Genomic characterization revealing the high rate of tet(X4)-positive Escherichia coli in animals associated with successful genetic elements.

Introduction: The rapid spread of plasmid-mediated tet(X4) conferring high tigecycline resistance poses a significant threat to public health. Escherichia coli as the most common pathogen which carries tet(X4) has been widely disseminated in China. Thus, comprehensive investigations are required to understand the mechanism of transmission of tet(X4)-positive E. coli. Methods: In this study, a total of 775 nonduplicate samples were collected in Guangdong, China from 2019 to 2020. We screened for tet(X4)-positive E. coli by PCR amplification and species identification. Furthermore, we analyzed the phylogenetics and genetic context of tet(X4)-positive E. coli through whole-genome sequencing and long-reads sequencing. Results: Overall, 146 (18.84%) tet(X4)-positive E. coli were isolated, comprising 2 isolates from humans and 144 isolates from pigs. The majority of tet(X4)-positive E. coli exhibited resistance to multiple antibiotics but all of them were susceptible to amikacin and colistin. Phylogenetic analysis showed that ST877, ST871, and ST195 emerged as the predominant sequence types in tet(X4)-positive E. coli. Further analysis revealed various genetic environments associated with the horizontal transfer of tet(X4). Notably, a 100-kbp large fragment insertion was discovered downstream of tet(X4), containing a replicon and a 40-kbp gene cluster for the bacterial type IV secretion system. Discussion: The high colonization rate of tet(X4)-positive E. coli in animals suggests that colonization as a key factor in its dissemination to humans. Diverse genetic context may contribute to the transfer of tet(X4). Our findings underline the urgent need for controlling the spread of plasmid-mediated tigecycline resistance.

Large-scale parameters framework with large convolutional kernel for encoding visual fMRI activity information.

Visual encoding models often use deep neural networks to describe the brain's visual cortex response to external stimuli. Inspired by biological findings, researchers found that large receptive fields built with large convolutional kernels improve convolutional encoding model performance. Inspired by scaling laws in recent years, this article investigates the performance of large convolutional kernel encoding models on larger parameter scales. This paper proposes a large-scale parameters framework with a sizeable convolutional kernel for encoding visual functional magnetic resonance imaging activity information. The proposed framework consists of three parts: First, the stimulus image feature extraction module is constructed using a large-kernel convolutional network while increasing channel numbers to expand the parameter size of the framework. Second, enlarging the input data during the training stage through the multi-subject fusion module to accommodate the increase in parameters. Third, the voxel mapping module maps from stimulus image features to functional magnetic resonance imaging signals. Compared to sizeable convolutional kernel visual encoding networks with base parameter scale, our visual encoding framework improves by approximately 7% on the Natural Scenes Dataset, the dedicated dataset for the Algonauts 2023 Challenge. We further analyze that our encoding framework made a trade-off between encoding performance and trainability. This paper confirms that expanding parameters in visual coding can bring performance improvements.

[Research progress on biological characteristics and propagation technology of Atractylodes lancea].

Atractylodes lancea is a perennial herb of the Asteraceae family and is one of the well-known traditional Chinese medicine(TCM). Several studies have documented polyene alkyne and sesquiterpenoid compounds as the main bioactive compounds of A. lancea, especially atractylodin, atractylon, ß-eudesmol, and hinesol in its rhizomes, which possess anti-virus, anti-inflammation, hypoglycemic, anti-hypoxia, liver protection, and diuresis activities. In parallel with the recent advancements in biotechnology, important achievements have been made in the study of biological characteristics and propagation technology of A. lancea. This study reviews the research progress on morphological features, cytogenetics, ecological planting, effective ingredients, and tissue culture techniques of A. lancea from the biology perspective, so as to provide a theoretical basis for reasonable development of A. lancea resources.

[Effect of combined application of organic and chemical fertilizers on yield and quality of Epimedium pubescens].

