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Breast cancer (BC) is one of the frequent tumors that seriously endanger the physical and mental well-being in women with strong heterogeneity, and its pathogenesis involves multiple risk factors. Depending on the type of BC, hormonal therapy, targeted therapy, and immunotherapy are the current systemic treatment options along with conventional chemotherapy. Despite significant progress in understanding BC pathogenesis and therapeutic options, there is still a need to identify new therapeutic targets and develop more effective treatments. According to recent sequencing and profiling studies, non-coding (nc) RNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation, and similarly, the expression of many ncRNAs is altered in breast cancer cell lines and tissues. The ability of single ncRNAs to regulate the expression of multiple downstream gene targets and related pathways provides a theoretical basis for studying them for cancer therapeutic drug development and targeted delivery. Therefore, it is far-reaching to explore the role of ncRNAs in tumor development and their potential as therapeutic targets. Here, our review outlines the potential of two major ncRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) as diagnostic and prognostic biomarkers as well as targets for new therapeutic strategies in breast cancer.

Abstract Background Chronic nonhealing wounds remain a considerable challenge in clinical treatment due to excessive inflammation and impeded reepithelialization and angiogenesis. Therefore, the discovery of novel prohealing agents for chronic skin wounds are urgent and important. Amphibian-derived prohealing peptides, especially immunomodulatory peptides, provide a promising strategy for the treatment of chronic skin trauma. However, the mechanism of immunomodulatory peptides accelerating the skin wound healing remains poorly understood. Methods The prohealing ability of peptide Andersonin-W1 (AW1) was assessed by cell scratch, cell proliferation, transwell, and tube formation. Next, full-thickness, deep second-degree burns and diabetic full-thickness skin wounds in mice were performed to detect the therapeutic effects of AW1. Moreover, the tissue regeneration and expression of inflammatory cytokines were evaluated by hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry staining. Molecular docking, colocalization, and western blotting were used to explore the mechanism of AW1 in promoting wound healing. Results We provide solid evidence to display excellent prohealing effects of AW1, identified as a short antimicrobial peptide in our previous report. At relative low concentration of nM, AW1 promoted the proliferation, migration, and scratch repair of keratinocyte, macrophage proliferation, and tube formation of HUVEC. AW1 also facilitated reepithelialization, granulation regeneration, and angiogenesis, thus significantly boosting the healing of full-thickness, deep second-degree burns and diabetic skin wounds in mice. Mechanistically, in macrophages, AW1 directly bound to Toll-like receptor 4 (TLR4) in the extracellular region and regulated the downstream nuclear factor‐κB (NF-κB) signaling pathway to facilitate the inflammatory factor secretion and suppress excessive inflammation induced by lipopolysaccharide (LPS). Moreover, AW1 regulated macrophage polarization to promote the transition from the inflammatory to the proliferative phase and then facilitated reepithelialization, granulation regeneration, and angiogenesis, thus exhibiting excellent therapeutic effects on diabetic skin wounds. Conclusions AW1 modulates inflammation and the wound healing process by the TLR4/NF-κB molecular axis, thus facilitating reepithelialization, granulation regeneration, and angiogenesis. These findings not only provided a promising multifunctional prohealing drug candidate for chronic nonhealing skin wounds but also highlighted the unique roles of “small” peptides in the elucidation of “big” human disease mechanisms. Graphical Abstract

