Design and Antimalarial Evaluation of Polydopamine-Modified Methyl Artelinate Nanoparticles.

Targeted nanodrug delivery systems are highly anticipated for the treatment of malaria. It is known that Plasmodium can induce new permeability pathways (NPPs) on the membrane of infected red blood cells (iRBCs) for their nutrient uptake. The NPPs also enable the uptake of nanoparticles (NPs) smaller than 80 nm. Additionally, Plasmodium maintains a stable, slightly acidic, and reductive internal environment with higher glutathione (GSH) levels. Based on this knowledge, methyl artelinate (MA, a prodrug-like derivative of dihydroartemisinin) nanoparticles (MA-PCL-NPs) were developed using poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) by a thin-film dispersion method and were further coated with polydopamine (PDA) to obtain MA-PCL@PDA-NPs with a particle size of ∼30 nm. The biomaterial PDA can be degraded in slightly acidic and reductive environments, thereby serving as triggers for drug release. MA could generate reactive oxygen species and decrease GSH levels, consequently causing parasite damage. The in vitro release experiment results indicated that the cumulative release percentage of MA from MA-PCL@PDA-NPs was considerably higher in phosphate buffer with 10 mM GSH at pH 5.5 (88.10%) than in phosphate buffer without GSH at pH 7.4 (16.98%). The green fluorescence within iRBCs of coumarin 6, the probe of NPs (C6-PCL@PDA-NPs), could be reduced significantly after adding the NPP inhibitor furosemide (p < 0.001), which demonstrated that MA-PCL@PDA-NPs could be ingested into iRBCs through NPPs. In vivo antimalarial pharmacodynamics in Plasmodium berghei K173-bearing mice showed that the inhibition ratio of MA-PCL@PDA-NPs (93.96%) was significantly higher than that of commercial artesunate injection (AS-Inj, 63.33%). The above results showed that the developed MA-PCL@PDA-NPs possessed pH-GSH dual-responsive drug release characteristics and targeting efficacy for iRBCs, leading to higher antimalarial efficacy against Plasmodium.

Genome-wide association study identifies the genetic basis of key agronomic traits in 207 sugar beet accessions.

Sugar beet (Beta vulgaris) has emerged as one of the two primary crops, alongside sugarcane, for global sugar production. Comprehensively understanding sucrose synthesis, transport, and accumulation in sugar beet holds great significance for enhancing sugar production. In this study, we collected a diverse set of 269 sugar beet accessions worldwide and measured 12 phenotypes, comprising biomass, soluble sugar content, and 10 taproot-related traits. We re-sequenced 207 accessions to explore genetic diversity and population structure. Then we employed a genome-wide association study (GWAS) and RNA-seq to identify single-nucleotide polymorphisms and genes associated with natural phenotypic variations. Our findings revealed a panel of genes potentially regulating biomass and sugar accumulation, notably the dual-role gene UDP-glucose 4-epimerase, which genetically balances sugar accumulation and cell wall synthesis. In summary, this study provides a foundation for molecular breeding in sugar beet.

Integrating Contrast-enhanced US to O-RADS US for Classification of Adnexal Lesions with Solid Components: Time-intensity Curve Analysis versus Visual Assessment.

Purpose To compare the diagnostic performance of time-intensity curve (TIC) analysis and subjective visual assessment of contrast-enhanced US (CEUS) when integrated with the Ovarian-Adnexal Reporting and Data System (O-RADS) US risk stratification system for characterizing adnexal lesions with solid components. Materials and Methods In this prospective multicenter study conducted from September 2021 to December 2022, female individuals with suspected adnexal lesions containing solid components detected at routine US were enrolled. All participants underwent preoperative CEUS examinations. Histopathologic findings were used as the reference standard for diagnosis. Lesions were classified according to the O-RADS US system. Enhancement of solid tissue compared with the outer myometrium was evaluated using both TIC analysis and subjective visual assessment. The diagnostic performance of O-RADS alone and each CEUS assessment method when integrated with the O-RADS US system was assessed and compared using receiver operating characteristic curve analysis. Results A total of 180 lesions (80 malignant and 100 benign histopathologic outcomes) in 175 participants (median age, 47 years [IQR, 33-56]) were analyzed. Incorporating CEUS (assessed through both TIC analysis and subjective visual assessment) with O-RADS US showed significantly improved diagnostic performance over O-RADS US alone, with an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI: 0.80, 0.91) compared with 0.78 (95% CI: 0.71, 0.84). No evidence of a difference was observed between the AUCs of TIC analysis and subjective visual assessment in the enhancement evaluation of solid tissue with CEUS for adnexal malignancy categorization (P = .83). Conclusion Subjective visual assessment and TIC analysis of CEUS features when integrated with the O-RADS US scoring system showed comparable diagnostic performance in assigning adnexal malignancy risk. Keywords: Adnexal Lesions, Contrast-enhanced US, O-RADS, Time-intensity Curve Analysis Supplemental material is available for this article. © RSNA, 2024.

