Application of radioactive iodine-125 microparticles in hepatocellular carcinoma with portal vein embolus.

BACKGROUND: Radioactive iodine-125 (125I) microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors, especially hepatocellular carcinoma. Patients with hepatocellular carcinoma frequently experience portal vein embolism, which exacerbates the difficulty and complexity of treatment. 125I particles, used in local radiotherapy, can directly act on tumor tissue and reduce damage to surrounding healthy tissue. Through retrospective analysis, this study discussed the efficacy and safety of radioactive 125I particles in portal vein embolization patients with hepatocellular carcinoma in order to provide more powerful evidence supporting clinical treatment. AIM: To investigate the effect of transcatheter arterial chemoembolization combined with portal vein 125I particle implantation in the treatment of primary liver cancer patients with portal vein tumor thrombus and its influence on liver function. METHODS: The clinical data of 96 patients with primary liver cancer combined with portal vein tumor thrombus admitted to our hospital between January 2020 and December 2023 were retrospectively analyzed. Fifty-two patients received treatment with transcatheter arterial chemoembolization and implantation of 125I particles in the portal vein (combination group), while 44 patients received treatment with transcatheter arterial chemoembolization alone (control group). The therapeutic effects on tumor lesions, primary liver cancer, and portal vein tumor embolisms were compared between the two groups. Changes in relevant laboratory indexes before and after treatment were evaluated. The t test was used to compare the measurement data between the two groups, and the χ 2 test was used to compare the counting data between groups. RESULTS: The tumor lesion response rate in the combination group (59.62% vs 38.64%) and the response rate of patients with primary liver cancer complicated with portal vein tumor thrombus (80.77% vs 59.09%) were significantly greater than those in the control group (χ 2 = 4.196, 5.421; P = 0.041, 0.020). At 8 wk after surgery, the serum alpha-fetoprotein, portal vein main diameter, and platelet of the combined group were significantly lower than those of the control group, and the serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin were significantly greater than those of the control group (t = 3.891, 3.291, 2.330, 3.729, 3.582, 4.126; P < 0.05). The serum aspartate aminotransferase, alanine aminotransferase, and total bilirubin levels of the two groups were significantly greater than those of the same group 8 wk after surgery (P < 0.05), and the peripheral blood platelet, alpha-fetoprotein, and main portal vein diameter were significantly less than those of the same group before surgery (P < 0.05). CONCLUSION: In patients with primary liver cancer and a thrombus in the portal vein, transcatheter arterial chemoembolization plus portal vein 125I implantation is more effective than transcatheter arterial chemoembolization alone. However, during treatment it is crucial to pay attention to liver function injury caused by transcatheter arterial chemoembolization.

The risk of asthma in singletons conceived by ART: a retrospective cohort study.

