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To clarify the effect mechanism of Alpinia katsumadai Hayata extract on the texture of duck meat, the effect of farnesol, the main component of Alpinia katsumadai Hayata extract, on the structure of myofibrillar protein was analyzed. The elasticity and hardness of duck meat in different treatment groups were determined. The flavor differences of duck meat in different treatment groups were detected using the electronic nose technique. The effects of farnesol on the structure of myofibrillar protein (MP) were analyzed, including carbonyl content, surface hydrophobicity, sulfhydryl content, and di-tyrosine fluorescence intensity. The results showed that the Alpinia katsumadai Hayata extracts significantly reduced the hardness by 54.61% compared with solid Alpinia katsumadai Hayata (P

Estimation of model accuracy plays a crucial role in protein structure prediction, aiming to evaluate the quality of predicted protein structure models accurately and objectively. This process is not only key to screening candidate models that are close to the real structure, but also provides guidance for further optimization of protein structures. With the significant advancements made by AlphaFold2 in monomer structure, the problem of single-domain protein structure prediction has been widely solved. Correspondingly, the importance of assessing the quality of single-domain protein models decreased, and the research focus has shifted to estimation of model accuracy of protein complexes. In this review, our goal is to provide a comprehensive overview of the reference and statistical metrics, as well as representative methods, and the current challenges within four distinct facets (Topology Global Score, Interface Total Score, Interface Residue-Wise Score, and Tertiary Residue-Wise Score) in the field of complex EMA.

Background: Document images such as statistical reports and scientific journals are widely used in information technology. Accurate detection of table areas in document images is an essential prerequisite for tasks such as information extraction. However, because of the diversity in the shapes and sizes of tables, existing table detection methods adapted from general object detection algorithms, have not yet achieved satisfactory results. Incorrect detection results might lead to the loss of critical information. Methods: Therefore, we propose a novel end-to-end trainable deep network combined with a self-supervised pretraining transformer for feature extraction to minimize incorrect detections. To better deal with table areas of different shapes and sizes, we added a dual-branch context content attention module (DCCAM) to high-dimensional features to extract context content information, thereby enhancing the network's ability to learn shape features. For feature fusion at different scales, we replaced the original 3×3 convolution with a multilayer residual module, which contains enhanced gradient flow information to improve the feature representation and extraction capability. Results: We evaluated our method on public document datasets and compared it with previous methods, which achieved state-of-the-art results in terms of evaluation metrics such as recall and F1-score. https://github.com/YongZ-Lee/TD-DCCAM

Abstract Background Emphysematous pyelonephritis is a rare and severe urinary tract infection that is potentially life-threatening and easily progresses to septic shock. In this report, we present a unique case of emphysematous pyelonephritis caused by Raoultella ornithinolytica. Case presentation An 86-year-old man presented with severe back pain of 3 days’ duration. He had a history of hypertension and diabetes for more than 20 years, and his infection indicators and serum creatinine were elevated. Abdominal computed tomography revealed an abnormal gas shadow around his right kidney and the anterior edge of his right psoas muscle. Consequently, he was initially diagnosed with emphysematous pyelonephritis. There was no evidence of nephrolithiasis or other anatomical or structural abnormalities that could have precipitated this focal renal infection. Both blood and drainage fluid cultures revealed R. ornithinolytica. After early anti-infection treatment, percutaneous drainage and moderate control of blood glucose, the patient gradually recovered. Conclusions Emphysematous pyelonephritis caused by R. ornithinolytica is rare but has a high drug resistance rate potentially and may cause severe infections. Early diagnosis, prompt use of antibiotics that are sensitive to the organism, and decompression drainage could be the key to treatment.

Abstract Background Tumorigenicity represents a critical challenge in stem cell-based therapies requiring rigorous monitoring. Conventional approaches for tumorigenicity evaluation are based on animal models and have numerous limitations. Brain organoids, which recapitulate the structural and functional complexity of the human brain, have been widely used in neuroscience research. However, the capacity of brain organoids for tumorigenicity evaluation needs to be further elucidated. Methods A cerebral organoid model produced from human pluripotent stem cells (hPSCs) was employed. Meanwhile, to enhance the detection sensitivity for potential tumorigenic cells, we created a glioblastoma-like organoid (GBM organoid) model from TP53 −/− /PTEN −/− hPSCs to provide a tumor microenvironment for injected cells. Midbrain dopamine (mDA) cells from human embryonic stem cells were utilized as a cell therapy product. mDA cells, hPSCs, mDA cells spiked with hPSCs, and immature mDA cells were then injected into the brain organoids and NOD SCID mice. The injected cells within the brain organoids were characterized, and compared with those injected in vivo to evaluate the capability of the brain organoids for tumorigenicity evaluation. Single-cell RNA sequencing was performed to identify the differential gene expression between the cerebral organoids and the GBM organoids. Results Both cerebral organoids and GBM organoids supported maturation of the injected mDA cells. The hPSCs and immature mDA cells injected in the GBM organoids showed a significantly higher proliferative capacity than those injected in the cerebral organoids and in NOD SCID mice. Furthermore, the spiked hPSCs were detectable in both the cerebral organoids and the GBM organoids. Notably, the GBM organoids demonstrated a superior capacity to enhance proliferation and pluripotency of spiked hPSCs compared to the cerebral organoids and the mouse model. Kyoto Encyclopedia of Genes and Genomes analysis revealed upregulation of tumor-related metabolic pathways and cytokines in the GBM organoids, suggesting that these factors underlie the high detection sensitivity for tumorigenicity evaluation. Conclusions Our findings suggest that brain organoids could represent a novel and effective platform for evaluating the tumorigenic risk in stem cell-based therapies. Notably, the GBM organoids offer a superior platform that could complement or potentially replace traditional animal-based models for tumorigenicity evaluation.

Abstract It is currently unclear whether there is a connection between Life’s Essential 8 (LE8) and cardiovascular disease (CVD), as well as mortality in people with nonalcoholic fatty liver disease (NAFLD). Our goal was to explore these relationships by examining data collected in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. We identified eligible participants with NAFLD based on NHANES 2005–2018 data. CVD status was acquired through self-reported information, and using the National Death Index, mortality data were prospectively matched. The diagnosis of NAFLD relied on noninvasive biomarkers. The research involved 9094 individuals who were identified as having NAFLD, with a mean age of 52.05 years. Each incremental LE8 score exhibited a significant association, leading to a 3%, 3%, 4%, 3%, 3%, 4%, and 4% reduction in the odds of experiencing CVD, ischemic heart disease, congestive heart failure, coronary heart disease, heart attack, angina, and stroke in individuals with NAFLD. A strong correlation was found between maintaining a superior level of Cardiovascular Health (CVH), as shown by a LE8 score ranging from 80 to 100, and a reduced occurrence of CVD and its various forms in NAFLD (all p for trend

Abstract Cleft palate (CP) is a congenital condition characterized by a complex etiology and limited diagnostic and therapeutic options. In this study, we delved into the molecular mechanisms associated with retinoic acid (RA)-induced CP in Kun Ming mice. Proteomic analysis of control and RA-induced CP samples at embryonic day 15.5 revealed 25 upregulated and 19 downregulated proteins. Further analysis identified these differentially expressed proteins (DEPs) as being involved in extracellular matrix organization, actin cytoskeleton, and myosin complex. Moreover, these DEPs were found to be enriched in pathways related to motor protein activity and extracellular matrix-receptor interaction. Protein-protein interaction network analysis identified 10 hub proteins, including motor proteins and ECM-related proteins, which exhibited higher expression levels in CP compared to control tissues. These findings provide insights into the molecular mechanisms underlying CP and highlight potential targets for diagnostic and therapeutic purposes.

