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Drawing on skill acquisition theory (DeKeyser, 2017) and the Information Feedforward and Feedback Loop model (de Bot, 1980), this study aimed to explore the effects of digital zoom technology as a visual reinforcement tool (VRT) in foreign language (FL) pronunciation instruction on learners' segmental production, and learners' attitudes toward and experience with it. The study was conducted during a two-week introductory FL Spvanish course with a cross-over design. In the experimental class, the teacher used a tablet to provide magnified visual feedforward for articulatory gestures during explicit instruction of target consonants that were new to Chinese learners, and the students used smartphone apps with digital zoom for augmented visual self-feedback during their practice. In the control class, the teacher adopted a traditional analytic-linguistic approach for explicit instruction and an audio-only intuitive-imitative approach for students' practice. The results of the production test show that the experimental group performed significantly better in the production of the postvocalic /[squat reversed esh]/ and the dental fricatives /[voiceless dental fricative]/ and /[voiced dental fricative]/, but not in the trill /r/. Interview data suggests that the VRT strategy was advantageous in directing the participants' attention to articulatory gestures, and that most students showed positive attitudes toward this new method.

Abstract This study explored subjective responses towards various environmental quality parameters. It would be helpful to approach an overall comfort improvement relating to physics. In order to investigate the combined effects of sound, light and heat on the overall comfort of pedestrians, which could be evaluated by overall comfort vote, two residential areas in Yubei District, Chongqing (a Cfa city in China) were selected for field measurements and questionnaires. Three were three key findings were concluded based on subjective responses to environmental parameters via multiple linear regression. First, the average outdoor neutral temperature, mean neutral sound level and neutral illumination intensity were determined to be 26.6 °C (determined by physiologically equivalent temperature), 56.5 dBA (determined by A-weighted equivalent continuous sound level) and 21.4 klx (determined by LUX), respectively. Second, considering the effects of both physiology and psychology, thermal perceptions varied for acoustic and light environments. Residents partially had lower neutral temperatures at the noisy condition. Third, environmental quality factors had a significant effect on overall comfort. Positive correlation between physiologically equivalent temperature and overall comfort vote was found (sig

Abstract In China, several expressways have been designed as prefabricated box culverts with hinge connections, which have different structural features from the prefabricated culverts in other countries. The difference would contribute to the culvert–soil interaction of prefabricated box culverts, which could affect the earth pressure on the culvert. Based on the field test and numerical simulation method, a hinged prefabricated box culvert (HPBC) with a span of 4 m and a rise of 4 m was investigated, which was applied to the Xi-Yu expressway in China. The objective of this research was to investigate the vertical earth pressure on the top slab of the HPBC culvert at different backfill heights through the field tests. The FLAC3D software was employed to conduct further analysis of the effects of backfill height, backfill modulus, and foundation modulus on the vertical earth pressure on the top slab of HPBC. The differences between the HPBC and monolithic box culvert (MBC) were also examined. Furthermore, a revised method for calculating the vertical earth pressure on the top slab was put proposed and compared with the AASHTO method for calculating earth pressure on the top of culverts and the values taken from the Chinese culvert design code. The proposed method is capable of improving the accuracy of the earth pressure approach, making it more representative of actual conditions. Subsequently, the sensitivity analysis of backfill height, backfill modulus and foundation modulus to the vertical earth pressure concentration coefficient of the top slab was carried out by using the principle of orthogonal array analysis and the modified calculation method proposed in this paper. The findings of this study offer valuable insights into the determination of culvert top earth pressure of HPBC.

Abstract Diagnosing individuals with autism spectrum disorder (ASD) accurately faces great challenges in clinical practice, primarily due to the data's high heterogeneity and limited sample size. To tackle this issue, the authors constructed a deep graph convolutional network (GCN) based on variable multi‐graph and multimodal data (VMM‐DGCN) for ASD diagnosis. Firstly, the functional connectivity matrix was constructed to extract primary features. Then, the authors constructed a variable multi‐graph construction strategy to capture the multi‐scale feature representations of each subject by utilising convolutional filters with varying kernel sizes. Furthermore, the authors brought the non‐imaging information into the feature representation at each scale and constructed multiple population graphs based on multimodal data by fully considering the correlation between subjects. After extracting the deeper features of population graphs using the deep GCN(DeepGCN), the authors fused the node features of multiple subgraphs to perform node classification tasks for typical control and ASD patients. The proposed algorithm was evaluated on the Autism Brain Imaging Data Exchange I (ABIDE I) dataset, achieving an accuracy of 91.62% and an area under the curve value of 95.74%. These results demonstrated its outstanding performance compared to other ASD diagnostic algorithms.

