Multi-omics analysis provides new insights into the changes of important nutrients and fructose metabolism in loquat bud sport mutant.

Bud sport is a common and stable somatic variation in perennial fruit trees, and often leads to significant modification of fruit traits and affects the breeding value. To investigate the impact of bud sport on the main metabolites in the fruit of white-fleshed loquat, we conducted a multi-omics analysis of loquat fruits at different developmental stages of a white-fleshed bud sport mutant of Dongting loquat (TBW) and its wild type (TBY). The findings from the detection of main fruit quality indices and metabolites suggested that bud sport resulted in a reduction in the accumulation of carotenoids, fructose, titratable acid and terpenoids at the mature stage of TBW, while leading to the accumulation of flavonoids, phenolic acids, amino acids and lipids. The comparably low content of titratable acid further enhances the balanced and pleasent taste profile of TBW. Expression patterns of differentially expressed genes involved in fructose metabolism exhibited a significant increase in the expression level of S6PDH (EVM0006243, EVM0044405) prior to fruit maturation. The comparison of protein sequences and promoter region of S6PDH between TBY and TBW revealed no structural variations that would impact gene function or expression, indicating that transcription factors may be responsible for the rapid up-regulation of S6PDH before maturation. Furthermore, correlation analysis helped to construct a comprehensive regulatory network of fructose metabolism in loquat, including 23 transcription factors, six structural genes, and nine saccharides. Based on the regulatory network and existing studies, it could be inferred that transcription factors such as ERF, NAC, MYB, GRAS, and bZIP may promote fructose accumulation in loquat flesh by positively regulating S6PDH. These findings improve our understanding of the nutritional value and breeding potential of white-fleshed loquat bud sport mutant, as well as serve as a foundation for exploring the genes and transcription factors that regulate fructose metabolism in loquat.

Enhancing Efficiency and Stability in Carbon-Based Perovskite Solar Cells by Double Passivation with Ultralow-Cost Coal-Derived Graphene and Its Derivatives.

Coal-derived carbon nanomaterials possess numerous superior features compared to other classic carbon, such as readily accessible surfaces, tunable pore structure, and facile and precise surface functionalization. Therefore, the controllable preparation of coal-derived carbon nanomaterials is anticipated to be of great significance for the performance improvement and commercialization process of carbon-based perovskite solar cells (C-PSCs). In this study, we successfully synthesized highly stable and commercially valuable graphene oxide (GO) and reduced graphene oxide (rGO) utilizing coal. Compared to traditional methods and commercial graphene, the chemical oxidation and pyrolysis process used in this study is mild and simple, offering the advantages of controlled composition and the absence of other impurities. GO or rGO was incorporated into the top of the SnO2 electron transport layer (ETL) of C-PSCs. Under optimized conditions and ultraviolet-ozone (UVO) irradiation, the ultimate power conversion efficiency (PCE) increased from the unmodified 12.4 to 14.04% (based on rGO) and 15.18% (based on GO), representing improvements of 22 and 31%, respectively. The improved photovoltaic performance is mainly owing to enhanced charge transport capabilities, denser interfacial contacts, improved carrier separation properties, increased conductivity, and abundance of hydrophilic functional groups in GO, which can form more stable hydrogen bonds with SnO2. After being stored at room temperature and ambient humidity for 30 days, the modified, unpacked devices retained 87% of the highest power conversion efficiency (PCE). This study introduces a practical and manageable method to enhance the performance of C-PSCs by using functional carbon nanomaterials derived from coal.

Structure-guided design of novel biphenyl-quinazoline derivatives as potent non-nucleoside reverse transcriptase inhibitors featuring improved anti-resistance, selectivity, and solubility.

In pursuit of enhancing the anti-resistance efficacy and solubility of our previously identified NNRTI 1, a series of biphenyl-quinazoline derivatives were synthesized employing a structure-based drug design strategy. Noteworthy advancements in anti-resistance efficacy were discerned among some of these analogs, prominently exemplified by compound 7ag, which exhibited a remarkable 1.37 to 602.41-fold increase in potency against mutant strains (Y181C, L100I, Y188L, F227L + V106A, and K103N + Y181C) in comparison to compound 1. Compound 7ag also demonstrated comparable anti-HIV activity against both WT HIV and K103N, albeit with a marginal reduction in activity against E138K. Of significance, this analog showed augmented selectivity index (SI > 5368) relative to compound 1 (SI > 37764), Nevirapine (SI > 158), Efavirenz (SI > 269), and Etravirine (SI > 1519). Moreover, it displayed a significant enhancement in water solubility, surpassing that of compound 1, Etravirine, and Rilpivirine. To elucidate the underlying molecular mechanisms, molecular docking studies were undertaken to probe the critical interactions between 7ag and both WT and mutant strains of HIV-1 RT. These findings furnish invaluable insights driving further advancements in the development of DAPYs for HIV therapy.

