Characterization and Genomic Analyses of dsDNA Vibriophage vB_VpaM_XM1, Representing a New Viral Family.

A novel vibriophage vB_VpaM_XM1 (XM1) was described in the present study. Morphological analysis revealed that phage XM1 had Myovirus morphology, with an oblate icosahedral head and a long contractile tail. The genome size of XM1 is 46,056 bp, with a G + C content of 42.51%, encoding 69 open reading frames (ORFs). Moreover, XM1 showed a narrow host range, only lysing Vibrio xuii LMG 21346 (T) JL2919, Vibrio parahaemolyticus 1.1997, and V. parahaemolyticus MCCC 1H00029 among the tested bacteria. One-step growth curves showed that XM1 has a 20-min latent period and a burst size of 398 plaque-forming units (PFU)/cell. In addition, XM1 exhibited broad pH, thermal, and salinity stability, as well as strong lytic activity, even at a multiplicity of infection (MOI) of 0.001. Multiple genome comparisons and phylogenetic analyses showed that phage XM1 is grouped in a clade with three other phages, including Vibrio phages Rostov 7, X29, and phi 2, and is distinct from all known viral families that have ratified by the standard genomic analysis of the International Committee on Taxonomy of Viruses (ICTV). Therefore, the above four phages might represent a new viral family, tentatively named Weiviridae. The broad physiological adaptability of phage XM1 and its high lytic activity and host specificity indicated that this novel phage is a good candidate for being used as a therapeutic bioagent against infections caused by certain V. parahaemolyticus strains.

Multifunctional human serum albumin-crosslinked and self-assembling nanoparticles for therapy of periodontitis by anti-oxidation, anti-inflammation and osteogenesis.

Periodontitis is a chronic inflammatory disease that can result in the irreversible loss of tooth-supporting tissues and elevate the likelihood and intensity of systemic diseases. The presence of reactive oxygen species (ROS) and associated related oxidative stress is intricately linked to the progression and severity of periodontal inflammation. Targeted removal of local ROS may serve to attenuate inflammation, improve the unfavorable periodontal microenvironment and potentially reverse ensuing pathological cascades. These ROS scavenging nanoparticles, which possess additional characteristics such as anti-inflammation and osteogenic differentiation, are highly sought after for the treatment of periodontitis. In this study, negative charged human serum albumin-crosslinked manganese-doped self-assembling Prussian blue nanoparticles (HSA-MDSPB NPs) were fabricated. These nanoparticles demonstrate the ability to scavenge multiple ROS including superoxide anion, free hydroxyl radicals, singlet oxygen and hydrogen peroxide. Additionally, HSA-MDSPB NPs exhibit the capacity to alleviate inflammation in gingiva and alveolar bone both in vitro and in vivo. Furthermore, HSA-MDSPB NPs have been shown to play a role in promoting the polarization of macrophages from the M1 to M2 phenotype, resulting in reduced production of pro-inflammatory cytokines. More attractively, HSA-MDSPB NPs have been demonstrated to enhance cellular osteogenic differentiation. These properties of HSA-MDSPB NPs contribute to decreased inflammation, extracellular matrix degradation and bone loss in periodontal tissue. In conclusion, the multifunctional nature of HSA-MDSPB NPs provides a promising therapeutic approach for the treatment of periodontitis.

The influence factors on pit and fissure sealing behavior of 12-year-old children: a cross-sectional study in Zhejiang, China.