Abstract Background Obesity is known as a risk factor for cardiovascular disease (CVD). However, there is an absence of preoperative cardiac risk assessment in bariatric surgery candidates and the incidence of CVD among these high-risk patients is still unknown. Methods A consecutive series of bariatric surgery candidates at two Chinese tertiary hospitals received coronary CT angiography or coronary angiography from 2017 to 2023. Patients were categorized as metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO) based on the presence or absence of MetS. CVD was diagnosed based on the maximum intraluminal stenosis > 1% in any of the segments of the major epicardial coronary arteries. Obstructive CVD was defined as coronary stenosis ≥ 50%. Binary multivariable logistic regression was performed to analyze the association between CVD and metabolic status. The number of principal MetS components was categorized into zero (without glycemic, lipid, and BP components), one (with one of the components), two (with any two components), and three (with all components) to explore their association with CVD. Results A total of 1446 patients were included in the study. The incidence of CVD and obstructive CVD were 31.7% and 9.6%. Compared with MHO patients, MUO patients had a significantly higher incidence of mild (13.7% vs. 6.1%, P

Constructing the first-class undergraduate specialty, deepening curriculum reform, incorporating innovation and entrepreneurship education throughout the entire talent development process, and consistently enhancing the standard of innovation and entrepreneurship education are crucial approaches to fostering scientific and technological aptitude among college students. This study, according to the nature and characteristics of the course "Comprehensive Utilization of Grain and Oil Processing By-Products", focusing on the objectives of course teaching, under the guidance of the concept of innovation and entrepreneurship education, aims to explore the development and implementation of a practical case teaching method tailored to grain engineering students within the framework of the provincial first-class undergraduate specialty construction. By improving challenges such as lecture-based teaching, limited practical links, and one-dimensional assessment, a collaborative education platform of 'trinity' innovation and entrepreneurship teaching is proposed based on the construction idea of "classroom-experiment-practice". This platform emphasizes several improvement initiatives, such as incorporating industry case-inspired teaching, conducting classroom presentations, fostering the development of innovative experimental designs in small groups, cultivating the spirit of scientists, expanding the teaching of science and innovation competitions on the extracurricular activities, implementing multi-dimensional assessment methods, and establishing continuity mechanisms. Our goal is to establish a collaborative platform that nurtures innovation and entrepreneurship through the professional curriculum. Ultimately, this platform seeks to promote balanced development between professional knowledge and entrepreneurial skills, elevating the cultivation of innovative talents in grain engineering.

Abstract Thermal comfort studies are usually employed to find subjective thermal responses [indicated by neutral temperature (NT), i.e. the temperature with no thermal stress] of residents from a region towards thermal environments. According to the recently published works in the literature, NTs are affected by many factors, such as geographical location and microenvironments. To elucidate the origins of these effects, the impact of microenvironment elements around a water surface on pedestrians’ thermal perceptions was systematically investigated in this work. The Fujiang River (FJR) in Mianyang City was taken as the sample site. The municipal meteorology station is located next to the site by around 2.5 km. By performing meteorology measurements combining questionnaires, it was found that the riverside NT (indicated by physiologically equivalent temperature, PET) of Mianyang in the summer of 2023 was 21.4 °C. The relationship between the distance from the water (DFW) and NT was quadratic linear. The same phenomenon took place by using either PET or Universal Thermal Climate Index (UTCI) indexes. Meanwhile, the meteorological contexts also affected NTs, including relative humidity (RH) and air velocity (Va). Regarding RH, the NPET increased from 15.2 °C (RH = 50%) to 26.9 °C (RH = 90%). In contrast, the NPET dropped from 23.0 to − 50.6 °C when the Va increased from 0.2 to 2.5 m/s, respectively. From our analysis, it was demonstrated that human thermal responses are significantly affected by both the microenvironmental and meteorological backgrounds around the water surface. Our work provides valuable insights for the proper use of water surfaces in urban design for adjusting thermal comfort.