STUDY QUESTION: Do singleton children conceived by ART have a higher asthma risk than naturally conceived (NC) singletons? SUMMARY ANSWER: The asthma risk was similar for ART-conceived singletons and NC singletons, and there were no clear differences between the various types of ART. WHAT IS KNOWN ALREADY: Whether ART increases asthma risk in offspring is questionable. The evidence is inconsistent and limited by ethnicity, geographic distribution, inadequate confounder adjustment, unsatisfactory control groups, and specific methods of ART. Furthermore, the mediating effects of obstetric and neonatal outcomes on the association between ART and asthma remain unclear. STUDY DESIGN SIZE DURATION: This observational, single-centre study was conducted at a reproductive centre of an affiliated university hospital between September 2009 and April 2023. A total of 3227 singletons aged 3-6 years conceived by IVF versus ICSI or fresh versus frozen embryo transfer were retrospectively enrolled, and a total of 1206 NC singletons of the same age were subsequently recruited. PARTICIPANTS/MATERIALS SETTING METHODS: Asthma was defined as a self-reported physician diagnosis or wheezing in the past 12 months. We performed multivariable logistic regression analyses to examine associations between asthma in offspring and ART use, adjusting for parental characteristics (age, education level, occupation type, BMI, asthma), smoking exposure, residence type, child sex, child age, and year of follow-up. Mediating effects were explored using longitudinal mediation structural equation modelling. MAIN RESULTS AND THE ROLE OF CHANCE: Asthma was reported for 51 (4.2%) of the 1206 NC singletons (median [interquartile range] age 5 [4-5] years; 48.1% females) and 169 (5.2%) of the 3227 ART-conceived singletons (5 [5-5] years; 47.6% females). We found that risks of childhood asthma in singletons conceived by ART were, overall, similar to those of NC singletons before (odds ratio [OR], 1.25 [95% CI, 0.92-1.74]; P = 0.170) and after adjustment (adjusted OR [aOR], 0.66 [95% CI, 0.44-1.03]; P = 0.126). The results were similar in multiple sensitivity analyses, and there were no clear differences in asthma risks according to the method of ART. Mediation analysis revealed a significant positive indirect effect of neonatal intensive care unit (NICU) admission (standard path coefficient, b = 0.025, P < 0.05) and a negative indirect effect of breastfeeding (b = -0.012, P < 0.05) on the association between ART and asthma in singleton offspring. LIMITATIONS REASONS FOR CAUTION: This study is limited to singletons only and cannot be generalized. The study is also limited by its retrospective observational single-centre nature and sample size. Mediation analyses were exploratory. Therefore, the findings need to be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: These findings can help infertile couples undergoing ART be reassured about the risk of childhood asthma in singleton offspring. Breastfeeding is recommended as a potentially feasible intervention to reduce the asthma risks in ART-conceived children who are at increased potential risk of asthma, such as those with NICU admissions. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Key Research and Development Program of Zhejiang Province (2021C03100), the National Key Research and Development Program of China (2021YFC2700603), and the Program for Key Subjects of Zhejiang Province in Medicine and Hygiene to Y. Z., the Zhejiang Province Natural Science Foundation (No. LQ22H040006) and the National Natural Science Foundation of China (No.82101759) to M.T., and the National Natural Science Foundation of China (No. 82201860) to J.Y. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: ChiCTR2300069906.

Circadian clock disruption stimulates bone loss via regulatory T cell-Mediated regulation of IL-10 expression.

Circadian rhythms play a crucial role in regulating various physiological processes, including specific immune functions that enhance the body's ability to anticipate and respond to threats effectively. However, research on the impact of circadian rhythms on osteoimmunology remains limited. Our study uncovered that circadian disruption leads to bone mass loss by reducing the population of Treg cells in the bone marrow. Furthermore, we observed a significant decrease in serum IL-10 cytokine levels in jet lagged mice. In our current investigation, we explored the anti-osteoclastogenic effects of IL-10 and found that IL-10 inhibits RANKL-induced osteoclastogenesis in a dose-dependent manner. Our findings suggest that the diminished anti-osteoclastogenic properties of Tregs under circadian disruption are mediated by IL-10 cytokine production. Moreover, our discoveries propose that administration of IL-10 or butyrate could potentially reverse bone mass loss in individuals experiencing jet lag.

AttentionCARE: replicability of a BCI for the clinical application of augmented reality-guided EEG-based attention modification for adolescents at high risk for depression.

Affect-biased attention is the phenomenon of prioritizing attention to emotionally salient stimuli and away from goal-directed stimuli. It is thought that affect-biased attention to emotional stimuli is a driving factor in the development of depression. This effect has been well-studied in adults, but research shows that this is also true during adolescence, when the severity of depressive symptoms are correlated with the magnitude of affect-biased attention to negative emotional stimuli. Prior studies have shown that trainings to modify affect-biased attention may ameliorate depression in adults, but this research has also been stymied by concerns about reliability and replicability. This study describes a clinical application of augmented reality-guided EEG-based attention modification ("AttentionCARE") for adolescents who are at highest risk for future depressive disorders (i.e., daughters of depressed mothers). Our results (n = 10) indicated that the AttentionCARE protocol can reliably and accurately provide neurofeedback about adolescent attention to negative emotional distractors that detract from attention to a primary task. Through several within and cross-study replications, our work addresses concerns about the lack of reliability and reproducibility in brain-computer interface applications, offering insights for future interventions to modify affect-biased attention in high-risk adolescents.