BACKGROUND: In the 21st century, dental caries remains a global burden, particularly severely affecting the growth and quality of life of 12-year-old children. Fortunately, pit and fissure sealing (PFS) procedures can effectively prevent molars from caries. Hence, this study focused on the relationship between PFS and oral epidemiological factors in 12-year-old children. METHODS: A cross-sectional survey was conducted in 12-year-old children from 11 cities in Zhejiang Province. Their dental conditions were collected through questionnaires, as well as basic information such as relevant family information, oral health knowledge and behavior. Then, logistic regression analysis was used to identify the influencing factors associated with PFS. RESULTS: A total of 1204 children were included, with 252 in the PFS group and 952 in the non-PFS group. There were significant differences between the two groups in terms of decayed, missing and filled teeth (DMFT) score, first permanent molar DMFT score, residential area, educational level of parents, tooth-brushing frequency, use of dental floss, oral examination in a medical institution, having taken courses on oral health care, as well as having knowledge that tooth brushing could effectively prevent gingival inflammation, PFS could protect teeth, and oral disease may affect general health. According to further logistic regression analysis, the independent factors influencing PFS included use of dental floss [odds ratios (OR) = 1.672, 95% confidence intervals (CI) = 1.235-2.263, P = 0.001], having taken courses on oral health care (OR = 0.713, 95% CI = 0.515-0.988, P = 0.042), having knowledge that tooth brushing is effective in preventing gingival inflammation (OR = 0.627, 95% CI = 0.389-0.987, P = 0.044) and having knowledge that PFS can protect teeth (OR = 0.589, 95% CI = 0.438-0.791, P < 0.001). CONCLUSION: PFS can reduce the mean DMFT score of 12-year-old children. Independent influencing factors of PFS consist of use of dental floss, having taken courses on oral health care, oral health behavior and knowledge level.

Knowledge, attitudes, and practice of physicians and pharmacists regarding the prevention and treatment of cardiovascular toxicity associated with cancer treatment.

This study aimed to explore physicians' and pharmacists' knowledge, attitudes, and practice (KAP) regarding the prevention and treatment of cardiovascular toxicity associated with cancer treatment. A multicenter cross-sectional study included physicians and pharmacists between April 2023 and June 2023. The study included 918 participants (514 physicians and 404 pharmacists). The average scores of knowledge, attitudes, and practice were 11.6 ± 3.39, 24.7 ± 2.6, and 26.3 ± 6.8 points. Sufficient knowledge was significantly associated with age ≥ 41 years (odds ratio (OR) = 2.745, 95% confidence interval (CI) 1.086-6.941, P = 0.033), male (OR = 2.745, 95% CI 1.150-2.223, P = 0.005), bachelor's degree (OR = 0.084, 95% CI 0.013-0.533, P = 0.009), master's degree and above (OR = 0.096, 95% CI 0.015-0.609, P = 0.013), physician occupation (OR = 7.601, 95% CI 1.337-43.207, P = 0.022), pharmacy department (OR = 18.858, 95% CI 3.245-109.57, P = 0.001), oncology department (OR = 4.304, 95% CI 2.426-7.634, P < 0.001), cardiology department (OR = 3.001, 95% CI 1.387-6.492, P = 0.005), hospitals located in Eastern China (OR = 1.957, 95% CI 1.120-3.418, P = 0.018), and hospitals located in Western China (OR = 3.137, 95% CI 1.783-5.518, P < 0.001). Positive attitudes were significantly associated with a senior professional title (OR = 2.989, 95% CI 1.124-7.954, P = 0.028) and hospitals located in Eastern China (OR = 0.424, 95% CI 0.257-0.698, P = 0.001), Western China (OR = 0.231, 95% CI 0.136-0.394, P < 0.001), and Southern China (OR = 0.341, 95% CI 0.198-0.587, P < 0.001). Proactive practice was significantly associated with male (OR = 1.414, 95% CI 1.029-1.943, P = 0.033), senior professional title (OR = 3.838, 95% CI 1.176-12.524, P = 0.026), oncology department (OR = 3.827, 95% CI 2.336-6.272, P < 0.001), and cardiology department (OR = 2.428, 95% CI 1.263-4.669, P = 0.008). Both physicians and pharmacists had positive attitudes toward the prevention and treatment of cardiovascular toxicity associated with cancer treatment, while their knowledge and practice were not as proactive.

Contrastive Unsupervised Representation Learning With Optimize-Selected Training Samples.