Expression Changes of miRNAs in Humans and Animal Models of Amyotrophic Lateral Sclerosis and Their Potential Application for Clinical Diagnosis.

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease. Current detection methods can only confirm the diagnosis at the onset of the disease, missing the critical window for early treatment. Recent studies using animal models have found that detecting changes in miRNA sites can predict the onset and severity of the disease in its early stages, facilitating early diagnosis and treatment. miRNAs show expression changes in motor neurons that connect the brain, spinal cord, and brain stem, as well as in the skeletal muscle in mouse models of ALS. Clinically, expression changes in some miRNAs in patients align with those in mouse models, such as the upregulation of miR-29b in the brain and the upregulation of miR-206 in the skeletal muscle. This study provides an overview of some miRNA study findings in humans as well as in animal models, including SOD1, FUS, TDP-43, and C9orf72 transgenic mice and wobbler mice, highlighting the potential of miRNAs as diagnostic markers for ALS. miR-21 and miR-206 are aberrantly expressed in both mouse model and patient samples, positioning them as key potential diagnostic markers in ALS. Additionally, miR-29a, miR-29b, miR-181a, and miR-142-3p have shown aberrant expression in both types of samples and show promise as clinical targets for ALS. Finally, miR-1197 and miR-486b-5p have been recently identified as aberrantly expressed miRNAs in mouse models for ALS, although further studies are needed to determine their viability as diagnostic targets.

Unsupervised and Self-supervised Learning in Low-Dose Computed Tomography Denoising: Insights from Training Strategies.

In recent years, X-ray low-dose computed tomography (LDCT) has garnered widespread attention due to its significant reduction in the risk of patient radiation exposure. However, LDCT images often contain a substantial amount of noises, adversely affecting diagnostic quality. To mitigate this, a plethora of LDCT denoising methods have been proposed. Among them, deep learning (DL) approaches have emerged as the most effective, due to their robust feature extraction capabilities. Yet, the prevalent use of supervised training paradigms is often impractical due to the challenges in acquiring low-dose and normal-dose CT pairs in clinical settings. Consequently, unsupervised and self-supervised deep learning methods have been introduced for LDCT denoising, showing considerable potential for clinical applications. These methods' efficacy hinges on training strategies. Notably, there appears to be no comprehensive reviews of these strategies. Our review aims to address this gap, offering insights and guidance for researchers and practitioners. Based on training strategies, we categorize the LDCT methods into six groups: (i) cycle consistency-based, (ii) score matching-based, (iii) statistical characteristics of noise-based, (iv) similarity-based, (v) LDCT synthesis model-based, and (vi) hybrid methods. For each category, we delve into the theoretical underpinnings, training strategies, strengths, and limitations. In addition, we also summarize the open source codes of the reviewed methods. Finally, the review concludes with a discussion on open issues and future research directions.

Effect of the nurse-led Hospital Elder Life Program on delirium reduction among delirious patients with COVID-19: A randomized clinical trial.