Abstract Previous observational investigations suggest that structural and diffusion imaging-derived phenotypes (IDPs) are associated with major neurodegenerative diseases; however, whether these associations are causal remains largely uncertain. Herein we conducted bidirectional two-sample Mendelian randomization analyses to infer the causal relationships between structural and diffusion IDPs and major neurodegenerative diseases using common genetic variants-single nucleotide polymorphism (SNPs) as instrumental variables. Summary statistics of genome-wide association study (GWAS) for structural and diffusion IDPs were obtained from 33,224 individuals in the UK Biobank cohort. Summary statistics of GWAS for seven major neurodegenerative diseases were obtained from the largest GWAS for each disease to date. The forward MR analyses identified significant or suggestively statistical causal effects of genetically predicted three structural IDPs on Alzheimer’s disease (AD), frontotemporal dementia (FTD), and multiple sclerosis. For example, the reduction in the surface area of the left superior temporal gyrus was associated with a higher risk of AD. The reverse MR analyses identified significantly or suggestively statistical causal effects of genetically predicted AD, Lewy body dementia (LBD), and FTD on nine structural and diffusion IDPs. For example, LBD was associated with increased mean diffusivity in the right superior longitudinal fasciculus and AD was associated with decreased gray matter volume in the right ventral striatum. Our findings might contribute to shedding light on the prediction and therapeutic intervention for the major neurodegenerative diseases at the neuroimaging level.

Abstract Background The ricefield eel Monopterus albus undergoes a natural sex change from female to male during its life cycle, and previous studies have shown the potential mechanisms of this transition at the transcriptional and protein levels. However, the changes in protein levels have not been fully explored, especially in the intersexual stage. Results In the present study, the protein expression patterns in the gonadal tissues from five different periods, the ovary (OV), early intersexual stage gonad (IE), middle intersexual stage gonad (IM), late intersexual stage gonad (IL), and testis (TE), were determined by untargeted proteomics sequencing. A total of 5125 proteins and 394 differentially expressed proteins (DEPs) were detected in the gonadal tissues. Of the 394 DEPs, there were 136 between the OV and IE groups, 20 between the IM and IE groups, 179 between the IL and IM groups, and 59 between the TE and IL groups. Three candidate proteins, insulin-like growth factor 2 mRNA-binding protein 3 isoform X1 (Igf2bp3), triosephosphate isomerase (Tpi), and Cu-Zn superoxide dismutase isoform X1 [(Cu-Zn) Sod1], were validated by western blotting to verify the reliability of the data. Furthermore, metal metabolite-related proteins were enriched in the IL vs. IM groups and TE vs. IL groups, which had close relationships with sex change, including Cu2+-, Ca2+-, Zn2+- and Fe2+/Fe3+-related proteins. Analysis of the combined transcriptome data revealed consistent protein/mRNA expression trends for two metal metabolite-related proteins/genes [LOC109953912 and calcium Binding Protein 39 Like (cab39l)]. Notably, we detected significantly higher levels of Cu2+ during the sex change process, suggesting that Cu2+ is a male-related metal metabolite that may have an important function in male reproductive development. Conclusions In summary, we analyzed the protein profiles of ricefield eel gonadal tissues in five sexual stages (OV, IE, IM, IL, and TE) and verified the plausibility of the data. After preforming the functional enrichment of metal metabolite-related DEPs, we detected the contents of the metal metabolites Zn2+, Cu2+, Ca2+, and Fe2+/Fe3+ at these five stages and screened for (Cu-Zn) Sod1 and Mmp-9 as possible key proteins in the sex reversal process.

Abstract Purpose To compare the difference in analgesic effect between femoral triangle block (FTB) and adductor canal block (ACB) during arthroscopic knee surgery. Methods Patients who underwent arthroscopic knee surgery were randomized preoperatively to FTB group or ACB group. For each group, 20 mL of 0.1% ropivacaine was injected. Primary outcomes: The numeric rating score (NRS) at 12 h after surgery at rest and during movement. Secondary outcome: (1) The NRS at post anesthesia care unit (PACU) and 2, 24 h after surgery at rest and during movement; (2) The quadriceps muscle strength at PACU and 2, 12, 24 h after surgery; (3) Consumption of Rescue analgesia; (4) Incidence of adverse reactions. Results The NRS at 12 h after surgery at rest and during movement of ACB group were higher than FTB group. Among secondary outcomes, the NRS at PACU at rest and during movement, 2 h after surgery during movement of FTB group lower than ACB group; the quadriceps muscle strength at 2 h after surgery of FTB group stronger than ACB group. After multiple linear regression model analysis, the data showed additional statistically significant reduction NRS at 24 h after surgery at rest (0.757, p = 0.037) in FTB group. Other outcomes were similar between two groups. Conclusions The FTB appears to provide superior pain control after knee arthroscopy than ACB, the FTB is superior to the ACB in quadriceps muscle strength at 2 h after surgery. Trial registration The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2300068765). Registration date: 28/02/2023.