Contrastive unsupervised representation learning (CURL) is a technique that seeks to learn feature sets from unlabeled data. It has found widespread and successful application in unsupervised feature learning, with the design of positive and negative pairs serving as the type of data samples. While CURL has seen empirical successes in recent years, there is still room for improvement in terms of the pair data generation process. This includes tasks such as combining and re-filtering samples, or implementing transformations among positive/negative pairs. We refer to this as the sample selection process. In this article, we introduce an optimized pair-data sample selection method for CURL. This method efficiently ensures that the two types of sampled data (similar pair and dissimilar pair) do not belong to the same class. We provide a theoretical analysis to demonstrate why our proposed method enhances learning performance by analyzing its error probability. Furthermore, we extend our proof into PAC-Bayes generalization to illustrate how our method tightens the bounds provided in previous literature. Our numerical experiments on text/image datasets show that our method achieves competitive accuracy with good generalization bounds.

Synergistic Effects of Shed-Derived Exosomes, Cu2+, and an Injectable Hyaluronic Acid Hydrogel on Antibacterial, Anti-inflammatory, and Osteogenic Activity for Periodontal Bone Regeneration.

The primary pathology of periodontitis involves the gradual deterioration of periodontal tissues resulting from the inflammatory reaction triggered by bacterial infection. In this study, a novel drug for periodontal pocket injection, known as the Shed-Cu-HA hydrogel, was developed by incorporating copper ions (Cu2+) and Shed-derived exosomes (Shed-exo) inside the hyaluronic acid (HA) hydrogel. Suitable concentrations of Cu2+ and Shed-exo released from Shed-Cu-HA enhanced cell viability and cell proliferation of human periodontal ligament stem cells. Additionally, the Shed-Cu-HA demonstrated remarkable antibacterial effects against the key periodontal pathogen (Aa) owing to the synergistic effect of Cu2+ and HA. Furthermore, the material effectively suppressed macrophage inflammatory response via the IL-6/JAK2/STAT3 pathway. Moreover, the Shed-Cu-HA, combining the inflammation-regulating properties of HA with the synergistic osteogenic activity of Shed-exo and Cu2+, effectively upregulated the expression of genes and proteins associated with osteogenic differentiation. The experimental findings from a mouse periodontitis model demonstrated that the administration of Shed-Cu-HA effectively reduced the extent of inflammatory cell infiltration and bacterial infections in gingival tissues and facilitated the regeneration of periodontal bone tissues and collagen after 2 and 4 weeks of injection. Consequently, it holds significant prospects for future applications in periodontitis treatment.

Determinants of sedentary behavior in community-dwelling older adults with type 2 diabetes based on the behavioral change wheel: a path analysis.

BACKGROUND: Sedentary behavior (SB) is deeply ingrained in the daily lives of community-dwelling older adults with type 2 diabetes mellitus (T2DM). However, the specific underlying mechanisms of the determinants associated with SB remain elusive. We aimed to explore the determinants of SB based on the behavior change wheel framework as well as a literature review. METHODS: This cross-sectional study recruited 489 community-dwelling older adults with T2DM in Jinan City, Shandong Province, China. Convenience sampling was used to select participants from relevant communities. This study used the Measure of Older Adults' Sedentary Time-T2DM, the Abbreviated-Neighborhood Environment Walkability Scale, the Social Support Rating Scale, the Lubben Social Network Scale 6, the Subjective Social Norms Questionnaire for Sedentary Behavior, the Functional Activities Questionnaire, the Numerical Rating Scale, the Short Physical Performance Battery, and the Montreal Cognitive Assessment Text to assess the levels of and the determinants of SB. Descriptive statistical analysis and path analysis were conducted to analyze and interpret the data. RESULTS: Pain, cognitive function, social isolation, and social support had direct and indirect effects on SB in community-dwelling older adults with T2DM (total effects: ß = 0.426, ß = -0.171, ß = -0.209, and ß = -0.128, respectively), and physical function, walking environment, and social function had direct effects on patients' SB (total effects: ß = -0.180, ß = -0.163, and ß = 0.127, respectively). All the above pathways were statistically significant (P < 0.05). The path analysis showed that the model had acceptable fit indices: RMSEA = 0.014, χ 2/df = 1.100, GFI = 0.999, AGFI = 0.980, NFI = 0.997, RFI = 0.954, IFI = 1.000, TLI = 0.996, CFI = 1.000. CONCLUSION: Capability (physical function, pain, and cognitive function), opportunity (social isolation, walking environment, and social support), and motivation (social function) were effective predictors of SB in community-dwelling older adults with T2DM. Deeper knowledge regarding these associations may help healthcare providers design targeted intervention strategies to decrease levels of SB in this specific population.

