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Abstract Modern facial surgical planning and therapeutic strategies rely heavily on the precise segmentation of the nasal cavity and paranasal sinuses from computed tomography (CT) images for quantitative analysis. Nevertheless, manual segmentation is labor-intensive and prone to inconsistencies, highlighting the need for automatic segmentation methods. A significant challenge in this field is the lack of publicly available clinical datasets for research. To address this issue, we introduce NagalSeg, the first large-scale, publicly available dataset for nasal cavity and paranasal sinus segmentation. In comparison to existing nasal structure segmentation datasets, which are either private or small-scale, NagalSeg stands out as the first publicly accessible dataset. It provides an order of magnitude more labeled data, consisting of 130 3D CT scans with pixel-wise annotations of five anatomical structures: the left nasal cavity, right nasal cavity, nasopharynx, left maxillary sinus, and right maxillary sinus. The NagalSeg dataset serves as an open-access resource to facilitate the development and evaluation of segmentation algorithms and promote future in-depth research towards the clinical application of artificial intelligence methods.

Abstract The microRNA156 (miR156) has been widely studied in plants, however, the characterization of the miR156 family of genes in wheat and their expression patterns under abiotic stress are not completely clear. In this study, a total of 20 miR156 family members, referred to as tae-miR156a to tae-miR156t, were identified in wheat with their loci mapped to various chromosomes. These members were divided into five subgroups: miR156a/b/c/d/e/f, miR156g/h/i, miR156j/k, miR156l/m/n/o/p/q, and miR156r/s/t. They were highly conserved during evolution. The prediction of cis-elements in the tae-MIR156(s) promoter region revealed that the tae-MIR156(s) had diverse cis-acting elements; of these, 15 tae-MIR156(s) and 6 tae-MIR156(s) were found to be drought-responsive elements and cold-responsive elements, respectively. And the prediction target genes of tae-miR156(s) are mainly SPL transcription factor genes. Expression analysis based on quantitative real-time polymerase chain reaction (qRT‒PCR) showed that miR156(s) have different expression levels in the various wheat tissues, and the subgroups’ response to abiotic stress varied. Among them, miR156g/h/i were strongly induced in the root of cold and heat stress, and miR156a/b/c/d/e/f were significantly increased in roots after drought stress, whereas miR156r/s/t were highly inhibited in leaves and roots after salt stress. These findings imply that tae-miR156(s) are involved in stress response in wheat, and they provide new fundamental knowledge for further analysis of the function of miR156 and its regulatory mechanism in response to abiotic stress.

Abstract Erythropoietic protoporphyria (EPP) is a genetic disease characterized by protoporphyrin IX-mediated painful phototoxicity. Currently, options for the management of EPP-associated phototoxicity are limited and no oral medication is available. Here, we investigated a novel therapy against EPP-associated phototoxicity by targeting the ATP-binding cassette subfamily G member 2 (ABCG2), the efflux transporter of protoporphyrin IX. Oral ABCG2 inhibitors were developed, and they successfully prevented EPP-associated phototoxicity in a genetically engineered EPP mouse model. Mechanistically, ABCG2 inhibitors suppress protoporphyrin IX release from erythroid cells and reduce the systemic exposure to protoporphyrin IX in EPP. In summary, our work establishes a novel strategy for EPP therapy by targeting ABCG2 and provides oral ABCG2 inhibitors that can effectively prevent protoporphyrin IX-mediated phototoxicity in mice.

Abstract The availability of large-scale learning data presents unprecedented opportunities for investigating student learning processes. However, it is challenging for instructors to fully make sense of this data and effectively support their teaching practices. This study introduces LearningViz, an interactive learning analytics dashboard to help instructors identify, analyze, and close performance gaps among students in their classes. In this dashboard, we incorporated three modules to enhance human and computer interactions for better supporting the teaching practices: the Student Overall Performance Analysis Module, which provides a comprehensive understanding of students’ learning in the course; the Student Group Performance Analysis Module, which examines performance gaps across different groups and identifies factors contributing to these gaps; and the Final Exam Item Analysis Module, which evaluates the quality of exam questions and identifies strategies for closing performance gaps. The overall design of the platform follows a user-centered approach, integrating data analysis with various visualization strategies in a unified platform. A case study is then conducted to highlight the effectiveness of LearningViz in supporting instructors analyzing students’ learning patterns and associated factors impacting learning performance. We further conduct a usability test with several domain experts, to evaluate the usefulness and effectiveness of this platform in supporting the teaching practices. Our findings underscore the platform's ability to support instructors in detecting performance gaps among students, investigating influential factors, evaluating assessment quality and implementing targeted instructional strategies for closing performance gaps.

Abstract Background Identifying DNA mismatch repair deficiency (MMRd) is important for prognosis risk stratification in patients with early-stage endometrial cancer (EC), but there is a notable absence of cost-effective and non-invasive preoperative assessment techniques. The study explored the co-reactivity pattern of glucose metabolism and blood perfusion in EC based on hybrid [18F]fluorodeoxyglucose ([18F]FDG) PET/dynamic contrast enhanced (DCE)-MRI to provide an imaging biomarker for identifying MMRd. Methods Patients with a history of postmenopausal bleeding and initially diagnosed with EC on ultrasound were recruited to perform a PET/DCE-MRI scan. Glucose metabolism parameters were calculated on PET, and blood perfusion parameters were calculated semi-automatically by the DCE-Tofts pharmacokinetic model. The MMRd of early-stage EC was evaluated by immunohistochemistry. The synchronous variation of PET and DCE-MRI parameters was compared between the MMRd and mismatch repair proficiency (MMRp). The association between PET/DCE-MRI and MMRd was analyzed by logistic regression to establish the digital biomarker for predicting MMRd. Receiver operating characteristic curve, decision curve analysis, and the net reclassification index (NRI) were used to evaluate the value of the digital biomarker in identifying MMRd. Results Eighty-six early-stage EC cases (58.92 ± 10.13 years old, 34 MMRd) were enrolled. The max/mean standardized uptake value (SUVmax/SUVmean), metabolic tumor volume, total lesion glycolysis, transfer constant (Ktrans), and efflux rate (Kep) were higher in MMRd than those in MMRp (P

Polysaccharides are one of the most important natural bioactive ingredients in pumpkin. Pumpkin polysaccharides have variable structure and complex monosaccharide composition, and possess a variety of biological activities such as hypoglycemia and antioxidant. In recent years, with the increasing incidence of diabetes, the hypoglycemic effect of pumpkin polysaccharides has attracted more and more attentions of scholars. The research focuses on the structure, monosaccharide composition and different mechanism of action of pumpkin polysaccharides. Therefore, this paper systematically summarizes the structural characteristics, mechanisms of hypoglycemic action and influence factors of hypoglycemic activity of pumpkin polysaccharides, and looks forward to its research direction and application prospects, and proposes the suggestions, with a view to providing reference for the subsequent research of pumpkin polysaccharides on diabetes.