Abstract Accurate preoperative differentiation of the chronic rhinosinusitis (CRS) endotype between eosinophilic CRS (eCRS) and non-eosinophilic CRS (non-eCRS) is an important topic in predicting postoperative outcomes and administering personalized treatment. To this end, we have constructed a sinus CT dataset, which comprises CT scan data and pathological biopsy results from 192 patients of chronic rhinosinusitis with nasal polyps (CRSwNP), treated at the Second Affiliated Hospital of Shantou University Medical College between 2020 and 2022. To differentiate CRSwNP endotype on preoperative CT and improve efficiency at the same time, we developed a multi-view fusion model that contains a mini-architecture with each network of 10 layers by modifying the deep residual neural network. The proposed model is trained on a training set and evaluated on a test set. The multi-view deep learning fusion model achieved the area under the receiver-operating characteristics curve (AUC) of 0.991, accuracy of 0.965 and F1-Score of 0.970 in test set. We compared the performance of the mini-architecture with other lightweight networks on the same Sinus CT dataset. The experimental results demonstrate that the developed ResMini architecture contribute to competitive CRSwNP endotype identification modeling in terms of accuracy and parameter number.

Abstract Objective Neuromyelitis optica (NMO) was a serious autoimmune inflammatory condition affecting the central nervous system. Currently, there was a lack of diagnostic biomarkers for AQP4‐IgG‐negative NMO patients. Methods A comparative proteomic analysis was conducted on the CSF of 10 patients with NMO and 10 patients with non‐inflammatory neurological disorders (NND) using tandem mass tagging technology. Differentially expressed proteins (DEPs) were analyzed using bioinformatic methods. The candidate proteins were then validated through ELISAs in a subsequent cohort of 160 samples, consisting of paired CSF and plasma samples from 50 NMO patients, CSF samples from 30 NND patients, and plasma samples from 30 healthy individuals. Results We identified 389 proteins via proteomics, screening 79 DEPs. NCAM1, SST and AHSG were selected as candidate molecules for further validation. Compared to NND patients, there were decreased levels of AHSG in CSF and increased levels of NCAM1 and SST in NMO patients. The ELISA results revealed significantly higher levels of AHSG, SST and NCAM1 in the CSF of the NMO group compared to the NND group. Similarly, the serum levels of these three proteins were also higher in the NMO group compared to the healthy control group. It was found that serum NCAM1 levels significantly decreased in patients with non‐relapsed NMO compared to patients with relapsed NMO and CSF NCAM1 level increased in patients with bilateral NMO compared to patients with unilateral NMO. Furthermore, CSF SST levels increased in AQP4 antibody‐positive NMO patients compared to AQP4 antibody‐negative patients. Interpretation CSF NCAM1, serum NCAM1 and serum SST may serve as potential biomarkers for NMO patients and aid in the diagnosis of AQP4 antibody‐negative NMO patients.

Abstract Thermoelectrics have great potential for use in waste heat recovery to improve energy utilization. Moreover, serving as a solid-state heat pump, they have found practical application in cooling electronic products. Nevertheless, the scarcity of commercial Bi2Te3 raw materials has impeded the sustainable and widespread application of thermoelectric technology. In this study, we developed a low-cost and earth-abundant PbS compound with impressive thermoelectric performance. The optimized n-type PbS material achieved a record-high room temperature ZT of 0.64 in this system. Additionally, the first thermoelectric cooling device based on n-type PbS was fabricated, which exhibits a remarkable cooling temperature difference of ~36.9 K at room temperature. Meanwhile, the power generation efficiency of a single-leg device employing our n-type PbS material reaches ~8%, showing significant potential in harvesting waste heat into valuable electrical power. This study demonstrates the feasibility of sustainable n-type PbS as a viable alternative to commercial Bi2Te3, thereby extending the application of thermoelectrics.