Passive cooling strategy shows great potential in mitigating global warming and reducing energy consumption. Because of the high emissivity in the atmospheric transparency window (λ ≈ 8–13 µm), cellulose is considered as a good candidate for radiative cooling. However, traditional cellulose coolers generally show poor solar reflection and can be polluted by dust outside, thereby resulting in poor daytime cooling efficiency. To address these drawbacks, we developed sustainable cellulose nanowhiskers (CNWs)/ZnO composite aerogel films with favorable optical performance, mechanical robustness, and self-cleaning function for efficient daytime radiative cooling, which can be achieved via freeze casting and hot-pressing process. Due to formation of multi-level porous structure and chemical bonds (Si-O-C/Si-O-Si), such aerogel film exhibited high solar reflectance (97%) and high infrared emittance (92.5%). It achieved a sub-ambient temperature drop of 6.9 °C under direct sunlight in hot weather. Most importantly, the surface roughness and low surface energy enable cellulose aerogel film hydrophobicity (contact angle = 133°), thereby resulting in an anti-dust function. This work provides insight into the design of sustainable thermal regulating materials to realize carbon neutrality.

ObjectiveTo evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) in Vibrio vulnificus (V. vulnificus) infection.MethodsA retrospective analysis of patients with V. vulnificus infection at the Fifth Affiliated Hospital of Sun Yat-Sen University from January 1, 2020 to April 23, 2023 was conducted. 14 enrolled patients were diagnosed by culture or mNGS. The corresponding medical records were reviewed, and the clinical data analyzed included demographics, epidemiology laboratory findings, physical examination, symptoms at presentation, antibiotic and surgical treatment, and outcome.ResultsIn this study, 78.6% (11/14) patients had a history of marine trauma (including fish stab, shrimp stab, crab splints and fish hook wounds), 7.1% (1/14) had eaten seafood, and the remaining 14.3% (2/14) had no definite cause. Isolation of V. vulnificus from clinical samples including blood, tissue, fester and secreta. 9 cases were positive for culture, 5 cases were detected synchronously by mNGS and got positive for V. vulnificus. 85.7% (12/14) cases accepted surgical treatment, with 1 patient suffering finger amputated. 14 enrolled patients received appropriate antibiotic therapy, and all of them had recovered and discharged. 9 strains V. vulnificus isolated in this study were sensitive to most beta-lactam antibiotics, aminoglycosides, quinolones, etc.ConclusionVibrio vulnificus infection is a common water-exposed disease in Zhuhai, which requires identification of a number of pathogens. Of severe infections with unknown pathogen, mNGS can be used simultaneously, and the potential to detect multiple pathogens is of great help in guiding treatment.

Since the beginning of the 21st century, vegetation greening in China has continuously increased and ranks among the top globally, especially in the western and northern regions of the country. This study analyzed the characteristics of the greening rates of different vegetation types in China's arid and semi-arid regions in the northwest, using satellite-derived Normalized Difference Vegetation Index (NDVI) data from 2002 to 2021. Furthermore, the study explored the response of greening rates to climate change and its temporal effect. The study found that in the past two decades, the vegetation greening rates in the southeastern region of China's arid and semi-arid areas are higher than that in the northwest. Vegetation change in the arid and semi-arid regions of China exhibits significant spatial heterogeneity in response to climate change. The vegetation greening rates in the southeast of the study area increases with precipitation, while in the northwest, it is promoted by daytime temperature and day-night temperature difference. The greening rates of cultivated vegetation, grassland, and meadow thicket is mainly affected by precipitation, while the greening rates of alpine grassland is mainly affected by day-night temperature difference. In addition, the response of vegetation greening rates to climate in China's arid and semi-arid regions has significant time lag and cumulative effects. Climate changes before the growing season (February to May) can also affect vegetation greening rates during the growing season (June to September). The cumulative climate changes over four months have a greater impact on vegetation greening rate than those over two months. Our study quantified the contribution of climate change to the greening rates of different vegetation types, which can provide references for predicting the dynamic changes of vegetation under future climate change.