Exploring genetic codon expansion for unnatural amino acid incorporation in filamentous fungus Aspergillus nidulans.

Genetic code expansion technology allows the incorporation of unnatural amino acids (UAAs) into proteins, which is useful in protein engineering, synthetic biology, and gene therapy. Despite its potential applications in various species, filamentous fungi remain unexplored. This study aims to address this gap by developing these techniques in Aspergillus nidulans. We introduced an amber stop codon into a specific sequence within the reporter gene expressed in A. nidulans and replaced the anticodon of the fungal tRNATyr with CUA. This resulted in the synthesis of the target protein, confirming the occurrence of amber suppression in the fungus. When exogenous E. coli tRNATyrCUA (Ec. tRNATyrCUA) and E. coli tyrosyl-tRNA (Ec.TyrRS) were introduced into A. nidulans, they successfully synthesized the target protein via amber suppression and were shown to be orthogonal to the fungal translation system. By replacing the wild-type Ec.TyrRS with a mutant with a higher affinity for the UAA O-methyl-L-tyrosine, the fungal system was able to initiate the synthesis of the UAA-labeled protein (UAA-protein). We further increased the expression level of the UAA-protein through several rational modifications. The successful development of a genetic code expansion technique for A. nidulans has introduced a potentially valuable approach to the study of fungal protein structure and function.

Icariin improves oxidative stress injury during ischemic stroke via inhibiting mPTP opening.

BACKGROUND: Ischemic stroke presents a significant threat to human health due to its high disability rate and mortality. Currently, the clinical treatment drug, rt-PA, has a narrow therapeutic window and carries a high risk of bleeding. There is an urgent need to find new effective therapeutic drugs for ischemic stroke. Icariin (ICA), a key ingredient in the traditional Chinese medicine Epimedium, undergoes metabolism in vivo to produce Icaritin (ICT). While ICA has been reported to inhibit neuronal apoptosis after cerebral ischemia-reperfusion (I/R), yet its underlying mechanism remains unclear. METHODS: PC-12 cells were treated with 200 µM H2O2 for 8 h to establish a vitro model of oxidative damage. After administration of ICT, cell viability was detected by Thiazolyl blue tetrazolium Bromide (MTT) assay, reactive oxygen species (ROS) and apoptosis level, mPTP status and mitochondrial membrane potential (MMP) were detected by flow cytometry and immunofluorescence. Apoptosis and mitochondrial permeability transition pore (mPTP) related proteins were assessed by Western blotting. Middle cerebral artery occlusion (MCAO) model was used to establish I/R injury in vivo. After the treatment of ICA, the neurological function was scored by ZeaLonga socres; the infarct volume was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining; HE and Nissl staining were used to detect the pathological state of the ischemic cortex; the expression changes of mPTP and apoptosis related proteins were detected by Western blotting. RESULTS: In vitro: ICT effectively improved H2O2-induced oxidative injury through decreasing the ROS level, inhibiting mPTP opening and apoptosis. In addition, the protective effects of ICT were not enhanced when it was co-treated with mPTP inhibitor Cyclosporin A (CsA), but reversed when combined with mPTP activator Lonidamine (LND). In vivo: Rats after MCAO shown cortical infarct volume of 32-40%, severe neurological impairment, while mPTP opening and apoptosis were obviously increased. Those damage caused was improved by the administration of ICA and CsA. CONCLUSIONS: ICA improves cerebral ischemia-reperfusion injury by inhibiting mPTP opening, making it a potential candidate drug for the treatment of ischemic stroke.

HST-MRF: Heterogeneous Swin Transformer With Multi-Receptive Field for Medical Image Segmentation.