BACKGROUND: Infectious diseases, such as COVID-19, are high-risk factors for delirium. However, the implementation of nonpharmacological interventions faces major challenges during an infectious disease pandemic. AIMS: To evaluate the effect of the nurse-led Hospital Elder Life Program (NL-HELP) on delirium reduction among delirious patients with COVID-19. DESIGN: A single-blind randomized clinical trial. METHODS: This study recruited 122 delirious patients with COVID-19 from internal medicine wards at West China Hospital in China between January 30 and March 31, 2023. Participants were randomized to the NL-HELP group (n = 62) or the usual care group (n = 60). Patients in the intervention group received the NL-HELP protocol three times daily for 7 days. Patients in the control group received usual care. The primary outcome was the absence/presence of delirium during the intervention period measured by the 3-min Diagnostic Confusion Assessment Method. RESULTS: Fewer patients remained delirious in the NL-HELP group than in the control group. There were significantly more delirium-free days in the NL-HELP group than in the usual care group. There were no statistically significant differences between the two groups in terms of delirium severity, length of hospital stay, delirium at 30 days after discharge, 30-day readmission, 30-day mortality, physical function or quality of life. CONCLUSIONS: This study demonstrated that NL-HELP could reduce the presence of delirium in delirious patients. No effect was observed in terms of shortening the length of hospital stay, reducing 30-day mortality, or improving quality of life. IMPACT: NL-HELP may be effective in reducing the presence of delirium in delirious patients. Further research is needed to determine whether the NL-HELP can improve patient outcomes (e.g. mortality and quality of life) in a larger study. PATIENT OR PUBLIC CONTRIBUTION: Caregivers of delirious patients were invited to provide intervention strategies to prevent or abate delirium, including environmental management, orientation communications and identification of alert signs. TRIAL REGISTRATION: This study was prospectively registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/) Identifier: ChiCTR2300067874.

Comparative evaluation of bonding performance between universal and self-etch adhesives: In vitro study.

Objective: This work aimed to assess the bonding performance of universal adhesive and self-etch adhesives, and a comparative study was conducted using the same acid etching mode. Methods: The selective acid-etching mode was used to simulate bonded restorations to teeth defects of isolated human molars including enamel and dentin. Microtensile bond strength and microleakage of all adhesives were tested and compared after 24 h and 5000 thermocycles, respectively. The morphology of the adhesive interfaces was observed by scanning electron microscopy (SEM) and fluorescent staining. Results: The bond strength and microleakage of Single Bond Universal (SBU) adhesive are comparable to those of self-etch adhesives, although Clearfil Tri-S Bond (S3) exhibited significantly lower bond strength compared to other two self-etch groups evaluated. No significant differences were found in the microleakage resistance of these four adhesives, suggesting their similar effectiveness in sealing the margins of the restorations, although SBU showed the highest resistance of microleakage. The SEM and fluorescent staining results of the resin-dentin interfaces further revealed the formation of abundant resin tags for all adhesives. Conclusions: Self-etch adhesives evaluated in this study performed similarly to universal adhesives in selective acid-etch mode for bond strength and microleakage resistance. Both types of adhesives exhibited effective penetration capabilities into the dentinal tubules. Clinical significance: During the adhesion processes involving both dentin and enamel, self-etch adhesives can serve as alternatives to universal adhesives in selective acid-etch mode.

RNA-binding protein AZGP1 inhibits epithelial cell proliferation by regulating the genes of alternative splicing in COPD.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity, disability, and mortality rates worldwide. RNA-binding proteins (RBPs) might regulate genes involved in oxidative stress and inflammation in COPD patients. Single-cell transcriptome sequencing (scRNA-seq) offers an accurate tool for identifying intercellular heterogeneity and the diversity of immune cells. However, the role of RBPs in the regulation of various cells, especially AT2 cells, remains elusive. MATERIALS AND METHODS: A scRNA-seq dataset (GSE173896) and a bulk RNA-seq dataset acquired from airway tissues (GSE124180) were employed for data mining. Next, RNA-seq analysis was performed in both COPD and control patients. Differentially expressed genes (DEGs) were identified using criteria of fold change (FC ≥ 1.5 or ≤ 1.5) and P value ≤ 0.05. Lastly, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and alternative splicing identification analyses were carried out. RESULTS: RBP genes exhibited specific expression patterns across different cell groups and participated in cell proliferation and mitochondrial dysfunction in AT2 cells. As an RBP, AZGP1 expression was upregulated in both the scRNA-seq and RNA-seq datasets. It might potentially be a candidate immune biomarker that regulates COPD progression by modulating AT2 cell proliferation and adhesion by regulating the expression of SAMD5, DNER, DPYSL3, GBP5, GBP3, and KCNJ2. Moreover, AZGP1 regulated alternative splicing events in COPD, particularly DDAH1 and SFRP1, holding significant implications in COPD. CONCLUSION: RBP gene AZGP1 inhibits epithelial cell proliferation by regulating genes participating in alternative splicing in COPD.