Abstract Background To introduce the serum total kappa/lambda ratio (K/L) in humoral immunity testing reports to improve the detection rate of M-proteinemia. Methods 156 M protein-positive and 5464 M protein-negative samples confirmed by serum immunofixation electrophoresis(sIFE) were accumulated from January 2021 to December 2023 in the First Affiliated Hospital of Soochow University and the contents of immunoglobulins (IgG, IgA, IgM, kappa and lambda) were tested by Beckman IMMAGE800. All the samples were divided into two groups by time: the modeling group and the validation group. The K/L values in the modeling group were analyzed by SPSS 27.0 to get the receiver operating characteristic curve (ROC). Furthermore, a more in-depth analysis was conducted to verify the reliability of the optimal cutoff values in the validation group. In addition, the levels of immunoglobulins of another group including 106 patients with definite diagnosis of monoclonal gammopathy ranging from January 2021 to June 2024 were traced back to improve the diagnostic efficiency. Results The optimal cutoff values of K/L were 2.31 and 1.43 corresponding to K-type and L-type M-proteinemia respectively by ROC analysis. The sensitivity and specificity were validated as 76.14% and 77.42%. False positives were mainly found in samples with systemic sclerosis (36.84%), hypohepatia (28.71%) and sicca syndrome (27.27%). While false negatives were mainly found in IgA monoclonal gammopathy (38.39%) and IgM monoclonal gammopathy (28.57%). Combining with the detection rules of IgG, IgA and IgM, the sensitivities for the diagnosis of immunoglobulin light chain amyloidosis(AL) and monoclonal gammopathy of undetermined significance(MGUS) can be increased to 83.33% and 85%. Conclusions K/L > 2.31 and K/L

Abstract Inspired by the great progress in the observations of charmonium-like states in recent years, we perform a systematic analysis about the ground states and the first radially excited states of $$qc\bar{q}\bar{c}$$ q c q ¯ c ¯ (q = u/d and s) tetraquark systems. Their mass spectra, root mean square (r.m.s.) radii and radial density distributions are predicted within the framework of relativized quark model. By comparing with experimental data, some potential candidates for hidden-charm tetraquark states are suggested. For $$qc\bar{q}\bar{c}$$ q c q ¯ c ¯ (q = u/d) system, if $$Z_{c}(3900)$$ Z c ( 3900 ) is supposed to be a compact tetraquark state with $$J^{PC}=1^{+-}$$ J PC = 1 + - , Z(4430) can be interpreted as the first radially excited states of $$Z_{c}(3900)$$ Z c ( 3900 ) . Another broad structure $$Z_{c}(4200)$$ Z c ( 4200 ) can also be explained as a partner of $$Z_{c}(3900)$$ Z c ( 3900 ) , and it arise from a higher state with $$J^{PC}=1^{+-}$$ J PC = 1 + - . In addition, theoretical predictions indicate that the possible assignments for X(3930), X(4050) and X(4250) are low lying $$0^{++}$$ 0 + + tetraquark states. As for the $$sc\bar{s}\bar{c}$$ s c s ¯ c ¯ system, X(4140) and X(4274) structures can be interpreted as this type of tetraquark states with $$J^{PC}=1^{++}$$ J PC = 1 + + , and X(4350) can be described as a $$sc\bar{s}\bar{c}$$ s c s ¯ c ¯ tetraquark with $$J^{PC}=0^{++}$$ J PC = 0 + + . With regard to $$qc\bar{s}\bar{c}$$ q c s ¯ c ¯ (q = u/d) system, we find two potential candidates for this type of tetraquark, which are $$Z_{cs}(4000)$$ Z cs ( 4000 ) and $$Z_{cs}(4220)$$ Z cs ( 4220 ) structures. The measured masses of these two structures are in agreement with theoretical predictions for the $$1^{+}$$ 1 + state.

Extended reality (XR) such as Virtual Reality (VR) and Augmented Reality (AR) has been heralded as a particularly promising technology for autistic people. However, prior studies have centered around curing or ameliorating deficits and impairments and are typically conducted by non-disabled and non-autistic researchers. Using co-design and a variety of learning experience design methods and processes, Project PHoENIX (Participatory, Human-centered, Equitable, Neurodiverse, and Inclusive XR) speaks to the need for research that applies a social-ecological perspective to the design and evaluation of VR experiences for autistic users, with the goal of decreasing environmental barriers and promoting a more inclusive society. In this study, we describe a multi-cycle process of educational design research (EDR), consisting of iterative human-centered formative design, development, implementation, and evaluation of Project PHoENIX from Spring 2021 to Spring 2022. A framework for conducting co-design and collaborative educational design research with autistic individuals in a VR environment is provided along with design principles that support this framework. Findings from 3 meso-cycles illustrate the dual outcomes of educational design research, namely, (1) a consistently maturing intervention and (2) improving theoretical understanding. Findings underscore the feasibility of our approach, and demonstrate potential to scale.

Abstract Background Actual evapotranspiration (ETa) is a crucial aspect of the hydrological cycle. It serves as a vital link between the soil–vegetation–atmosphere continuum. Quantifying the leading factors of regional ETa change and revealing the multi-factor compound driving mechanism of ETa evolution is necessary. Structural equation modeling (SEM) has been widely used to study the structural relationships between variables in large-scale areas. However, there is an urgent need for more in-depth exploration of these complex relationships at the grid scale. Therefore, the Yiluo River Basin, a representative area of soil and water conservation engineering demonstration in the Loess Plateau, was selected as the study area, and the SEM at the basin scale and grid-scale were constructed to carry out the research. Results The data indicate that ETa decreased at 1.97 mm per year at the watershed scale from 1982 to 2020. Climate change had the greatest impact on the change of ETa in the watershed, with a total impact coefficient of over 0.9. The direct impact of climate change on ETa increased by 0.571 from 1982–1992 to 1993–2020. The direct impact coefficients of vegetation cover and soil moisture decreased by 0.402 and 0.102, respectively, while the impact coefficient of the water body factors increased by 0.096. At the scale of individual grid cells, the ETa in the watershed was affected by changes in watershed climate, vegetation, and soil moisture, with contributions ranging from − 0.31 to 0.22, − 1.09 to − 0.08, and 0.61 to 0.90, respectively. Spatially, vegetation and soil moisture had a stronger impact on ETa in the upstream area, while climate change had a negative effect, and the downstream region had the opposite effect. Furthermore, the regulatory impact of large reservoirs mitigated the response of water surface evaporation to climate change in the upstream region. Conclusions The application of SEM at different spatial and temporal scales has effectively quantified the driving mechanisms behind actual evapotranspiration in the Yiluo River Basin, while visually representing the spatial distribution characteristics of various influencing factors on ETa. This research provides a theoretical foundation for studying slope water consumption processes and circulation mechanisms.

Abstract Background SQ109 is a promising candidate drug for the treatment of patients with drug-resistant tuberculosis (DR-TB). The purpose of this study was to investigate the activity of SQ109 against clinical isolates of Mycobacterium tuberculosis (MTB) from patients with multidrug-resistant TB (MDR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB), and to explore new drug-resistant mechanisms of SQ109. Methods We evaluated the in vitro activity of SQ109 against clinical isolates from patients with MDR-TB and pre-XDR-TB using minimal inhibitory concentration (MIC) assay. The drug-resistant gene, mmpL3 of SQ109-resistant strains was sequenced, and a quantitative real-time PCR assay was used to analyze 28 efflux pump genes in SQ109-resistant strains without mmpL3 mutations. The role of candidate efflux pumps mmpL5 and mmpL7 on the MIC of SQ109 was evaluated using recombinantly cloned MmpL5 and MmpL7 expressed in Mycobacterium smegmatis. Results The MIC90, MIC95 and MIC99 values of SQ109 for 225 clinical isolates of MTB were 0.25 mg/L, 0.5 mg/L and 1.0 mg/L, respectively. Among the pre-XDR strains, six showed resistance to SQ109 despite the absence of gene mutations in mmpL3. In six resistant pre-XDR strains, the MIC of SQ109 decreased with the use of an efflux pump inhibitor, and there was significant upregulation of mmpL5 and mmpL7 in two strains after exposure to SQ109. The presence of MmpL7 in Mycobacterium smegmatis resulted in decreased susceptibility to SQ109, with the MIC increasing from 16 mg/L to 32 mg/L. Conclusions Our data demonstrated that SQ109 exhibited excellent levels of in vitro activity against MTB. MmpL7 may be a potential gene for MTB resistance to SQ109, providing a useful target for detecting SQ109 resistance in MTB.

Abstract Background The mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer’s Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity. Methods This is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography–functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization. Results A total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus. Conclusion Effects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS. Trial registration ClinicalTrials.gov, NCT 03920826; Registration Date: 2019-04-19.

