Establishment and verification of anthropogenic speciated VOCs emission inventory of Central China.

Improving the accuracy of anthropogenic volatile organic compounds (VOCs) emission inventory is crucial for reducing atmospheric pollution and formulating control policy of air pollution. In this study, an anthropogenic speciated VOCs emission inventory was established for Central China represented by Henan Province at a 3 km × 3 km spatial resolution based on the emission factor method. The 2019 VOCs emission in Henan Province was 1003.5 Gg, while industrial process source (33.7%) was the highest emission source, Zhengzhou (17.9%) was the city with highest emission and April and August were the months with the more emissions. High VOCs emission regions were concentrated in downtown areas and industrial parks. Alkanes and aromatic hydrocarbons were the main VOCs contribution groups. The species composition, source contribution and spatial distribution were verified and evaluated through tracer ratio method (TR), Positive Matrix Factorization Model (PMF) and remote sensing inversion (RSI). Results show that both the emission results by emission inventory (EI) (15.7 Gg) and by TR method (13.6 Gg) and source contribution by EI and PMF are familiar. The spatial distribution of HCHO primary emission based on RSI is basically consistent with that of HCHO emission based on EI with a R-value of 0.73. The verification results show that the VOCs emission inventory and speciated emission inventory established in this study are relatively reliable.

Long-term spatiotemporal variations of ammonia in the Yangtze River Delta region of China and its driving factors.

This study focuses on the spatiotemporal distribution, urban-rural variations, and driving factors of ammonia Vertical Column Densities (VCDs) in China's Yangtze River Delta region (YRD) from 2008 to 2020. Utilizing data from the Infrared Atmospheric Sounding Interferometer (IASI), Generalized Additive Models (GAM), and the GEOS-Chem chemical transport model, we observed a significant increase of NH3 VCDs in the YRD between 2014 and 2020. The spatial distribution analysis revealed higher NH3 concentrations in the northern part of the YRD region, primarily due to lower precipitation, alkaline soil, and intensive agricultural activities. NH3 VCDs in the YRD region increased significantly (65.18%) from 2008 to 2020. The highest growth rate occurs in the summer, with an annual average growth rate of 7.2% during the period from 2014 to 2020. Agricultural emissions dominated NH3 VCDs during spring and summer, with high concentrations primarily located in the agricultural areas adjacent to densely populated urban zones. Regions within several large urban areas have been discovered to exhibit relatively stable variations in NH3 VCDs. The rise in NH3 VCDs within the YRD region was primarily driven by the reduction of acidic gases like SO2, as emphasized by GAM modeling and sensitivity tests using the GEOS-Chem model. The concentration changes of acidic gases contribute to over 80% of the interannual variations in NH3 VCDs. This emphasizes the crucial role of environmental policies targeting the reduction of these acidic gases. Effective emission control is urgent to mitigate environmental hazards and secondary particulate matter, especially in the northern YRD.

Peroxisomal homeostasis in metabolic diseases and its implication in ferroptosis.

Peroxisomes are dynamic organelles involved in various cellular processes, including lipid metabolism, redox homeostasis, and intracellular metabolite transfer. Accumulating evidence suggests that peroxisomal homeostasis plays a crucial role in human health and disease, particularly in metabolic disorders and ferroptosis. The abundance and function of peroxisomes are regulated by a complex interplay between biogenesis and degradation pathways, involving peroxins, membrane proteins, and pexophagy. Peroxisome-dependent lipid metabolism, especially the synthesis of ether-linked phospholipids, has been implicated in modulating cellular susceptibility to ferroptosis, a newly discovered form of iron-dependent cell death. This review discusses the current understanding of peroxisome homeostasis, its roles in redox regulation and lipid metabolism, and its implications in human diseases. We also summarize the main mechanisms of ferroptosis and highlight recent discoveries on how peroxisome-dependent metabolism and signaling influence ferroptosis sensitivity. A better understanding of the interplay between peroxisomal homeostasis and ferroptosis may provide new insights into disease pathogenesis and reveal novel therapeutic strategies for peroxisome-related metabolic disorders and ferroptosis-associated diseases.