Co-delivery of doxorubicin-dihydroartemisinin prodrug/TEPP-46 nano-liposomes for improving antitumor and decreasing cardiotoxicity in B16-F10 tumor-bearing mice.

In order to reduce the cardiotoxicity of doxorubicin (DOX) and improve its antitumor effect, dihydroartemisinin (DHA) and DOX prodrug (DOX-S-DHA) synthesized via a single sulfur bond was used with TEPP-46 to prepare nano-liposomes (DOX-S-DHA@TEPP-46 Lips). In which, TEPP-46 was expected to exert p53 bidirectional regulation to promote the synergistic antitumor effect of DOX and DHA while reducing cardiotoxicity. DOX-S-DHA@TEPP-46 Lips exhibited uniform particle size, good stability, and excellent redox-responsive activity. DOX-S-DHA@TEPP-46 Lips could significantly inhibit the proliferation of tumor cells, but had less cytotoxicity on normal cells. The presence of TEPP-46 increased the content of p53 protein, which further induced tumor cell apoptosis. DOX-S-DHA@TEPP-46 Lips had satisfactory long circulation to enhance the antitumor efficacy and reversed the cardiotoxicity of DOX in B16-F10 tumor-bearing mice. In conclusion, DOX-S-DHA@TEPP-46 Lips provides a new insight on creating sophisticated redox-sensitive nano-liposomes for cancer therapy as well as the decreased cardiotoxicity of DOX.

Enhancement of anti-PD-L1 antibody plus anlotinib efficacy due to downregulation of PD-L1 in the micro-conduit endothelium within the tumor: a randomized double-blind trial.

OBJECTIVE: The possible enhancing effect of anlotinib on programmed death receptor ligand (PD-L1) antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium, including lymphatic endothelial cells (LECs) and blood endothelial cells (BECs), were determined to identify patients who would benefit from this treatment. METHODS: PD-L1 positivity in LECs, BECs, and tumor cells (TCs) was assessed using paraffin sections with multicolor immunofluorescence in an investigator's brochure clinical trial of TQB2450 (PD-L1 antibody) alone or in combination with anlotinib in patients with non-small cell lung cancer. Progression-free survival (PFS) with different levels of PD-L1 expression was compared between the two groups. RESULTS: Among 75 patients, the median PFS (mPFS) was longer in patients who received TQB2450 with anlotinib [10 and 12 mg (161 and 194 days, respectively)] than patients receiving TQB2450 alone (61 days) [hazard ratio (HR)10 mg = 0.390 (95% confidence interval {CI}, 0.201-0.756), P = 0.005; HR12 mg = 0.397 (0.208-0.756), P = 0.005]. The results were similar among 58 patients with high PD-L1 expression in LECs and TCs [159 and 209 vs. 82 days, HR10 mg = 0.445 (0.210-0.939), P = 0.034; HR12 mg = 0.369 (0.174-0.784), P = 0.009], and 53 patients with high PD-L1 expression in BECs and TCs [161 and 209 vs. 41 days, HR10 mg = 0.340 (0.156-0.742), P = 0.007; HR12 mg = 0.340 (0.159-0.727), P = 0.005]. No differences were detected in the mPFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 cases. CONCLUSIONS: Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs. Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs, which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.

Surface modifications of short quartz fibers and their influence on the physicochemical properties and in vitro cell viability of dental composites.