To investigate the effects of different ratios of organic and chemical fertilizers on the yield and quality of Epimedium pubescens,so as to provide a scientific basis for the fertilization of high-yield and high-quality E. pubescens cultivation. In this experiment,a field plot test was conducted,and CK(without fertilizer) was set as the control group,with five treatment groups with different ratios of organic fertilizers and chemical fertilizers set up,namely OF0(100% chemical fertilizers),OF25(25% organic fertilizers),OF50(50% organic fertilizers),OF75(75% organic fertilizers),and OF100(100% organic fertilizers). The effects of different fertilization patterns on the agronomic traits,yield,effective component content,nutrient accumulation,and soil physicochemical properties of E. pubescens were determined,and the yield and quality of the medicinal herb were comprehensively evaluated by using the CRITIC weights method. It was found that the herb yield of each treatment group was significantly increased compared with the CK group,although the yield of the groups with both organic fertilizer and chemical fertilizer was slightly lower than that of OF0. However,there was no significant difference,which indicated that the organic fertilizer combined with chemical fertilizer could ensure the herb yield. With the increase in organic fertilizer ratios,the medicinal components epimedin A,epimedin B,and epimedin C showed a tendency of first increasing and then decreasing,with the highest content in the OF25,while icariin showed a rising trend,with the best in the OF100. However,overall,the total flavonol glycosides ABCI accumulated the most in the OF25. The results of the CRITIC method showed that the top three fertilization treatments in terms of the comprehensive scores of the medicinal herb were OF25,OF50,and OF75. Organic fertilizer combined with chemical fertilizer is conducive to improving the soil's fertilizer holding and supply capacity,and the soil indexes are optimal in OF100. The soil enzyme activity is the highest in OF75. Meanwhile,organic fertilizer combined with chemical fertilizer can help the plant's uptake and accumulation of nutrients,and OF25 shows the most obvious effect.By comprehensively considering the influence of different ratios of organic and chemical fertilizers on the yield,effective component content,nutrient accumulation,and other indexes of E. pubescens,it is recommended that a 25% ratio(7 500 kg·hm~(-2)) of organic fertilizers and chemical fertilizers should be used in E. pubescens production in the first year,so as to promote the E. pubescens industry to increase yield and improve quality.

One-step inverse generation network for sparse-view dual-energy CT reconstruction and material imaging.

Objective.Sparse-view dual-energy spectral computed tomography (DECT) imaging is a challenging inverse problem. Due to the incompleteness of the collected data, the presence of streak artifacts can result in the degradation of reconstructed spectral images. The subsequent material decomposition task in DECT can further lead to the amplification of artifacts and noise.Approach.To address this problem, we propose a novel one-step inverse generation network (OIGN) for sparse-view dual-energy CT imaging, which can achieve simultaneous imaging of spectral images and materials. The entire OIGN consists of five sub-networks that form four modules, including the pre-reconstruction module, the pre-decomposition module, and the following residual filtering module and residual decomposition module. The residual feedback mechanism is introduced to synchronize the optimization of spectral CT images and materials.Main results.Numerical simulation experiments show that the OIGN has better performance on both reconstruction and material decomposition than other state-of-the-art spectral CT imaging algorithms. OIGN also demonstrates high imaging efficiency by completing two high-quality imaging tasks in just 50 seconds. Additionally, anti-noise testing is conducted to evaluate the robustness of OIGN.Significance.These findings have great potential in high-quality multi-task spectral CT imaging in clinical diagnosis.

Cation-π Interaction-Enhanced Self-Healing Injectable Hydrogels for Gastric Perforation Repair.

Surgical operations are the preferred treatment for gastric perforation (GP) but incur postoperative complications such as gastrointestinal adhesions and bacterial infections, leading to inefficient wound healing and serious complications that may even threaten the life of the patient. Developing hydrogel dressings capable of adapting to the gastric environment (acid) and decreasing visceral adhesions and bacterial infections after GP treatment is crucial. In this article, we developed an injectable, self-healing hydrogel using cation-π interactions between protonated amines and aromatic rings under acidic conditions and explored it for GP repair. The hydrogels demonstrate exceptional self-healing capabilities under acidic conditions and can be effectively tailored for the gastric environment. In addition, the hydrogel demonstrated significant efficacy in preventing gastrointestinal adhesion, reducing inflammation, promoting angiogenesis, and effectively facilitating wound healing in a rat GP model. This novel hydrogel demonstrates adaptability to the gastric environment, rendering it highly promising for potential applications in gastric trauma healing.

Policy Learning for Actively Labeled Sample Selection on Lumbar Semi-supervised Classification.