Efficacy and safety of lenvatinib combined with anti-PD-1 antibodies plus GEMOX chemotherapy as non-first-line systemic therapy in advanced gallbladder cancer.

BACKGROUND: Lenvatinib, programmed cell death 1 (PD-1) antibodies, and gemcitabine and oxaliplatin (GEMOX) chemotherapy have shown significant antitumor activity as first-line therapy against biliary tract cancer. This study evaluated their efficacy and safety as non-first-line therapy in advanced gallbladder cancer (GBC). METHODS: Patients with advanced GBC who received lenvatinib combined with anti-PD-1 antibodies and GEMOX chemotherapy as a non-first-line therapy were retrospectively analyzed. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR) and safety. RESULTS: A total of 36 patients with advanced GBC were included in this study. The median follow-up time was 11.53 (95% confidence interval (CI): 2.2-20.9) months, and the ORR was 36.1%. The median OS and PFS were 15.1 (95% CI: 3.2-26.9) and 6.1 (95% CI: 4.9-7.2) months, respectively. The disease control rate (DCR) and clinical benefit rate (CBR) were 75% and 61.1%, respectively. Subgroup analysis demonstrated that patients with programmed cell death-ligand 1 (PD-L1) expression had significantly longer PFS and OS than those without PD-L1 expression. Additionally, patients with a neutrophil-lymphocyte ratio (NLR) < 5.57 had a longer OS than those with an NLR ≥ 5.57. All patients experienced adverse events (AEs), with 61.1% experiencing grade 3 or 4 AEs, including myelosuppression (13.9%) and fatigue (13.3%), alanine transaminase or aspartate transaminase levels (8.3%), and diarrhea (8.3%). No grade 5 AEs were reported. CONCLUSION: Anti-PD-1 antibodies combined with lenvatinib and GEMOX chemotherapy are effective and well-tolerated as a non-first-line therapy in advanced GBC. PD-L1 expression and baseline NLR may potentially predict treatment efficacy.

Effectiveness, safety, and biomarker analysis of lenvatinib plus toripalimab as chemo-free therapy in advanced intrahepatic cholangiocarcinoma: a real-world study.

BACKGROUND: Treatment options for advanced intrahepatic cholangiocarcinoma (ICC) are currently limited. Chemo-containing regimens are the mainstay treatments but associated with notable toxicity, poor tolerance, and reduced compliance, necessitating exploration of alternative therapies. Lenvatinib plus PD-1 inhibitors has shown substantial clinical activity in preliminary studies. This study aimed to assess the effectiveness and safety of lenvatinib plus toripalimab (a novel PD-1 antibody) as chemo-free therapy in advanced ICC. METHODS: This retrospective study included consecutive advanced ICC patients receiving lenvatinib plus toripalimab between February 2019 and December 2023. The main outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors and exploratory analyses for genetic alternations were also conducted. RESULTS: A total of 78 patients were included, with a median follow-up of 25.9 months. Median OS and PFS were 11.3 (95% CI: 9.5-13.1) and 5.4 (95% CI: 3.8-7.0) months, respectively. ORR was 19.2% and DCR was 75.6%. The incidence of grade 3 or 4 adverse events (AEs) was 50.0%, with no grade 5 AEs reported. Patients with normal baseline CA19-9 levels exhibited a higher ORR (p = 0.011), longer PFS (11.5 versus 4.6 months; HR 0.47; p=0.005), and OS (21.0 versus 9.7 months; HR 0.43; p=0.003). The presence of IDH1 mutations correlated with increased ORR (60.0% versus 8.9%, p=0.016). CONCLUSION: Lenvatinib plus toripalimab represents an effective and well-tolerated chemo-free therapeutic option for advanced ICC. Baseline CA19-9 levels and IDH1 mutations may serve as predictive treatment-related biomarkers.