The Transformer has been successfully used in medical image segmentation due to its excellent long-range modeling capabilities. However, patch segmentation is necessary when building a Transformer class model. This process ignores the tissue structure features within patch, resulting in the loss of shallow representation information. In this study, we propose a Heterogeneous Swin Transformer with Multi-Receptive Field (HST-MRF) model that fuses patch information from different receptive fields to solve the problem of loss of feature information caused by patch segmentation. The heterogeneous Swin Transformer (HST) is the core module, which achieves the interaction of multi-receptive field patch information through heterogeneous attention and passes it to the next stage for progressive learning, thus complementing the patch structure information. We also designed a two-stage fusion module, multimodal bilinear pooling (MBP), to assist HST in further fusing multi-receptive field information and combining low-level and high-level semantic information for accurate localization of lesion regions. In addition, we developed adaptive patch embedding (APE) and soft channel attention (SCA) modules to retain more valuable information when acquiring patch embedding and filtering channel features, respectively, thereby improving model segmentation quality. We evaluated HST-MRF on multiple datasets for polyp, skin lesion and breast ultrasound segmentation tasks. Experimental results show that our proposed method outperforms state-of-the-art models and can achieve superior performance. Furthermore, we verified the effectiveness of each module and the benefits of multi-receptive field segmentation in reducing the loss of structural information through ablation experiments and qualitative analysis.

Osteocyte ferroptosis induced by ATF3/TFR1 contributes to cortical bone loss during ageing.

Cortical bone loss is intricately associated with ageing and coincides with iron accumulation. The precise role of ferroptosis, characterized by iron overload and lipid peroxidation, in senescent osteocytes remains elusive. We found that ferroptosis was a crucial mode of osteocyte death in cortical bone during ageing. Using a single-cell transcriptome analysis, we identified activating transcription factor 3 (ATF3) as a critical driver of osteocyte ferroptosis. Elevated ATF3 expression in senescent osteocytes promotes iron uptake by upregulating transferrin receptor 1 while simultaneously inhibiting solute carrier family 7-member 11-mediated cystine import. This process leads to an iron overload and lipid peroxidation, culminating in ferroptosis. Importantly, ATF3 inhibition in aged mice effectively alleviated ferroptosis in the cortical bone and mitigated cortical bone mass loss. Taken together, our findings establish a pivotal role of ferroptosis in cortical bone loss in older adults, providing promising prevention and treatment strategies for osteoporosis and fractures.

Causes and global, regional, and national burdens of traumatic brain injury from 1990 to 2019.

PURPOSE: Traumatic brain injury (TBI), currently a major global public health problem, imposes a significant economic burden on society and families. We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence, prevalence, and years lived with disability (YLDs). The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention, treatment, and incidence-reducing measures for TBI. METHODS: A secondary analysis was performed on the incidence, prevalence, and YLDs of TBI by sex, age group, and region (n = 21,204 countries and territories) between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported. RESULTS: In 2019, there were 27.16 million (95% uncertainty intervals (UI): 23.36 - 31.42) new cases of TBI worldwide, with age-standardized incidence and prevalence rates of 346 per 100,000 population (95% UI: 298-401) and 599 per 100,000 population (95% UI: 573-627), respectively. From 1990 to 2019, there were no significant trends in global age-standardized incidence (estimated annual percentage changes: -0.11%, 95% UI: -0.18% - -0.04%) or prevalence (estimated annual percentage changes: 0.01%, 95% UI: -0.04% - 0.06%). TBI caused 7.08 million (95% UI: 5.00 - 9.59) YLDs in 2019, with age-standardized rates of 86.5 per 100,000 population (95% UI: 61.1 - 117.2). In 2019, the countries with higher incidence rates were mainly distributed in Central Europe, Eastern Europe, and Australia. The 2019 global age-standardized incidence rate was higher in males than in females. The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population, accounting for 52.8% of all TBI, with falls and road traffic injuries being the main causes in most regions. CONCLUSIONS: The incidence of moderate and severe TBI was slightly higher in 2019, and TBI still accounts for a significant portion of the global injury burden. The likelihood of moderate to severe TBI and the trend of major injury under each injury cause from 1990 to 2019 and the characteristics of injury mechanisms in each age group are presented, providing a basis for further research on injury causes in each age group and the future establishment of corresponding policies and protective measures.