Electrical impedance tomography as a bedside assessment tool for COPD treatment during hospitalization.

For patients with chronic obstructive pulmonary disease (COPD), the assessment of the treatment efficacy during hospitalization is of importance to the optimization of clinical treatments. Conventional spirometry might not be sensitive enough to capture the regional lung function development. The study aimed to evaluate the feasibility of using electrical impedance tomography (EIT) as an objective bedside evaluation tool for the treatment of acute exacerbation of COPD (AECOPD). Consecutive patients who required hospitalization due to AECOPD were included prospectively. EIT measurements were conducted at the time of admission and before the discharge simultaneously when a forced vital capacity maneuver was conducted. EIT-based heterogeneity measures of regional lung function were calculated based on the impedance changes over time. Surveys for attending doctors and patients were designed to evaluate the ease of use, feasibility, and overall satisfaction level to understand the acceptability of EIT measurements. Patient-reported outcome assessments were conducted. User's acceptance of EIT technology was investigated with a five-dimension survey. A total of 32 patients were included, and 8 patients were excluded due to the FVC maneuver not meeting the ATS criteria. Spirometry-based lung function was improved during hospitalization but not significantly different (FEV1 %pred.: 35.8% ± 6.7% vs. 45.3% ± 8.8% at admission vs. discharge; p = 0.11. FVC %pred.: 67.8% ± 0.4% vs. 82.6% ± 5.0%; p = 0.15. FEV1/FVC: 0.41 ± 0.09 vs. 0.42 ± 0.07, p = 0.71). The symptoms of COPD were significantly improved, but the correlations between the improvement of symptoms and spirometry FEV1 and FEV1/FVC were low (R = 0.1 and -0.01, respectively). The differences in blood gasses and blood tests were insignificant. All but one EIT-based regional lung function parameter were significantly improved after hospitalization. The results highly correlated with the patient-reported outcome assessment (R > 0.6, p < 0.001). The overall acceptability score of EIT measurement for both attending physicians and patients was high (4.1 ± 0.8 for physicians, 4.5 ± 0.5 for patients out of 5). These results demonstrated that it was feasible and acceptable to use EIT as an objective bedside evaluation tool for COPD treatment efficacy.

Novel cow dung-doped sludge biochar as an efficient ozone catalyst: Synergy between graphitic structure and defects induces free radical pathways.

A composite material, cow dung-doped sludge biochar (Zn@SBC-CD), was synthesized by one-step pyrolysis using ZnCl2 as an activating agent and applied to a catalytic ozonation process (COP) for methylene blue (MB) removal. SEM, XRD, FTIR, XPS and BET analyses were performed to characterize the biochar (BC) catalysts. Zn@SBC-CD had high graphitization degree, abundant active sites and uniform distribution of Zn on its surface. Complete removal of MB was achieved within 10 min, with a removal rate much higher than that of ozone alone (32.4%), implying the excellent ozone activation performance of Zn@SBC-CD. The influence of experimental parameters on MB removal efficiency was examined. Under the optimum conditions in terms of ozone dose 0.04 mg/mL, catalyst dose 400 mg/L and pH 6.0, COD was completely removed after 20 min. Electron paramagnetic resonance (EPR) analysis revealed radical and non-radical pathways were involved in MB degradation. The Zn@SBC-CD/O3 system generated superoxide anion radicals (•O2-), which were the main active species for MB removal, through adsorption, transformation, and transfer, Furthermore, Zn@SBC-CD exhibited good reusability and stability in cycling experiments. This study provides a novel approach for the utilization of cow dung and sludge in synthesis of functional biocatalysts and application in organic wastewater treatment.