MEF2C Alleviates Postoperative Cognitive Dysfunction by Repressing Ferroptosis.

BACKGROUND: Ferroptosis, a form of programmed cell death featured by lipid peroxidation, has been proposed as a potential etiology for postoperative cognitive dysfunction (POCD). Myocyte-specific enhancer factor 2C (MEF2C), a transcription factor expressed in various brain cell types, has been implicated in cognitive disorders. This study sought to ascertain whether MEF2C governs postoperative cognitive capacity by affecting ferroptosis. METHODS: Transcriptomic analysis of public data was used to identify MEF2C as a candidate differentially expressed gene in the hippocampus of POCD mice. The POCD mouse model was established via aseptic laparotomy under isoflurane anesthesia after treatment with recombinant adeno-associated virus 9 (AAV9)-mediated overexpression of MEF2C and/or the glutathione peroxidase 4 (GPX4) inhibitor RSL3. Cognitive performance, Nissl staining, and ferroptosis-related parameters were assessed. Dual-luciferase reporter gene assays and chromatin immunoprecipitation assays were implemented to elucidate the mechanism by which MEF2C transcriptionally activates GPX4. RESULTS: MEF2C mRNA and protein levels decreased in the mouse hippocampus following anesthesia and surgery. MEF2C overexpression ameliorated postoperative memory decline, hindered lipid peroxidation and iron accumulation, and enhanced antioxidant capacity, which were reversed by RSL3. Additionally, MEF2C was found to directly bind to the Gpx4 promoter and activate its transcription. CONCLUSIONS: Our findings suggest that MEF2C may be a promising therapeutic target for POCD through its negative modulation of ferroptosis.

The Exploration of Ink Formulations in Binder Jet 3D Printing Drugs.

The application of binder jet 3D printing technology in the pharmaceutical field is developing rapidly. The properties of the ink are very important, affecting the stability of the ejection and the precision of the finished product, but there is a great lack of research on pharmaceutical inks. This study used solvents and excipients commonly used in pharmaceuticals to quantify the printability of inks using printability Z value theory, while using an ink-jet printing and observation platform to analyze the droplet ejection state of different composition inks from microscopic level. Studies have shown that compared to ethanol, the ejection effect of droplets was better when isopropanol was added to the ink, and the proportion added should not be greater than 40%; as the molecular weight of polyvinylpyrrolidone (PVP) increased, the concentration of PVP tolerated by the ink decreased; glycerin has a high ejection efficiency when the proportion is within 10%. In summary, a superior ink formulation of 40% aqueous isopropanol plus 0.1% PVP K30 and 4% glycerin was obtained. With this ink, levetiracetam dispersible tablets were prepared with a smooth printing process and the tablets had good appearance, good mechanical properties, and rapid release. This study provides a mutual validation of the Z value theory and the results of droplet ejection and tablet printing, while providing good ideas.

CircSSR1 regulates pyroptosis of pulmonary artery smooth muscle cells through parental protein SSR1 mediating endoplasmic reticulum stress.