Abstract Fibrosis is an excessive wound-healing response induced by repeated or chronic external stimuli to tissues, significantly impacting quality of life and primarily contributing to organ failure. Organ fibrosis is reported to cause 45% of all-cause mortality worldwide. Despite extensive efforts to develop new antifibrotic drugs, drug discovery has not kept pace with the clinical demand. Currently, only pirfenidone and nintedanib are approved by the FDA to treat pulmonary fibrotic illness, whereas there are currently no available antifibrotic drugs for hepatic, cardiac or renal fibrosis. The development of fibrosis is closely related to epigenetic alterations. The field of epigenetics primarily studies biological processes, including chromatin modifications, epigenetic readers, DNA transcription and RNA translation. The bromodomain and extra-terminal structural domain (BET) family, a class of epigenetic readers, specifically recognizes acetylated histone lysine residues and promotes the formation of transcriptional complexes. Bromodomain-containing protein 4 (BRD4) is one of the most well-researched proteins in the BET family. BRD4 is implicated in the expression of genes related to inflammation and pro-fibrosis during fibrosis. Inhibition of BRD4 has shown promising anti-fibrotic effects in preclinical studies; however, no BRD4 inhibitor has been approved for clinical use. This review introduces the structure and function of BET proteins, the research progress on BRD4 in organ fibrosis, and the inhibitors of BRD4 utilized in fibrosis. We emphasize the feasibility of targeting BRD4 as an anti-fibrotic strategy and discuss the therapeutic potential and challenges associated with BRD4 inhibitors in treating fibrotic diseases.

Abstract The application of exogenous paclobutrazol (PP333) can improve the ability of winter warming to promote flowering in Chaenomeles speciosa, but the underlying mechanism is unclear. In this study, the cultivar ‘Changshouguan’ was sprayed with different concentrations of PP333 during flower bud differentiation, and the changes in the anatomical structures and physiological characteristics of the flower buds during the differentiation process, as well as the growth state of the flower buds and the effect on flowering promotion after winter warming treatment, were comprehensively investigated. The results showed that different concentrations of PP333 could advance the flowering time of ‘Changshouguan’ by 15–24 d under the warming treatment and increase the flowering duration to 17 d compared with those under the warming treatment alone (CK), and 1000 mg/L was the best treatment. Compared with the CK treatment, the PP333 treatment decreased the contents of indole acetic acid (IAA) and gibberellic acid (GAs) and increased the contents of zeatin ribosides (ZRs) and abscisic acid (ABA), thus changing the balance of hormones during flower bud differentiation. The inflection point (low point) of the curve shapes of the ZRs/GAs and ZRs/IAA ratios appeared significantly earlier, which showed a pattern consistent with soluble sugar and protein content and antioxidant activity. Interestingly, the above changes also corresponded to earlier flowering times during the warming process. Taken together, these results indicate that spraying an appropriate concentration of PP333 in the early stage of ‘Changshouguan’ flower bud differentiation promotes the early differentiation of flower buds and early flowering under winter warming treatment by altering their endogenous hormone content and homeostasis and changing their physiological state. The key to maintaining a relatively long flowering period in plants in the PP333 treatment group after flowering promotion was the increased accumulation of sugars and proteins.

Abstract Glucose is an indispensable nutrient for metabolism in living organisms and is widely used in food, industry, and medical fields. Glucose is often added as a sweetener in food and often used in industry as a reducing agent for various products. In medical treatment, glucose is added to many drugs as a nutritional additive, and it is also an indicator that diabetics need to pay attention to at all time. Therefore, the market has a great demand for low-cost, high-sensitivity, fast, and convenient glucose sensors, and the industry has always attached great importance to the work of creating new glucose sensor devices. Therefore, we proposed a SnO2 nanofibers/Au structure multimode-single-mode-multimode (MSM) fiber surface plasmon resonance (SPR) glucose sensor. SnO2 nanofibers were fixed to a single-mode fiber core that had been plated with the Au film by electrospinning. When the glucose concentration increased at 5 vol% intervals, the corresponding resonance wavelengths had different degrees of redshifts. Comparing the two structures, as the glucose concentration range increased from 0 vol% to 60 vol%, the sensitivity increased from 228.7 nm/vol% in the Au structure to 337.3 nm/vol% in the SnO2 nanofiber/Au structure. At the same time, the linear correlation between the resonant wavelength and the refractive index of the two structures was greater than 0.98. Moreover, the SnO2 nanofibers/Au structure significantly improved the practical application performance of SPR sensors.

Abstract The clinical diagnosis of biliary atresia (BA) poses challenges, particularly in distinguishing it from cholestasis (CS). Moreover, the prognosis for BA is unfavorable and there is a dearth of effective non-invasive diagnostic models for detection. Therefore, the aim of this study is to elucidate the metabolic disparities among children with BA, CS, and normal controls (NC) without any hepatic abnormalities through comprehensive metabolomics analysis. Additionally, our objective is to develop an advanced diagnostic model that enables identification of BA. The plasma samples from 90 children with BA, 48 children with CS, and 47 NC without any liver abnormalities children were subjected to metabolomics analysis, revealing significant differences in metabolite profiles among the 3 groups, particularly between BA and CS. A total of 238 differential metabolites were identified in the positive mode, while 89 differential metabolites were detected in the negative mode. Enrichment analysis revealed 10 distinct metabolic pathways that differed, such as lysine degradation, bile acid biosynthesis. A total of 18 biomarkers were identified through biomarker analysis, and in combination with the exploration of 3 additional biomarkers (LysoPC(18:2(9Z,12Z)), PC (22:5(7Z,10Z,13Z,16Z,19Z)/14:0), and Biliverdin-IX-α), a diagnostic model for BA was constructed using logistic regression analysis. The resulting ROC area under the curve was determined to be 0.968. This study presents an innovative and pioneering approach that utilizes metabolomics analysis to develop a diagnostic model for BA, thereby reducing the need for unnecessary invasive examinations and contributing to advancements in diagnosis and prognosis for patients with BA.

The formation mechanism of a recrystallisation internal friction (IF) peak superimposed on a grain boundary (GB) IF peak for deformed copper was studied. The P1 peak, associated with the recrystallisation process, was observed at ∼ 599 K (2 K/min) during the first heating process. Subsequently, the P2 peak, located at ∼ 510 K (0.2 Hz), corresponded to GB relaxation during the cooling process. The P1 peak showed minor relaxation at higher frequencies owing to the influence of GB relaxation. To accurately determine the temperature of the P1 peak in this scenario, two methods were used: fitting the measured IF spectra and performing IF measurements at lower frequencies and/or with faster heating rates to minimise the impact of GB relaxation. This work investigated the formation mechanism of the recrystallisation peak and supplemented the method for determining the recrystallisation temperature through IF measurements when the GB peak occurs at a nearby temperature.

Osteoarthritis (OA) remains a challenging degenerative joint disease, largely associated with chondrocyte apoptosis during its development. Preserving chondrocytes stands as a promising strategy for OA treatment. Rapamycin (RP) exhibits chondrocyte protection by fostering autophagy. Nevertheless, the swift clearance of intra-articular injections and the dense cartilage extracellular matrix (ECM) hinder RP from effectively reaching chondrocytes. Herein, we developed a ''two-stage'' drug delivery system (RP@PEG-PA@P-Lipo). This system comprises primary nanoparticles (P-Lipo), liposomes modified with a collagen II targeting peptide (WYRGRLC), and secondary nanoparticles (RP@PEG-PA), PEG-modified PAMAM encapsulating rapamycin (RP). RP@PEG-PA@P-Lipo demonstrates adherence to the cartilage surface with WYRGRLC, substantially prolonging retention within the joint cavity. Subsequently, released RP@PEG-PA can effectively penetrate the cartilage and deliver RP to chondrocytes through small size and charge-driven forces. In vitro and in vivo experiments corroborate its notable therapeutic effects on OA. This study holds promise in offering a novel approach for clinical drug delivery and OA treatment.