Large labeled data bring significant performance improvement, but acquiring labeled medical data is particularly challenging due to the laborious, time-consuming, and medically qualified annotation. Semi-supervised learning has been employed to leverage unlabeled data. However, the quality and quantity of annotated data have a great influence on the performance of the semi-supervised model. Selecting informative samples through active learning is crucial and could improve model performance. Therefore, we propose a unified semi-supervised active learning architecture (RL-based SSAL) that alternately trains a semi-supervised network and performs active sample selection. Semi-supervised model is first well trained for sample selection, and selected label-required samples are annotated and added to the previously labeled dataset for subsequent semi-supervised model training. To learn to select the most informative samples, we adopt a policy learning-based approach that treats sample selection as a decision-making process. A novel reward function based on the product of predictive confidence and uncertainty is designed, aiming to select samples with high confidence and uncertainty. Comparisons with a semi-supervised baseline on collected lumbar disc herniation dataset demonstrate the effectiveness of the proposed RL-based SSAL, achieving over 3% promotion across different amounts of labeled data. Comparisons with other active learning methods and ablation studies reveal the superiority of proposed policy learning based on active sample selection and reward function. Our model trained with only 200 labeled data achieves an accuracy of 89.32% which is comparable to the performance achieved with the entire labeled dataset, demonstrating its significant advantage.

Endometriosis Typology and Ovarian Cancer Risk.

Importance: Endometriosis has been associated with an increased risk of ovarian cancer; however, the associations between endometriosis subtypes and ovarian cancer histotypes have not been well-described. Objective: To evaluate the associations of endometriosis subtypes with incidence of ovarian cancer, both overall and by histotype. Design, Setting, and Participants: Population-based cohort study using data from the Utah Population Database. The cohort was assembled by matching 78 893 women with endometriosis in a 1:5 ratio to women without endometriosis. Exposures: Endometriosis cases were identified via electronic health records and categorized as superficial endometriosis, ovarian endometriomas, deep infiltrating endometriosis, or other. Main Outcomes and Measures: Estimated adjusted hazard ratios (aHRs), adjusted risk differences (aRDs) per 10 000 women, and 95% CIs for overall ovarian cancer, type I ovarian cancer, and type II ovarian cancer comparing women with each type of endometriosis with women without endometriosis. Models accounted for sociodemographic factors, reproductive history, and past gynecologic operations. Results: In this Utah-based cohort, the mean (SD) age at first endometriosis diagnosis was 36 (10) years. There were 597 women with ovarian cancer. Ovarian cancer risk was higher among women with endometriosis compared with women without endometriosis (aHR, 4.20 [95% CI, 3.59-4.91]; aRD, 9.90 [95% CI, 7.22-12.57]), and risk of type I ovarian cancer was especially high (aHR, 7.48 [95% CI, 5.80-9.65]; aRD, 7.53 [95% CI, 5.46-9.61]). Ovarian cancer risk was highest in women with deep infiltrating endometriosis and/or ovarian endometriomas for all ovarian cancers (aHR, 9.66 [95% CI, 7.77-12.00]; aRD, 26.71 [95% CI, 20.01-33.41]), type I ovarian cancer (aHR, 18.96 [95% CI, 13.78-26.08]; aRD, 19.57 [95% CI, 13.80-25.35]), and type II ovarian cancer (aHR, 3.72 [95% CI, 2.31-5.98]; aRD, 2.42 [95% CI, -0.01 to 4.85]). Conclusions and Relevance: Ovarian cancer risk was markedly increased among women with ovarian endometriomas and/or deep infiltrating endometriosis. This population may benefit from counseling regarding ovarian cancer risk and prevention and could be an important population for targeted screening and prevention studies.

The chromosome-level genome assembly of Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae).

Aphidoletes aphidimyza is widely recognized as an effective predator of aphids in agricultural systems. However, there is limited understanding of its predation mechanisms. In this study, we generated a high-quality chromosome level of the A. aphidimyza genome by combining PacBio, Illumina, and Hi-C data. The genome has a size of 192.08 Mb, with a scaffold N50 size of 46.85 Mb, and 99.08% (190.35 Mb) of the assembly is located on four chromosomes. The BUSCO analysis of our assembly indicates a completeness of 97.8% (n = 1,367), including 1,307 (95.6%) single-copy BUSCOs and 30 (2.2%) duplicated BUSCOs. Additionally, we annotated a total of 13,073 protein-coding genes, 18.43% (35.40 Mb) repetitive elements, and 376 non-coding RNAs. Our study is the first time to report the chromosome-scale genome for the species of A. aphidimyza. It provides a valuable genomic resource for the molecular study of A. aphidimyza.