OBJECTIVE: Although glass fibers are more common, quartz fibers (QFs) are also considered as the ideal reinforcing material in dentistry, due to their superior mechanical strength, high purity, and good photoconductive properties. However, the relatively inert surfaces limit their further applications. Therefore, the aim of this study is to modify the fiber surface properties to improve the interfacial interactions with polymeric resins. METHODS: In this study, we systematically introduced four different surface modification strategies onto short quartz fibers (SQFs) for the preparation of dental composites. Particularly, the acid etching was a facile way to create mechanical interlocking structures. In addition, the silanization process, the sol-gel treatment, and the polymer grafting were further proposed to increase the surface roughness and the reactive sites. The effect of surface modifications on the fiber surface morphological changes, mechanical properties, water stability, and in vitro cell viability of dental composites were investigated. RESULTS: Among all surface-modified SQFs, SQFs-POSS (SQFs modified with methacrylate-POSS) exhibited the roughest surface morphology and highest grafting rates compared with other three materials. Furthermore, all these SQFs were applied as reinforcements to make dimethacrylate-based dental resin composites. Of all fillers, SQFs-POSS demonstrated the best reinforcing effect, providing significantly higher improvements of 55.7 %, 114.3 %, and 164.7 % for flexural strength, flexural modulus, and breaking energy, respectively, over those of SQFs-filled composite. The related reinforcing mechanism was further investigated. The SQFs-POSS-filled composite also exhibited the best water stability performance and in vitro cell viability. SIGNIFICANCE: This work provided valuable insights into the optimization of filler-matrix interaction through fiber surface modifications. Specifically, SQFs-POSS markedly outperformed other formulations in terms of the physicochemical performance and in vitro cytotoxicity, which offers possibilities for developing high-performance dental composites for clinical applications in restorative dentistry.

Synthesis of polymerizable betulin maleic diester derivative for dental restorative resins with antibacterial activity.

OBJECTIVE: Bisphenol A glycidyl methacrylate (Bis-GMA) is of great importance for dental materials as the preferred monomer. However, the presence of bisphenol-A (BPA) core in Bis-GMA structure causes potential concerns since it is associated with endocrine diseases, developmental abnormalities, and cancer lesions. Therefore, it is desirable to develop an alternative replacement for Bis-GMA and explore the intrinsic relationship between monomer structure and resin properties. METHODS: Here, the betulin maleic diester derivative (MABet) was synthesized by a facile esterification reaction using plant-derived betulin and maleic anhydride as raw materials. Its chemical structure was confirmed by 1H and 13C NMR spectra, FT-IR spectra, and HR-MS, respectively. The as-synthesized MABet was then used as polymerizable comonomer to partially or completely substitute Bis-GMA in a 50:50 Bis-GMA: TEGDMA resin (5B5T) to formulate dental restorative resins. These were then determined for the viscosity behavior, light transmittance, real-time degree of conversion, residual monomers, mechanical performance, cytotoxicity, and antibacterial activity against Streptococcus mutans (S. mutans) in detail. RESULTS: Among all experimental resins, increasing the MABet concentration to 50 wt% made the resultant 5MABet5T resin have a maximum in viscosity and appear dark yellowish after polymerization. In contrast, the 1MABet4B5T resin with 10 wt% MABet possessed comparable shear viscosity and polymerization conversion (46.6 ± 1.0% in 60 s), higher flexural and compressive strength (89.7 ± 7.8 MPa; 345.5 ± 14.4 MPa) to those of the 5B5T control (48.5 ± 0.6%; 65.7 ± 6.7 MPa; 223.8 ± 57.1 MPa). This optimal resin also had significantly lower S. mutans colony counts (0.35 ×108 CFU/mL) than 5B5T (7.6 ×108 CFU/mL) without affecting cytocompatibility. SIGNIFICANCE: Introducing plant-derived polymerizable MABet monomer into dental restorative resins is an effective strategy for producing antibacterial dental materials with superior physicochemical property.

Comparative Assessments of Dental Resin Composites: A Focus on Dense Microhybrid Materials.

The performance of dental resin composites is crucially influenced by the sizes and distributions of inorganic fillers. Despite the investigation of a variety of functional particles, glass fillers and nanoscale silica are still the predominant types in dental materials. However, achieving an overall improvement in the performance of resin composites through the optimization of their formulations remains a challenge. This work introduced a "dense" microhybrid filler system with 85 wt % filler loading, leading to the preparation of self-developed resin composites (SRCs). Comparative evaluations of these five SRCs against four commercial products were performed, including mechanical property, polymerization conversion, and shrinkage, along with water sorption and solubility and wear resistance. The results showed that among all SRC groups, SRC3 demonstrated superior mechanical performance, high polymerization conversion, reduced shrinkage, low water absorption and solubility, and acceptable wear resistance. In contrast to commercial products, this optimal SRC3 material was comparable to Z350 XT in flexural and diametral tensile strength and better in flexural modulus and surface hardness. The use of a "dense" microhybrid filler system in the development of resin composites provides a balance between physicochemical property and wear resistance, which may be a promising strategy for the development of composite products.