Background/Objective Approximately 30% of patients with MDS eventually develop to acute myeloid leukemia (AML). Our study aimed to investigate the mutation landscape of Chinese MDS patients and identify the mutated genes which are closely implicated in the transformation of MDS to AML.Methods In total, 412 sequencing data collected from 313 patients were used for analysis. Mutation frequencies between different groups were compared by Fisher's exact. A predictive model for risk of transformation/death of newly diagnosed patients was constructed by logistic regression.Results The most frequently mutated genes in newly diagnosed patients were TP53, TET2, RUNX1, PIGA, and BCOR and mutations of RUNX1, TP53, BCORL1, TET2, and BCOR genes were more common in the treated MDS patients. Besides, we found that the mutation frequencies of IDH2, TET2, and EZH2 were significantly higher in MDS patients aged over 60 years. Moreover, two mutation sites, KRASG12A and TP53H140N were detected only at transformation in one patient, while not detected at diagnosis. In addition, the mutation frequencies of EZH2 V704F and TET2 I1873N were stable from diagnosis to transformation in two patients. Finally, we constructed a predictive model for risk of transformation/death of newly diagnosed patients combing detected data of 10 genes and the number of to leukocyte, with a sensitivity of 63.3% and a specificity of 84.6% in distinguishing individuals with and without risk of transformation/death.Conclusion In summary, our study found several mutations associated with the transformation from MDS to AML, and constructed a predictive model for risk of transformation/death of MDS patients.

Objectives Previous research has extensively explored the factors associated with psychotic-like experiences (PLEs). However, the characteristics and associated factors of remitted PLEs, which refer to the absence of current PLEs following previous PLEs, remain unclear. Therefore, this study aims to describe the characteristics of adolescents who reported remitted PLEs.Design Cross-sectional study.Setting The survey was conducted from October to December 2020 in three colleges located in Guangzhou, China.Participants A total of 4208 college freshmen aged from 15 to 24 participated in our survey.Primary and secondary outcome measures The 15-item positive subscale of the Community Assessment of the Psychic Experience was used to assess both lifetime and current PLEs. Multivariate logistic regression models were used to examine the associations between remitted PLEs and a range of demographic factors, lifestyle, psychosocial factors, lifetime affective symptoms and sleep problems.Results Three groups of PLEs were observed: non-PLEs (47.27% of the sample), remitted PLEs (40.42%) and current PLEs (12.31%). Several factors have been identified as shared correlates of remission and absence of PLEs, including fewer recent adverse life events, greater resilience, fewer symptoms of depression and anxiety, and early waking. Furthermore, higher levels of social support (OR 1.48, 95% CI 1.01 to 2.17; OR 1.53, 95% CI 1.18 to 1.97) was a specific factor associated with the remission of PLEs. Compared with individuals without PLEs, those with remitted PLEs were more likely to be female (OR 1.50, 95% CI 1.28 to 1.75), less likely to be younger (OR 0.88, 95% CI 0.81 to 0.95) and prone to have more chronic physical illness (OR 1.67, 95% CI 1.29 to 2.16), habitual alcohol intake (OR 1.85, 95% CI 1.19 to 2.88), more childhood trauma (OR for low vs high=0.72, 95% CI 0.57 to 0.91) and the sleep problems of waking up easily (OR 1.36, 95% CI 1.12 to 1.65).Conclusion These findings suggest that remitted PLEs play a vital, unique role among three groups and provide preliminary targets for the intervention for adolescents at risk of mental health problems. Further investigation may shed light on the causality of the relationship between remitted PLEs and associated factors.

The excessive usage of nanoplastics (NPs) has posed a serious threat to the ecological environment and human health, which can enter the brain and then result in neurotoxicity. However, research on the neurotoxic effects of NPs based on different exposure routes and modifications of functional groups is lacking. In this study, the neurotoxicity induced by NPs was studied using polystyrene nanoplastics (PS-NPs) of different modifications (PS, PS-COOH, and PS-NH2). It was found that PS-NH2 through intranasal administration (INA) exposure route exhibited the greatest accumulation in the mice brain after exposure for 7 days. After the mice were exposed to PS-NH2 by INA means for 28 days, the exploratory ability and spatial learning ability were obviously damaged in a dose-dependent manner. Further analysis indicated that these damages induced by PS-NH2 were closely related to the decreased ability of glymphatic system to clear β-amyloid (Aβ) and phosphorylated Tau (P-Tau) proteins, which was ascribed to the loss of aquaporin-4 (AQP4) polarization in the astrocytic endfeet. Moreover, the loss of AQP4 polarization might be regulated by the NF-κB pathway. Our current study establishes the connection between the neurotoxicity induced by PS-NPs and the glymphatic system dysfunction for the first time, which will contribute to future research on the neurotoxicity of NPs.

ABSTRACT: Marek's disease (MD), an immunosuppression disease induced by Marek's disease virus (MDV), is one of the significant diseases affecting the health and productive performance of poultry. The roles of circular RNAs (circRNAs) in MD development were poorly understood. In this study, we found a circRNA derived from exon 6 of RUNX family transcription factor 2 (RUNX2) gene, named circRUNX2.2, was highly expressed in chicken tumorous spleens (TS) induced by MDV. Through fluorescence in situ hybridization and nuclear-cytoplasmic separation assay, we determined circRUNX2.2 was mainly located in the nucleus. Knockout experiments confirmed that the flanking complementary sequences (RCMs) mediated its circularization. Gain of function assay and dual luciferase reporter gene assay revealed that circRUNX2.2 could promote the expression of RUNX2 via binding with its promoter region. RNA antisense purification assay and mass spectrometry assay showed circRUNX2.2 could recruit proteins such as CHD9 protein. Knocking down CHD9 expression decreased the expression of RUNX2 gene, which confirmed the positive regulation that circRUNX2.2 on RUNX2 expression was probably facilitated via recruiting CHD9 protein. Functional experiments showed that circRUNX2.2 promoted the proliferation of the MD lymphoma-derived chicken cell line, MDCC-MSB1, which confirmed the potential oncogenic role of circRNX2.2 in tumor development. In conclusion, we found that the RUNX2-derived circRUNX2.2 can positively regulate the transcription of the parental gene RUNX2 in a cis-acting manner. The high expression of circRUNX2.2 in MD tumor tissues indicated that it might mediate MD lymphoma progression.

Abstract Purpose Vibrio parahaemolyticus is a leading seafood borne pathogen worldwide. The aim of this study was to decipher the response mechanism of V. parahaemolyticus isolates of clinical and aquatic animal origins to the hypoxic condition, which challenges the bacterial survival in the host and in the environment. Methods Growth profiles of V. parahaemolyticus isolates (n = 5) of clinical and aquatic animal origins were examined at different stress conditions (osmolality, acid, temperature, and O2 concentrations). Draft genomes of the V. parahaemolyticus isolates were determined using the Illumina sequencing technique. Comparative genomic analysis were performed to identify and validate the hypoxic tolerance-related genes. Results The V. parahaemolyticus isolates had an oxygen concentration-dependent growth mode, and the 10% O2 condition strongly inhibited the bacterial growth, when incubated in TSB medium (pH 8.5, 3% NaCl) at 37 °C. Unexpectedly, in marked contrast to the normal 21% O2 condition, the 10% O2 treatment for 24 h significantly increased biofilm formation of V. parahaemolyticus isolates (p

Abstract Medulloblastoma is a malignant neuroepithelial tumor of the central nervous system. Accurate prediction of prognosis is essential for therapeutic decisions in medulloblastoma patients. We analyzed data from 2,322 medulloblastoma patients using the SEER database and randomly divided the dataset into training and testing datasets in a 7:3 ratio. We chose three models to build, one based on neural networks (DeepSurv), one based on ensemble learning that Random Survival Forest (RSF), and a typical Cox Proportional-hazards (CoxPH) model. The DeepSurv model outperformed the RSF and classic CoxPH models with C-indexes of 0.751 and 0.763 for the training and test datasets. Additionally, the DeepSurv model showed better accuracy in predicting 1-, 3-, and 5-year survival rates (AUC: 0.767–0.793). Therefore, our prediction model based on deep learning algorithms can more accurately predict the survival rate and survival period of medulloblastoma compared to other models.