Factors affecting the compliance of hepatocellular carcinoma screening among high-risk populations: A systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer mortality. HCC has high morbidity, high mortality, and low survival rates. Screening is one of the most significant methods of lowering incidence and death while also increasing survival. OBJECTIVES: The aim of this study was to identify the facilitators and barriers to participation in HCC screening among high-risk populations. METHODS: A comprehensive and systematic search was undertaken in PubMed, Web of Science, MEDLINE, EMBACE, EBSCOhost and the Cochrane Library. A combination of synonyms of the keywords including HCC, screening, factors and adherence were used for searching. Studies addressing the facilitators and barriers to HCC screening compliance in at-risk individuals were included. Data were synthesized using Review Manager version 5.4. A random/fixed effects model meta-analysis was performed to estimate the pooled data and expressed with odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of seven articles met the inclusion criteria. Qualitative (n = 1) and quantitative (n = 6) studies using various types of surgery were conducted. The most commonly mentioned barriers were insufficient knowledge and awareness of HCC screening, unawareness of the necessity for early detection of HCC and lack of physician recommendation. A meta-analysis of seven studies showed that individuals with a family history of HCC increased screening uptake by nearly three times (OR: 2.69, 95% CI: 1.93, 3.75). Other most frequently reported facilitators include age, education level, and perceived risk et al. CONCLUSIONS: Many barriers to HCC screening were found. Meanwhile, this review points out that improving the awareness of high-risk populations toward HCC screening is expected to enhance compliance, thereby promoting early diagnosis of liver cancer, reducing mortality, and alleviating the burden of HCC.

Visualizing pursed lips breathing of patients with chronic obstructive pulmonary disease through evaluation of global and regional ventilation using electrical impedance tomography.

Objective. This study aims to explore the possibility of using electrical impedance tomography (EIT) to assess pursed lips breathing (PLB) performance of patients with chronic obstructive pulmonary disease (COPD).Methods. 32 patients with COPD were assigned equally to either the conventional group or the EIT guided group. All patients were taught to perform PLB by a physiotherapist without EIT in the conventional group or with EIT in the EIT guided group for 10 min. The ventilation of all patients in the final test were continuously monitored using EIT and the PLB performances were rated by another physiotherapist before and after reviewing EIT. The global and regional ventilation between two groups as well as between quite breathing (QB) and PLB were compared and rating scores with and without EIT were also compared.Results.For global ventilation, the inspiratory depth and the ratio of expiratory-to-inspiratory time during PLB was significantly larger than those during QB for both group (P< 0.001). The inspiratory depth and the ratio of expiratory-to-inspiratory time during PLB in the EIT guided group were higher compared to those in the conventional group (P< 0.001), as well as expiratory flow expiratory uniformity and respiratory stability were better (P< 0.001). For regional ventilation, center of ventilation significantly decreased during PLB (P< 0.05). The expiratory time constant during PLB in the EIT guided group was greater than that in the conventional group (P< 0.001). Additionally, Bland-Altman plots analysis suggested a high concordance between subjective rating and rating with the help of EIT, but the score rated after EIT observation significantly lower than that rated subjectively in both groups (score drop of -2.68 ± 1.1 in the conventional group and -1.19 ± 0.72 in the EIT guided group,P< 0.01).Conclusion.EIT could capture the details of PLB maneuver, which might be a potential tool to quantitatively evaluate PLB performance and thus assist physiotherapists to teach PLB maneuver to patients.

Alterations in HCN1 expression and distribution during epileptogenesis in rats.