Abstract Background The triglyceride-glucose (TyG) index is recognized as a robust indicator for evaluating insulin resistance (IR). Despite the well-documented anti-aging biological functions of Klotho protein, its correlation with the TyG index remains unexplored. Methods A cross-sectional analysis was conducted involving participants from the National Health and Nutrition Examination Surveys (NHANES) 2007–2016. The TyG index was computed using laboratory data, while serum Klotho concentrations was determined using ELISA kit. After adjusting potential confounding variables, multivariate regression models were employed to evaluate the association between the TyG index and Klotho protein levels among middle-aged and elderly females and males separately. Additionally, smooth curve fitting and segmented regression model were applied to investigate potential threshold effects and identify the inflection point. Results A total of 6,573 adults qualified for inclusion, comprising 3,147 (47.88%) males and 3,426 (52.12%) females. Multivariate regression analysis revealed that females with a higher TyG index exhibited significantly lower serum Klotho concentrations (β=-83.41, 95% CI: -124.23 to -42.60, P

Abstract Background It is not fully established whether plasma β-amyloid(Aβ)42/Aβ40 and phosphorylated Tau181 (p-Tau181) can effectively detect Alzheimer’s disease (AD) pathophysiology in older Chinese adults and how these biomarkers correlate with astrocyte reactivity, Aβ plaque deposition, tau tangle aggregation, and neurodegeneration. Methods We recruited 470 older adults and analyzed plasma Aβ42/Aβ40, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) using the Simoa platform. Among them, 301, 195, and 70 underwent magnetic resonance imaging, Aβ and tau positron emission tomography imaging. The plasma Aβ42/Aβ40 and p-Tau181 thresholds were defined as ≤0.0609 and ≥2.418 based on the receiver operating characteristic curve analysis using the Youden index by comparing Aβ-PET negative cognitively unimpaired individuals and Aβ-PET positive cognitively impaired patients. To evaluate the feasibility of using plasma Aβ42/Aβ40 (A) and p-Tau181 (T) to detect AD and understand how astrocyte reactivity affects this process, we compared plasma GFAP, Aβ plaque, tau tangle, plasma NfL, hippocampal volume, and temporal-metaROI cortical thickness between different plasma A/T profiles and explored their relations with each other using general linear models, including age, sex, APOE-ε4, and diagnosis as covariates. Results Plasma A+/T + individuals showed the highest levels of astrocyte reactivity, Aβ plaque, tau tangle, and axonal degeneration, and the lowest hippocampal volume and temporal-metaROI cortical thickness. Lower plasma Aβ42/Aβ40 and higher plasma p-Tau181 were independently and synergistically correlated with higher plasma GFAP and Aβ plaque. Elevated plasma p-Tau181 and GFAP concentrations were directly and interactively associated with more tau tangle formation. Regarding neurodegeneration, higher plasma p-Tau181 and GFAP concentrations strongly correlated with more axonal degeneration, as measured by plasma NfL, and lower plasma Aβ42/Aβ40 and higher plasma p-Tau181 were related to greater hippocampal atrophy. Higher plasma GFAP levels were associated with thinner cortical thickness and significantly interacted with lower plasma Aβ42/Aβ40 and higher plasma p-Tau181 in predicting more temporal-metaROI cortical thinning. Voxel-wise imaging analysis confirmed these findings. Discussion This study provides a valuable reference for using plasma biomarkers to detect AD in the Chinese community population and offers novel insights into how astrocyte reactivity contributes to AD progression, highlighting the importance of targeting reactive astrogliosis to prevent AD.

Abstract Background This study aims to evaluate the effect of various background reference regions on spinal 18F-FET PET imaging, with a focus on distinguishing between spinal tumors and myelitis. To enhance diagnostic accuracy, we investigated the pons and several other spinal cord area as potential references, given the challenges in interpreting spinal PET results. Results A retrospective analysis was conducted on 30 patients, 15 with cervical myelitis and 15 with cervical tumors, who underwent O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET/MR imaging. The stability of uptake across four regions, including the pons, C2, C2–C7, and T1–T3, was compared. The standardized uptake value ratio (SUVR) was then evaluated using various background regions, and their effectiveness in differentiating between spinal tumors and myelitis was compared. Additionally, we correlated the SUVR values derived from these regions with the Ki-67 proliferation index in tumor patients. The study found no significant difference in SUVmax (U = 110, p = 0.93) and SUVmean (U = 89, p = 0.35) values at lesion sites between myelitis and tumor patients. The pons had the highest average uptake (p

Abstract Background To explore a novel ultrasound (US) modality for lumbar transforaminal epidural injections (TFEIs) in patients with low back pain (LBP) and L5 radicular pain combined with high iliac crest (HIC). Methods One-hundred and forty-one patients were retrospectively stratified into two groups based on the treatment they received: novel group, receiving US-guided and fluoroscopy (FL)-controlled TFEIs using a sagittal oblique approach between the superior articular process of L5 and S1, and control group, receiving US-guided TFEIs with conventional transverse approach combined with FL confirmation. Accuracy of contrast dispersing into lumbar epidural space was set as the primary endpoint. Radiation dosages, procedure time, numeric rating scale (NRS) scores, Modified Oswestry Disability Questionnaire (MODQ) scores, adverse events, and rescue analgesic requirement were also recorded. The generalized liner mixed model (GLMMs) was employed to compare the repeatedly measured variables between groups, taking individual confounding factors as covariance. Results The accuracy of TFEIs was 92.8% and 65.2% in novel and control group, with a significant difference of 26.7% (95% CI: 15.4%, 39.8%) between two modalities (p

The water retention service of the forest ecosystem has ecological functions such as adjusting the climate and maintaining the ecological water balance. The Qinghai-Tibet Plateau is an alpine region. Due to its high altitude and harsh environment, it is difficult to manually observe the water retention in the field, and it is impossible to better evaluate the water retention function. In order to better obtain the water retention in the alpine region, hyperspectral technology is introduced and applied to the acquisition of surface vegetation information, and the water retention in a specific area is obtained by constructing a model. In this study, the Bayi District of Nyingchi Prefecture was used as the research area. The main tree species in the study area are Picea likiangensis var. linzhiensis(PLVL), Quercus aquifolioides(QA), Pinus densata(PD) and Rhododendron nivale(RN). In actual situations, it is not easy to directly obtain water retention information, so a model can be found to quantitatively express the relationship between leaf spectrum and water retention. Then based on the leaf spectrum to invert the water retention. In order to study the quantitative relationship between different vegetation and water retention, each type of vegetation collects leaf samples and water retention data at 30 sampling points. Use ASD Fildsoec Handheld spectrometer to obtain hyperspectral data. Seven band indexes of red edge, green peak, NDVI, NDWI, EVI, WBI and NDPI were selected, and the relationship between vegetation band index and water conservation was fitted through many kinds of regression models. Comparing the fitting results, construct water retention prediction model. The interception of vegetation canopy, litter water holding capacity and soil water content are obtained through experiments. The sum of the three represents the water retention capacity of vegetation. The reflectance spectra of the four types of vegetation leaves all show similar regularities, and the difference in the visible light band is not obvious. The near-infrared to mid-infrared bands show four distinct water absorption bands, with the highest reflectivity in the red to near-infrared bands (700 nm-1400 nm). The reflectance of the four types of vegetation varies across different spectral bands, with the reflectance levels exhibiting the characteristic order of QA > PD > PLVL ≈ RN. Comparing the fitting results of different regression models with seven waveband parameters, the R2 of the four types of vegetation are higher in the regression models of EVI and NDPI, and reach a significant level. According to the regression model corresponding to each kind of vegetation, the water retention prediction model is composed, and the simulation accuracy is tested by R2 and RMSE. The overall simulation accuracy R2 is greater than 0.7 and the RMSE is basically less than 10 t·hm−2, indicating that the forecasting model has a good forecasting effect and the model can effectively estimate the water retention of the forest ecosystem.