Abstract Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive ages. Our previous study has implicated a possible link between RNA editing and PCOS, yet the actual role of RNA editing, its association with clinical features, and the underlying mechanisms remain unclear. Methods Ten RNA-Seq datasets containing 269 samples of multiple tissue types, including granulosa cells, T helper cells, placenta, oocyte, endometrial stromal cells, endometrium, and adipose tissues, were retrieved from public databases. Peripheral blood samples were collected from twelve PCOS and ten controls and subjected to RNA-Seq. Transcriptome-wide RNA-Seq data analysis was conducted to identify differential RNA editing (DRE) between PCOS and controls. The functional significance of DRE was evaluated by luciferase reporter assays and overexpression in human HEK293T cells. Dehydroepiandrosterone and lipopolysaccharide were used to stimulate human KGN granulosa cells to evaluate gene expression. Results RNA editing dysregulations across multiple tissues were found to be associated with PCOS in public datasets. Peripheral blood transcriptome analysis revealed 798 DRE events associated with PCOS. Through weighted gene co-expression network analysis, our results revealed a set of hub DRE events in PCOS blood. A DRE event in the eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2:chr2:37,100,559) was associated with PCOS clinical features such as luteinizing hormone (LH) and the ratio of LH over follicle-stimulating hormone. Luciferase assays, overexpression, and knockout of RNA editing enzyme adenosine deaminase RNA specific (ADAR) showed that the ADAR-mediated editing cis-regulated EIF2AK2 expression. EIAF2AK2 showed a higher expression after dehydroepiandrosterone and lipopolysaccharide stimulation, triggering changes in the downstrean MAPK pathway. Conclusions Our study presented the first evidence of cross-tissue RNA editing dysregulation in PCOS and its clinical associations. The dysregulation of RNA editing mediated by ADAR and the disrupted target EIF2AK2 may contribute to PCOS development via the MPAK pathway, underlining such epigenetic mechanisms in the disease.

Abstract Introduction Dental implantation has emerged as an efficient substitute for missing teeth, which is essential for restoring oral function and aesthetics. Compared to traditional denture repair approaches, dental implants offer better stability and sustainability. The position, angle, and depth of dental implants are crucial factors for their long-term success and necessitate high-precision operation and technical support. Method We propose an integrated dual-arm high-precision oral implant surgery navigation positioning system and a corresponding control strategy. Compared with traditional implant robots, the integrated dual-arm design greatly shortens the preparation time before surgery and simplifies the operation process. We propose a novel control flow and module for the proposed structure, including an Occluded Target Tracking Module (OTTM) for occlusion tracking, a Planting Plan Development Module (PPDM) for generating implant plans, and a Path Formulation Module (PFM) for controlling the movement path of the two robot arms. Result Under the coordinated control of the aforementioned modules, the robot achieved excellent accuracy in clinical trials. The average angular error and entry point error for five patients who underwent implant surgery using the proposed robot were 2.1° and 0.39 mm, respectively. Conclusion In essence, our study introduces an integrated dual-arm high-precision navigation system for oral implant surgery, resolving issues like lengthy preoperative preparation and static surgical planning. Clinical results confirm its efficacy, emphasizing its accuracy and precision in guiding oral implant procedures.

Abstract Background The flower colour of H. syriacus ‘Qiansiban’ transitions from fuchsia to pink–purple and finally to pale purple, thereby enhancing the ornamental value of the cultivars. However, the molecular mechanism underlying this change in flower colour in H. syriacus has not been elucidated. In this study, the transcriptomic data of H. syriacus ‘Qiansiban’ at five developmental stages were analysed to investigate the impact of flavonoid components on flower colour variation. Additionally, five cDNA libraries were constructed from H. syriacus ‘Qiansiban’ during critical blooming stages, and the transcriptomes were sequenced to investigate the molecular mechanisms underlying changes in flower colouration. Results High-performance liquid chromatography‒mass spectrometry detected five anthocyanins in H. syriacus ‘Qiansiban’, with malvaccin-3-O-glucoside being the predominant compound in the flowers of H. syriacus at different stages, followed by petunigenin-3-O-glucoside. The levels of these five anthocyanins exhibited gradual declines throughout the flowering process. In terms of the composition and profile of flavonoids and flavonols, a total of seven flavonoids were identified: quercetin-3-glucoside, luteolin-7-O-glucoside, Santianol-7-O-glucoside, kaempferol-O-hexosyl-C-hexarbonoside, apigenin-C-diglucoside, luteolin-3,7-diglucoside, and apigenin-7-O-rutinoside. A total of 2,702 DEGs were identified based on the selected reference genome. Based on the enrichment analysis of differentially expressed genes, we identified 9 structural genes (PAL, CHS, FLS, DRF, ANS, CHI, F3H, F3’5’H, and UFGT) and 7 transcription factors (3 MYB, 4 bHLH) associated with flavonoid biosynthesis. The qRT‒PCR results were in good agreement with the high-throughput sequencing data. Conclusion This study will establish a fundamental basis for elucidating the mechanisms underlying alterations in the flower pigmentation of H. syriacus.

The ensemble Kalman filter (EnKF) is one of the most widely used data assimilation methods. However, it exhibits limitations in handling non-Gaussian problems. To effectively address such issues and accurately describe the connectivity of aquifers, a novel approach named NS-ES-MDA is developed in this study. The proposed NS-ES-MDA synergistically combines the normal-score transformation (NST) with ensemble smoother with multiple data assimilation (ES-MDA). Through comparative experiments, the efficacy of NS-ES-MDA in estimating the hydraulic conductivity of non-Gaussian distributed aquifers is demonstrated. By assimilating the same dataset, NS-ES-MDA exhibits approximately 34% improvement in parameter estimation accuracy and about 35% enhancement in computational efficiency compared to the restart normal-score ensemble Kalman filter (rNS-EnKF). Furthermore, the NS-ES-MDA shows case robustness against the “equifinality” and displays remarkable updating capabilities, which leads to more precise parameter estimates. This study provides an effective solution for parameter estimation in non-Gaussian distributed aquifers.

Abstract Aims This two-wave, longitudinal study aimed to examine the potential moderating and mediating effects of resilience on the association between perceived school bullying and psychotic-like experiences among Chinese sexual minority adolescents. Methods A total of 4192 senior high students were included and 984 (23.5%) of them were identified as a sexual minority (mean age = 16.68 years, SD = 0.71). Participants completed two online surveys during April 21 to May 12, 2021 and December 17 to 26, 2021, respectively, as well as completed self-report measures of sample characteristics, perceived school bullying, resilience, and psychotic-like experiences (including two dimensions: delusional experiences and hallucinatory experiences). Results Perceived school bullying and resilience were associated with psychotic-like experiences in sexual minority adolescents. Resilience mediated the relationship between perceived school bullying and subsequent psychotic-like experiences (b = 0.03, 95% CI = 0.01 ~ 0.04)/ delusional experiences (b = 0.03, 95% CI = 0.01 ~ 0.04)/ hallucinatory experiences (b = 0.02, 95% CI = 0.01 ~ 0.03). Additionally, resilience only moderated the associations of perceived school bullying with hallucinatory experiences (b = −0.06, 95% CI = −0.12 ~ −0.01). Conclusions These findings indicated that resilience plays a crucial role in mediating or moderating the relationship between perceived school bullying and psychotic-like experiences. Assessing and reducing school bullying, as well as promoting resilience, may have important clinical implications for reducing the risk of psychotic-like experiences in sexual minority adolescents.