This paper introduces a multi-layered cross-genre corpus, annotated for coreference resolution, causal relations, and temporal relations, comprising a variety of genres, from news articles and children’s stories to Reddit posts. Our results reveal distinctive genre-specific characteristics at each layer of annotation, highlighting unique challenges for both annotators and machine learning models. Children’s stories feature linear temporal structures and clear causal relations. In contrast, news articles employ non-linear temporal sequences with minimal use of explicit causal or conditional language and few first-person pronouns. Lastly, Reddit posts are author-centered explanations of ongoing situations, with occasional meta-textual reference. Our annotation schemes are adapted from existing work to better suit a broader range of text types. We argue that our multi-layered cross-genre corpus not only reveals genre-specific semantic characteristics but also indicates a rich contextual interplay between the various layers of semantic information. Our MLCG corpus is shared under the open-source Apache 2.0 license.

Snake venom is considered a “toxin arsenal”, and it often induces a series of clinical and pathophysiological symptoms in snakebite victims. Interestingly, toxin inhibitors are commonly found in the serum of snakes and their predators. Sinonatrix annularis is a type of non-venomous snake that was reported to contain an “inhibitor cocktail”, including phospholipase A2 inhibitors (PLIs), metalloproteinase inhibitors (SVMPIs), and small serum protein (SSP). However, the sequences and activities of these components remain obscure. In this study, we performed envenomation challenges on S. annularis using venoms from Deinagkistrodon acutus, Agkistrodon halys and Naja atra. In brief, the maximum injected amount of venom was 360 mg/kg for D. acutus, 72 mg/kg for A. halys, and 18 mg/kg for N. atra. The mRNA expression of the inhibitors PLIα, PLIβ, PLIγ, SVMPI, serpin A1, and SSP showed a dose-dependent effect on envenomation. Liver homogenate from S. annularis (LH) was prepared and used to evaluate its inhibitory effect on snake venoms. As a result, LH showed significant neutralization of venom PLA2, mitigated hemorrhage, venom-induced muscle damage, and system toxicity. In the presence of LH, envenomated mice exhibited attenuated inflammation, apoptosis, oxidative damage, and mitigated changes in serum biochemical markers caused by venom. The study reveals the secret of “natural immunity” in snakes, namely, the “antivenom”, which consists of an inhibitor proteome or cocktail.

The increasing number of voltage domains along with the size of the data bus requires an exponential increase in the number level shifter (LS) circuits for signal interfacing, creating an exploding in silicon area and power consumption. Higher area-efficiency can be attained by further improving the integration density of the LS circuit. In this paper, we present a multi-function ultra-low-voltage LS with re-configurable logic with embedded time-borrowing latch. The proposed circuit is implemented on CMOS 45nm technology. It is capable of converting the input voltage of 0.3 V to an output voltage of 1.8 V with an input frequency of 1 MHz. The proposed architecture has achieved a superior area efficiency with reduced transistors number of $2.4\times $ and reduced power delay product (PDP) of $4.65\times $ compared with its discrete logic block level implementation when the input voltage, output voltage, and the input frequency are 0.3 V, 1.8 V, and 1 MHz, respectively. The average propagation delay and power consumption are 52.7 ns and 34.6 nW, respectively.

With the increasing demand for transparent/flexible displays, healthcare sensors, and robotics, there is a need to advance the development of thin-film transistors (TFTs) manufacturing and large-scale circuits. This paper has proposed an IGZO-TFT-PDK to aid the educators and research community to explore the circuit design space of dual-gate IGZO-TFT devices. To solve the tensile force-induced current variation problem in IGZO-TFT devices, an omni-directional device and its layout template with a compensation methodology that mitigates its variation are proposed. A layout template is also proposed to speed up the design development flow of both analog and digital IGZO-TFT circuits. Based on the proposed layout template, a tensile force-insensitive standard cell library is proposed. We have implemented a 32-bit carry select adder to validate the usability of the standard cell library.