Background: Excessive iron accumulation in the brain has been implicated in Parkinson's disease (PD). However, the patterns and probable sequences of iron accumulation across the PD brain remain largely unknown. This study aimed to explore the sequence of iron accumulation across the PD brain using R2* mapping and a relaxometry covariance network (RCN) approach. Methods: R2* quantification maps were obtained from PD patients (n = 34) and healthy controls (n = 25). RCN was configured on R2* maps to identify covariance differences in iron levels between the two groups. Regions with excessive iron accumulation and large covariance changes in PD patients compared to controls were defined as propagators of iron. In the PD group, causal RCN analysis was performed on the R2* maps sequenced according to disease duration to investigate the dynamics of iron accumulations from the propagators. The associations between individual connections of the RCN and clinical information were analyzed in PD patients. Results: The left substantia nigra pars reticulata (SNpr), left substantia nigra pars compacta (SNpc), and lobule VII of the vermis (VER7) were identified as primary regions for iron accumulation and propagation (propagator). As the disease duration increased, iron accumulation in these three propagators demonstrated positive causal effects on the bilateral pallidum, bilateral gyrus rectus, right middle frontal gyrus, and medial and anterior orbitofrontal cortex (OFC). Furthermore, individual connections of VER7 with the left gyrus rectus and anterior OFC were positively associated with disease duration. Conclusions: Our results indicate that the aberrant iron accumulation in PD involves several regions, mainly starts from the SN and cerebellum and extends to the pallidum and cortices. These findings provide preliminary information on sequences of iron accumulation in PD, which may advance our understanding of the disease.

As a kind of pressurized combustion, pulse detonation combustion brings many possibilities for the improvement of aero-engine performance.In this paper, energy and exergy analyses of pulse detonation combustor (PDC) and pulse detonation turbine engine (PDTE) cycles based on unsteady analysisare conducted. A simplified exergy flow model is proposed to describe the exergy flow of PDC under different inlet conditions, and based on this, the exergy efficiency of PDC is compared with that of an isobaric combustion chamber. In addition, the energy and exergy flows of ideal and real PDTE cycles are analyzed, and the cycle thermal and exergy efficiencies under different inlet conditions are obtained. The results show that the exergy efficiency of PDC is higher than that of an isobaric combustion chamber from an inlet pressure ratio of 3–45, but the efficiency improvement decreases from 13.2 % to 7.2 %. The thermal efficiency of the ideal PDTE cycle is higher than that of the Brayton cycle, but the efficiency improvement decreases from 78.2 % to 4.7 %. The irreversible losses in the real process will lead to energy loss during compression and expansion processes in the PDTE cycle, thus reducing its exergy efficiency and thermal efficiency.

The form factors of Bc→ηc and Bc→J/ψ are analyzed in the framework of three-point QCD sum rules. In the calculations, the contributions of the vacuum condensate terms 〈gs2GG〉 and 〈gs3GGGf〉 are considered. In addition, the decay widths and branching ratios of several decay channels are predicted by using the calculated form factors. These decay processes include the nonleptonic decays Bc−→ηcπ−, ηcK−, ηcρ−, ηcK⁎−, J/ψπ−, J/ψK−, J/ψρ−, J/ψK⁎−, and the semileptonic decays Bc−→ηclν¯, J/ψlν¯. These results about the form factors and decay properties of Bc meson provide useful information for us to study the heavy-quark dynamics and find new physics beyond Standard Model.

Background: RECQL4 is a member of the DNA helicase family and is critical for DNA replication, DNA damage repair, and tumor progression. However, its specific role in cervical cancer remains uncertain. Methods: In this study, we aimed to investigate the impact of RECQL4 on cervical cancer prognosis using clinical specimens from The Cancer Genome Atlas. We evaluated the malignant effects of RECQL4 through various experimental assays including cell Cell Counting Kit-8, EdU, colony formation, cell cycle analysis, cell apoptosis, scratch, and Transwell assays. We explored the mechanisms of RECQL4-regulated malignancy using analyses of bioinformatics, RNA sequencing data, polymerase chain reaction (PCR), western blotting, and cell immunofluorescence experiments. Furthermore, we validated the effects of RECQL4 knockdown on tumor growth using subcutaneous tumor models in nude mice. Results: RECQL4 was upregulated in cervical cancer and correlated with prognosis, demonstrating a positive relationship with tumor mutational burden. Knockdown of RECQL4 inhibits cervical cancer cell proliferation, migration, and invasion, suppresses epithelial-mesenchymal transition status, induces cell cycle arrest, and promotes apoptosis. Mechanistically, RECQL4 mediated malignancy through the PI3K/AKT pathway and reduced nuclear β-catenin expression. In vivo studies further confirmed that RECQL4 knockout significantly inhibited tumor growth. Conclusions: Our findings provide novel insights into the mechanism behind RECQL4-mediated cervical cancer progression through the PI3K/AKT pathway. Furthermore, our study suggests potential therapeutic strategies for targeting RECQL4 in cervical cancer treatment.

The performance of pulse detonation turbine engines (PDTE) surpasses that of conventional turbine engines, primarily due to the pressure gain combustion process inherent in PDTE. A U-bend pulse detonation combustor (PDC) with a compact axial length was designed to meet the requirements of PDTE. However, the PDC introduces complex thermal management challenges. In this study, the wall temperature along the U-bend PDC was experimentally measured under various operating conditions, the thermal load characteristics were investigated. The results indicate that the external wall temperature increases monotonically with prolonged operation, whereas the internal wall temperature exhibits periodic fluctuations corresponding to the periodic filling and combustion process in the PDC. The temperature difference between the internal and external walls increases, then decreases over time, eventually fluctuates within a narrow temperature range. The wall temperature was observed to increase along the flow direction, peaking at 811 °C at 30 Hz at the location where the detonation wave is generated. Similarly, the heat flux of the PDC first increases, then decreases, and eventually reaches a constant value, indicating thermal equilibrium. The heat flux represents a significant energy loss, with the detonation section being the area of highest heat loss, reaching approximately 90.5 kW/m2 at 30 Hz.

Abstract In this study, the performance of memristive devices made of oxygen‐deficient HfO2 films is investigated when exposed to various electrical pulse stimulations. The devices exhibited signs of fatigue with the number increasing of a fixed frequency pulse, mirroring the synaptic adaptation to repeat stimuli. Interestingly, the synaptic behavior can be highly simulated by logic function, and the pulse frequency and magnitude play different roles in changing the synaptic curves. Only pulses with certain quantized frequencies can reshape the synaptic current response curve. In addition, a similarity is observed between the frequency stability of these devices and the biological lifespan in response to external stimuli. These observations strengthen the case for the potential of memristors in emulating cognitive functions.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are characterized by excessive triglyceride accumulation in the liver. However, due to an incomplete understanding of its pathogenesis, more efforts are needed to identify specific and effective treatments. N4-acetylcytidine (ac4C) is a newly discovered RNA modification to regulate mRNA. N-acetyltransferase 10 (NAT10) has not been fully explored in MASLD and MASH. Methods: The clinical relevance of NAT10 was evaluated based on its expression in various mouse and human models of MASLD and MASH. Acetylated RNA immunoprecipitation sequencing and mRNA stability assays were used to explore the role of NAT10 in regulating ac4C modification and expression of target genes. Genetically engineered mice were employed to investigate the role of NAT10 in MASLD and MASH progression. Results: Hepatic NAT10 expression was significantly increased in multiple mice and humans of MASLD and MASH. Genetic knockout of NAT10 protected mice from diet-induced hepatic steatosis and steatohepatitis, whereas overexpression of NAT10 exacerbated high-fat-diet-induced liver steatosis. Mechanistically, NAT10 binds to Srebp-1c mRNA, promoting its stability and expression, thereby upregulating lipogenic enzymes. Treatment with Remodelin, a NAT10-specific inhibitor, effectively ameliorates liver steatosis and dyslipidemia in a preclinical mouse model. Conclusions: Our findings indicate that NAT10 could regulate lipid metabolism in MASLD and MASH by stabilizing Srebp-1c mRNA and upregulating lipogenic enzymes. This study highlights the role of NAT10 and RNA acetylation in the pathogenesis of MASLD and MASH. Thus, our findings suggest a promising new therapeutic approach, such as the use of NAT10 inhibitor, for treating metabolic liver disease.