Insight to the Catalytic Activity of Atomically Precise Ag4Ni2 Nanoclusters on Silicon Carbide for Nitroarene Reduction.

Atomically precise Ag4Ni2 nanoclusters with 2,4-dimethylbenzenethiol as the ligands were synthesized and characterized as a cocatalyst of SiC for the selective hydrogenation of nitroarenes to arylamine in the presence of NaBH4. The obtained Ag4Ni2/SiC samples exhibited extraordinary catalytic activity, and a self-accelerated catalytic process was observed with the reduction of nitrophenol to aminophenol as the model reaction. Experimental comparison between the Ag4Ni2/SiC samples before and after the catalysis showed that the transformation of Ag4Ni2 clusters to polydisperse Ag particles as well as amorphous NiOx on the surface of SiC in the catalysis was the key to their high activity. AIMD calculations revealed that the transformation of Ag4Ni2 was driven by the presence of multiple hydrides on the cluster, which induced the detachment of the thiol ligand of the nanoclusters.

Matrix stiffness regulates macrophage polarisation via the Piezo1-YAP signalling axis.

Macrophages play a pivotal role in the immunological cascade activated in response to biomedical implants, which predetermine acceptance or rejection of implants by the host via pro- and anti-inflammatory polarisation states. The role of chemical signals in macrophage polarisation is well-established, but how physical cues regulate macrophage function that may play a fundamental role in implant-bone interface, remains poorly understood. Here we find that bone marrow-derived macrophages (BMDM) cultured on polyacrylamide gels of varying stiffness exhibit different polarisation states. BMDM are 'primed' to a pro-inflammatory M1 phenotype on stiff substrates, while to an anti-inflammatory M2 phenotype on soft and medium stiffness substrates. It is further observed that matrix stiffening increases Piezo1 expression, as well as leads to subsequent activation of the mechanotransduction signalling effector YAP, thus favouring M1 polarisation whilst suppressing M2 polarisation. Moreover, upon treatment with YAP inhibitor, we successfully induce macrophage re-polarisation to the M2 state within the implant site microenvironment, which in turn promotes implant osseointegration. Collectively, our present study thus characterises the critical role of the Piezo1-YAP signalling axis in macrophage mechanosensing and stiffness-mediated macrophage polarisation and provides cues for the design of immuno-modulatory biomaterials that can regulate the macrophage phenotype.

Protein disulfide isomerase 1 is required for RodA assembling-based conidial hydrophobicity of Aspergillus fumigatus.

The hydrophobic layer of Aspergillus conidia, composed of RodA, plays a crucial role in conidia transfer and immune evasion. It self-assembles into hydrophobic rodlets through intramolecular disulfide bonds. However, the secretory process of RodA and its regulatory elements remain unknown. Since protein disulfide isomerase (PDI) is essential for the secretion of many disulfide-bonded proteins, we investigated whether PDI is also involved in RodA secretion and assembly. By gene knockout and phenotypic analysis, we found that Pdi1, one of the four PDI-related proteins of Aspergillus fumigatus, determines the hydrophobicity and integrity of the rodlet layer of the conidia. Preservation of the thioredoxin-active domain of Pdi1 was sufficient to maintain conidial hydrophobicity, suggesting that Pdi1 mediates RodA assembly through its disulfide isomerase activity. In the absence of Pdi1, the disulfide mismatch of RodA in conidia may prevent its delivery from the inner to the outer layer of the cell wall for rodlet assembly. This was demonstrated using a strain expressing a key cysteine-mutated RodA. The dormant conidia of the Pdi1-deficient strain (Δpdi) elicited an immune response, suggesting that the defective conidia surface in the absence of Pdi1 exposes internal immunogenic sources. In conclusion, Pdi1 ensures the correct folding of RodA in the inner layer of conidia, facilitating its secretion into the outer layer of the cell wall and allowing self-assembly of the hydrophobic layer. This study has identified a regulatory element for conidia rodlet assembly.IMPORTANCEAspergillus fumigatus is the major cause of invasive aspergillosis, which is mainly transmitted by the inhalation of conidia. The spread of conidia is largely dependent on their hydrophobicity, which is primarily attributed to the self-assembly of the hydrophobic protein RodA on the cell wall. However, the mechanisms underlying RodA secretion and transport to the outermost layer of the cell wall are still unclear. Our study identified a critical role for Pdi1, a fungal protein disulfide isomerase found in regulating RodA secretion and assembly. Inhibition of Pdi1 prevents the formation of correct S-S bonds in the inner RodA, creating a barrier to RodA delivery and resulting in a defective hydrophobic layer. Our findings provided insight into the formation of the conidial hydrophobic layer and suggested potential drug targets to inhibit A. fumigatus infections by limiting conidial dispersal and altering their immune inertia.