iGlarLixi for type 2 diabetes: a systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy and tolerability of iGlarLixi-a novel, fixed-ratio, soluble combination of insulin glargine and lixisenatide-for the treatment of type 2 diabetes (T2D). METHODS: The PubMed, Embase, Cochrane Library and ClinicalTrials.gov databases were searched from inception to November 15, 2023 to identify randomized controlled trials (RCTs) comparing iGlarLixi with a placebo or any other antidiabetic agent in adults with T2D. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated to evaluate the outcomes. RESULTS: A total of 10 trials enrolling 6071 T2D patients were included. Compared with placebos or other antidiabetic agents, iGlarLixi exerted beneficial effects on changes in HbA1c, the percentage of patients who achieved an HbA1c < 7%, the percentage of patients who achieved an HbA1c < 6.5%, the percentage of patients who achieved an HbA1c < 7.0% without weight gain and/or without severe or blood glucose-confirmed hypoglycemic episodes, changes in fasting plasma glucose, and changes in self-measured plasma glucose. Regarding safety, iGlarLixi did not increase the incidence of severe hypoglycemia or serious adverse events but did increase the incidence of gastrointestinal adverse events, symptomatic hypoglycemia, and adverse events (e.g., nausea, vomiting, diarrhea). CONCLUSIONS: iGlarLixi showed improved efficacy and safety in patients with T2D. Additional large, multicenter RCTs are warranted to obtain deeper insights into the efficacy and safety of iGlarLixi, thereby providing guidance for clinical treatment decisions.

Redox-induced controllable engineering of MnO2-MnxCo3-xO4 interface to boost catalytic oxidation of ethane.

Multicomponent oxides are intriguing materials in heterogeneous catalysis, and the interface between various components often plays an essential role in oxidations. However, the underlying principles of how the hetero-interface affects the catalytic process remain largely unexplored. Here we report a unique structure design of MnCoOx catalysts by chemical reduction, specifically for ethane oxidation. Part of the Mn ions incorporates with Co oxides to form spinel MnxCo3-xO4, while the rests stay as MnO2 domains to create the MnO2-MnxCo3-xO4 interface. MnCoOx with Mn/Co ratio of 0.5 exhibits an excellent activity and stability up to 1000 h under humid conditions. The synergistic effects between MnO2 and MnxCo3-xO4 are elucidated, in which the C2H6 tends to be adsorbed on the interfacial Co sites and subsequently break the C-H bonds on the reactive lattice O of MnO2 layer. Findings from this study provide valuable insights for the rational design of efficient catalysts for alkane combustion.

Ruxolitinib-loaded cytokine nanosponge alleviated the cytokine storm and dampened macrophage overactivation for the treatment of hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by a positive feedback loop between cytokine storm and macrophages and lymphocytes overactivation, which could serve as a valid therapeutic target for HLH treatment. In this study, the clinically extensively used JAK1/2 inhibitor ruxolitinib was encapsulated into macrophage membrane-coated nanoparticles (M@NP-R) with high drug-loading efficiency for targeted HLH treatment. In vitro and in vivo studies demonstrated that M@NP-R not only efficiently adsorbed extracellular proinflammation cytokines, like IFN-γ and IL-6 to alleviate the cytokine storm, but also effectively dampened macrophage activation and proliferation by intracellular JAK/STAT signaling pathway inhibition. M@NP-R treatment significantly ameliorated the clinical and laboratory manifestations of HLH in mouse models, including trilineage cytopenia, hypercytokinemia, organomegaly, hepatorenal dysfunction, and tissue inflammation. Importantly, M@NP-R significantly enhanced the survival of the lethal HLH mice. Altogether, M@NP-R successfully blocked the positive feedback loop between the cytokine storm and macrophage overactivation by depleting extracellular inflammatory cytokines and inhibiting the intracellular JAK/STAT signaling pathway, both of which worked synergistically in HLH treatment. As ruxolitinib has already been extensively used in clinics with favorable safety, and M@NP is biodegradable and highly biocompatible, M@NP-R has good prospects for clinical translation.