Abstract Tuberculosis (TB), the leading cause of death from bacterial infections worldwide, results from infection with Mycobacterium tuberculosis (Mtb). The antitubercular agents delamanid (DLM) and pretomanid (PMD) are nitroimidazole prodrugs that require activation by an enzyme intrinsic to Mtb; however, the mechanism(s) of action and the associated metabolic pathways are largely unclear. Profiling of the chemical‐genetic interactions of PMD and DLM in Mtb using combined CRISPR screening reveals that the mutation of rv2073c increases susceptibility of Mtb to these nitroimidazole drugs both in vitro and in infected mice, whereas mutation of rv0078 increases drug resistance. Further assays show that Rv2073c might confer intrinsic resistance to DLM/PMD by interfering with inhibition of the drug target, decaprenylphophoryl‐2‐keto‐b‐D‐erythro‐pentose reductase (DprE2), by active nicotinamide adenine dinucleotide (NAD) adducts. Characterization of the metabolic pathways of DLM/PMD in Mtb using a combination of chemical genetics and comparative liquid chromatography‐mass spectrometry (LC‐MS) analysis of DLM/PMD metabolites reveals that Rv0077c, which is negatively regulated by Rv0078, mediates drug resistance by metabolizing activated DLM/PMD. These results might guide development of new nitroimidazole prodrugs and new regimens for TB treatment.

Cytochrome P450 F3 (CYP4F3) is recognized as a disease-associated immune response initiator that is involved in the synthesis of cholesterol, steroids, and lipids. This study identified the upregulation of CYP4F3 expression in colorectal cancer (CRC) and its association with poor patient prognosis through a comparative analysis between CRC tumor tissues with normal tissues from public databases. The overexpression of CYP4F3 in CT26.wt and SW620, promoted cell proliferation and migration, a reduction of cellular oxidative stress, an up-regulation of the oxidative stress-related pathway NRF2, and an inhibition of cellular ferroptosis. Additionally, inhibition of NRF2 activity stimulated cellular ferroptosis when CYP4F3 was overexpressed. Ferroptosis, characterized by iron-dependent lipid peroxidation, is a non-apoptotic way of cell death with a critical role in cancer development. When given a ferroptosis agonist to CYP4F3-overexpression CRC cells, NRF2 was activated, and cell proliferation and migration were reduced. Furthermore, the mice subcutaneously injected with CYP4F3-overexpression CT26.wt cells formed significantly larger tumors compared to the CYP4F3-vector CT26.wt cell group. This study systematically identified an important role of CYP4F3 in CRC development as a regulator of CRC cells to escape ferroptosis via NRF2, highlighting the significance of CYP4F3 as a potential therapeutic target for CRC.

4,4-Difluoro-4-bora-3a,4a-diaza-sindacene (BODIPY) is a sort of photofunctional dye which possesses advantages including strong light-capturing property, high photon-resistance, etc. Meso-N substituted aza-BODIPY is a crucial derivative of BODIPY scaffold that has the favorable optical properties and a significant spectral redshift. The photophysical properties can be tuned by molecular design, and the attenuation path of the excited state energy release of absorbed light energy can be well controlled via structural modifications, enabling tailored application. It has been extensively employed in life medicine fields including fluorescence imaging diagnosis, photodynamic therapy photosensitizer and photothermal therapy reagent and so forth. Extensive research and review have been performed in these areas. However, BODIPYs/aza-BODIPYs have a significant role in energy, catalysis, optoelectronics, photo-responsive materials and other fields. Nevertheless, there are relatively few studies and reviews in these fields on the modification and application based on BODIPY/aza-BODIPY scaffold. Herein, in this review we summarized the application of BODIPY/aza-BODIPY in the aforementioned fields, with the molecular regulation of dye as the foundation and the utilization in the above fields as the objective, in the intention of providing inspiration for the exploration of innovative BODIPY/aza-BODIPY research in the field of light resource conversion and functional materials.

Abstract In this comprehensive genome-wide study, we identified and classified 83 Xylanase Inhibitor Protein (XIP) genes in wheat, grouped into five distinct categories, to enhance understanding of wheat's resistance to Fusarium head blight (FHB), a significant fungal threat to global wheat production. Our analysis reveals the unique distribution of XIP genes across wheat chromosomes, particularly at terminal regions, suggesting their role in the evolutionary expansion of the gene family. Several XIP genes lack signal peptides, indicating potential alternative secretion pathways that could be pivotal in plant defense against FHB. The study also uncovers the sequence homology between XIPs and chitinases, hinting at a functional diversification within the XIP gene family. Additionally, the research explores the association of XIP genes with plant immune mechanisms, particularly their linkage with plant hormone signaling pathways like abscisic acid and jasmonic acid. XIP-7A3, in particular, demonstrates a significant increase in expression upon FHB infection, highlighting its potential as a key candidate gene for enhancing wheat's resistance to this disease. This research not only enriches our understanding of the XIP gene family in wheat but also provides a foundation for future investigations into their role in developing FHB-resistant wheat cultivars. The findings offer significant implications for wheat genomics and breeding, contributing to the development of more resilient crops against fungal diseases.

Abstract Background Class III peroxidases (PODs) perform crucial functions in various developmental processes and responses to biotic and abiotic stresses. However, their roles in wheat seed dormancy (SD) and germination remain elusive. Results Here, we identified a wheat class III POD gene, named TaPer12-3A, based on transcriptome data and expression analysis. TaPer12-3A showed decreasing and increasing expression trends with SD acquisition and release, respectively. It was highly expressed in wheat seeds and localized in the endoplasmic reticulum and cytoplasm. Germination tests were performed using the transgenic Arabidopsis and rice lines as well as wheat mutant mutagenized with ethyl methane sulfonate (EMS) in Jing 411 (J411) background. These results indicated that TaPer12-3A negatively regulated SD and positively mediated germination. Further studies showed that TaPer12-3A maintained H2O2 homeostasis by scavenging excess H2O2 and participated in the biosynthesis and catabolism pathways of gibberellic acid and abscisic acid to regulate SD and germination. Conclusion These findings not only provide new insights for future functional analysis of TaPer12-3A in regulating wheat SD and germination but also provide a target gene for breeding wheat varieties with high pre-harvest sprouting resistance by gene editing technology.

Abstract Background B-box (BBX) proteins are a type of zinc finger proteins containing one or two B-box domains. They play important roles in development and diverse stress responses of plants, yet their roles in wheat remain unclear. Results In this study, 96 BBX genes were identified in the wheat genome and classified into five subfamilies. Subcellular localization prediction results showed that 68 TaBBXs were localized in the nucleus. Protein interaction prediction analysis indicated that interaction was one way that these proteins exerted their functions. Promoter analysis indicated that TaBBXs may play important roles in light signal, hormone, and stress responses. qRT-PCR analysis revealed that 14 TaBBXs were highly expressed in seeds compared with other tissues. These were probably involved in seed dormancy and germination, and their expression patterns were investigated during dormancy acquisition and release in the seeds of wheat varieties Jing 411 and Hongmangchun 21, showing significant differences in seed dormancy and germination phenotypes. Subcellular localization analysis confirmed that the three candidates TaBBX2-2 A, TaBBX4-2 A, and TaBBX11-2D were nuclear proteins. Transcriptional self-activation experiments further demonstrated that TaBBX4-2A was transcriptionally active, but TaBBX2-2A and TaBBX11-2D were not. Protein interaction analysis revealed that TaBBX2-2A, TaBBX4-2A, and TaBBX11-2D had no interaction with each other, while TaBBX2-2A and TaBBX11-2D interacted with each other, indicating that TaBBX4-2A may regulate seed dormancy and germination by transcriptional regulation, and TaBBX2-2A and TaBBX11-2D may regulate seed dormancy and germination by forming a homologous complex. Conclusions In this study, the wheat BBX gene family was identified and characterized at the genomic level by bioinformatics analysis. These observations provide a theoretical basis for future studies on the functions of BBXs in wheat and other species.