Revealing the performance of farmland conservation policies that use different types of policy instruments can provide a basis for optimizing such policies. Based on farmers’ perceptions of farmland conservation policies, this paper conducted an empirical analysis using data on 986 rural households which were collected from seven towns/districts in three provinces of China. More specifically, this paper first uses propensity score matching to analyze the impact of the comprehensive application of economic incentive and command-and-control policy instruments on farmland conservation. Then, it explores the differences between the effects of local economic incentive farmland conservation policies (FCP-LE) that employed different policy instruments. Finally, the factors affecting farmers’ perceptions of FCP-LE performance were identified. The results show that the combination of economic incentives and command-and-control policy instruments significantly improved the performance of farmland conservation policies. Furthermore, after comparing FCP-LE with payments to rural communities in the form of monetary compensation only, it is evident that a combination of FCP-LE with payments to farmers and integrated monetary compensation and social security subsidies yields better farmland conservation. Additionally, there are differences between the factors affecting farmers’ perceptions of FCP-LE performance in different areas. Our findings aim to help encourage more areas to develop diversified local incentive policies in order to conserve farmland.

Ticks are a major arthropod vector of zoonotic diseases affecting both humans and domestic animals worldwide. Thus, studying tick microbiota would aid in understanding of the potential threats posed by ticks. Approximately 8,000 unfed ticks, identified as Dermacentor nuttalli , were collected from the sylvosteppe in the western Tianshan mountains. To investigate their potential pathogens, we divided the ticks into 36 groups of 200–300 individuals each for examination with culturomics and 16S rDNA amplicon sequencing. A total of 237 bacterial genera were identified with the two methods. Culturomics identified 46 bacterial species from 23 genera, predominantly Pseudomonas , Pantoea , and Bacillus , whereas 16S rDNA sequencing identified 461 OTUs from 233 genera, predominantly Pseudomonas (53.8%), Coxiella (17.2%), and Pantoea (6.4%). Coxiella , Rickettsia , and ten other genera were discovered only by sequencing, because optimal cultivating conditions were not used for their isolation, whereas Arthrobacter and three other genera were discovered only through culturomics. Several of the identified bacteria, such as line-related sepsis-causing Delftia acidovorans and the pneumonia agent Acinetobacter pittii , can cause human diseases. Thus, both sequencing and culturomics methods are crucial for comprehensive understanding of the microbiota of D. nuttalli .

The ecological environment is suffering from great human disturbance. Scientific assessment of landscape ecological risks can provide scientific guidance for land use management. This study focused on Chaoyang County in China, used ecological risk assessment methods to characterize the impact of land use/land cover (LUCC) change, and revealed the risk aggregation pattern with the help of spatial autocorrelation analysis. The results showed that ecological risk was increased from 2000 to 2010 but decreased from 2010 to 2018. The ecological risk of the Daling River and Xiaoling River basin was at a relatively high level, and low in the northwest and southeast of the study which covered by forest land. Occupying cultivated land for built-up and large-scale deforestation were two of the main factors to contribute to the increase of ecological risk. The distribution of High-High (HH) and Low-Low (LL) risk agglomeration areas was basically the same as risk levels, but the scope is smaller and more precise. Thus, HH and LH risk agglomeration area should be paid more attention to prevent the adverse impact of adjacent areas. Our study gave a novel perspective to investigate the pattern of ecological risk in order for government managers to identify key risk areas.

The effects that solid–liquid interfaces exert on the aggregation of proteins and peptides are of high relevance for various fields of basic and applied research, ranging from molecular biology and biomedicine to nanotechnology. While the influence of surface chemistry has received a lot of attention in this context, the role of surface topography has mostly been neglected so far. In this work, therefore, we investigate the aggregation of the type 2 diabetes-associated peptide hormone hIAPP in contact with flat and nanopatterned silicon oxide surfaces. The nanopatterned surfaces are produced by ion beam irradiation, resulting in well-defined anisotropic ripple patterns with heights and periodicities of about 1.5 and 30 nm, respectively. Using time-lapse atomic force microscopy, the morphology of the hIAPP aggregates is characterized quantitatively. Aggregation results in both amorphous aggregates and amyloid fibrils, with the presence of the nanopatterns leading to retarded fibrillization and stronger amorphous aggregation. This is attributed to structural differences in the amorphous aggregates formed at the nanopatterned surface, which result in a lower propensity for nucleating amyloid fibrillization. Our results demonstrate that nanoscale surface topography may modulate peptide and protein aggregation pathways in complex and intricate ways.

