1α-Induced Mitophagy Regulates the Regenerative Outcomes of Stem Cells in Fat Transplantation.

Hypoxia is a crucial factor with type diversity that plays an important role in stem cell transplantation. However, the effects of hypoxia on adipose-derived stem cells (ADSCs) are largely unclear in the autologous fat transplantation (AFT) model, which shows a special type of "acute-progressively resolving hypoxia." Here, an AFT model in nude mice and a hypoxic culture model for ADSCs were combined to explore the link between hypoxia-inducible factor-1 α subunit (HIF-1α) and mitophagy under hypoxic conditions. The results showed that the activity of ADSCs in the first 7 days after grafting was the key stage for volume retention, and the expression of HIF-1α, light chain 3 beta (LC3B), and Beclin1 in ADSCs increased during this period. We also found that hypoxia for longer than 48 h damaged the differentiation and mitochondrial respiration of ADSCs in vitro, but hypoxia signals also activate HIF-1α to initiate mitophagy and maintain the activities of ADSCs. Pre-enhancing mitophagy by rapamycin effectively improves mitochondrial respiration in ADSCs after grafting and ultimately improves AFT outcomes.