Alternative splicing has been shown to participate in tumor progression, including hepatocellular carcinoma. The poor prognosis of patients with HCC calls for molecular classification and biomarker identification to facilitate precision medicine. We performed ssGSEA analysis to quantify the pathway activity of RNA splicing in three HCC cohorts. Kaplan–Meier and Cox methods were used for survival analysis. GO and GSEA were performed to analyze pathway enrichment. We confirmed that RNA splicing is significantly correlated with prognosis, and identified an alternative splicing-associated protein LUC7L3 as a potential HCC prognostic biomarker. Further bioinformatics analysis revealed that high LUC7L3 expression indicated a more progressive HCC subtype and worse clinical features. Cell proliferation-related pathways were enriched in HCC patients with high LUC7L3 expression. Consistently, we proved that LUC7L3 knockdown could significantly inhibit cell proliferation and suppress the activation of associated signaling pathways in vitro. In this research, the relevance between RNA splicing and HCC patient prognosis was outlined. Our newly identified biomarker LUC7L3 could provide stratification for patient survival and recurrence risk, facilitating early medical intervention before recurrence or disease progression.

A few observational neuroimaging investigations have reported subcortical structural changes in the individuals who recovered from the coronavirus disease‐2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the causal relationships between COVID-19 and longitudinal changes of subcortical structures remain unclear. We performed two-sample Mendelian randomization (MR) analyses to estimate putative causal relationships between three COVID-19 phenotypes (susceptibility, hospitalization, and severity) and longitudinal volumetric changes of seven subcortical structures derived from MRI. Our findings demonstrated that genetic liability to SARS-CoV-2 infection had a great long-term impact on the volumetric reduction of subcortical structures, especially caudate. Our investigation may contribute in part to the understanding of the neural mechanisms underlying COVID-19-related neurological and neuropsychiatric sequelae.

To explore the effect of interchange spacing on drivers' visual characteristics in the merging areas of interchange, a high-density group of five interchanges on the expressway of Chongqing, China, was selected as the test site. An naturalistic driving test was conducted with 47 participants, and the Tobii Glasses II portable eye tracker was used to collect gaze data during driving. The drivers' fixation field was divided into six areas by applying a K-means dynamic clustering algorithm combined with the actual scenario. Markov chains were used to calculate the drivers' gaze transition probability matrices under different driving conditions, and the analysis of gaze transition behaviors was directed at common spacing interchanges, small spacing interchanges, and composite interchanges. Under the ramp-mainline condition, drivers’ fixations were primarily concentrated on the near ahead and the left side areas, with higher rates of repeated fixations on the left rearview mirror and left-side line areas. The average value of fixation duration, saccade distance, and saccade speed of small spacing interchange is higher than common spacing interchange. Additionally, under the mainline condition, the probability of one-step transition and repeated fixation rates significantly increased for the right-side lane areas, and the average values of fixation index and saccade index of small spacing interchange are lower than those of common spacing interchange. The results show that the highest probabilities of repeated fixation by drivers occurred in the near ahead and far ahead areas in the interchange merging areas. Insufficient spacing resulted in more frequent occurrences of zero values in one-step transition probability matrices. The research conclusions provide theoretical support for the optimal design and safe operation of the merging area of high-density interchange group of urban expressway.

A long noncoding RNA (lncRNA) is longer than 200 bp. It regulates various biological processes mainly by interacting with DNA, RNA, or protein in multiple kinds of biological processes. Adenosine monophosphate-activated protein kinase (AMPK) is activated during nutrient starvation, especially glucose starvation and oxygen deficiency (hypoxia), and exposure to toxins that inhibit mitochondrial respiratory chain complex function. AMPK is an energy switch in organisms that controls cell growth and multiple cellular processes, including lipid and glucose metabolism, thereby maintaining intracellular energy homeostasis by activating catabolism and inhibiting anabolism. The AMPK signalling pathway consists of AMPK and its upstream and downstream targets. AMPK upstream targets include proteins such as the transforming growth factor β-activated kinase 1 (TAK1), liver kinase B1 (LKB1), and calcium/calmodulin-dependent protein kinase β (CaMKKβ), and its downstream targets include proteins such as the mechanistic/mammalian target of rapamycin (mTOR) complex 1 (mTORC1), hepatocyte nuclear factor 4α (HNF4α), and silencing information regulatory 1 (SIRT1). In general, proteins function relatively independently and cooperate. In this article, a review of the currently known lncRNAs involved in the AMPK signalling pathway is presented and insights into the regulatory mechanisms involved in human ageing and age-related diseases are provided.