Sialylation on vesicular integrin ß1 determined endocytic entry of small extracellular vesicles into recipient cells.

BACKGROUND: Small extracellular vesicles (sEV) are closely associated with the development and metastasis of many types of mammalian cancer. Glycoconjugates are highly expressed on sEV and play important roles in sEV biogenesis and their interaction with other cells. However, the study on vesicular glycoconjugates are far behind proteins and nucleic acids. Especially, the functions of sialic acids which are the terminal components of glycoconjugates, are poorly understood in sEV. METHODS: Sialic acid levels on sEV from plasma and bladder cancer cells were determined by ELISA and lectin blotting. Effects of sialylation on sEV uptake were determined by flow cytometry. Vesicular glycoproteins bearing sialic acids responsible for sEV uptake was identified by proteomics and density gradient centrifugation, and their site-specific sialylation functions were assayed by N-glycosylation site mutation. Effects of integrin ß1 bearing sialic acids on the pro-metastatic function of sEV in vivo were explored using Balb/c nu/nu mice. RESULTS: (1) Increased sialic acid levels were observed in sEV from malignant bladder cancer cells. (2) Elimination of sialic acids on sEV impaired sEV uptake by recipient cells. (3) Vesicular integrin ß1 bearing sialic acids was identified to play a key role in sEV uptake. (4) Desialylation of the hybrid domain of vesicular integrin ß1 inhibited its binding to matrix fibronectin, and reduced sEV entry into recipient cells. (5) Sialylation on integrin ß1 affected pro-metastatic function of sEV in Balb/c nu/nu mice. CONCLUSIONS: Taken together, our findings indicate important functional roles of sialic acids in sEV uptake and reprogramming plasticity of surrounding normal epithelial cells.

Exploration of Personalized Treatment for Advanced Hepatocellular Carcinoma: Combination Therapy of Selinexor, Palbociclib, and Pembrolizumab with Umbilical Cord Blood NK Cells.

Objective: To report the efficacy and safety of combination therapy with selinexor, palbociclib, pembrolizumab, and umbilical cord blood NK cells for advanced hepatocellular carcinoma (HCC).Advanced HCC has a poor prognosis and limited effective treatment options. Exploring personalized combination treatment strategies is critically important for improving outcomes in patients with advanced HCC. This study aims to provide preliminary evaluation of the clinical effectiveness and safety of this combination regimen in this high-risk population, and lay the groundwork for larger studies to bring more treatment choices to patients with advanced HCC. Methods: A 67-year-old male patient with advanced HCC and multiple metastases was treated with palbociclib 75mg on days 1-14 of a 28-day cycle, pembrolizumab 200mg intravenous infusion, selinexor 40mg weekly, and umbilical cord blood NK cell (12×109 cells) infusion on days 1, 14, 28 and 42. Imaging examinations and tumor marker detection were performed before and after two cycles of treatment to evaluate response. Results: After two cycles of combination treatment, follow-up PET-CT showed partial response with the liver tumors reduced in size by approximately 60%, lung metastases reduced by approximately 90%, and FDG uptake decreased more than 90% in lymph nodes and bone metastases. The AFP level decreased compared to baseline. Liver function tests including albumin, bilirubin and prothrombin time improved. The patient's performance status also improved from ECOG 2 to ECOG 1. Conclusions: This case report describes preliminary signals that the combination of selinexor, palbociclib, pembrolizumab, and umbilical cord blood NK cells may warrant further investigation for the treatment of advanced HCC. Objective response was observed based on standardized response criteria. However, due to the limitations of a single-arm case study design, definitive conclusions cannot be drawn regarding the efficacy or safety profile of this personalized combination approach. Larger and more robust clinical trials are needed to fully validate if this treatment strategy can achieve clinical benefit for advanced HCC. Future studies should aim to elucidate potential biomarkers that may help identify patients most likely to respond to this combination regimen. Exploring optimal patient selection criteria could also help maximize clinical benefit. Further research is warranted to continue exploring precision medicine combinations involving immunotherapy, targeted agents and cellular therapies for advanced HCC.