Abstract Objectives To develop and validate radiomics model based on computed tomography (CT) for preoperative prediction of CN0 status in patients with papillary thyroid carcinoma (PTC). Methods A total of 548 pathologically confirmed LNs (243 non-metastatic and 305 metastatic) two distinct hospitals were retrospectively assessed. A total of 396 radiomics features were extracted from arterial-phase CT images, where the strongest features containing the most predictive potential were further selected using the least absolute shrinkage and selection operator (LASSO) regression method. Delong test was used to compare the AUC values of training set, test sets and cN0 group. Results The Rad-score showed good discriminating performance with Area Under the ROC Curve (AUC) of 0.917(95% CI, 0.884 to 0.950), 0.892 (95% CI, 0.833 to 0.950) and 0.921 (95% CI, 868 to 0.973) in the training, internal validation cohort and external validation cohort, respectively. The test group of CN0 with a AUC of 0.892 (95% CI, 0.805 to 0.979). The accuracy was 85.4% (sensitivity = 81.3%; specificity = 88.9%) in the training cohort, 82.9% (sensitivity = 79.0%; specificity = 88.7%) in the internal validation cohort, 85.4% (sensitivity = 89.7%; specificity = 83.8%) in the external validation cohort, 86.7% (sensitivity = 83.8%; specificity = 91.3%) in the CN0 test group.The calibration curve demonstrated a significant Rad-score (P-value in H-L test > 0.05). The decision curve analysis indicated that the rad-score was clinically useful. Conclusions Radiomics has shown great diagnostic potential to preoperatively predict the status of cN0 in PTC.

In recent years, thermosensitive polysaccharide-based injectable hydrogels have gained increasing attention in biomedical applications, including wound healing, drug delivery, and cartilage repair. These hydrogels have favorable biocompatibility, biodegradability, and tunable physical and chemical properties. Thermosensitive polysaccharide-based injectable hydrogels are a class of intelligent soft matter material. They can undergo a reversible liquid-solid transition when exposed to temperature stimuli. Therefore, their precursor solutions can be accurately inserted into target sites with irregular geometries in a minimally invasive way and then transformed into gels in situ by the organism's temperature stimulation to deliver biologically active molecules. This review summarizes the recent developments of thermosensitive injectable polysaccharide-based hydrogels. The focus is on the mechanism of sol-gel phase transition, as well as the design and preparation of thermosensitive polysaccharides and their applications in biomedical fields. In addition, the outlook of the challenges in biomedical applications is provided at the end of the paper.

Abstract Sepsis is recognized as a major contributor to the global disease burden, but there is a lack of specific and effective therapeutic agents. Utilizing Mendelian randomization (MR) methods alongside evidence of causal genetics presents a chance to discover novel targets for therapeutic intervention. MR approach was employed to investigate potential drug targets for sepsis. Pooled statistics from IEU-B-4980 comprising 11,643 cases and 474,841 controls were initially utilized, and the findings were subsequently replicated in the IEU-B-69 (10,154 cases and 454,764 controls). Causal associations were then validated through colocalization. Furthermore, a range of sensitivity analyses, including MR-Egger intercept tests and Cochran's Q tests, were conducted to evaluate the outcomes of the MR analyses. Three drug targets (PSMA4, IFNAR2, and LY9) exhibited noteworthy MR outcomes in two separate datasets. Notably, PSMA4 demonstrated not only an elevated susceptibility to sepsis (OR 1.32, 95% CI 1.20–1.45, p = 1.66E−08) but also exhibited a robust colocalization with sepsis (PPH4 = 0.74). According to the present MR analysis, PSMA4 emerges as a highly encouraging pharmaceutical target for addressing sepsis. Suppression of PSMA4 could potentially decrease the likelihood of sepsis.

Abstract Thyroid nodules are a common occurrence, and although most are non-cancerous, some can be malignant. The American College of Radiology has developed the Thyroid Imaging Reporting and Data System (TI-RADS) to standardize the interpretation and reporting of thyroid ultrasound results. Within TI-RADS, a category 4 designation signifies a thyroid nodule with an intermediate level of suspicion for malignancy. Accurate classification of these nodules is crucial for proper management, as it can potentially reduce unnecessary surgeries and improve patient outcomes. This study utilized deep learning techniques to effectively classify TI-RADS category 4 thyroid nodules as either benign or malignant. A total of 500 patients were included in the study and randomly divided into a training group (350 patients) and a test group (150 patients). The YOLOv3 model was constructed and evaluated using various metrics, achieving an 84% accuracy in the classification of TI-RADS category 4 thyroid nodules. Based on the predictions of the model, along with clinical and ultrasound data, a nomogram was developed. The performance of the nomogram was superior in both the training and testing groups. Furthermore, the calibration curve demonstrated good agreement between predicted probabilities and actual outcomes. Decision curve analysis further confirmed that the nomogram provided greater net benefits. Ultimately, the YOLOv3 model and nomogram successfully improved the accuracy of distinguishing between benign and malignant TI-RADS category 4 thyroid nodules, which is crucial for proper management and improved patient outcomes.

Cultivated land’s ecological security ensures human well-being and is critical to global food security. However, the unchecked expansion and excessive exploitation of agricultural resources have led to considerable land degradation issues in China, including soil erosion, contamination, and environmental degradation, raising concerns over the cultivated land ecological security (CLES). Current research on cultivated land (CLES is relatively limited, particularly at the national level across different provinces. In addition, a unified and comprehensive CLES evaluation index system has yet to be formed. To fill this research gap, we construct a CLES evaluation system with 35 indicators from three dimensions of “society-natural-economy” based on the DPSIR model framework and entropy weight TOPSIS model. Simultaneously, we conducted a spatial–temporal analysis of CLES in 31 provinces of China from 2012 to 2021 and applied the obstacle degree model to analyze the main factors impeding the CLES in China. The results showed that: (1) During the study period, the CLES and its subsystems showed a good development trend. Spatially, the CLES in China presents a regional difference of “high in the east and low in the west” and a significant regional difference among provinces. (2) The spatial CLES in different provinces of China presents a significant positive correlation, and the spatial clustering effect of CLES is gradually strengthening. The “High-High” clusters are mainly distributed in the northeast and eastern regions, while the “Low-Low” clusters are mainly located in the western region. (3) From the perspective of the criterion level, the state subsystem and the impact subsystem are the main obstacles hindering the improvement of CLES in China. At the indicator level, the common obstacle factors affecting the enhancement of CLES across provinces in China include soil erosion control intensity, number of green food certifications, per capita agricultural loans, per capita cultivated land area, and per capita grain production. Our research results can provide practical policy reference for further improving the ecological protection of cultivated land.

This study intended to determine the molecular subtypes of liver hepatocellular carcinoma (LIHC) on the strength of anoikis-related genes (ARGs) and to assess their prognostic value and prospective relationship with immune cell infiltration and cancer-associated fibroblasts (CAFs). Univariate Cox regression analysis yielded 66 prognosis-related ARGs and classified LIHC into two distinct subtypes, with subtype A demonstrating overexpression of most prognosis-related ARGs and a significant survival disadvantage. Furthermore, a reliable prediction model was developed using ARGs to evaluate the risk of LIHC patients. This model served as an independent prognostic indicator and a quantitative tool for clinical prognostic prediction. Additionally, subtype-specific differences in immune cell infiltration were observed, and the risk score was potentially linked to immune-related characteristics. Moreover, the study identified a significant association between CAF score and LIHC prognosis, with a low CAF score indicating a favorable patient prognosis. In conclusion, this study reveals the molecular mechanisms underlying the development and progression of LIHC and identifies potential therapeutic targets for the disease.