Purpose: Spectral-domain OCT angiography (SD-OCTA) scans were used in an algorithm developed for swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the measurement of hyperreflective foci (HRF) in intermediate age-related macular degeneration (iAMD). Design: Retrospective study. Participants: Forty eyes from 35 patients with iAMD. Methods: Patients underwent SD-OCTA and SS-OCTA imaging at the same visit using a 6 × 6 mm OCTA scan pattern. Hyperreflective foci were detected as hypotransmission defects on en face structural images generated from a custom slab positioned 64 to 400 μm beneath Bruch’s membrane and confirmed on corresponding B-scans by the presence of well circumscribed lesions within the neurosensory retina or along the retinal pigment epithelium (RPE) that are of equal or greater reflectivity than that of the RPE. Two independent graders evaluated the en face images and B-scans for the presence of these lesions. Outlines of HRF on en face images were generated using a published semiautomated algorithm developed for SS-OCTA scans and manually corrected by the graders when necessary. The total area measurements of the HRF within the 5-mm circle centered on the fovea were obtained from the algorithm using each imaging method. Main Outcome Measures: Agreement of the square root (sqrt) of the HRF total areas obtained from SS-OCTA and SD-OCTA. Results: The sqrt total areas of the HRF from both imaging modalities were highly concordant, with Lin’s concordance correlation coefficient (rc) of 0.94 (95% confidence interval: 0.86–0.97; P

Study region: The source regions of the Yangtze and Yellow Rivers Study focus: The purpose of this study is to analyze the latest evolution trends of runoff and sediment load in the source areas of the Yangtze and Yellow Rivers, quantitatively attribute the evolution drivers of runoff and sediment load in the region by Structural Equation Model, and predict the future evolution trends. New hydrological insights for the region: The results showed that from 2000 to 2020, the runoff of the source region Yangtze and Yellow Rivers increased at rates of 2.56 × 108 m3/a and 5.98 × 108 m3/a, and the sediment load increased at rates of 33.24 × 104t/a and 36.82 × 104t/a, respectively. Attribution analysis found precipitation has the greatest impact on runoff and sediment changes. Although snowmelt is also an important factor, its contribution is still relatively small compared to precipitation. The vegetation in the region did not significantly reduce sediment under freeze-thaw conditions. The prediction results show that the runoff and sediment load in the region will continue to increase in the future. From 2025–2098, the runoff in the source area of the Yangtze River and the source area of the Yellow River will increase at a rate of 0.21–1.11 × 108 m3/a and 0.14–0.68 × 108 m3/a, and the sediment load will increase at a rate of 1.62–6.12 × 105t/a and 2.44–5.78 × 105t/a, respectively.

Purpose: Spectral-domain OCT angiography (SD-OCTA) scans were tested in an algorithm developed for use with swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the detection and measurement of persistent choroidal hypertransmission defects (hyperTDs). Design: Retrospective study. Participants: Forty pairs of scans from 32 patients with late-stage nonexudative age-related macular degeneration (AMD). Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 × 6 mm OCTA scan patterns. Using a semiautomatic algorithm that helped with outlining the hyperTDs, 2 graders independently validated persistent hyperTDs, which are defined as having a greatest linear dimension ≥250 μm on the en face images generated using a slab extending from 64 to 400 μm beneath Bruch’s membrane. The number of lesions and square root (sqrt) total area of the hyperTDs were obtained from the algorithm using each imaging method. Main Outcome Measures: The mean sqrt area measurements and the number of hyperTDs were compared. Results: The number of lesions and sqrt total area of the hyperTDs were highly concordant between the 2 instruments (rc = 0.969 and rc = 0.999, respectively). The mean number of hyperTDs was 4.3 ± 3.1 for SD-OCTA scans and 4.5 ± 3.3 for SS-OCTA scans (P = 0.06). The mean sqrt total area measurements were 1.16 ± 0.64 mm for the SD-OCTA scans and 1.17 ± 0.65 mm for the SS-OCTA scans (P < 0.001). Because of the small standard error of the differences, the mean difference between the scans was statistically significant but not clinically significant. Conclusions: Spectral-domain OCTA scans provide similar results to SS-OCTA scans when used to obtain the number and area measurements of persistent hyperTDs through a semiautomated algorithm previously developed for SS-OCTA. This facilitates the detection of atrophy with a more widely available scan pattern and the longitudinal study of early to late-stage AMD. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abstract The “Mlx” and “Myc” transcription factor networks cross‐communicate and share many common gene targets. Myc's activity depends upon its heterodimerization with Max, whereas the Mlx Network requires that the Max‐like factor Mlx associate with the Myc‐like factors MondoA or ChREBP. The current work demonstrates that body‐wide Mlx inactivation, like that of Myc, accelerates numerous aging‐related phenotypes pertaining to body habitus and metabolism. The deregulation of numerous aging‐related Myc target gene sets is also accelerated. Among other functions, these gene sets often regulate ribosomal and mitochondrial structure and function, genomic stability, and aging. Whereas “MycKO” mice have an extended lifespan because of a lower cancer incidence, “MlxKO” mice have normal lifespans and a higher cancer incidence. Like Myc, the expression of Mlx, MondoA, and ChREBP and their control over their target genes deteriorate with age in both mice and humans. Collectively, these findings underscore the importance of lifelong and balanced cross‐talk between the two networks to maintain proper function and regulation of the many factors that can affect normal aging.

Currently, with the gradual advancement of urbanization and industrialization, ecological patches are severely fragmented and corridors are cut off, leading to the construction of regional ecological networks that can connect fragmented patches and corridors with regional characteristics. However, there is limited research on the relationship between ecological networks and Carbon Utilization Efficiency (CUE) based on complex network theory. This paper takes the ecologically fragile Southeast Tibet as the research area and investigates the variation patterns of CUE through the establishment of ecological spatial networks. The Graphab Model is employed to extract the ecological space network of Southeast Tibet. The Graphab Model integrates the complex network with the ecological space network to compute the topological index of ecological nodes and the overall ecological network. Later, MOD17A2HGF GPP and MOD17A2HGF PSNnet data from 2013 to 2021 are used as the primary data for calculating the CUE of ecological nodes. The connection between topological index and ecological nodes is analysed. The results indicate that, with interannual variations, ecological nodes dropped by 15, and the number of ecological galleries decreased by 7. However, the average values of various topological indices showed an increasing trend, suggesting that the ecological remediation items in Southeast Tibet have made some achievements. Nevertheless, the analysis of CUE in Southeast Tibet reveals a downward trend in the carbon fixation rate of vegetation in recent years. Through correlation analysis, it was found that the correlation between various topological indices and CUE was the lowest and insignificant in 2013, while from 2015 to 2021, all topological indices were significantly positively correlated with CUE. Through Principal Component Analysis (PCA), It is recommended to reduce and shorten redundant ecological corridors by aggregating small ecological patches and increasing stepping stone patches, and increase ecological galleries to enhance the carbon fixation ability of plants. This research lays a scientific foundation for addressing ecological issues, landscape patterns, and developing ecological networks in Southeast Tibet.

In this study, we take a machine learning-based approach to measure institutional investor attention to corporate social responsibility (CSR) issues when communicating with firms during site visits. We find that institutional investors can effectively enhance CSR performance through CSR-related communication. This effect remains robust to various checks and is more pronounced for non-state-owned enterprises and firms with lower levels of institutional ownership and in periods following the issuance of Green Investment Guidelines. We also identify information asymmetry and financing constraints as the two mechanisms underlying this effect. Overall, our findings highlight the importance of private interactions between management and institutional investors in promoting CSR.

ABSTRACT The gut microbiota is essential for providing colonization resistance against pathogens. Dietary sugars markedly shift the composition of the intestinal microbiota and alter host susceptibility to enteric infections. Here, we demonstrate the effect of L-arabinose on bacterial infection by using a mouse infection model with Salmonella enterica serovar Typhimurium (S. Tm). In the presence of microbiota, L-arabinose induces a dramatic expansion of Enterobacteriaceae, thereby decreasing the microbiota diversity and causing more severe systemic infection. However, L-arabinose supplementation does not alter the disease progression of Salmonella infection in a microbiota-depleted mouse model. More importantly, short-term supplementation of L-arabinose fails to exert anti-diabetic effects in Salmonella-infected hyperglycemia mice and still promotes infection. Overall, our work reveals that a high intake of dietary L-arabinose supports a bloom of Enterobacteriaceae in Salmonella-infected gut, further accelerating the process of systemic infection.IMPORTANCEL-arabinose is a promising natural sweetener and food additive for the regulation of hyperglycemia. Since diabetic subjects are more susceptible to infections, the safety of dietary L-arabinose in diabetic patients experiencing infection remains a concern. Our findings reveal that L-arabinose exacerbates Salmonella infection outcome by inducing gut microbiota dysbiosis in mice. High dietary intake of L-arabinose may be deleterious for diabetic individuals undergoing infection.