Navß2 Intracellular Fragments Contribute to Aß1-42-Induced Cognitive Impairment and Synaptic Deficit Through Transcriptional Suppression of BDNF.

A pathological hallmark of Alzheimer's disease (AD) is the region-specific accumulation of the amyloid-beta protein (Aß), which triggers aberrant neuronal excitability, synaptic impairment, and progressive cognitive decline. Previous works have demonstrated that Aß pathology induced aberrant elevation in the levels and excessive enzymatic hydrolysis of voltage-gated sodium channel type 2 beta subunit (Navß2) in the brain of AD models, accompanied by alteration in excitability of hippocampal neurons, synaptic deficits, and subsequently, cognitive dysfunction. However, the mechanism is unclear. In this research, by employing cell models treated with toxic Aß1-42 and AD mice, the possible effects and potential mechanisms induced by Navß2. The results reveal that Aß1-42 induces remarkable increases in Navß2 intracellular domain (Navß2-ICD) and decreases in both BDNF exons and protein levels, as well as phosphorylated tropomyosin-related kinase B (pTrkB) expression in cells and mice, coupled with cognitive impairments, synaptic deficits, and aberrant neuronal excitability. Administration with exogenous Navß2-ICD further enhances these effects induced by Aß1-42, while interfering the generation of Navß2-ICD and/or complementing BDNF neutralize the Navß2-ICD-conducted effects. Luciferase reporter assay verifies that Navß2-ICD regulates BDNF transcription and expression by targeting its promoter. Collectively, our findings partially elucidate that abnormal enzymatic hydrolysis of Navß2 induced by Aß1-42-associated AD pathology leads to intracellular Navß2-ICD overload, which may responsible to abnormal neuronal excitability, synaptic deficit, and cognition dysfunction, through its transcriptional suppression on BDNF. Therefore, this work supplies novel evidences that Navß2 plays crucial roles in the occurrence and progression of cognitive impairment of AD by transcriptional regulatory activity of its cleaved ICD.

Primary Sjogren syndrome - A bibliometric analysis via CiteSpace.

This study employs CiteSpace software to analyze the research status, hotspots, and trends of primary Sjogren syndrome (pSS). Relevant publications from 1999 to 2023 were searched in the Web of Science Core Collection (WoSCC) set, followed by generating a network map using CiteSpace software to identify top authors, institutions, countries, keywords, journals, references, and research trends. A total of 3564 valid articles were included in this study. The People Republic of China had the highest number of articles (n = 524), while the University of Bergen emerged as the institution with the highest publication count (n = 94). Mariette X was identified as the author with the most publications (n = 67), whereas Vitali C received recognition as the most cited author (n = 1706). Annals of Rheumatic Diseases stood out as the journal with the highest citation count (n = 2530). Notably, an article published in the Annals of Rheumatic Diseases in 2017 garnered significant attention by being cited a remarkable 304 times. The bibliometric analysis reveals that key areas of research in pSS encompass investigating pathogenesis; advancing and applying targeted biological agents; and establishing treatment and diagnostic standards.

Acceleration of Photoinduced Electron Transfer by Modulating Electronegativity of Substituents in Stable Zr-Metal-Organic Frameworks to Boost Photocatalytic CO2 Reduction.