Breast cancer (BC) is one of the frequent tumors that seriously endanger the physical and mental well-being in women with strong heterogeneity, and its pathogenesis involves multiple risk factors. Depending on the type of BC, hormonal therapy, targeted therapy, and immunotherapy are the current systemic treatment options along with conventional chemotherapy. Despite significant progress in understanding BC pathogenesis and therapeutic options, there is still a need to identify new therapeutic targets and develop more effective treatments. According to recent sequencing and profiling studies, non-coding (nc) RNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation, and similarly, the expression of many ncRNAs is altered in breast cancer cell lines and tissues. The ability of single ncRNAs to regulate the expression of multiple downstream gene targets and related pathways provides a theoretical basis for studying them for cancer therapeutic drug development and targeted delivery. Therefore, it is far-reaching to explore the role of ncRNAs in tumor development and their potential as therapeutic targets. Here, our review outlines the potential of two major ncRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) as diagnostic and prognostic biomarkers as well as targets for new therapeutic strategies in breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: Staphylococcus aureus was associated with more than 1 million deaths in 2019. The coronavirus disease 2019 (COVID-19) pandemic has lasted three years. In China, measures to control COVID-19 cases were adjusted in December 2022. In this study, we investigated the effects of the COVID-19 pandemic on the drug resistance of S. aureus infection. Aim: Understanding the impact of the adjustment of COVID-19 control measures on the drug sensitivity of S. aureus will provide a reference for empirical drug use and the prevention of clinical S. aureus infection. Methods: A retrospective analysis was performed, focusing on the clinical distribution and drug resistance of distributions of S. aureus isolated from the Fifth Affiliated Hospital of Sun Yat-sen University during the COVID-19 pandemic from January 2020 to March 2023. The effects of COVID-19 control measures on the drug resistance of S. aureus infection were further investigated. Results: A total of 1,437 strains of S. aureus were isolated, with a methicillin-resistant S. aureus detection rate of 19.2%. The department with the highest detection rate was the oncology department (17.0%, 244/1,437), followed by the intensive care unit (11.1%, 159/1,437), the dermatology department (10.7%, 154/1,437), and the wound repair and burn department (9.7%, 139/1,437). The most frequent specimens were secretions (42.0%, 603/1,437), followed by sputum (23.3%, 335/1,437), blood (10.7%, 154/1,437), and pus (5.4%, 78/1,437). The population distribution was primarily male (62.3%, 895/1,437). S. aureus infections were most common among those aged 50-65 (32.8%, 472/1,437), followed by those aged 18-49 (30.7%, 441/1,437). Staphylococcus aureus was most resistant to penicillin G (86.3%), followed by erythromycin (37.9%) and clindamycin (37.3%). The antibiotics with no resistance were linezolid, teicoplanin, tigecycline, and vancomycin. There was no significant difference in the drug-resistance rate between COVID-19-positive and COVID-19-negative patients. Conclusion: The outbreak of COVID-19 in 2020 and the adjustment of control measures had no significant impact on the drug resistance of S. aureus infection. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) in Vibrio vulnificus (V. vulnificus) infection. Methods: A retrospective analysis of patients with V. vulnificus infection at the Fifth Affiliated Hospital of Sun Yat-Sen University from January 1, 2020 to April 23, 2023 was conducted. 14 enrolled patients were diagnosed by culture or mNGS. The corresponding medical records were reviewed, and the clinical data analyzed included demographics, epidemiology laboratory findings, physical examination, symptoms at presentation, antibiotic and surgical treatment, and outcome. Results: In this study, 78.6% (11/14) patients had a history of marine trauma (including fish stab, shrimp stab, crab splints and fish hook wounds), 7.1% (1/14) had eaten seafood, and the remaining 14.3% (2/14) had no definite cause. Isolation of V. vulnificus from clinical samples including blood, tissue, fester and secreta. 9 cases were positive for culture, 5 cases were detected synchronously by mNGS and got positive for V. vulnificus. 85.7% (12/14) cases accepted surgical treatment, with 1 patient suffering finger amputated. 14 enrolled patients received appropriate antibiotic therapy, and all of them had recovered and discharged. 9 strains V. vulnificus isolated in this study were sensitive to most beta-lactam antibiotics, aminoglycosides, quinolones, etc. Conclusion: Vibrio vulnificus infection is a common water-exposed disease in Zhuhai, which requires identification of a number of pathogens. Of severe infections with unknown pathogen, mNGS can be used simultaneously, and the potential to detect multiple pathogens is of great help in guiding treatment. [ABSTRACT FROM AUTHOR]