Alzheimer’s disease (AD) is the most common form of age-related dementia worldwide. Although the neuropathology of AD is clear, its pathogenesis remains unclear. Recently, conceptualising AD as brain-centred has reoriented many scientists because the close functional relationship between the peripheral and central nerves is increasingly recognised. Recently, various studies have focused on the crosstalk between peripherals and centrals. A new hotspot of research and new therapeutic strategies have emerged from this great progress. This mini-review is an overview of the potential molecular mechanism in AD via the bidirectional lung-brain axis, providing a new perspective for the systemic understanding of AD onset.

To effectively grasp the interactive evolution mechanism of relevant entities in the process of competitive neutrality and reveal the impact of the implementation effect of the principle of competitive neutrality on the evolution path of the game system is the key to guiding the development of the government, industry associations and enterprises with reasonable policies. The equilibrium point of the game is analyzed by the four-party evolutionary game model, and the influence of the change of relevant parameters on the evolution result of the game system is further simulated by numerical simulation. The results show that the central government supervision plays an important role in guiding the strategy selection of different game players. By raising the penalty standards for non-neutral competitive behavior of market players and increasing the non-neutral penalty for local governments, the system can evolve faster to the ideal state of “loose supervision by the central government, neutral implementation by local governments, strong supervision by industry associations, and active cooperation by enterprises.” Therefore, to improve the execution effect of competitive neutrality, the central government shall formulate a reasonable regulatory system, and to maximize inspire the enthusiasm of local government, industry associations and enterprises, to promote stability in the sustainable development of the market.

Abstract Background SARS-CoV-2 belongs to the coronaviridae family and infects human cells by directly interacting with the angiotensin-converting enzyme-2 (ACE-2) through the viral Spike Protein (SP). While vaccines are crucial, much attention has been directed towards managing the symptoms of acute respiratory distress syndrome. Our present study highlights the potential in counteracting lung inflammation triggered by SARS-CoV-2 SP of the intranasal administration of the engineered probiotic Lactobacillus paracasei F19 expressing the enzyme NAPE-PLD (pNAPE-LP) able to in situ release palmitoylethanolamide (PEA) under a super-low boost of palmitate. Methods C57BL/6J mice undergo prophylactic treatment with intranasal pNAPE-LP/palmitate for 7 days before a 7 days challenge with intranasal SARS-CoV-2 SP. Then the capability of pNAPE-LP of colonizing the lungs and actively release PEA in situ have been determined by immunofluorescence, western blot and HPLC-MS. Moreover, the innate immune system downregulation and the histological damage rescue exerted by pNAPE-LP have been tested by immunofluorescence, hematoxylin and eosin staining, western blot analysis and ELISA test for the release of the pro-inflammatory mediators. Results pNAPE-LP effectively colonizes mice lungs and releases the anti-inflammatory compound PEA. Moreover, pNAPE-LP exhibits a protective effect on alveolar morphology, innate immune cells infiltration and in the reduction of neutrophil count, effectively reducing lung injury induced by SARS-CoV-2 SP. This is achieved by mitigating TLR4-mediated NLRP3 activation and the downstream pro-inflammatory products such as ILs, TNFα, C-reactive protein and the myeloperoxidase activity. Interestingly we observed a global reduction ACE2 expression in the lungs. Conclusion pNAPE-LP actively protect from severe inflammatory-related symptoms in SP-challenged mice. Also, it can downregulate the expression of ACE-2 receptors at the lung site potentially preventing the spreading of the infection.

Abstract AURKA is an established target for cancer therapy; however, the efficacy of its inhibitors in clinical trials is hindered by differential response rates across different tumor subtypes. In this study, we demonstrate AURKA regulates amino acid synthesis, rendering it a vulnerable target in KEAP1-deficient non-small cell lung cancer (NSCLC). Through CRISPR metabolic screens, we identified that KEAP1-knockdown cells showed the highest sensitivity to the AURKA inhibitor MLN8237. Subsequent investigations confirmed that KEAP1 deficiency heightens the susceptibility of NSCLC cells to AURKA inhibition both in vitro and in vivo, with the response depending on NRF2 activation. Mechanistically, AURKA interacts with the eIF2α kinase GCN2 and maintains its phosphorylation to regulate eIF2α-ATF4-mediated amino acid biosynthesis. AURKA inhibition restrains the expression of asparagine synthetase (ASNS), making KEAP1-deficient NSCLC cells vulnerable to AURKA inhibitors, in which ASNS is highly expressed. Our study unveils the pivotal role of AURKA in amino acid metabolism and identifies a specific metabolic indication for AURKA inhibitors. These findings also provide a novel clinical therapeutic target for KEAP1-mutant/deficient NSCLC, which is characterized by resistance to radiotherapy, chemotherapy, and targeted therapy.

Abstract Background Myocardial bridging (MB) is common in patients with hypertrophic cardiomyopathy (HCM). There are sparse data on the impact of MB on myocardial fibrosis in HCM. This study was designed to evaluate the relationship between MB and myocardial fibrosis in patients with obstructive HCM. Methods In this cohort study, retrospective data were collected from a high-volume HCM center. Patients with obstructive HCM who underwent septal myectomy and preoperative cardiac magnetic resonance (CMR) were screened from 2011 to 2018. Results Finally, 492 patients were included in this study, with an average age of 45.7 years. Of these patients, 76 patients had MB. MB occurred mostly in the left anterior descending artery (73/76). The global extent of late gadolinium enhancement (LGE) was correlated with the degree of systolic compression (r = 0.33, p = 0.003). Multivariable linear regression analysis revealed that the degree of systolic compression was an independent risk factor for LGE (β = 0.292, p = 0.007). The LGE fraction of basal and mid anteroseptal segments in patients with severe MB (compression ratio ≥ 80%) was significantly greater than that in patients with mild to moderate MB (compression ratio

Abstract Background Ovarian stimulation (OS) during assisted reproductive technology (ART) appears to be an independent factor influencing the risk of low birth weight (LBW). Previous studies identified the association between LBW and placenta deterioration, potentially resulting from disturbed genomic DNA methylation in oocytes caused by OS. However, the mechanisms by which OS leads to aberrant DNA methylation patterns in oocytes remains unclear. Methods Mouse oocytes and mouse parthenogenetic embryonic stem cells (pESCs) were used to investigate the roles of OS in oocyte DNA methylation. Global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels were evaluated using immunofluorescence or colorimetry. Genome-wide DNA methylation was quantified using an Agilent SureSelectXT mouse Methyl-Seq. The DNA methylation status of mesoderm-specific transcript homologue (Mest) promoter region was analyzed using bisulfite sequencing polymerase chain reaction (BSP). The regulatory network between estrogen receptor alpha (ERα, ESR1) and DNA methylation status of Mest promoter region was further detected following the knockdown of ERα or ten-eleven translocation 2 (Tet2). Results OS resulted in a significant decrease in global 5mC levels and an increase in global 5hmC levels in oocytes. Further investigation revealed that supraphysiological β-estradiol (E2) during OS induced a notable decrease in DNA 5mC and an increase in 5hmC in both oocytes and pESCs of mice, whereas inhibition of estrogen signaling abolished such induction. Moreover, Tet2 may be a direct transcriptional target gene of ERα, and through the ERα-TET2 axis, supraphysiological E2 resulted in the reduced global levels of DNA 5mC. Furthermore, we identified that MEST, a maternal imprinted gene essential for placental development, lost its imprinted methylation in parthenogenetic placentas originating from OS, and ERα and TET2 combined together to form a protein complex that may promote Mest demethylation. Conclusions In this study, a possible mechanism of loss of DNA methylation in oocyte caused by OS was revealed, which may help increase safety and reduce epigenetic abnormalities in ART procedures.