High Intensity Focused Ultrasound-Driven Nanomotor for Effective Ferroptosis-Immunotherapy of TNBC.

The heterogeneity of triple-negative breast cancers (TNBC) remains challenging for various treatments. Ferroptosis, a recently identified form of cell death resulting from the unrestrained peroxidation of phospholipids, represents a potential vulnerability in TNBC. In this study, a high intensity focused ultrasound (HIFU)-driven nanomotor is developed for effective therapy of TNBC through induction of ferroptosis. Through bioinformatics analysis of typical ferroptosis-associated genes in the FUSCCTNBC dataset, gambogic acid is identified as a promising ferroptosis drug and loaded it into the nanomotor. It is found that the rapid motion of nanomotors propelled by HIFU significantly enhanced tumor accumulation and penetration. More importantly, HIFU not only actuated nanomotors to trigger effective ferroptosis of TNBC cells, but also drove nanomotors to activate ferroptosis-mediated antitumor immunity in primary and metastatic TNBC models, resulting in effective tumor regression and prevention of metastases. Overall, HIFU-driven nanomotors show great potential for ferroptosis-immunotherapy of TNBC.

The possible neural mechanism of neuropathic pain evoked by motor imagery in pediatric patients with complete spinal cord injury: A preliminary brain structure study based on VBM.

In this study, we observed pediatric complete spinal cord injury (CSCI) patients receiving MI training and divided them into different groups according to the effect of motor imagery (MI) training on neuropathic pain (NP). Then, we retrospectively analysed the differences in brain structure of these groups before the MI training, identifying brain regions that may predict the effect of MI on NP. Thirty pediatric CSCI patients were included, including 12 patients who experienced NP during MI and 18 patients who did not experience NP during MI according to the MI training follow-up. The 3D high-resolution T1-weighted images of all subjects were obtained using a 3.0 T MRI system before MI training. A two-sample t-test was performed to evaluate the differences in gray matter volume (GMV) between patients who experienced NP and those who did not experience NP during MI. Receiver operating characteristic (ROC) analysis was performed to compute the sensitivity and specificity of the imaging biomarkers for the effect of MI on NP in pediatric CSCI patients. MI evoked NP in some of the pediatric CSCI patients. Compared with patients who did not experience NP, patients who experienced NP during MI showed larger GMV in the right primary sensorimotor cortex (PSMC) and insula. When using the GMV of the right PSMC and insula in combination as a predictor, the area under the curve (AUC) reached 0.824. Our study demonstrated that MI could evoke NP in some pediatric CSCI patients, but not in others. The individual differences in brain reorganization of the right PSMC and insula may contribute to the different effects of MI on NP. Moreover, the GMV of the right PSMC and insula in combination may be an effective indicator for screening pediatric CSCI patients before MI training therapy.

Photocatalytic antibacterial agents based on inorganic semiconductor nanomaterials: a review.

Microbial contamination and antibiotic pollution have threatened public health and it is important to develop a rapid and safe sterilization strategy. Among various disinfection strategies, photocatalytic antibacterial methods have drawn increasing attention due to their efficient disinfection performances and environment-friendly properties. Although there are some reviews about bacterial disinfection, specific reviews on photocatalysis focused on inorganic semiconductor nanomaterials are rarely reported. Herein, we present a systematic summary of recent disinfection developments based on inorganic nanomaterials (including metal oxides, sulfides, phosphides, carbon materials, and corresponding heterostructures) over the past five years. Moreover, key factors and challenges for inorganic nanomaterial-based photocatalytic disinfection are outlined, which holds great potential for future photocatalytic antibacterial applications.