BACKGROUND: The hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN1) is predominantly located in key regions associated with epilepsy, such as the neocortex and hippocampus. Under normal physiological conditions, HCN1 plays a crucial role in the excitatory and inhibitory regulation of neuronal networks. In temporal lobe epilepsy, the expression of HCN1 is decreased in the hippocampi of both animal models and patients. However, whether HCN1 expression changes during epileptogenesis preceding spontaneous seizures remains unclear. OBJECTIVE: The aim of this study was to determine whether the expression of HCN1 is altered during the epileptic prodromal phase, thereby providing evidence for its role in epileptogenesis. METHODS: We utilized a cobalt wire-induced rat epilepsy model to observe changes in HCN1 during epileptogenesis and epilepsy. Additionally, we also compared HCN1 alterations in epileptogenic tissues between cobalt wire- and pilocarpine-induced epilepsy rat models. Long-term video EEG recordings were used to confirm seizures development. Transcriptional changes, translation, and distribution of HCN1 were assessed using high-throughput transcriptome sequencing, total protein extraction, membrane and cytoplasmic protein fractionation, western blotting, immunohistochemistry, and immunofluorescence techniques. RESULTS: In the cobalt wire-induced rat epilepsy model during the epileptogenesis phase, total HCN1 mRNA and protein levels were downregulated. Specifically, the membrane expression of HCN1 was decreased, whereas cytoplasmic HCN1 expression showed no significant change. The distribution of HCN1 in the distal dendrites of neurons decreased. During the epilepsy period, similar HCN1 alterations were observed in the neocortex of rats with cobalt wire-induced epilepsy and hippocampus of rats with lithium pilocarpine-induced epilepsy, including downregulation of mRNA levels, decreased total protein expression, decreased membrane expression, and decreased distal dendrite expression. CONCLUSIONS: Alterations in HCN1 expression and distribution are involved in epileptogenesis beyond their association with seizure occurrence. Similarities in HCN1 alterations observed in epileptogenesis-related tissues from different models suggest a shared pathophysiological pathway in epileptogenesis involving HCN1 dysregulation. Therefore, the upregulation of HCN1 expression in neurons, maintenance of the HCN1 membrane, and distal dendrite distribution in neurons may represent promising disease-modifying strategies in epilepsy.

[Simultaneous Immobilization of Cadmium and Arsenic in Paddy Soils with Novel Fe-Mn Combined Graphene Oxide].

Novel Fe-Mn combined graphene oxide （GO-FM） material was produced and tested for its efficacy in remediating agricultural soil co-contaminated by Cd and As. In a 60-day soil incubation experiment， the remediation mechanism and immobilization effects of GO and GO-FM at different addition ratios （0.1%， 0.2%， and 0.3%） were investigated in Shangyu and Foshan soils， which had varying physicochemical properties and contamination degrees. The dynamic changes in pH， DOC concentration， bioavailable Cd and As content， and morphology of Cd and As were explored to determine the remediation efficacy of the materials. The results demonstrated that compared with that in the blank control， GO-FM increased the pH in Shangyu soil but decreased the pH in Foshan soil. After culture， both GO and GO-FM increased the soil DOC content. GO-FM decreased the soluble Cd concentration by 5.08%-19.19% and the bioavailability of Cd by 36.57%-42.8% in Foshan soil， and the main immobilization mechanism was electrostatic adsorption， complexation， and hydroxylated metal ion formation. The immobilization ability of GO-FM on Cd was lower than that of Foshan soil due to the influence of electrostatic repulsion in Shangyu acidic soil. However， with the increase in the amount of GO-FM， the trend of increasing the bioavailability of Cd by graphene oxide was inhibited. The addition of 0.2% and 0.3% GO-FM decreased the bioavailability of Cd by 6.45%-13.56% in Shangyu soil. Additionally， GO-FM decreased the bioavailability of As in Shangyu soil and Foshan soil by 4.34%-9.15% and 0.87%-5.71%， respectively. This was due to the immobilization mechanism of oxidation of As by manganese oxides and inner surface chelate between As and the surface hydroxyl group of iron oxides. In summary， the immobilization effect of GO-FM on Cd in Foshan soil was better than that in Shangyu soil， and the immobilization effect of GO-FM on As in Shangyu soil was better than that in Foshan soil， which can provide a theoretical basis and reference for the prevention and control of Cd and As co-contamination in different types of soil.

Phenanthrothiophene-Triazine Star-Shaped Discotic Liquid Crystals: Synthesis, Self-Assembly, and Stimuli-Responsive Fluorescence Properties.