Abstract Aims The present study aimed to phenotype the cerebral structural and glucose metabolic alterations in patients with heart failure (HF) using simultaneous positron emission tomography (PET)/magnetic resonance (MR) and to investigate their relationship to cardiac biomarkers and cognitive performance. Methods and results Forty‐two HF patients caused by ischaemic heart disease (mean age 67.2 ± 10.4, 32 males) and 32 age‐ and sex‐matched healthy volunteers (mean age 61.3 ± 4.8, 18 males) were included in this study. Participants underwent simultaneous cerebral fluorine‐18 (18F) fluorodeoxyglucose PET/MR followed by cardiac MR scan, and neuropsychological scores were obtained to assess cognitive performance. The grey matter volume (GMV) and standardized uptake value ratio (SUVR) were calculated to examine cerebral structural and metabolic alterations. Cardiac biomarkers included cardiac MR parameters and cardiac serum laboratory tests. Mediation analysis was performed to explore the associations among cerebral alterations, cardiac biomarkers, and cognitive performance. HF patients demonstrated notable cognitive impairment compared with normal controls (P

Advanced data mining methods have shown a promising capacity in building energy management. However, in the past decade, such methods are rarely applied in practice, since they highly rely on users to customize solutions according to the characteristics of target building energy systems. Hence, the major barrier is that the practical applications of such methods remain laborious. It is necessary to enable computers to have the human-like ability to solve data mining tasks. Generative pre-trained transformers (GPT) might be capable of addressing this issue, as some GPT models such as GPT-3.5 and GPT-4 have shown powerful abilities on interaction with humans, code generation, and inference with common sense and domain knowledge. This study explores the potential of the most advanced GPT model (GPT-4) in three data mining scenarios of building energy management, i.e., energy load prediction, fault diagnosis, and anomaly detection. A performance evaluation framework is proposed to verify the capabilities of GPT-4 on generating energy load prediction codes, diagnosing device faults, and detecting abnormal system operation patterns. It is demonstrated that GPT-4 can automatically solve most of the data mining tasks in this domain, which overcomes the barrier of practical applications of data mining methods in this domain. In the exploration of GPT-4, its advantages and limitations are also discussed comprehensively for revealing future research directions in this domain.

This study aimed to assess the safety and toxicity of peony protein and provide a scientific basis for its application in food industry. The safety evaluation included acute oral toxicity tests in mice, as well as 28 d and 90 d oral toxicity tests in rats. The results demonstrated that no signs of poisoning or mortality were observed in the acute oral toxicity test (intragastric dose of 11700 mg/kg) conducted on mice. Furthermore, in the 28 d and 90 d oral toxicity tests conducted on rats, no abnormal changes were observed in terms of food utilization, organ weight ratios, and various physiological activities, when compared to the control group (1500, 3000, 6000 mg/kg). Additionally, there were no significant differences (P>0.05) in blood routine and blood biochemical indices between the treatment groups and the control group. Histopathological examination of organ tissues revealed intact morphology without any toxic lesions. These findings provided solid evidence that peony protein was non-toxic in the dose range of less than 11700 mg/kg and hold promising potential for application in the food industry.

Abstract Background Developing biomarkers for early stage AD patients is crucial. Glucose metabolism measured by 18F-FDG PET is the most common biomarker for evaluating cellular energy metabolism to diagnose AD. Arterial spin labeling (ASL) MRI can potentially provide comparable diagnostic information to 18F-FDG PET in patients with neurodegenerative disorders. However, the conclusions about the diagnostic performance of AD are still controversial between 18F-FDG PET and ASL. This study aims to compare quantitative cerebral blood flow (CBF) and glucose metabolism measured by 18F-FDG PET diagnostic values in patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) using integrated PET/MR. Results Analyses revealed overlapping between decreased regional rCBF and 18F-FDG PET SUVR in patients with AD compared with NC participants in the bilateral parietotemporal regions, frontal cortex, and cingulate cortex. Compared with NC participants, patients with aMCI exclusively demonstrated lower 18F-FDG PET SUVR in the bilateral temporal cortex, insula cortex, and inferior frontal cortex. Comparison of the rCBF in patients with aMCI and NC participants revealed no significant difference (P > 0.05). The ROC analysis of rCBF in the meta-ROI could diagnose patients with AD (AUC, 0.87) but not aMCI (AUC, 0.61). The specificity of diagnosing aMCI has been improved to 75.56% when combining rCBF and 18F-FDG PET SUVR. Conclusion ASL could detect similar aberrant patterns of abnormalities compared to 18F-FDG PET in patients with AD compared with NC participants but not in aMCI. The diagnostic efficiency of 18F-FDG-PET for AD and aMCI patients remained higher to ASL. Our findings support that applying 18F-FDG PET may be preferable for diagnosing AD and aMCI.

Isocitrate dehydrogenase (IDH) and O6-methylguanine-DNA methyltransferase (MGMT) genes are critical molecular markers in determining treatment options and predicting the prognosis of adult-type diffuse gliomas. Objectives: this study aimed to investigate whether multimodal MRI enables the differentiation of genotypes in adult-type diffuse gliomas. Methods: a total of 116 adult-type diffuse glioma patients (61 males, 51.5 (37, 62) years old) who underwent multimodal MRI before surgery were retrospectively analysed. Multimodal MRI included conventional MRI, proton magnetic resonance spectroscopy (1H-MRS), and diffusion tensor imaging (DTI). Conventional visual features, N-acetyl-aspartate (NAA)/Creatine (Cr), Choline (Cho)/Cr, Cho/NAA, fractional anisotropy (FA), mean diffusivity (MD), and diffusion histogram parameters were extracted on the whole tumour. Multimodal MRI parameters of IDH-mutant and IDH-wildtype gliomas were compared using the Mann–Whitney U test, Student’s t-test, or Pearson chi-square tests. Logistic regression was used to select the MRI parameters to predict IDH-mutant gliomas. Furthermore, multimodal MRI parameters were selected to establish models for predicting MGMT methylation in the IDH-wildtype gliomas. The performance of models was evaluated by the receiver operating characteristics curve. Results: a total of 56 patients with IDH-mutant gliomas and 60 patients with IDH-wildtype glioblastomas (GBM) (37 with methylated MGMT and 17 with unmethylated MGMT) were diagnosed by 2021 WHO classification criteria. The enhancement degree (OR = 4.298, p < 0.001), necrosis/cyst (OR = 5.381, p = 0.011), NAA/Cr (OR = 0.497, p = 0.037), FA-Skewness (OR = 0.497, p = 0.033), MD-Skewness (OR = 1.849, p = 0.035), FAmean (OR = 1.924, p = 0.049) were independent factors for the multimodal combined prediction model in predicting IDH-mutant gliomas. The combined modal based on conventional MRI, 1H-MRS, DTI parameters, and histogram performed best in predicting IDH-wildtype status (AUC = 0.890). However, only NAA/Cr (OR = 0.17, p = 0.043) and FA (OR = 0.38, p = 0.015) were associated with MGMT methylated in IDH-wildtype GBM. The combination of NAA/Cr and FA-Median is more accurate for predicting MGMT methylation levels than using these elements alone (AUC, 0.847 vs. 0.695/0.684). Conclusions: multimodal MRI based on conventional MRI, 1H-MRS, and DTI can provide compound imaging markers for stratified individual diagnosis of IDH mutant and MGMT promoter methylation in adult-type diffuse gliomas.

High-resolution planetary remote sensing imagery provides detailed information for geomorphological and topographic analyses. However, acquiring such imagery is constrained by limited deep-space communication bandwidth and challenging imaging environments. Conventional super-resolution methods typically employ separate models for different scales, treating them as independent tasks. This approach limits deployment and real-time applications in planetary remote sensing. Moreover, capturing global context is crucial in planetary remote sensing images due to their contextual similarities. To address these limitations, we propose Discrete Cosine Transform (DCT)–Global Super Resolution Neural Operator (DG-SRNO), a global context-aware arbitrary-scale super-resolution model. DG-SRNO achieves super-resolution at any scale using a single framework by learning the mapping between low-resolution (LR) and high-resolution (HR) function spaces. We mathematically prove the global receptive field of DG-SRNO. To evaluate DG-SRNO’s performance in planetary remote sensing tasks, we introduce the Ceres 800 dataset, a planetary remote sensing super-resolution dataset. Extensive quantitative and qualitative experiments demonstrate DG-SRNO’s impressive reconstruction capabilities.