Block mapping and dual-matrix-based watermarking for image authentication with self-recovery capability.

Numerous image authentication techniques have been devised to address the potential security issue of malicious tampering with image content since digital images can be easily duplicated, modified, transformed and diffused via the Internet transmission. However, the existing works still remain many shortcomings in terms of the recovery incapability and detection accuracy with extensive tampering. To improve the performance of tamper detection and image recovery, we present a block mapping and dual-matrix-based watermarking scheme for image authentication with self-recovery capability in this paper. The to-be-embedded watermark information is composed of the authentication data and recovery data. The Authentication Feature Composition Calculation algorithm is proposed to generate the authentication data for image tamper detection and localization. Furthermore, the recovery data for tampered region recovery is comprised of self-recovery bits and mapped-recovery bits. The Set Partition in Hierarchical Trees encoding algorithm is applied to obtain the self-recovery bits, whereas the Rehashing Model-based Block Mapping algorithm is proposed to obtain the mapped-recovery bits for retrieving the damaged codes caused by tampering. Subsequently, the watermark information is embedded into the original image as digital watermarking with the guidance of a dual-matrix. The experimental results demonstrate that comparing with other state-of-the-art works, our proposed scheme not only improves the performance in recovery, but also extends the limitation of tampering rate up to 90%. Furthermore, it obtains a desirable image quality above 40 dB, large watermark payload up to 3.169 bpp, and the effective resistance to malicious attack, such as copy-move and collage attacks.

IDegLira for type 2 diabetes: a systematic review and meta-analysis.

OBJECTIVES: IDegLira is a novel fixed-ratio soluble combination of insulin degludec and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide approved for type 2 diabetes (T2D) patients. Individual trials have assessed the clinical profile of IDegLira vs different comparators. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of IDegLira for T2D. METHODS: PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched from inception to August 15, 2023. The primary outcomes included change from baseline in haemoglobin A1c (HbA1c) and body weight. Risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated to evaluate the outcomes. RESULTS: This meta-analysis identified 1044 citations, and included 13 eligible trials, enroling 7773 patients. Compared with the control groups, IDegLira was optimal in change in HbA1c, percentage of patients achieving HbA1c < 7%, percentage of patients achieving HbA1c < 6.5%, HbA1c < 7.0% without weight gain and without severe or blood glucose (BG)-confirmed hypoglycaemia episodes, HbA1c < 6.5% without weight gain and without severe or BG-confirmed hypoglycaemia episodes, change in fasting plasma glucose, change in self-measured plasma glucose, change in systolic pressure, and total daily insulin dose. No difference was found between the IDegLira and control groups in terms of change in body weight, change in diastolic pressure, severe or BG-confirmed symptomatic hypoglycaemia, nocturnal severe or BG-confirmed symptomatic hypoglycaemia, adverse events or serious adverse events. CONCLUSIONS: In patients with T2D, IDegLira improved glycaemic control whilst balancing out risk for hypoglycaemia and gastrointestinal side effects.

Separation of bile acid isomer plays a pivotal role in bioequivalence evaluation of ursodeoxycholic acid.