Photoreduction of CO2 with water into chemical feedstocks of fuels provides a green way to help solve both the energy crisis and carbon emission issues. Metal-organic frameworks (MOFs) show great potential for CO2 photoreduction. However, poor water stability and sluggish charge transfer could limit their application. Herein, three water-stable MOFs functionalized with electron-donating methyl groups and/or electron-withdrawing trifluoromethyl groups are obtained for the CO2 photoreduction. Compared with UiO-67-o-CF3-CH3 and UiO-67-o-(CF3)2, UiO-67-o-(CH3)2 achieves excellent performance with an average CO generation rate of 178.0 µmol g-1 h-1 without using any organic solvent or sacrificial reagent. The superior photocatalytic activity of UiO-67-o-(CH3)2 is attributed to the fact that compared with trifluoromethyl groups, methyl groups could not only elevate CO2 adsorption capacity and reduction potential but also promote photoinduced charge separation and migration. These are evidenced by gas physisorption, photoluminescence, time-resolved photoluminescence, electrochemical impedance spectroscopy, transient photocurrent characteristics, and density functional theory calculations. The possible working mechanisms of electron-donating methyl groups are also proposed. Moreover, UiO-67-o-(CH3)2 demonstrates excellent reusability for the CO2 reduction. Based on these results, it could be affirmed that the strategy of modulating substituent electronegativity could provide guidance for designing highly efficient photocatalysts.

Acid-Promoted Multicomponent Reaction To Synthesize 4-Phosphorylated 4H-Chromenes.

An effective multicomponent reaction for the synthesis of 4-phosphorylated 4H-chromenes via a tandem phosphorylation/alkylation/cyclization/dehydration sequence with water as the only byproduct was developed. Extensive mechanistic investigations involving in situ NMR experiments, time control experiments, and in situ HRMS experiment allowed us to elucidate the order of each subreaction to arrive at a complete understanding of the underlying mechanism of this multicomponent reaction. Mechanistic data confirm that the reaction begins with a phospha-aldol-elimination, followed by addition of a ketone enolate, intermolecular alkylation, intramolecular cyclization, and dehydration under acidic conditions.

Clinical comprehensive treatment protocol for managing diabetic foot ulcers: A retrospective cohort study.

BACKGROUND: Diabetic foot ulcers (DFUs) are a common complication of diabetes, often leading to severe infections, amputations, and reduced quality of life. The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications. A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs. The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing, reduced amputation rates, and improved overall patient outcomes compared to standard treatment protocols. AIM: To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol. METHODS: This retrospective study included 62 patients with DFUs, enrolled between January 2022 and January 2024, randomly assigned to the experimental (n = 32) or control (n = 30) group. The experimental group received a comprehensive treatment comprising blood circulation improvement, debridement, vacuum sealing drainage, recombinant human epidermal growth factor and anti-inflammatory dressing, and skin grafting. The control group received standard treatment, which included wound cleaning and dressing, antibiotics administration, and surgical debridement or amputation, if necessary. Time taken to reduce the white blood cell count, number of dressing changes, wound healing rate and time, and amputation rate were assessed. RESULTS: The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate, wound healing time, and amputation rate. Additionally, the comprehensive treatment protocol was safe and well tolerated by the patients. CONCLUSION: Comprehensive treatment for DFUs is more effective than standard treatment, promoting granulation tissue growth, shortening hospitalization time, reducing pain and amputation rate, improving wound healing, and enhancing quality of life.

[Effects of Fly Ash on the Efficiency and Bacterial Community Structure of Urban Multi-source Organic Solid Waste].

To achieve efficient resource utilization of fly ash and multi-source organic waste, a composting experiment was carried out to investigate the effects of fly ash on co-aerobic composting using kitchens, chicken manure, and sawdust (15:5:2). The effects of different application doses (5 % and 10 %, calculated in total wet weight of organic solid waste) of fly ash on physical and chemical properties, nutrient elements, and bacterial community structure during co-composting were evaluated. The results showed that the addition dose of 5 % and 10 % fly ash significantly increased the highest temperature (56.6 ℃ and 56.9 ℃) and extended the thermophilic period to nine days. Compared with that in the control, the total nutrient content of compost products in the treatments of 5 % FA and 10 % FA was increased by 4.09 % and 13.55 %, respectively. The bacterial community structure changed greatly throughout the composting, and the bacterial diversity of all treatments increased obviously. In the initial stage of composting, Proteobacteria was the dominant phylum of bacteria, with a relative abundance ranging from 35.26 % to 39.40 %. In the thermophilic period, Firmicutes dominated; its relative abundance peaked at 52.46 % in the 5 % FA treatment and 67.72 % in the 10 % FA treatment. Bacillus and Thermobifida were the predominant groups in the thermophilic period of composting. The relative abundance of Bacillus and Thermobifida in the 5 % FA and 10 % FA treatments were 33.41 % and 62.89 %(Bacillus) and 33.06 % and 12.23 %(Thermobifida), respectively. The results of the redundancy analysis (RDA) revealed that different physicochemical indicators had varying degrees of influence on bacteria, with organic matter, pH, available phosphorus, and available potassium being the main environmental factors influencing bacterial community structure. In summary, the addition of fly ash promoted the harmlessness and maturation of co- aerobic composting of urban multi-source organic waste, while optimizing microbial community structure and improving the quality and efficiency of composting.