Abstract Aging is characterized by the accumulation of proteins that display amyloid-like behavior. However, the molecular mechanisms by which these proteins arise remain unclear. Here, we demonstrate that amyloid-like proteins are produced in a variety of human cell types, including stem cells, brain organoids and fully differentiated neurons by mistakes that occur in messenger RNA molecules. Some of these mistakes generate mutant proteins already known to cause disease, while others generate proteins that have not been observed before. Moreover, we show that these mistakes increase when cells are exposed to DNA damage, a major hallmark of human aging. When taken together, these experiments suggest a mechanistic link between the normal aging process and age-related diseases.

Abstract The genetic analysis of potato is hampered by the complexity of tetrasomic inheritance. An ongoing effort aims to transform the clonally propagated tetraploid potato into a seed-propagated diploid crop, which would make genetic analyses much easier owing to disomic inheritance. Here, we construct and report the large-scale genetic and heterotic characteristics of a diploid F2 potato population derived from the cross of two highly homozygous inbred lines. We investigate 20,382 traits generated from multi-omics dataset and identify 25,770 quantitative trait loci (QTLs). Coupled with gene expression data, we construct a systems-genetics network for gene discovery in potatoes. Importantly, we explore the genetic basis of heterosis in this population, especially for yield and male fertility heterosis. We find that positive heterotic effects of yield-related QTLs and negative heterotic effects of metabolite QTLs (mQTLs) contribute to yield heterosis. Additionally, we identify a PME gene with a dominance heterotic effect that plays an important role in male fertility heterosis. This study provides genetic resources for the potato community and will facilitate the application of heterosis in diploid potato breeding.

Abstract Objectives Creeping fat (CF) is associated with stricture formation in Crohn’s disease (CD). This study evaluated the feasibility of intestinal ultrasound (IUS) for semiquantitative analysis of CF and compared the agreement between IUS and computed tomography enterography (CTE). Methods In this retrospective study, we recruited consecutive CD patients who underwent IUS and CTE. CF wrapping angle was analyzed on the most affected bowel segment and was independently evaluated by IUS and CTE. We evaluated the wrapping angle of CF in the cross- and vertical sections of the diseased bowel. CF wrapping angle was divided into