Lipophilic biphenylthiophene- and phenanthrothiophene-triazine compounds, BPTTn and CPTTn, respectively, were prepared by a tandem procedure involving successive Suzuki-Miyaura coupling and Scholl cyclodehydrogenation reactions. These compounds display photoluminescence in solution and in thin film state, solvatochromism with increasing solvent's polarity, as well as acidochromism and metal ion recognition stimuli-responsive fluorescence. Protonation of BPTT10 and CPTT10 by trifluoroacetic acid results in fluorescence quenching, which is reversibly restored once treated with triethylamine (ON-OFF switch). DFT computational studies show that intramolecular charge transfer (ICT) phenomena occurs for both molecules, and reveal that protonation enhances the electron-withdrawing ability of the triazine core and reduces the band gap. This acidochromic behavior was applied to a prototype fluorescent anti-counterfeiting device. They also specifically recognize Fe3+ through coordination, and the recognition mechanism is closely related to the photoinduced electron transfer between Fe3+ and BPTT10/CPTT10. CPTTn self-assemble into columnar rectangular (Colrec) mesophase, which can be modulated by oleic acid via the formation of a hydrogen-bonded supramolecular liquid crystal hexagonal Colhex mesophase. Finally, CPTTn also form organic gels in alkanes at low critical gel concentration (3.0 mg/mL). Therefore, these star-shaped triazine molecules possess many interesting features and thus hold great promises for information processing, liquid crystal semiconductors and organogelators.

Transcriptomic analysis and carbohydrate metabolism-related enzyme expression across different pH values in Rhizopus delemar.

Introduction: pH is one of the important factors affecting the growth and performance of microorganisms. Methods: We studied the pH response and plant growth-promoting (PGP) ability of Rhizopus delemar using cultivation experiments and transcriptomics, and verified the expression profiles using quantitative real-time PCR. Results: pH affected the growth and PGP properties of R. delemar. At pH 7, the growth rate of R. delemar was rapid, whereas pH 4 and 8 inhibited mycelial growth and PGP ability, respectively. In the pot experiment, the plant height was the highest at pH 7, 56 cm, and the lowest at pH 4 and pH 5, 46.6 cm and 47 cm, respectively. Enzyme activities were highest at pH 6 to pH 7. Enzyme activities were highest at pH 6 to pH 7. Among the 1,629 differentially expressed genes (DEGs), 1,033 genes were up-regulated and 596 were down-regulated. A total of 1,623 DEGs were annotated to carbohydrate-active enzyme coding genes. Discussion: The PGP characteristics, e.g., Phosphorus solubilization ability, of R. delemar were strongest at pH 7. The results provide useful information regarding the molecular mechanism of R. delemar pH response.

Stepwise degradable PGA-SF core-shell electrospinning scaffold with superior tenacity in wetting regime for promoting bone regeneration.

Regenerating bone in the oral and maxillofacial region is clinically challenging due to the complicated osteogenic environment and the limitation of existing bone graft materials. Constructing bone graft materials with controlled degradation and stable mechanical properties in a physiological environment is of utmost importance. In this study, we used silk fibroin (SF) and polyglycolic acid (PGA) to fabricate a coaxial PGA-SF fibrous scaffold (PGA-SF-FS) to meet demands for bone grafts. The SF shell exerted excellent osteogenic activity while protecting PGA from rapid degradation and the PGA core equipped scaffold with excellent tenacity. The experiments related to biocompatibility and osteogenesis (e.g., cell attachment, proliferation, differentiation, and mineralization) demonstrated the superior ability of PGA-SF-FS to improve cell growth and osteogenic differentiation. Furthermore, in vivo testing using Sprague-Dawley rat cranial defect model showed that PGA-SF-FS accelerates bone regeneration as the implantation time increases, and its stepwise degradation helps to match the remodeling kinetics of the host bone tissue. Besides, immunohistochemical staining of CD31 and Col-1 confirmed the ability of PGA-SF-FS to enhance revascularization and osteogenesis response. Our results suggest that PGA-SF-FS fully utilizing the advantages of both components, exhibites stepwise degradation and superior tenacity in wetting regime, making it a promising candidate in the treatment of bone defects.

Strain regulates the photovoltaic performance of thick-film perovskites.

Perovskite photovoltaics, typically based on a solution-processed perovskite layer with a film thickness of a few hundred nanometres, have emerged as a leading thin-film photovoltaic technology. Nevertheless, many critical issues pose challenges to its commercialization progress, including industrial compatibility, stability, scalability and reliability. A thicker perovskite film on a scale of micrometres could mitigate these issues. However, the efficiencies of thick-film perovskite cells lag behind those with nanometre film thickness. With the mechanism remaining elusive, the community has long been under the impression that the limiting factor lies in the short carrier lifetime as a result of defects. Here, by constructing a perovskite system with extraordinarily long carrier lifetime, we rule out the restrictions of carrier lifetime on the device performance. Through this, we unveil the critical role of the ignored lattice strain in thick films. Our results provide insights into the factors limiting the performance of thick-film perovskite devices.