Effect of China national centralized drug procurement policy on anticoagulation selection and hemorrhage events in patients with AF in Suining.

Background: Launched in March 2019, the National Centralized Drug Procurement (NCDP) initiative aimed to optimize the drug utilization framework in public healthcare facilities. Following the integration of Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) into the procurement catalog, healthcare establishments in Suining swiftly transitioned to the widespread adoption of NOACs, beginning 1 March 2020. Objective: This study aims to comprehensively assess the impact of the NCDP policy on the efficacy of anticoagulation therapy, patient medication adherence, and the incidence of hemorrhagic events in individuals with non-valvular atrial fibrillation (NVAF) residing in Suining. The analysis seeks to elucidate the broader impacts of the NCDP policy on this patient demographic. Methods: This study analyzed patient hospitalization records from the Department of Cardiology at Suining County People's Hospital, spanning 1 January 2017, to 30 June 2022. The dataset included demographic details (age, sex), type of health insurance, year of admission, hospitalization expenses, and comprehensive information on anticoagulant therapy utilization. The CHA2DS2-VASc scoring system, an established risk assessment tool, was used to evaluate stroke risk in NVAF patients. Patients with a CHA2DS2-VASc score of 2 or higher were categorized as high-risk, while those with scores below 2 were considered medium or low-risk. Results: 1. Treatment Cost Analysis: The study included 3,986 patients diagnosed with NVAF. Following the implementation of the NCDP policy, a significant increase in the average treatment cost for hospitalized patients was observed, rising from 8,900.57 ± 9,023.02 CNY to 9,829.99 ± 10,886.87 CNY (p < 0.001). 2. Oral Anticoagulant Utilization: Overall, oral anticoagulant use increased from 40.02% to 61.33% post-NCDP (p < 0.001). Specifically, NOAC utilization among patients dramatically rose from 15.41% to 90.99% (p < 0.001). 3. Hemorrhagic Events: There was a significant decrease in hemorrhagic events following the NCDP policy, from 1.88% to 0.66% (p = 0.01). Hypertension [OR = 1.979, 95% CI (1.132, 3.462), p = 0.017], history of stroke [OR = 1.375, 95% CI (1.023, 1.847), p = 0.035], age ≥65 years [OR = 0.339, 95% CI (0.188, 0.612), p < 0.001], combination therapy of anticoagulants and antiplatelets [OR = 3.620, 95% CI (1.752, 7.480), p < 0.001], hepatic and renal insufficiency [OR = 4.294, 95% CI (2.28, 8.084), p < 0.001], and the NCDP policy [OR = 0.295, 95% CI (0.115, 0.753), p = 0.011] are significant risk factors for bleeding in patients with atrial fibrillation. 4. Re-hospitalization and Anticoagulant Use: Among the 219 patients requiring re-hospitalization, there was a notable increase in anticoagulant usage post-NCDP, from 36.07% to 59.82% (p < 0.001). NOACs, in particular, saw a substantial rise in usage among these patients, from 11.39% to 80.92% (p < 0.001). 5. Anticoagulant Type Change: The NCDP policy [OR = 28.223, 95% CI (13.148, 60.585), p < 0.001] and bleeding events [OR = 27.772, 95% CI (3.213, 240.026), p = 0.003] were significant factors influencing the alteration of anticoagulant medications in patients. Conclusion: The NCDP policy has markedly improved anticoagulation management in patients with AF. This policy has played a crucial role in enhancing medication adherence and significantly reducing the incidence of hemorrhagic events among these patients. Additionally, the NCDP policy has proven to be a key factor in guiding the selection and modification of anticoagulant therapies in the AF patient population.

Unleashing the Power of PET-RAFT Polymerization: Journey from Porphyrin-Based Photocatalysts to Combinatorial Technologies and Advanced Bioapplications.