Abstract Spontaneous reversion from mild cognitive impairment (MCI) to normal cognition (NC) is little known. Based on the data of the Genetics of Personality Consortium and MCI participants from Alzheimer's Disease Neuroimaging Initiative, the authors investigate the effect of polygenic scores (PGS) for personality traits on the reversion of MCI to NC and its underlying neurobiology. PGS analysis reveals that PGS for conscientiousness (PGS‐C) is a protective factor that supports the reversion from MCI to NC. Gene ontology enrichment analysis and tissue‐specific enrichment analysis indicate that the protective effect of PGS‐C may be attributed to affecting the glutamatergic synapses of subcortical structures, such as hippocampus, amygdala, nucleus accumbens, and caudate nucleus. The structural covariance network (SCN) analysis suggests that the left whole hippocampus and its subfields, and the left whole amygdala and its subnuclei show significantly stronger covariance with several high‐cognition relevant brain regions in the MCI reverters compared to the stable MCI participants, which may help illustrate the underlying neural mechanism of the protective effect of PGS‐C.

Objective: Shenmai injection is a classic herbal prescription, and is often recommended for the treatment of anthracycline-induced cardiotoxicity. However, the efficacy and safety of Shenmai injection for the treatment of anthracycline-induced cardiotoxicity have not been reported. Materials and methods: We conducted a comprehensive search of eight literature databases and two clinical trial registries, retrieving all randomized controlled trials (RCTs) related to the treatment of anthracycline-induced cardiotoxicity with Shenmai injection from the establishment of the databases to July 1, 2023. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. The GRADE pro3.6.1 software was utilized for assessing the quality of evidence. Results: A total of 16 RCTs including 2140 patients were included in this study. Meta-analysis showed that Shenmai injection had an advantage in improving ST-T segment changes (RR = 0.28; 95 % CI, 0.20 to 0.39; P

Spiral ganglia neurons (SGNs) impairment can cause deafness. One important therapeutic approach involves utilizing stem cells to restore impaired auditory circuitry. Nevertheless, the inadequate implementation of research methodologies poses a challenge in accurately assessing the functionality of derived cells within the circuit. Here, we describe a novel method for converting human embryonic stem cells (hESCs) into otic neurons (ONs) and assess their functional connectivity using an optogenetic approach with cells or an organotypic slice of rat cochlear nucleus (CN) in coculture. Embryonic stem cell-derived otic neurons (eONs) exhibited SGN marker expression and generated functional synaptic connection when cocultured with cochlear nucleus neurons (CNNs). Synapsin 1 and VGLUT expression are found in the cochlear nucleus of brain slices, where eONs projected processes during the coculture of eONs and CN brain slices. Action potential spikes and I Na+ /I K+ of CNNs increased in tandem with light stimulations to eONs. These findings provide further evidence that eONs may be a candidate source to treat SGN-deafness.

Abstract Cardiac microtissues provide a promising platform for disease modeling and developmental studies, which require the close monitoring of the multimodal excitation-contraction dynamics. However, no existing assessing tool can track these multimodal dynamics across the live tissue. We develop a tissue-like mesh bioelectronic system to track these multimodal dynamics. The mesh system has tissue-level softness and cell-level dimensions to enable stable embedment in the tissue. It is integrated with an array of graphene sensors, which uniquely converges both bioelectrical and biomechanical sensing functionalities in one device. The system achieves stable tracking of the excitation-contraction dynamics across the tissue and throughout the developmental process, offering comprehensive assessments for tissue maturation, drug effects, and disease modeling. It holds the promise to provide more accurate quantification of the functional, developmental, and pathophysiological states in cardiac tissues, creating an instrumental tool for improving tissue engineering and studies.

Melanocytic nevi (MN), which are the most prevalent benign skin tumors, can be classified into three subtypes based on the depth of the nevus cell nests: junctional, compound, and intradermal nevi. Among these subtypes, intradermal nevi pose a lower risk of malignancy, whereas junctional nevi carry a higher risk of malignancy. To facilitate early stage diagnosis, mitigate unnecessary biopsies, and reduce medical costs, this paper presents the first study on the classification of benign melanocytic nevi. We propose an algorithm that utilizes depth-relevant, channel-specific, and channel-shared information from dermoscopy images. This approach draws inspiration from the physical principles underlying dermoscopy imaging and the physiological essence of nevi. We employed CNN and transformer blocks to capture local and long-range contextual information. In addition, our physiology-inspired module focuses on learning depth-related features from the color channels. To assess the performance of our proposed method, we curated a dataset of dermoscopic images of MN and compared it with two human experts as well as classic CNN and Transformer baseline models. Our results showed that the proposed automated method achieved an average accuracy of 70.23%, surpassing the best-performing baseline by 3.6%, and outperforming human experts by nearly 20%. Furthermore, we conducted an ablation study to confirm the effectiveness of our algorithm and to analyze its clinical significance.