Excessive iron deposition in root apoplast is involved in growth arrest of roots in response to proton stress.

The rhizotoxicity of protons (H+) in acidic soils is a fundamental constraint that results in serious yield losses. However, the mechanisms underlying H+-mediated inhibition of root growth are poorly understood. In this study, we revealed that H+-induced root growth inhibition depends considerably on excessive iron deposition in root apoplasts. Reducing such aberrant iron deposition by decreasing the iron supply or disrupting the ferroxidases LOW PHOSPHATE ROOT 1 (LPR1) and LOW PHOSPHATE ROOT 2 (LPR2) attenuates the inhibitory effect of H+ on primary root growth efficiently. Further analysis showed that excessive iron deposition triggers a burst of highly reactive oxygen species, consequently impairing normal root development. Our study uncovered a valuable strategy for improving the ability of plants to tolerate H+ toxicity by manipulating iron availability.

The role of self-related information in the sense of agency.

Sense of agency (SoA) refers to the subjective experience of controlling one's actions and their subsequent consequences. The present study endeavors to investigate the impact of how different degrees of self-related stimuli as action outcomes on the sense of agency by observing the temporal binding effect. Results showed that self-related sound significantly altered temporal binding, notably influencing outcome binding. A post-hoc explanation model effectively elucidated the role of self-related information in the formation of the sense of agency.

Image-based vegetation analysis of desertified area by using a combination of ImageJ and Photoshop software.

Fractional vegetation cover (FVC) is a crucial indicator to estimate degradation and desertification for grasslands. However, traditional small-scale FVC analysis methods, such as visual estimation and point-sampling, are cumbersome and imprecise. Innovative methods like image-based FVC analysis methods, while accurate, face challenges such as complex analytical procedures and the necessary training for operations. Therefore, in this study, a combined application of ImageJ and Photoshop was employed to achieve a more effective analysis of FVC values in desertification areas. Our results showed that the FVC results obtained by combination of Photoshop and ImageJ were dependable and precise (R2 > 0.98), demonstrating equivalency to results obtained through either visual estimation or Photoshop-based methods. Furthermore, even in the face of background interference and varied shooting angles, the combination of ImageJ and Photoshop software was still able to maintain a low error rate when analyzing FVC values (average error rate = - 2.6%). In conclusion, the imaged-based combined FVC analysis method employed in our research was an effective, precise, and efficient technique for analyzing small-scale FVC, promising substantial improvement over conventional methods.

Monitoring of spontaneous pneumothorax using electrical impedance tomography: A case report.

Pneumothorax is an emergency in thoracic surgeries and respiratory medicine. A technique is warranted for real-time monitoring of pneumothorax at the bedside so that rapid diagnosis and timely intervention can be achieved. We report herein a case in which electrical impedance tomography (EIT) was employed at the bedside to monitor lung ventilation of a patient with spontaneous pneumothorax during treatment. It was found that the affected side/healthy side ventilation ratio and global inhomogeneity were strongly correlated with the severity of pneumothorax. The use of EIT allowed intuitive observation of the effect of pneumothorax on ventilation, which helped the doctors make immediate diagnosis and intervention. After timely and successful treatment, the patient was discharged. This is the first case reporting a complete therapeutic course of spontaneous pneumothorax assessed with EIT. Our case demonstrated that EIT could monitor regional ventilation loss of the affected side of pneumothorax patients at the bedside, and dynamically assess the treatment effect of pneumothorax, which provides an important imaging basis for clinical pneumothorax treatment.

A CT-based multitask deep learning model for predicting tumor stroma ratio and treatment outcomes in patients with colorectal cancer: a multicenter cohort study.