Based on our experiences in bile acid profiling, this work developed and validated a liquid chromatography electrospray ionization tandem mass spectrometry method to separate endogenous bile acid isomers and quantitatively determine ursodeoxycholic acid (UDCA), glycoursodeoxycholic acid (GUDCA) and tauroursodeoxycholic acid (TUDCA) in human plasma. The separation was performed on a CORTECS C18 column with the mobile phase consisting of 1.0 mM ammonium acetate and acetonitrile-methanol (80:20, v/v). UDCA, GUDCA and TUDCA were detected in the negative mode on a triple-quadrupole mass spectrometer at the ion transitions of m/z 391 > 391, m/z 448 > 74, m/z 498 > 80, respectively. Phosphate buffer was employed as the surrogate matrix to establish the isotope internal standard corrected calibration curves of analytes. The background-method with a linearity range of 10-200 ng/mL was partially validated to determine the endogenous levels of analytes in blank human plasma, which was incorporated into the validation of bioequivalence-method with a linearity range of 50-10000 ng/mL. The bioequivalence (BE)-method was fully validated with special focus on matrix effects, which have been critically evaluated using the precision and accuracy of quality control samples prepared from the blank human plasma of 12 individuals. It is disclosed for the first time that the BE results of UDCA formulation may yield false results when the method is insufficient to separate UDCA from isoursodeoxycholic acid, a microbial metabolite of both endogenous and exogenous UDCA. The present method has established a milestone for the evaluation of UDCA formulations and is expected to provide a valuable reference for the bioanalytical development of endogenous medicinal products.

Crocetin inhibits choroidal neovascularization in both in vitro and in vivo models.

Choroidal neovascularization (CNV) is the primary pathogenic process underlying wet age-related macular degeneration, leading to severe vision loss. Despite current anti-vascular endothelial growth factor (VEGF) therapies, several limitations persist. Crocetin, a major bioactive constituent of saffron, exhibits multiple pharmacological activities, yet its role and mechanism in CNV remain unclear. Here, we investigated the potential effects of crocetin on CNV using in vitro and in vivo models. In human umbilical vein endothelial cells, crocetin demonstrated inhibition of VEGF-induced cell proliferation, migration, and tube formation in vitro, as assessed by CCK-8 and EdU assays, transwell and scratch assays, and tube formation analysis. Additionally, crocetin suppressed choroidal sprouting in ex vivo experiments. In the human retinal pigment epithelium (RPE) cell line ARPE-19, crocetin attenuated cobalt chloride-induced hypoxic cell injury, as evidenced by CCK-8 assay. As evaluated by quantitative PCR and Western blot assay, it also reduced hypoxia-induced expression of VEGF and hypoxia-inducible factor 1α (HIF-1α), while enhancing zonula occludens-1 expression. In a laser-induced CNV mouse model, intravitreal administration of crocetin significantly reduced CNV size and suppressed elevated expressions of VEGF, HIF-1α, TNFα, IL-1ß, and IL-6. Moreover, crocetin treatment attenuated the elevation of phospho-S6 in laser-induced CNV and hypoxia-induced RPE cells, suggesting its potential anti-angiogenic effects through antagonizing the mechanistic target of rapamycin complex 1 (mTORC1) signaling. Our findings indicate that crocetin may hold promise as an effective drug for the prevention and treatment of CNV.

"All about the value?" Decisional needs of breast reconstruction for breast cancer patients in the Chinese context: A mixed-methods study.

OBJECTIVE: To explore breast cancer (BC) patients' participation in breast reconstruction (BR) decision-making and specific decisional needs, especially the manifestations and causes of decisional conflicts, in China. METHODS: A mixed-methods study was conducted using triangulation of data from interviews and a questionnaire survey with health care professionals (HCPs) and BC patients with BR decision-making experience at 5 Beijing centers. The Ottawa Decision Support Framework guided (ODSF) the qualitative and quantitative data analyses. RESULTS: A total of 82.53% of Chinese BC patients would consider BR. Seven themes captured patients' BR decisional needs per the ODSF: inadequate support/resources (100%, 58.82%) and knowledge (75%, 52.94%) were most frequently cited. Health beliefs (unclear values) reflected Chinese characteristics. Patients had inadequate knowledge (M=19.99/50, SD=8.67) but positive BR attitudes (M=59.48/95, SD=10.45). CONCLUSIONS: BR decisions for Chinese BC patients are complex and often accompanied by decisional conflicts. Inadequate knowledge and inadequate support and resources contribute to these conflicts, emphasizing the need for culturally tailored information and support to promote SDM. PRACTICE IMPLICATIONS: HCPs need specialized training in SDM to guide patients in decision-making. It is essential to provide relevant resources and support that are culturally and clinically appropriate for Chinese patients.