Abstract Objective To analyze the risk factors affecting psychiatric behavior and study the psychobehavioral conditions of children with epilepsy. Method We randomly selected and enrolled 294 children with epilepsy who visited and were hospitalized in the pediatric clinic of Hebei General Hospital between January 2017 and January 2022, as the study participants. We comprehensively assessed their cognitive functions using the Gesell development schedule or Wechsler Intelligence Scales. The participants were divided into the study group (n = 123) with cognitive impairment and the control group (n = 171) with normal cognitive functions, for analysis. Results There were statistically significant differences between the two groups in disease course, frequency of epilepsy, status epilepticus, and the number of antiseizure medications (ASMs) used (P 0.05). Based on multivariate logistic regression analysis, the course of disease, frequency of onset, status epilepticus and number of ASMs used were identified as high-risk factors for cognitive impairment in children with epilepsy. Similarly, early onset, long course of disease, known etiology, and combination of multiple drugs have a negative impact on behavioral problems, school education, and social adaptability. Conclusion The course of disease, the frequency of onset, status epilepticus, and the number of ASMs used are high-risk factors for cognitive impairment in children with epilepsy, which can be prevented and controlled early. When selecting ASMs, their advantages and disadvantages should be weighed. Moreover, the availability of alternative treatment options must be considered. With the help of genomic technology, the causes of epilepsy should be identified as early as possible, and precision medicine and gene therapy for children with epilepsy should be actively developed.

In order to clarify the microflora structure in Cheddar cheese processing, MiSeq high-throughput sequencing technology was used to analyze the community structure of Cheddar cheese at three stages of processing (post-pasteurization, curdling, and ripening 0, 30, 60 and 90 d) in this study. The results showed that the community structure varies widely of cheddar cheese during processing. The highest microbial community diversity and abundance were found after pasteurization (Chao1 index and Shannon index mean values were 6.09 and 1415.78, respectively). The dominant microflora in the pasteurization stage at the genus level was Stenotrophomonas (21.04%). The community structure was relatively similar in the curd and ripening stages, Lactococcus were the dominant flora in both stages, with abundance averaging more than 85%. During the ripening period, the relative abundance of Lactococcus increased first and then decreased. The community structure in the pasteurized cheeses was different compared to the other groups, and there was less change in the community structure of the groups during the ripening period. This study provides a basis for clarifying the community structure of Cheddar cheese, and has a certain reference value for the expansion of Cheddar cheese microbiome information.

Utilizing observations by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument, we quantitatively assessed the dawn–dusk asymmetry in temperature disturbances within the high-latitude mesosphere and lower thermosphere (MLT) during the main phase of geomagnetic storms in this study. An analysis of five geomagnetic superstorm events indicated that during the main phase, negative temperature disturbances were more prevalent on the dawn side than on the dusk side in the high-latitude MLT region. Results of a statistical analysis of 54 geomagnetic storm events also revealed a notable disparity in temperature disturbances between the dawn and dusk sides. At high latitudes, 38.2% of the observational points on the dawn side exhibited negative temperature disturbances (less than −5 K), whereas on the dusk side, this percentage was only 29.5%. In contrast, at mid-latitudes, these proportions were 34.1% and 36.5%, respectively, showing no significant difference. We also conducted a statistical analysis of temperature disturbances at different altitudes, which revealed an increase in the proportion of warming disturbances with altitude. Conversely, the proportion of cooling disturbances initially rose with altitude, reaching a peak around 105 km, and subsequently decreased. These temperature disturbance differences could be explained by the day–night asymmetry in vertical wind disturbances during storm conditions.

The effect of irradiation sterilization on the quality of low-salt sliced bacon was investigated by subjecting the samples to high-energy electron gas pedal treatment at 2, 3 and 4 kGy at room temperature. The samples were stored at 4 ℃ and the unsterilized group was used as the control group. The total number of colonies of the samples, flavor substances and the physicochemical indexes were determined when the storage time was 0, 60, 120 and 180 days, respectively. The results showed that the nitrite content of low-salt sliced bacon decreased significantly (P0.05), and the POV values were significantly lower than those of the control group (P

Abstract Background noises are usually treated as redundant or even harmful to voice conversion. Therefore, when converting noisy speech, a pretrained module of speech separation is usually deployed to estimate clean speech prior to the conversion. However, this can lead to speech distortion due to the mismatch between the separation module and the conversion one. In this paper, a noise-robust voice conversion model is proposed, where a user can choose to retain or to remove the background sounds freely. Firstly, a speech separation module with a dual-decoder structure is proposed, where two decoders decode the denoised speech and the background sounds, respectively. A bridge module is used to capture the interactions between the denoised speech and the background sounds in parallel layers through information exchanging. Subsequently, a voice conversion module with multiple encoders to convert the estimated clean speech from the speech separation model. Finally, the speech separation and voice conversion module are jointly trained using a loss function combining cycle loss and mutual information loss, aiming to improve the decoupling efficacy among speech contents, pitch, and speaker identity. Experimental results show that the proposed model obtains significant improvements in both subjective and objective evaluation metrics compared with the existing baselines. The speech naturalness and speaker similarity of the converted speech are 3.47 and 3.43, respectively.

Using an inedible portion of mature mung bean biomass, methane fermentation experiments were carried out where the digestates were mechanically thickened to extend the solids retention time. The chemical analysis revealed that the conventional COD analytical method with dichromate could not perfectly oxidise the lignocellulosic compound. The measured COD was underestimated by about 10% from the elemental formulae of the biomass. In the kinetic analysis based on the IWA-ADM1 model, the enzymatic decomposition of the lignocellulosic compound limited the overall process performance, and was expressed in a first-order rate expression with 0.051 d∁E and 0.071 d∁E for the leaf fraction and the stem fraction respectively. During the continuous experiment, an unusual accumulation of soluble carbohydrates was recognised. This phenomenon was also modelled as a fragmentation of the lignocellulosic compound where very small unbiodegradable organic particles were released into the liquid. According to the steady-state calculation using the model, about 70% of the plant biomass COD could be converted to methane when the reactor was operated at the solids retention time of 100 E00 days with a volumetric loading rate of 10 E2 Eg-COD/m3/d. The model also showed the reactor volume could be reduced by 6 E times compared to conventional chemostat reactors.

This study is aimed at investigating the poisoning effect of sulphide on methanogenic cultures. Using cultures enriched with either acetate or formate as a sole electron donor, sets of 1-week batch inhibition tests were performed to analyse the dynamic change of the living microorganism concentrations under the varied sulphide concentrations between zero and 400 mg-S L∁E. In both cultures, the cellular decay was doubled when the cultures were placed in 100 mg-S L E of total sulphide. When the cultures were exposed to higher sulphide, higher specific decay rates were obtained. Because of the low correlations of the unionised sulphide concentrations to the specific decay rates, the total sulphide concentration was thought to be the dominant inhibition factor rather than its unionised form. To express the acceleration of cellular decay, a mathematical model was developed. Since the decay phenomena of both cultures were quite similar to each other, a culture-wide empirical formula was obtained to calculate the specific decay rate. In the model equation, the specific decay rate of the methanogenic cultures was linearly expressed with a coefficient of 0.30∁E0∁E ± 0.05∁E0∁E mg-S∁E L d∁E for sulphide concentration and a coefficient of 0.044 ± 0.013 d E for the inherent specific decay rate.

Abstract Background The coronavirus disease (COVID-19) pandemic has seriously impacted the mental and sexual health of the general population. Patients dealing with infertility constitute a unique subset within society, susceptible to heightened sensitivity amid pressures and crises. However, to the best of our knowledge, the impact of the different stages of the COVID-19 pandemic on the mental and sexual health of patients with infertility has not been investigated. Therefore, this study aimed to investigate the mental and sexual health of patients with infertility during different stages of the COVID-19 pandemic (during the lockdown, when controls were fully liberalized, and during the post-pandemic era). Methods This prospective before-and-after study was conducted between April and May 2022 (during the lockdown), December and January 2023 (when controls were fully liberalized), and May and August 2023 (during the post-pandemic era). This study explored the sexual and mental health of women with infertility during the three stages of the COVID-19 pandemic using standardized mental health and sexual function questionnaires. The Chi-square test was used to compare categorical data, and the ANOVA test was used to compare numerical data. Results Patients had the highest 7-item Generalized Anxiety Disorder Scale (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9) scores and the highest rates of anxiety and depression during the immediate full-release phase. During the complete liberalization phase, patients had the lowest Female Sexual Function Index (FSFI) scores and the highest incidence of sexual dysfunction. Conclusion This study is the first one to report the repercussions of COVID-19 on the mental and sexual well-being of individuals experiencing infertility across various phases of the pandemic. Upon the complete lifting of control measures, close to 99% of participants exhibited varying degrees of anxiety and depression. Our research underscores that individuals with infertility faced elevated levels of anxiety, depression, and sexual dysfunction during the phase of full liberalization of COVID-19 control measures, in stark contrast to the periods of lockdown and the post-pandemic era.