Background: Human epidermal growth factor receptor 2 (HER2)-targeted agents have significantly improved the outcomes of patients with HER2-positive breast cancer; however, a large proportion of patients still develop resistance to trastuzumab. In this study, we investigated the efficacy and safety of inetetamab, another anti-HER2 antibody, combined with pyrotinib and oral vinorelbine in patients with HER2-positive advanced breast cancer so as to provide new ideas for the treatment. Methods: In this prospective, single-arm, phase 2 trial, patients with HER2-positive advanced breast cancer with disease progression after trastuzumab were recruited. Patients received a combination of inetetamab (loading dose of 8 mg/kg and subsequent doses of 6 mg/kg intravenously once every 3 weeks), pyrotinib (400 mg orally once daily), and vinorelbine (60 mg/m2 orally once weekly) until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), overall survival (OS), disease control rate (DCR), and safety. Results: Between February 13, 2022 and December 25, 2022, 30 patients were screened and enrolled in this study. The median age of the patients at enrollment was 54 years, 12 patients (40.0 %) had hormone-receptor-positive disease and 23 patients (76.7 %) had visceral metastasis. The median PFS was 8.63 months (95 % confidence interval [CI] 4.15–13.12 months). The median OS was not reached. The ORR was 53.3 % (16/30) and the DCR was 96.7 % (29/30). The most common Grade III/IV adverse events were leukopenia (n = 5, 16.7 %), neutropenia (n = 4, 13.3 %), and diarrhea (n = 3, 10 %). No treatment-related serious adverse events or deaths occurred. Conclusions: The combination regimen of inetetamab, pyrotinib, and oral vinorelbine showed encouraging efficacy and favorable safety in patients with HER2-positive advanced breast cancer and could be considered as an alternative treatment option for the patients. Trial registration: No.NCT05823623; https://www.clinicaltrials.gov/.

Goal: The purpose of this paper is to recognize autism spectrum disorders (ASD) using graph attention network. Methods: we propose a node features graph attention network (NF-GAT) for learning functional connectivity (FC) features to achieve ASD diagnosis. Firstly, node features are modelled based on functional magnetic resonance imaging (fMRI) data, with each subject modelled as a graph. Next, we use the graph attention layer to learn the node features and gets the node information of different nodes for ASD classification. Results: Compared with other models, the NF-GAT has significant advantages in terms of classification results. Conclusions: NF-GAT can be effectively used for ASD classification.

Abstract Land is an increasingly scarce resource that plays a critical role in achieving many Sustainable Development Goals (SDGs). Land scarcity, namely the imbalance state between cropland availability and demand, can be mitigated by the trade of agricultural products, but how effective it is remains unclear. Here, by integrating grid-level data on cropland into multi-regional input–output analysis, this paper accounts for the scarce land footprint and virtual scarce land flows within China at a 1 km × 1 km resolution. Results show that over 70% of China’s land footprint and scarce land footprint can be attributed to less than 20% of the land, and nearly 38% of the land footprint and scarce land footprint hotspot clusters are found to cross provinces. Generally, while virtual land trade mitigates the land scarcity of land-importing provinces by 50.8%, it disproportionately aggravates the land scarcity of land-exporting provinces by 119.8%. These findings challenge the dominant thinking about food trading and call for new policies to improve land resources management and promote collaborative governance across administrative boundaries. Our study also highlights the critical importance of considering land scarcity, shedding lights on how it may be integrated into environmental footprints to better assist the SDG framework.

Evaluation for biological impact of food emulsions is fundamental for their application. In present study, we utilized a NaCas-DGMO (sodium caseinate-decylglycerol monooleate) stabilized emulsion to improve resveratrol's (Res) stability, and bioavailability. The in vivo interaction between complex emulsion and gut microbiota was further explored. Results indicated NaCas-DGMO emulsion achieved a loading rate of 92 % for Res and significantly enhanced storage and photo stability of Res. In vitro gastrointestinal digestion highlighted a significant improvement in Res's bioaccessibility. In vivo pharmacokinetic tests showed a notable 3.1-fold increase in oral bioavailability, with a prolonged Tmax of 6 h post-administration. Gut microbiota analysis revealed that the emulsion promoted beneficial bacteria, like Blautia, which produce short-chain fatty acids. Consequently, the findings proved potential of NaCas-DGMO stabled emulsion as carriers for bioactive substances in the food industry. The innovative methodology employed in assessing biological effects provides valuable insights for future research in related field.