INTRODUCTION: Pyroptosis, inflammatory necrosis of cells, is a programmed cell death involved in the pathological process of diseases. Endoplasmic reticulum stress (ERS), as a protective stress response of cell, decreases the unfold protein concentration to inhibit the unfold protein agglutination. Whereas the relationship between endoplasmic reticulum stress and pyroptosis in pulmonary hypertension (PH) remain unknown. Previous evident indicated that circular RNA (circRNA) can participate in several biological process, including cell pyroptosis. However, the mechanism of circRNA regulate pyroptosis of pulmonary artery smooth muscle cells through endoplasmic reticulum stress still unclear. Here, we proved that circSSR1 was down-regulate expression during hypoxia in pulmonary artery smooth muscle cells, and over-expression of circSSR1 inhibit pyroptosis both in vitro and in vivo under hypoxic. Our experiments have indicated that circSSR1 could promote host gene SSR1 translation via m6A to activate ERS leading to pulmonary artery smooth muscle cell pyroptosis. In addition, our results showed that G3BP1 as upstream regulator mediate the expression of circSSR1 under hypoxia. These results highlight a new regulatory mechanism for pyroptosis and provide a potential therapy target for pulmonary hypertension. METHODS: RNA-FISH and qRT-PCR were showed the location of circSSR1 and expression change. RNA pull-down and RIP verify the circSSR1 combine with YTHDF1. Western blotting, PI staining and LDH release were used to explore the role of circSSR1 in PASMCs pyroptosis. RESULTS: CircSSR1 was markedly downregulated in hypoxic PASMCs. Knockdown CircSSR1 inhibited hypoxia induced PASMCs pyroptosis in vivo and in vitro. Mechanistically, circSSR1 combine with YTHDF1 to promote SSR1 protein translation rely on m6A, activating pyroptosis via endoplasmic reticulum stress. Furthermore, G3BP1 induce circSSR1 degradation under hypoxic. CONCLUSION: Our findings clarify the role of circSSR1 up-regulated parental protein SSR1 expression mediate endoplasmic reticulum stress leading to pyroptosis in PASMCs, ultimately promoting the development of pulmonary hypertension.

Surface Electromyography and Gait Features in Patients after Anterior Cruciate Ligament Reconstruction.

OBJECTIVE: An important reason for the poor recovery of anterior cruciate ligament (ACL) injuries is the poor recovery of muscle function. Therefore, we used surface electromyography (sEMG) and gait analysis to explore the muscle activation patterns and gait characteristics between lower limbs under different exercise states in patients, following anterior cruciate ligament reconstruction (ACLR). METHODS: Forty-one adults with unilateral ACL injuries in Binzhou Medical University Hospital from October 2022 to June 2023 were allocated to three groups according to the time after ACL reconstruction: group A (≤3 months, 16), group B (3 months-1 year, 13), and group C (>1 year, 12). Patients were tested by sEMG and gait, while straight leg raising (SLR), walking at normal speed, fast walking, and walking up and down the stairs. Two related sample tests were performed for the normalized root mean square (RMS) values and gait parameters. RESULTS: Muscle function changes varied in different training tasks. The RMS value of the involved side was more than the uninvolved side in biceps femoris and semitendinosus of group A (p < 0.010), and for the bilateral rectus femoris (RS), vastus medialis (VM), and vastus lateralis in group B, only the comparison of the RS was significant in group C during fast walking and going up and down the stairs. The ground impact (0.90 [0.63, 1.33] vs. 0.71 [0.43, 1.02], p = 0.035) of the uninvolved side was significantly decreased compared to those of the involved side in patients with ACLR when going down the stairs. CONCLUSION: Different muscles need to be focused on at different stages of the postoperative period. sEMG and gait analysis can guide the development of a rehabilitation program.

Decafluorinated and Perfluorinated Warped Nanographenes: Synthesis, Structural Analysis, and Properties.

Fluorination is a useful approach for tailoring the physicochemical properties of nanocarbon materials. However, owing to the violent reactivity of fluorination, achieving edge-perfluorination of nanographene while maintaining its original π-conjugated structure is challenging. Instead of using traditional fluorination, here, we employed a bottom-up strategy involving fluorine preinstallation and synthesized decafluorinated and perfluorinated warped nanographenes (DFWNG and PFWNG, respectively) through a 10-fold Suzuki-Miyaura coupling followed by a harsh Scholl reaction, whereby precisely edge-perfluorinated nanographene with an intact π-conjugated structure was achieved for the first time. X-ray crystallography confirmed the intact π-conjugated structure and more twisted saddle-shaped geometry of PFWNG compared to that of DFWNG. Dynamic study revealed that the 26-ring carbon framework of PFWNG is less flexible than that of DFWNG and the pristine WNG, enabling chirality resolution of PFWNG and facilitating the achievement of CD spectra at -10 °C. The edge-perfluorination of PFWNG resulted in improved solubility, lower lowest unoccupied molecular orbital, and a surface electrostatic potentials/dipole moment direction opposite those of the pristine WNG. Likely owing to its intact π-conjugated structure, PFWNG exhibits comparable electron mobility with well-known PC61BM. Furthermore, perfluorination improves thermal stability and hydrophobicity, making PFWNG suitable for use as a thermostable/hydrophobic n-type semiconductor material. In the future, this fluorination strategy can be used to synthesize other perfluorinated nanocarbon materials, such as perfluorinated graphene nanoribbons and porous nanocarbon.