The effect of ultra-high pressure (UHP) sterilization technology on the quality of low-salt sliced bacon was investigated by treating samples under 200, 400 and 600 MPa for 10 min at 22 ℃. The samples were stored at 4 ℃ and the unsterilized group was used as the control group. The physicochemical indexes, flavor substances and the total number of colonies of the samples were determined when the storage time was 0, 60, 120 and 180 days, respectively. The results indicated that the moisture content, nitrite content, hardness, a* value, b* value, and total bacterial counts of the low-salt sliced bacon decreased, while the pH value, POV value, L* value, elasticity, recovery, and cohesiveness increased after ultra-high pressure treatment. During the storage process, ultra-high pressure conditions enhanced the water-holding capacity of the bacon, slowed down lipid oxidation, and effectively inhibited the microbial growth. At 180 days, the moisture content, L* value, a* value, elasticity, and cohesiveness of the ultra-high pressure group were higher than those of the control group, while the pH value, nitrite content, hardness, and total bacterial counts were lower than those of the control group. The experimental results of gas chromatography-mass spectrometry (GC-MS) and electronic nose showed that the flavor components of ultra-high pressure group were similar to those of the control group, and then the difference of the content was small. Moreover, UHP treatment promoted and protected the flavor formation of bacon. However, excessive pressure (600 MPa) not only aggravated lipid oxidation, but also affected the color and texture of the bacon, thus affecting the sensory score of bacon. Overall, the optimal treatment pressure was determined to be 400 MPa in this study.

Most of the existing direction of arrival (DOA) estimation methods in impulsive noise scenario are based on the fractional low-order moment statistics (FLOSs), such as the robust covariation-based (ROC), fractional low-order moment (FLOM), and phased fractional low-order moment (PFLOM). However, an unknown order moment parameter $p$ needs to be selected in these approaches, which inevitably increases the computational load if the optimal value of the parameter $p$ is determined by a large number of Monte Carlo experiments. To address this issue, we propose the adaptive order moment function (AOMF) and improved AOMF (IAOMF), which are applicable to the existing FLOSs-based methods and can also be extended to the case of sparse arrays. Moreover, we analyze the performance of AOMF and IAOMF, and simulation experiments verify the effectiveness of proposed methods.

Abstract Recent advances in the genomics of glioblastoma (GBM) led to the introduction of molecular neuropathology but failed to translate into treatment improvement. This is largely attributed to the genetic and phenotypic heterogeneity of GBM, which are considered the major obstacle to GBM therapy. Here, we use advanced human GBM-like organoid (LEGO: Laboratory Engineered Glioblastoma-like Organoid) models and provide an unprecedented comprehensive characterization of LEGO models using single-cell transcriptome, DNA methylome, metabolome, lipidome, proteome, and phospho-proteome analysis. We discovered that genetic heterogeneity dictates functional heterogeneity across molecular layers and demonstrates that NF1 mutation drives mesenchymal signature. Most importantly, we found that glycerol lipid reprogramming is a hallmark of GBM, and several targets and drugs were discovered along this line. We also provide a genotype-based drug reference map using LEGO-based drug screen. This study provides new human GBM models and a research path toward effective GBM therapy.

Snake robots require autonomous localization and mapping capabilities for field applications. However, the characteristics of their motion, such as large turning angles and fast rotation speeds, can lead to issues like drift or even failure in positioning and map building. In response to this situation, this paper starts from the gait motion characteristics of the snake robot itself, proposing an improved gait motion method and a tightly coupled method based on IMU and visual information to solve the problem of poor algorithm convergence caused by head-shaking in snake robot SLAM. Firstly, the adaptability of several typical gaits of the snake robot to SLAM methods was evaluated. Secondly, the serpentine gait was selected as the object of gait improvement, and a head stability control method for the snake robot was proposed, thereby reducing the interference of the snake robot’s motion on the sensors. Thirdly, a visual–inertial tightly coupled SLAM method for the snake robot’s serpentine gait and Arc-Rolling gait was proposed, and the method was verified to enhance the robustness of the visual SLAM algorithm and improve the positioning and mapping accuracy of the snake robot. Finally, experiments proved that the methods proposed in this paper can effectively improve the accuracy of positioning and map building for snake robots.

Liver fibrosis, a common characteristic in various chronic liver diseases, is largely influenced by glycolysis. Quercetin (QE), a natural flavonoid known to regulate glycolysis, was studied for its effects on liver fibrosis and its underlying mechanism. Results showed that QE effectively improved liver injury and fibrosis caused by carbon tetrachloride (CCl4). This was supported by evidence of improved pathological features and reduced levels of serum markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), hyaluronic acid (HA), laminin (LN), and procollagen type III. QE also decreased lactate production and downregulated the expression of glycolysis-related enzymes – pyruvate kinase M2 (PKM2), phosphofructokinase platelet (PFKP), and hexokinase 2 (HK2) – at both the mRNA and protein levels. In liver sinusoidal endothelial cells (LSECs), QE reduced the expression and activity of these enzymes, resulting in reduced glucose consumption, ATP production, and lactate generation. Further analysis revealed that QE inhibited the production of chemokine (C-X-C motif) ligand 1 (CXCL1) and suppressed neutrophil recruitment. Overall, QE showed promising therapeutic potential for liver fibrosis by targeting LSEC glycolysis and reducing neutrophil infiltration.

Estrogen receptor-positive (ER+) breast cancer seriously endangers the women's physical and mental health worldwide and ER targeting therapy is vital. Here, we found that a citrus polymethoxyflavones (PMFs)-rich hydrolysate (C–H) and its major components (nobiletin and 3-methoxynobiletin) potently degrade ERα protein via the ubiquitin-proteasome pathway, thereby impairing the proliferation of ER+ breast cancer cells. Moreover, our study exhibited that C–H combined with tamoxifen (TAM) inhibited the cell proliferation of ER+ breast cancer in vitro. It was further confirmed that C–H decreased tumor growth of ER+ breast cancer in tumor-bearing 129 mice in vivo and improved the efficacy of tamoxifen. Our study revealed that the citrus PMFs have potential applications as pharmaceutical and healthcare products in breast cancer treatment by targeting ERα protein degradation.

Heat wave events have frequently occurred worldwide in recent years, and continuous high temperatures have severely impacted human life and ecosystems. Given this problem, the government and the public must cooperate closely to participate in global environmental governance. Among them, pro-environmental behavior is the most significant form for citizens to participate in environmental protection and fulfill social responsibilities. It plays an essential role in mitigating extremely high temperatures worldwide and achieving ''carbon neutrality'' and sustainable development of the world environment. Based on this, the study utilized the field survey data of 554 respondents from 14 villages in Xi'an and applied a structural equation model that integrates the theory of planned behavior and protection motivation theory to identify the main determinants of the pro-environmental behavior of rural dwellers. The research reported that: 1) The integrated model of the theory of planned behavior and protection motivation theory is suitable for studying people's pro-environmental behavior in the context of heat waves. 2) Heat risk perception, response efficacy, self-efficacy, and subjective norms significantly improved rural residents' pro-environmental behavior. In contrast, response cost had an opposite negative impact on rural residents' pro-environmental behavior. Among them, subjective norms had the most considerable effect. Based on these, we recommend that local governments promote public participation in environmental governance through the following methods: 1) Strengthen the publicity and education of heat wave knowledge and improve public awareness of heat wave risks. 2) Increase investment in environmental protection facilities and reward the public for environmental protection behavior to reduce the cost of the public's pro-environmental behavior. 3) Give full play to the leading role of government cadres and improve the public's awareness of environmental protection through the impact of the social environment.