DBNet-SI: Dual branch network of shift window attention and inception structure for skin lesion segmentation.

The U-shaped convolutional neural network (CNN) has attained remarkable achievements in the segmentation of skin lesion. However, given the inherent locality of convolution, this architecture cannot capture long-range pixel dependencies and multiscale global contextual information effectively. Moreover, repeated convolutions and downsampling operations can readily result in the omission of intricate local fine-grained details. In this paper, we proposed a U-shaped network (DBNet-SI) equipped with a dual-branch module that combines shift window attention and inception structures. First, we proposed a dual-branch module that combines shift window attention and inception structures (MSI) to better capture multiscale global contextual information and long-range pixel dependencies. Specifically, we have devised a cross-branch bidirectional interaction module within the MSI module to enable information complementarity between the two branches in the channel and spatial dimensions. Therefore, MSI is capable of extracting distinguishing and comprehensive features to accurately identify the skin lesion boundaries. Second, we have devised a progressive feature enhancement and information compensation module (PFEIC), which progressively compensates for fine-grained features through reconstructed skip connections and integrated global context attention modules. The results of the experiment show the superior segmentation performance of DBNet-SI compared with other deep learning models for skin lesion segmentation in the ISIC2017 and ISIC2018 datasets. Ablation studies demonstrate that our model can effectively extract rich multiscale global contextual information and compensate for the loss of local details.

Immune-Enhancing Treatment among Acute Necrotizing Pancreatitis Patients with Metabolic Abnormalities: A Post Hoc Analysis of a Randomized Clinical Trial.

Background/Aims: : Metabolic syndrome is common in patients with acute pancreatitis and its components have been reported to be associated with infectious complications. In this post hoc analysis, we aimed to evaluate whether metabolic abnormalities impact the effect of immune-enhancing thymosin alpha-1 (Tα1) therapy in acute necrotizing pancreatitis (ANP) patients. Methods: : All data were obtained from the database for a multicenter randomized clinical trial that evaluated the efficacy of Tα1 in ANP patients. Patients who discontinued the Tα1 treatment prematurely were excluded. The primary outcome was 90-day infected pancreatic necrosis (IPN) after randomization. Three post hoc subgroups were defined based on the presence of hyperglycemia, hypertriglyceridemia, or both at the time of randomization. In each subgroup, the correlation between Tα1 and 90-day IPN was assessed using the Cox proportional-hazards regression model. Multivariable propensity-score methods were used to control potential bias. Results: : Overall, 502 participants were included in this post hoc analysis (248 received Tα1 treatment and 254 received matching placebo treatment). Among them, 271 (54.0%) had hyperglycemia, 371 (73.9%) had hypertriglyceridemia and 229 (45.6%) had both. Tα1 therapy was associated with reduced incidence of IPN among patients with hyperglycemia (18.8% vs 29.7%: hazard ratio, 0.80; 95% confidence interval, 0.37 to 0.97; p=0.03), but not in the other subgroups. Additional multivariate regression models using three propensity-score methods yielded similar results. Conclusions: : Among ANP patients with hyperglycemia, immune-enhancing Tα1 treatment was associated with a reduced risk of IPN (ClinicalTrials.gov, Registry number: NCT02473406).