BACKGROUND: Tumor-stroma interactions, as indicated by tumor-stroma ratio (TSR), offer valuable prognostic stratification information. Current histological assessment of TSR is limited by tissue accessibility and spatial heterogeneity. We aimed to develop a multitask deep learning (MDL) model to noninvasively predict TSR and prognosis in colorectal cancer (CRC). MATERIALS AND METHODS: In this retrospective study including 2268 patients with resected CRC recruited from four centers, we developed an MDL model using preoperative CT images for the simultaneous prediction of TSR and overall survival. Patients in the training cohort (n=956) and internal validation cohort (IVC, n=240) were randomly selected from center I. Patients in the external validation cohort1(EVC1, n=509), EVC2 (n=203), and EVC3 (n=360) were recruited from other three centers. Model performance was evaluated with respect to discrimination and calibration. Furthermore, we evaluated whether the model could predict the benefit from adjuvant chemotherapy. RESULTS: The MDL model demonstrated strong TSR discrimination, yielding areas under the receiver operating curves (AUCs) of 0.855 (95%CI, 0.800-0.910), 0.838(95% CI, 0.802-0.874), and 0.857(95% CI, 0.804-0.909) in the three validation cohorts, respectively. The MDL model was also able to predict overall survival and disease-free survival across all cohorts. In multivariable Cox analysis, the MDL score (MDLS) remained an independent prognostic factor after adjusting for clinicopathological variables (all P<0.05). For stage II and stage III disease, patients with a high MDLS benefited from adjuvant chemotherapy (hazard ratio [HR] 0.391 [95%CI, 0.230-0.666], P=0.0003; HR=0.467[95%CI, 0.331-0.659], P<0.0001, respectively), whereas those with a low MDLS did not. CONCLUSION: The multitask DL model based on preoperative CT images effectively predicted TSR status and survival in CRC patients, offering valuable guidance for personalized treatment. Prospective studies are needed to confirm its potential to select patients who might benefit from chemotherapy.

Restoration of nNOS Expression Rescues Autistic-Like Phenotypes Through Normalization of AMPA Receptor-Mediated Neurotransmission.

Autism spectrum disorder (ASD) is associated with a range of abnormalities characterized by deficits in socialization, communication, repetitive behaviors, and restricted interests. We have recently shown that neuronal nitric oxide synthase (nNOS) expression was decreased in the basolateral amygdala (BLA) of mice after postnatal valproic acid exposure. Neuronal activity-regulated pentraxin (Narp) could contribute to the regulation of the GluA4 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) subunits which are predominantly expressed in interneurons. However, the specific role of nNOS re-expression on excitatory neurotransmitter with relevance to ASD core symptoms in VPA-treated animals remains to be elucidated. Herein, nNOS overexpression using a lentiviral vector and L-arginine-activating PI3K-Akt-mTOR signaling can restore nNOS expression in the BLA induced by VPA. Restoration of nNOS expression in these mice was sufficient to reduce the severity of ASD-like behavioral patterns such that animals exhibited decreases in abnormal social interactions and communication, stereotyped/repetitive behaviors, and anxiety-like traits. Most strikingly, re-expression of nNOS upregulated surface expression of Narp and GluA4 in nNOS-positive interneuron as shown by immunoprecipitation and Western blotting. Whole-cell patch-clamp recordings demonstrated that restoration of nNOS had a significant enhancing effect on AMPA receptor-mediated excitatory glutamatergic synaptic neurotransmission, which was inhibited by disturbing the interaction between Narp and GluA4 in acutely dissociated BLA slices. Overall, these data offer a scientific basis for the additional study of nNOS re-expression as a promising therapeutic target by correcting AMPA receptor-mediated synaptic function in ASD and related neurodevelopmental disorders.

Photothermal metasurface with polarization and wavelength multiplexing.

Controlling temperature distribution at the micro/nano-scale brings new applications in many fields such as physics, chemistry and biology. This paper proposes a photothermal metasurface that employs polarization and wavelength multiplexing to regulate various temperature distributions at the micro/nano-scale. Such a photothermal metasurface is numerically validated by the finite element method. Firstly, the inversion algorithm is used to calculate the thermal power density distribution, which is decided by a given temperature distribution. Then, based on the bottom-up design method, (a) the library of absorption cross sections of gold nanoparticles is established by resizing nanoparticles; (b) the single pixel is constructed for wavelength and polarization multiplexing; (c) the overall structure of a photothermal metasurface is optimized and established. Finally, four given temperature distributions, combining the multiplexing of two orthogonal polarizations and two wavelengths, are achieved in the same area. The simulation results well confirm the feasibility of photothermal multiplexing. Such photothermal metasurface provides solutions for flexible control of temperature distribution at the micro/nano-scale.