Mitochondrial Lipid Metabolism Genes as Diagnostic and Prognostic Indicators in Hepatocellular Carcinoma.

Background: Due to the heterogeneity of Hepatocellular carcinoma (HCC), there is an urgent need for reliable diagnosis and prognosis. Mitochondria-mediated abnormal lipid metabolism affects the occurrence and progression of HCC. Objective: This study aims to investigate the potential of mitochondrial lipid metabolism (MTLM) genes as diagnostic and independent prognostic biomarkers for HCC. Methods: MTLM genes were screened from the Gene Expression Omnibus (GEO) and Gene Set Enrichment Analysis (GSEA) databases, followed by an evaluation of their diagnostic values in both The Cancer Genome Atlas Program (TCGA) and the Affiliated Cancer Hospital of Guangxi Medical University (GXMU) cohort. The TCGA dataset was utilized to construct a gene signature and investigate the prognostic significance, immune infiltration, and copy number alterations. The validity of the prognostic signature was confirmed through GEO, International Cancer Genome Consortium (ICGC), and GXMU cohorts. Results: The diagnostic receiver operating characteristic (ROC) curve revealed that eight MTLM genes have excellent diagnostic of HCC. A prognostic signature comprising 5 MTLM genes with robust predictive value was constructed using the lasso regression algorithm based on TCGA data. The results of the Stepwise regression model showed that the combination of signature and routine clinical parameters had a higher area under the curve (AUC) compared to a single risk score. Further, a nomogram was constructed to predict the survival probability of HCC, and the calibration curves demonstrated a perfect predictive ability. Finally, the risk score also unveiled the different immune and mutation statuses between the two different risk groups. Conclusion: MTLT-related genes may serve as diagnostic and prognostic biomarkers for HCC as well as novel therapeutic targets, which may be beneficial for facilitating further understanding the molecular pathogenesis and providing potential therapeutic strategies for HCC.

Clinical Study of Glutamine Combined with Early Enteral Nutrition Support on Nutritional Status of Gastric Cancer Patients Undergoing Neoadjuvant Chemotherapy.

Objective: To explore the clinical study of glutamine combined with early enteral nutrition support on the nutritional status of gastric cancer patients undergoing neoadjuvant chemotherapy. Methods: Divided into control and observation groups, a control group received routine enteral nutrition, while the observation group received an additional 0.5 g/kg/d of glutamine. The researchers measured nutritional indicators, immunoglobulins, T lymphocyte subsets, and stress indexes such as fasting blood sugar and C-reactive protein throughout the study. Results: Before nutritional support, there was no significant difference in the HGB, TP, and ALB levels. During nutritional support, however, the observation group began registering significantly higher levels of HGB, TP, and ALB, suggesting that glutamine intervention can improve the nutritional status of patients. Throughout the study, the CD4+ level showed a consistent increase in the observation group. The levels of IgA and IgG in the observation group also grew significantly higher. Both groups had higher blood glucose levels before nutritional support. However, on day 8 and day 15, the levels decreased. The observation group had significantly lower fasting blood glucose (FBG) levels than the control group. By day 15, the FBG levels in the observation group were close to normal. The CRP level showed a consistent decrease in the observation group compared to the control group on day 8 and day 15. Glutamine intervention appears to improve the stress capacity of gastric cancer patients undergoing neoadjuvant chemotherapy. Overall, the findings suggest that glutamine intervention in enteral nutrition can significantly improve immune function, nutritional status, and stress capacity in gastric cancer patients undergoing neoadjuvant chemotherapy and appears to be more effective than conventional enteral nutrition. Conclusion: The combination of glutamine and early enteral nutrition support can significantly improve gastric cancer patients undergoing neoadjuvant chemotherapy's nutritional status and immune function levels. It is a safe and reliable enteral nutrition support method worthy of clinical promotion.