The emergence of photoinduced energy/electron transfer-reversible addition-fragmentation chain transfer polymerization (PET-RAFT) not only revolutionized the field of photopolymerization but also accelerated the development of porphyrin-based photocatalysts and their analogues. The continual expansion of the monomer family compatible with PET-RAFT polymerization enhances the range of light radiation that can be harnessed, providing increased flexibility in polymerization processes. Furthermore, the versatility of PET-RAFT polymerization extends beyond its inherent capabilities, enabling its integration with various technologies in diverse fields. This integration holds considerable promise for the advancement of biomaterials with satisfactory bioapplications. As researchers delve deeper into the possibilities afforded by PET-RAFT polymerization, the collaborative efforts of individuals from diverse disciplines will prove invaluable in unleashing its full potential. This Review presents a concise introduction to the fundamental principles of PET-RAFT, outlines the progress in photocatalyst development, highlights its primary applications, and offers insights for future advancements in this technique, paving the way for exciting innovations and applications.

A modified CEUS risk stratification model for adnexal masses with solid components: prospective multicenter study and risk adjustment.

OBJECTIVES: To evaluate the additional advantages of integrating contrast-enhanced ultrasound (CEUS) into the Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound (US) for the characterization of adnexal lesions with solid components. MATERIALS AND METHODS: This prospective multicenter study recruited women suspected of having adnexal lesions with solid components between September 2021 and December 2022. All patients scheduled for surgery underwent preoperative CEUS and US examinations. The lesions were categorized according to the O-RADS US system, and quantitative CEUS indexes were recorded. Pathological results served as the reference standard. Univariable and multivariable analyses were performed to identify risk factors for malignancy in adnexal lesions with solid components. Receiver operating characteristic (ROC) curve analysis was employed to assess diagnostic performance. RESULTS: A total of 180 lesions in 175 women were included in the study. Among these masses, 80 were malignant and 100 were benign. Multivariable analysis revealed that serum CA-125, the presence of acoustic shadowing, and peak intensity (PI) ratio (PImass/PIuterus) of solid components on CEUS were independently associated with adnexal malignancy. The modified CEUS risk stratification model demonstrated superior diagnostic value in assessing adnexal lesions with solid components compared to O-RADS US (AUC: 0.91 vs 0.78, p < 0.001) and exhibited comparable performance to the Assessment of Different NEoplasias in the adnexa (ADNEX) model (AUC 0.91 vs 0.86, p = 0.07). CONCLUSION: Our findings underscore the potential value of CEUS as an adjunctive tool for enhancing the precision of diagnostic evaluations of O-RADS US. CLINICAL RELEVANCE STATEMENT: The promising performance of the modified CEUS risk stratification model suggests its potential to mitigate unnecessary surgeries in the characterization of adnexal lesions with solid components. KEY POINTS: • The additional value of CEUS to O-RADS US in distinguishing between benign and malignant adnexal lesions with solid components requires further evaluation. • The modified CEUS risk stratification model displayed superior diagnostic value and specificity in characterizing adnexal lesions with solid components when compared to O-RADS US. • The inclusion of CEUS demonstrated potential in reducing the need for unnecessary surgeries in the characterization of adnexal lesions with solid components.

Adaptation mechanisms of leaf vein traits to drought in grassland plants.

Leaf veins play an important role in water transport, and are closely associated with photosynthesis and transpiration. Resource heterogeneity in the environment, particularly in water resources, causes changes in leaf vein structure and function, thereby affecting plant growth and community assemblages. Therefore, it is necessary to explore the spatial variation and evolutionary mechanisms of leaf veins in natural communities. Natural communities are composed of dominant and non-dominant species. However, few studies to date have explored the trait variation of dominant and non-dominant species on a large scale. In this study, we set up 10 sampling sites along the water gradient (from east to west) in the Loess Plateau of China, and measured and calculated the vein density (vein length per unit area, VLA), vein diameter (VD), and vein volume ratio (VVR) of 173 species, including dominant and non-dominant species. The mean values of VLA, VD, and VVR were 10.95 mm mm-2, 22.24 µm, and 3%, respectively. VD and VVR of the dominant species were significantly higher than those of the non-dominant species. Unexpectedly, there was no significant change in the VLA with the water gradient, although the VD increased with drought. Leaf vein traits did not change significantly with evolution. There was a significant trade-off between VLA and VD. Our findings demonstrate that the response of veins to environmental changes is dependent on the degree of drought and provide new insights for further large-scale studies.