Abstract Background Medication Treatment Satisfaction (M-TS) from the patients’ perspective is important for comprehensively evaluating the effect of medicines. The extent to which current patient-reported outcome measures (PROMs) for M-TS are valid, reliable, responsive, and interpretable remains unclear. To assess the measurement properties of existing PROMs for M-TS and to highlight research gaps. Methods Using PubMed, Embase (Ovid), Cochrane library (Ovid), IPA (Ovid), PsycINFO, Patient-Reported Outcome and Quality of Life Questionnaires biomedical databases, and four Chinese databases, we performed a systematic search for studies addressing the development and validation of PROMs for M-TS. Based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, pairs of reviewers independently assessed the measurement properties of the PROMs and rated the quality of evidence on the measurement properties of each PROM. (The Open Science Framework registration: https://doi.org/10.17605/OSF.IO/8S5ZM ). Results This review identified 69 PROMs for M-TS in 114 studies (four generic, 32 disease-specific, and 33 drug-specific) of which 60 were intended for adults. All provided limited or no information regarding interpretability. Most demonstrated appropriate construct validity including convergent validity (39/69) and discriminative or known-groups validity (40/69) (high to moderate quality of evidence). Only a few provided evidence of sufficient content validity (8/69), structural validity (13/69), and internal consistency (11/69). Of 38 PROMs reporting test–retest reliability, results in 24 provided evidence of satisfactory test–retest reliability (18 with high to moderate, 6 with low to very low quality of evidence). Few PROMs reported responsiveness (16/69). Two generic PROMs (Treatment Satisfaction Questionnaire for Medication initial Version 1.4, TSQM-1.4; Treatment Satisfaction with Medicines Questionnaire, SATMED-Q) and one drug-specific PROM (Insulin Treatment Satisfaction Questionnaire, ITSQ) demonstrated both satisfactory validity and reliability. Conclusions Most existing PROMs for M-TS require further exploration of measurement properties. Reporting guidelines are needed to enhance the reporting quality of the development and validation of PROMs for M-TS.

Abstract Background The Sleep Condition Indicator (SCI), an insomnia measurement tool based on the updated Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria with sound psychometric properties when applied in various populations, was evaluated here among healthcare students longitudinally, to demonstrate its measurement properties and invariance in this particularly high-risk population. Methods Healthcare students of a Chinese university were recruited into this two-wave longitudinal study, completing the simplified Chinese version of the SCI (SCI-SC), Chinese Regularity, Satisfaction, Alertness, Timing, Efficiency, Duration (RU_SATED-C) scale, Chinese Patient Health Questionnaire-4 (PHQ-4-C), and sociodemographic variables questionnaire (Q-SV) between September and November 2022. Structural validity, measurement invariance (MI), convergent and discriminant validity, internal consistency, and test–retest reliability of the SCI-SC were examined. Subgroups of gender, age, home location, part-time job, physical exercise, and stress-coping strategy were surveyed twice to test cross-sectional and longitudinal MI. Results We identified 343 valid responses (62.9% female, mean age = 19.650 ± 1.414 years) with a time interval of seven days. The two-factor structure was considered satisfactory (comparative fit index = 0.953–0.989, Tucker–Lewis index = 0.931–0.984, root means square error of approximation = 0.040–0.092, standardized root mean square residual = 0.039–0.054), which mostly endorsed strict invariance except for part-time job subgroups, hence establishing longitudinal invariance. The SCI-SC presented acceptable convergent validity with the RU_SATED-C scale (r ≥ 0.500), discriminant validity with the PHQ-4-C (0.300 ≤ r

Abstract Background To investigate whether the intraoperative superb microvascular imaging(SMI) technique helps evaluate lesion boundaries compared with conventional grayscale ultrasound in brain tumor surgery and to explore factors that may be associated with complete radiographic resection. Methods This study enrolled 57 consecutive brain tumor patients undergoing surgery. During the operation, B-mode and SMI ultrasound evaluated the boundaries of brain tumors. MRI before and within 48h after surgery was used as the gold standard to evaluate gross-total resection(GTR). The ultrasound findings and GTR results were analyzed to determine the imaging factors related to GTR. Results A total of 57 patients were enrolled in the study, including 32 males and 25 females, with an average age of 53.4 ± 14.1 years old(range 19 ~ 80). According to the assessment criteria of MRI, before and within 48 h after the operation, 37(63.9%) cases were classified as GTR, and 20(35.1%) cases were classified as GTR. In comparing tumor interface definition between B-mode and SMI mode, SMI improved HGG boundary recognition in 5 cases(P = 0.033). The results showed that the tumor size ≥ 5 cm and unclear ultrasonic boundary were independent risk factors for nGTR (OR>1, P

Abstract Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence‐related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3‐rich extracellular vesicles to NPCs, thereby alleviating aging‐associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane‐bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2‐TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia‐induced BMSC exosomes deliver BNIP3‐rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.