The osteoclastic activity in apical distal region of molar mesial roots affects orthodontic tooth movement and root resorption in rats.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment. However, the sensitivity of existing detection techniques is not sufficient, and the criteria for evaluating optimal force have not been yet established. Here, by employing 3D finite element analysis methodology, we found that the apical distal region (A-D region) of mesial roots is particularly sensitive to orthodontic force in rats. Tartrate-resistant acidic phosphatase (TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams (g), leading to alveolar bone resorption and tooth movement. When the force reached 80 g, TRAP-positive osteoclasts started appearing on the root surface in the A-D region. Additionally, micro-computed tomography revealed a significant root resorption at 80 g. Notably, the A-D region was identified as a major contributor to whole root resorption. It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement, inclination, and hyalinization. These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model. Collectively, our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients' orthodontic treatment.

Antibacterial p-terphenyl and α­pyrone derivates isolated from the marine-derived actinomycete Nocardiopsis sp. HDN154086.

Assisted by OSMAC strategy, one new p-terphenyl and two new α­pyrone derivates, namely nocarterphenyl I (1) and nocardiopyrone D-E (2-3), were obtained and characterized from the marine sediment-derived actinomycete Nocardiopsis sp. HDN154086. The structures of these compounds were determined on the basis of MS, NMR spectroscopic data and single-crystal X-ray diffraction. Compound 1 with a rare 2,2'-bithiazole structure among natural products showed promising activity against five bacteria with MIC values ranging from 0.8 to 1.6 µM and 3 exhibited notable antibacterial activity against MRSA compared the positive control ciprofloxacin.

A Dual-Attention Learning Network With Word and Sentence Embedding for Medical Visual Question Answering.

Research in medical visual question answering (MVQA) can contribute to the development of computer-aided diagnosis. MVQA is a task that aims to predict accurate and convincing answers based on given medical images and associated natural language questions. This task requires extracting medical knowledge-rich feature content and making fine-grained understandings of them. Therefore, constructing an effective feature extraction and understanding scheme are keys to modeling. Existing MVQA question extraction schemes mainly focus on word information, ignoring medical information in the text, such as medical concepts and domain-specific terms. Meanwhile, some visual and textual feature understanding schemes cannot effectively capture the correlation between regions and keywords for reasonable visual reasoning. In this study, a dual-attention learning network with word and sentence embedding (DALNet-WSE) is proposed. We design a module, transformer with sentence embedding (TSE), to extract a double embedding representation of questions containing keywords and medical information. A dual-attention learning (DAL) module consisting of self-attention and guided attention is proposed to model intensive intramodal and intermodal interactions. With multiple DAL modules (DALs), learning visual and textual co-attention can increase the granularity of understanding and improve visual reasoning. Experimental results on the ImageCLEF 2019 VQA-MED (VQA-MED 2019) and VQA-RAD datasets demonstrate that our proposed method outperforms previous state-of-the-art methods. According to the ablation studies and Grad-CAM maps, DALNet-WSE can extract rich textual information and has strong visual reasoning ability.

Structural connectivity from DTI to predict mild cognitive impairment in de novo Parkinson's disease.