Analysis of the functional role and mRNA expression of GABABR in the nucleus accumbens of cocaine-addicted rats.

BACKGROUND: Drug addiction is a social and medical problem that must be urgently addressed. The nucleus accumbens (NAc) is closely related to addiction-related learning memory, and γ-aminobutyric acid type B receptor (GABABR) is a potential target for the treatment of drug addiction. However, the role of GABABR activity levels in the NAc in cocaine addiction is unclear. METHODS: In this study, we established an animal model of cocaine dependence, modulated the level of GABABR activity, applied a conditioned place preference assay (CPP) to assess the role of the NAc in reconsolidation of addiction memory, evaluated learning and memory functions by behavioral experiments, examined the expression of GB1, GB2, CREB, p-CREB, PKA, ERK, and BDNF in the NAc by molecular biology experiments, and screened differentially significantly expressed genes by transcriptome sequencing. RESULTS: Our study showed that the GABAB receptor agonist BLF had a significant effect on locomotor distance in rats, promoted an increase in GABA levels and significantly inhibited the PKA and ERK1/2/CREB/BDNF signaling pathways. Moreover, transcriptome sequencing showed that GABABR antagonist intervention identified a total of 21 upregulated mRNAs and 21 downregulated mRNAs. The DE mRNA genes were mainly enriched in tyrosine metabolism; however, further study is needed. CONCLUSION: GABABR activity in the NAc is involved in the regulation of cocaine addiction and may play an important role through key mRNA pathways.

Reprogrammed IDO-Induced Immunosuppressive Microenvironment Synergizes with Immunogenic Magnetothermodynamics for Improved Cancer Therapy.

Indoleamine 2,3-dioxygenase (IDO), highly expressed in hepatocellular carcinoma (HCC), plays a pivotal role in creating an immune-suppressive tumor microenvironment. Inhibiting IDO activity has emerged as a promising immunotherapeutic strategy; however, the delivery of IDO inhibitors to the tumor site is constrained, limiting their therapeutic efficacy. In this study, we developed a magnetic vortex nanodelivery system for the targeted delivery of the IDO inhibitor NLG919, integrated with magnetic hyperthermia therapy to reverse the immune-suppressive microenvironment of liver cancer and inhibit tumor growth. This system comprises thermoresponsive polyethylenimine-coated ferrimagnetic vortex-domain iron oxide nanorings (PI-FVIOs) loaded with NLG919 (NLG919/PI-FVIOs). Under thermal effects, NLG919 can be precisely released from the delivery system, counteracting IDO-mediated immune suppression and synergizing with NLG919/PI-FVIOs-mediated magnetothermodynamic (MTD) therapy-induced immunogenic cell death (ICD), resulting in effective HCC suppression. In vivo studies demonstrate that this combination therapy significantly inhibits tumor growth and metastasis by enhancing the accumulation of cytotoxic T lymphocytes and suppressing regulatory T cells within the tumor. Overall, our findings reveal that NLG919/PI-FVIOs can induce a potent antitumor immune response by disrupting the IDO pathway and activating the ICD, offering a promising therapeutic avenue for HCC treatment.

Semantic contrast with uncertainty-aware pseudo label for lumbar semi-supervised classification.