BackgroundThe standardized extract of milk thistle seeds, known as silibinin, has been utilized in herbal medicine for over two centuries, with the aim of safeguarding the liver against the deleterious effects of various toxic substances. However, the role of silibinin in Particulate Matter (PM2.5)-induced intrahepatic triglyceride accumulation remains unclear. This study seeks to investigate the impact of silibinin on PM2.5-induced intrahepatic triglyceride accumulation and elucidate potential underlying mechanisms.MethodsA model of intrahepatic triglyceride accumulation was established in male C57BL/6J mice through intratracheal instillation of PM2.5, followed by assessment of liver weight, body weight, liver index, and measurements of intrahepatic triglycerides and cholesterol after treatment with silibinin capsules. Hep G2 cells were exposed to PM2.5 suspension to create an intracellular triglyceride accumulation model, and after treatment with silibinin, cell viability, intracellular triglycerides and cholesterol, fluorescence staining for Nile Red (lipid droplets), and DCFH-DA (Reactive Oxygen Species, ROS), as well as proteomics, real-time PCR, and mitochondrial function assays, were performed to investigate the mechanisms involved in reducing triglycerides.ResultsPM2.5 exposure leads to triglyceride accumulation, increased ROS production, elevated expression of inflammatory factors, decreased expression of antioxidant factors, and increased expression of downstream genes of aryl hydrocarbon receptor. Silibinin can partially or fully reverse these factors, thereby protecting cells and animal livers from PM2.5-induced damage. In vitro studies show that silibinin exerts its protective effects by preserving oxidative phosphorylation of mitochondrial complexes I and II, particularly significantly enhancing the function of mitochondrial complex II. Succinate dehydrogenase (mitochondrial complex II) is a direct target of silibinin, but silibinin A and B exhibit different affinities for different subunits of complex II.ConclusionSilibinin improved the accumulation of intrahepatic triglycerides induced by PM2.5, and this was, at least in part, explained by an enhancement of oxidative phosphorylation in mitochondrial Complexes I and II.

BackgroundAlzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder that has become one of the major health concerns for the elderly. Computer-aided AD diagnosis can assist doctors in quickly and accurately determining patients' severity and affected regions.MethodsIn this paper, we propose a method called MADNet for computer-aided AD diagnosis using multimodal datasets. The method selects ResNet-10 as the backbone network, with dual-branch parallel extraction of discriminative features for AD classification. It incorporates long-range dependencies modeling using attention scores in the decision-making layer and fuses the features based on their importance across modalities. To validate the effectiveness of our proposed multimodal classification method, we construct a multimodal dataset based on the publicly available ADNI dataset and a collected XWNI dataset, which includes examples of AD, Mild Cognitive Impairment (MCI), and Cognitively Normal (CN).ResultsOn this dataset, we conduct binary classification experiments of AD vs. CN and MCI vs. CN, and demonstrate that our proposed method outperforms other traditional single-modal deep learning models. Furthermore, this conclusion also confirms the necessity of using multimodal sMRI and DTI data for computer-aided AD diagnosis, as these two modalities complement and convey information to each other. We visualize the feature maps extracted by MADNet using Grad-CAM, generating heatmaps that guide doctors' attention to important regions in patients' sMRI, which play a crucial role in the development of AD, establishing trust between human experts and machine learning models.ConclusionWe propose a simple yet effective multimodal deep convolutional neural network model MADNet that outperforms traditional deep learning methods that use a single-modality dataset for AD diagnosis.