Soybean-derived phosphatidylethanolamine (PE) is a valuable phospholipid component yet its high-purity form is costly and its molecular structure is poorly understood. The present study combined solvent extraction and cryopurification to purify PE. The optimal extraction conditions were as follows: material-liquid ratio 1:15 (g/mL), ethanol base concentration 100:4 (Vanhydrous ethanol /V25% ammonia), extraction temperature 40 °C, time 60 min, extraction twice. The cryopurification conditions were: material-liquid ratio 1:60, ethanol base concentration 100:6 (Vanhydrous ethanol/V25% ammonia), freezing temperature − 20 °C, time 20 h. UPLC-QTOF-MS/MS analysis revealed phospholipid composition of raw material, crude product, and purified product. The results showed that the purity of PE in the purified products was 76.74%, and the yield was 72.43% under optimal conditions. 181 phospholipid molecules were quantified. The study successfully explored high-purity PE preparation method and the composition of PE product. It provides a basis for the subsequent exploration of its biofunction and potential applications.

It has been reported that PM2.5 causes endothelial cell injury and promotes atherosclerosis. However, the exact mechanism through which coal-fired PM2.5 induces endothelial cell injury, and the involvement of the p38 and JNK signaling pathways in this process remain unclear. In this study, EA.hy926 cells were exposed to coal-fired PM2.5 at concentrations of 25, 50, and 100 μg/mL, and the toxic effects were observed. The phosphorylation of the JNK and p38 signaling pathways was investigated through western blot analysis. Additionally, the expression of adhesion molecules (ICAM-1 and E-selectin) was assessed using ELISA and flow cytometry. Changes in cellular toxicity and adhesion molecules were evaluated after pretreatment with the p38 inhibitor SB203580 (10 μM) and the JNK inhibitor SP600125 (25 μM). We observed that exposure to coal-fired PM2.5 led to a decrease in cell survival rate and proliferation while promoting apoptosis. Exposure to coal-fired PM2.5 promoted the expression of ICAM-1 and E-selectin, as well as the phosphorylation of p38 and JNK in EA.hy926 cells. After using p38 and JNK inhibitors, there was an observed increase in cell survival rate and proliferation, accompanied by a decrease in apoptosis. The levels of ICAM-1 and E-selectin showed no significant changes with the addition of p38 and JNK inhibitors. Our results indicated that coal-fired PM2.5 caused cellular toxicity and increased the levels of ICAM-1 and E-selectin. The p38 and JNK signaling pathways might play a role in the reduction of cell viability, while the regulation of ICAM-1 and E-selectin might not be influenced by these pathways.

Osteoarthritis (OA) is a degenerative joint disease, Increasingly, mitochondrial autophagy has been found to play an important regulatory role in the prevention and treatment of osteoarthritis. Koumine is a bioactive alkaloid extracted from the plant Gelsemium elegans. In previous research, Koumine was found to have potential in improving the progression of OA in rats. However, the specific mechanism of its action has not been fully explained. Therefore, the aim of this study was to investigate whether Koumine can alleviate OA in rats by influencing mitochondrial autophagy. In the in vitro study, rat chondrocytes (RCCS-1) were induced with IL-1β (10 ng/mL) to induce inflammation, and Koumine (50 μg/mL) was co-treated. In the in vivo study, a rat OA model was established by intra-articular injection of 2% papain, and Koumine was administered orally (1 mg/kg, once daily for two weeks). It was found that Koumine effectively reduced cartilage erosion in rats with osteoarthritis. Additionally, it decreased the levels of inflammatory factors such as IL-1β, IL-6, and extracellular matrix (ECM) components MMP13 and ADAMTS5 in chondrocytes and articular cartilage tissue, while increasing the level of Collagen II.Koumine inhibited the production of reactive oxygen species (ROS) in cartilage tissue and increased the number of autophagosomes in chondrocytes and articular cartilage tissue. Additionally, it upregulated the expression of mitochondrial autophagy proteins LC3Ⅱ/Ⅰ, PINK1, Parkin, and Drp1. The administration of Mdivi-1 (50 μM) reversed the enhanced effect of Koumine on mitochondrial autophagy, as well as its anti-inflammatory and anti-ECM degradation effects in rats with OA. These findings suggest that Koumine can alleviate chondrocyte inflammation and improve the progression of OA in rats by activating PINK1/Parkin-mediated mitochondrial autophagy.