BACKGROUND: Lumbar disc herniation (LDH) is a prevalent spinal disease that can result in severe pain, with Magnetic resonance imaging (MRI) serving as a commonly diagnostic tool. However, annotating numerous MRI images, necessary for deep learning based LDH diagnosis, can be challenging and labor-intensive. Semi-supervised learning, mainly utilizing pseudo labeling and consistency regularization, can leverage limited labeled images and abundant unlabeled images. However, consistency regularization solely focuses on maintaining the semantic consistency of transformed unlabeled data but fails to utilize the semantic information from labeled data to guide the unlabeled data, and additionally, pseudo labeling is prone to confirmation bias. METHOD: We propose SeCoFixMatch, an innovative approach that seamlessly integrates semantic contrast and uncertainty-aware pseudo labeling into semi-supervised learning. Semantic contrast constraints the semantic consistency between labeled and unlabeled images. Pseudo labels are generated by combining predictive confidence and uncertainty, with uncertainty computing by optimizing the Kullback-Leibler (KL) loss between predictive and target Dirichlet distribution. RESULTS: Comparison with other semi-supervised models and ablation experiment with varying labeled data demonstrate the effectiveness and generalization of proposed model. Notably, SeCoFixMatch, trained with just 40 labels, outperforms the baseline model trained with 200 labels, reducing the annotation effort by a remarkable 80%. CONCLUSIONS: Proposed pseudo labeling algorithm generates more precise pseudo labels for semantic contrastive learning and semantic contrastive learning facilitates better feature representation, thereby further improving the prediction accuracy of pseudo label. The mutual reinforcement of pseudo labeling and semantic contrast constraints boosts the performance of semi-supervised algorithm.

Intracellular magnetic hyperthermia reverses sorafenib resistance in hepatocellular carcinoma through its action on signaling pathways.

Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), unfortunately encounters resistance in most patients, leading to disease progression. Traditional approaches to counteract this resistance, particularly those targeting the RAF-MEK-ERK pathway, often face clinical feasibility limitations. Magnetic hyperthermia (MH), unlike conventional thermal therapies, emerges as a promising alternative. It uniquely combines magnetothermal effects with an increase in reactive oxygen species (ROS). This study found the potential of intracellular MH enhanced the efficacy of sorafenib, increased cellular sensitivity to sorafenib, and reversed sorafenib resistance by inhibiting the RAF-MEK-ERK pathway in an ROS-dependent manner in a sorafenib-resistant HCC cell. Further, in a sorafenib-resistant HCC mouse model, MH significantly sensitized tumors to sorafenib therapy, resulting in inhibited tumor growth and improved survival rates. This presents a promising strategy to overcome sorafenib resistance in HCC, potentially enhancing therapeutic outcomes for patients with this challenging condition.

Association of Life's essential 8 score with the risk of all-cause mortality and cardio-cerebrovascular mortality in patients with stroke.

BACKGROUND: A higher Life's Essential 8 (LE8)-based cardiovascular health (CVH) has been reported to be associated with a lower risk of both all-cause mortality and cardio-cerebrovascular diseases (CCVDs) related mortality in adults in the United States. At the same time, multiple studies have shown a significant negative association of CVH with the risk of stroke and CCVDs. Since no research has investigated the applicability of the LE8 in stroke patients, this study aimed to explore the association of LE8 with all-cause mortality and cardio-cerebrovascular mortality in stroke patients. METHODS: Data of patients were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2007-2018 in this retrospective cohort study. Weighted univariate and multivariate COX regression analyses were utilized to investigate the associations of LE8 with all-cause mortality and cardio-cerebrovascular mortality. We further explored these relationships in subgroups of age, gender, body mass index (BMI), cancer, congestive heart failure (CHF), and coronary heart disease (CHD). The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among the eligible patients, 278 died from all-cause and 89 (8.38%) of them died due to CCVDs. After adjusting for covariates, patients with LE8 score ≥ 58.75 seemed to have both lower risk of all-cause mortality (HR = 0.46, 95%CI: 0.31-0.69) and cardio-cerebrovascular mortality (HR = 0.51, 95%CI: 0.26-0.98), comparing to those with LE8 score < 48.123. Higher LE8 scores were associated with lower risk of all-cause mortality in patients aged < 65 years old, without cancer, and whatever the gender, BMI, CHF or CHD conditions (all P < 0.05). The relationships between high LE8 scores and low cardio-cerebrovascular mortality risk were only found in age < 65 years old and non-cancer subgroups (all P < 0.05). CONCLUSION: A higher LE8 score was associated with lower risk of both all-cause mortality and cardio-cerebrovascular mortality in patients with stroke, which may provide some reference for risk management and prognosis improvement in stoke. However, more evidences are needed to verify this beneficial role of high LE8 score in stroke prognosis.