BACKGROUND: Early detection of Parkinson's disease (PD) patients at high risk for mild cognitive impairment (MCI) can help with timely intervention. White matter structural connectivity is considered an early and sensitive indicator of neurodegenerative disease. OBJECTIVES: To investigate whether baseline white matter structural connectivity features from diffusion tensor imaging (DTI) of de novo PD patients can help predict PD-MCI conversion at an individual level using machine learning methods. METHODS: We included 90 de novo PD patients who underwent DTI and 3D T1-weighted imaging. Elastic net-based feature consensus ranking (ENFCR) was used with 1000 random training sets to select clinical and structural connectivity features. Linear discrimination analysis (LDA), support vector machine (SVM), K-nearest neighbor (KNN) and naïve Bayes (NB) classifiers were trained based on features selected more than 500 times. The area under the ROC curve (AUC), accuracy (ACC), sensitivity (SEN) and specificity (SPE) were used to evaluate model performance. RESULTS: A total of 57 PD patients were classified as PD-MCI nonconverters, and 33 PD patients were classified as PD-MCI converters. The models trained with clinical data showed moderate performance (AUC range: 0.62-0.68; ACC range: 0.63-0.77; SEN range: 0.45-0.66; SPE range: 0.64-0.84). Models trained with structural connectivity (AUC range, 0.81-0.84; ACC range, 0.75-0.86; SEN range, 0.77-0.91; SPE range, 0.71-0.88) performed similar to models that were trained with both clinical and structural connectivity data (AUC range, 0.81-0.85; ACC range, 0.74-0.85; SEN range, 0.79-0.91; SPE range, 0.70-0.89). CONCLUSIONS: Baseline white matter structural connectivity from DTI is helpful in predicting future MCI conversion in de novo PD patients.

Road traffic mortality in Zunyi city, China: A 10 - year data analysis (2013-2022).

PURPOSE: The study aimed to examine the pattern of motorization and the mortality rate related to road traffic crashes in Zunyi (a city in northern Guizhou province of China) from 2013 to 2022, and to identify the epidemiological characteristics of these crashes with to provide insights that could help improve road safety. METHODS: Data were obtained from the Zunyi traffic management data platform, and the mortality rates were calculated. We deployed various analytical methods, including descriptive analysis, Chi-square test or Fisher's exact test of categorical variable, circular distribution map analysis, and Rayleigh test to characterize the traits of road traffic crashes in the region. RESULTS: During the 10-year study period, 7488 people died due to road traffic accidents, with males accounting for 70.4% and females 29.6% (χ2 = 101.97, p < 0.001). The mortality rate increased from 7.80 deaths per 100,000 people in 2013 to 10.70 deaths per 100,000 people in 2016, but then decreased to 9.54 deaths per 100,000 people in 2019. A notable finding was that the death rate per 10,000 vehicles declined from 16.09 deaths per 10,000 vehicles in 2013 to 5.48 deaths per 10,000 vehicles in 2022. The study also found that vulnerable road users represented nearly half (48.76%) of all accident fatalities, and unlicensed or inexperienced driving contributed significantly to the occurrence of road traffic accidents. CONCLUSION: Although the number of road traffic accidents in Zunyi has decreased, there are still some critical issues that need to be addressed, particularly for vulnerable road users and unlicensed drivers. Our results highlight the need of targeted interventions to address the specific risk factors of road traffic crashes, particularly those affecting vulnerable road users and drivers without sufficient experience or license.

Gene delivery to breast cancer by incorporated EpCAM targeted DARPins into AAV2.

OBJECTIVE: The aim of this study is to evaluate an AAV vector that can selectively target breast cancer cells and to investigate its specificity and anti-tumor effects on breast cancer cells both in vitro and in vivo, offering a new therapeutic approach for the treatment of EpCAM-positive breast cancer. METHODS: In this study, a modified AAV2 viral vector was used, in which EpCAM-specific DARPin EC1 was fused to the VP2 protein of AAV2, creating a viral vector that can target breast cancer cells. The targeting ability and anti-tumor effects of this viral vector were evaluated through in vitro and in vivo experiments. RESULTS: The experimental results showed that the AAV2MEC1 virus could specifically infect EpCAM-positive breast cancer cells and accurately deliver the suicide gene HSV-TK to tumor tissue in mice, significantly inhibiting tumor growth. Compared to the traditional AAV2 viral vector, the AAV2MEC1 virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth. CONCLUSION: This study demonstrates that AAV2MEC1 is a gene delivery vector capable of targeting breast cancer cells and achieving selective targeting in mice. The findings offer a potential gene delivery system and strategies for gene therapy targeting EpCAM-positive breast cancer and other tumor types.