ObjectiveExisting studies have reported sustained changes in the cortical structure of rats due to coffee-related factors, which are speculated to occur in the human body. However, there is a lack of research on this topic. Additionally, previous observational studies have found the impact of diseases on cortical structure and the potential therapeutic effects of coffee on these diseases. Our aim was to study the causal effects of coffee-related factors on the human brain using SNPs (single nucleotide polymorphisms). We will connect these discovered causal effects to the impact of diseases on the brain. Through triangulating evidence, we will reveal the potential active areas of coffee in preventing diseases.MethodsWe utilized GWAS data from multiple cohorts and their databases, selecting instrumental variables for genetic prediction of coffee intake and plasma levels of caffeine and its direct metabolites. We applied these instrumental variables to individual data on cortical thickness and surface area, as well as hippocampal volume, from the ENIGMA and CHARGE consortium for Mendelian randomization analysis (MR). Triangular evidence was obtained by integrating existing evidence through a specified retrieval strategy, calculating the overlap between coffee's effects on brain regions and disease-related brain regions to identify potential regions of action.ResultsThe MR analysis yielded 93 positive results for 9 exposures, among which theobromine, a metabolite in the caffeine pathway, was found to be associated with increased hippocampal volume. For cortical structure, theobromine in the caffeine pathway was associated with a decrease in total surface area, while theobromine and caffeine in the pathway were associated with an increase in total thickness. The overlap rate of triangular evidence showed no difference in both overall and subgroup analyses, indicating a high overlap between the effects of coffee on brain regions and disease.ConclusionsFrom predicted outcomes from causal effects, coffee intake-related factors may have lasting effects on cortical structure. Additionally, theobromine and theophylline have the greatest impact on certain brain gyri, rather than caffeine. Triangulation evidence indicates that disease and coffee intake-related factors act on the same cortical regions, suggesting the presence of potential shared or antagonistic pathways.

ObjectiveThe pathological classification and imaging manifestation of parotid gland tumors are complex, while accurate preoperative identification plays a crucial role in clinical management and prognosis assessment. This study aims to construct and compare the performance of clinical models, traditional radiomics models, deep learning (DL) models, and deep learning radiomics (DLR) models based on ultrasound (US) images in differentiating between benign parotid gland tumors (BPGTs) and malignant parotid gland tumors (MPGTs).MethodsRetrospective analysis was conducted on 526 patients with confirmed PGTs after surgery, who were randomly divided into a training set and a testing set in the ratio of 7:3. Traditional radiomics and three DL models (DenseNet121, VGG19, ResNet50) were employed to extract handcrafted radiomics (HCR) features and DL features followed by feature fusion. Seven machine learning classifiers including logistic regression (LR), support vector machine (SVM), RandomForest, ExtraTrees, XGBoost, LightGBM and multi-layer perceptron (MLP) were combined to construct predictive models. The most optimal model was integrated with clinical and US features to develop a nomogram. Receiver operating characteristic (ROC) curve was employed for assessing performance of various models while the clinical utility was assessed by decision curve analysis (DCA).ResultsThe DLR model based on ExtraTrees demonstrated superior performance with AUC values of 0.943 (95% CI: 0.918-0.969) and 0.916 (95% CI: 0.861-0.971) for the training and testing set, respectively. The combined model DLR nomogram (DLRN) further enhanced the performance, resulting in AUC values of 0.960 (95% CI: 0.940- 0.979) and 0.934 (95% CI: 0.876-0.991) for the training and testing sets, respectively. DCA analysis indicated that DLRN provided greater clinical benefits compared to other models.ConclusionDLRN based on US images shows exceptional performance in distinguishing BPGTs and MPGTs, providing more reliable information for personalized diagnosis and treatment plans in clinical practice.

Aims: The formation of anti-drug antibodies (ADAs) during anti-tumor necrosis factor (anti-TNF) therapy is reported to lead to reducing serum drug levels, which may bring about a loss of response to treatment. Previous research has suggested an association between specific antibiotic classes and ADA formation during anti-TNF therapy. However, there are few studies specifically examining this association in Chinese inflammatory bowel disease (IBD) patients. Therefore, our study aimed to evaluate the possible effect of antibiotic use on ADA formation to anti-TNF therapy in Chinese patients with IBD.Methods: A total of 166 patients with IBD, including 149 with Crohn’s disease (CD) and 17 with ulcerative colitis (UC), were included in this retrospective analysis. These patients were initially treated with anti-TNF therapy (infliximab or adalimumab) after January 2018 and reviewed with available ADA levels before October 2023. After univariable analysis of all the variables, a multivariate Cox proportional hazards model was used to assess the association between antibiotic use and ADA development.Results: Among 166 IBD patients treated with infliximab (108/166, 65.1%) or adalimumab (58/166, 34.9%), 31 patients (18.7%) were measured as positive ADA levels. Cox proportional hazard model demonstrated an increased risk of ADA formation in IBD patients who used β-lactam-β-lactamase inhibitor combinations (BL-BLIs) (HR = 5.143, 95%CI 1.136–23.270, p = 0.033), or nitroimidazoles (HR = 4.635, 95%CI 1.641–13.089, p = 0.004) during 12 months before the ADA test. On the contrary, a reduced risk was noted in patients treated with fluoroquinolones (HR = 0.258, 95% CI 0.072–0.924, p = 0.037). Moreover, the median serum infliximab or adalimumab concentration in patients with positive ADA levels was significantly lower than that in patients with negative ADA levels (infliximab: 0.30 vs. 1.85 μg/mL, p < 0.0001; adalimumab: 0.45 vs. 7.55 μg/mL, p = 0.0121).Conclusion: ADA development is associated with various antibiotic classes. BL-BLIs and nitroimidazoles might increase the risk of ADA formation during anti-TNF therapy in Chinese IBD patients, while the treatment with fluoroquinolones could probably reduce such risk. There were certain limitations in the retrospective analysis of the study, therefore, the results are just for reference, and other studies are needed to further confirm our findings.

Background and objectivesEarly neurological deterioration (END) occurs in up to one-third of patients with acute ischemic stroke (AIS) and associated with poor outcome. The role of serum bilirubin in END remains controversial. This study aims to investigate the association of total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) with END.MethodsThis study was a cross-sectional retrospective study with 344 AIS patients enrolled. We retrospectively reviewed consecutive AIS patients with END through a medical record retrieval system and enrolled patients as control randomly from the AIS patients without END at the same period. The bilirubin levels were compared between the END group and No END group. The correlations of bilirubin with END were assessed according to the bilirubin tertiles on the cohort of different genders.ResultsIn women, as the bilirubin level increased, the occurrence of END showed an increasing trend. The linear association was significant based on the tertiles of all bilirubin types (TBIL p = 0.003; DBIL p = 0.025; IBIL p = 0.025), while in men no similar trend was observed. After adjustment for confounders, higher TBIL (p for trend 0.009) and DBIL (p for trend 0.033) levels were associated with increased risk of END in women. The adjusted OR for T3 relative to T1 was 5.240 (95% CI 1.496–18.347) in TBIL and 3.549 (95% CI 1.089–11.566) in DBIL. Multivariate logistic regression showed that DBIL was independently associated with END in women (OR 1.717, 95% CI 1.106–2.666). The study also found that DBIL was superior to TBIL and IBIL in prediction of END occurrence in women, with greater predictive value.DiscussionThere were gender differences in the relationship between bilirubin and END, and DBIL level was positively associated with END occurrence in women, not in men. DBIL had greater incremental predictive value for END than TBIL and IBIL.