"Will ICER's 'shared savings' approach decrease value-based prices most for the most severe diseases?"

OBJECTIVES: To identify the types of disease most likely to be impacted by the Institute for Clinical and Economic Review's (ICER) shared savings assumptions. METHODS: For diseases with treatments that were FDA-approved between 2019 and 2023, annual direct and indirect economic burden and characteristics of each disease were extracted from peer-reviewed literature. ICER's shared savings methodology was applied two ways: 50/50 shared savings and $150,000 cost-offset cap. The primary outcome was the difference in eligible cost savings provided by a hypothetical disease cure under ICER's 2 shared savings methods. Characteristics of diseases most impacted by these 2 methods were evaluated descriptively. RESULTS: FDA approved 260 therapies for 89 unique diseases between 2019 and 2023. Shared savings reduced value of a hypothetical cure for hemophilia A most (50/50 method: -$367,670 per year; cap method: -$585,340 per year), followed by acute hepatic porphyria (50/50 method: -$333,948; cap method: -$517,896) and paroxysmal nocturnal hemoglobinuria (50/50 method: -$291,997; cap method: -$433,993). Compared to diseases with annual burdens <$150,000, those ≥$150,000 had earlier disease onset by 22.0 years (age 12.3 vs. 34.3), lower life expectancy by 10.6 years (55.8 vs. 66.4 years), and lower disease prevalence (4.7 vs. 1981.5 per 100,000). Shared savings' impact on health benefit price benchmarks was projected to be larger for diseases with shorter life expectancy (ρ=-0.319; p=0.005), worse quality-of-life (ρ=-0.263; p=0.020), and lower prevalence (ρ=-0.418; p<0.001). CONCLUSIONS: ICER's shared savings assumptions would most likely have the largest negative impact on health benefit price benchmarks for rare, severe, and pediatric diseases.

Understanding the Adsorption Kinetics of Acetone in Humid Activated Carbons: Perspectives from Adsorption-Breakthrough Experiments and Molecular Simulations.

The presence of water vapor influences the adsorption equilibrium and kinetics of volatile organic compounds (VOCs) in porous materials. By combination of breakthrough experiments and molecular simulations, the competitive adsorption mechanisms of water vapor and acetone on activated carbon with different textures and surface chemical properties at different humidity levels were investigated. Adsorption capacity decreases with increasing relative humidity owing to the formation of preferential adsorption sites between water and the activated carbon surface, while the adsorption rate initially increases and then decreases with increasing relative humidity. Experimental and simulation results revealed that the existence of a small amount of water changed the pore size distributions of activated carbon, thereby promoting the diffusion of acetone molecules. As the relative humidity increased, a portion of the acetone dissolved in water, resulting in a reduction in the adsorption rate. The response of different functional groups to relative humidity was further clarified by molecular simulation. Activated carbons with a high electrostatic interaction with acetone were less affected by humidity and thus exhibit greater potential as adsorbents.

SubCELL: the landscape of subcellular compartment-specific molecular interactions.

The subcellular compartment-specific molecular interactions (SCSIs) are the building blocks for most molecular functions, biological processes and disease pathogeneses. Extensive experiments have therefore been conducted to accumulate the valuable information of SCSIs, but none of the available databases has been constructed to describe those data. In this study, a novel knowledge base SubCELL is thus introduced to depict the landscape of SCSIs among DNAs/RNAs/proteins. This database is UNIQUE in (a) providing, for the first time, the experimentally-identified SCSIs, (b) systematically illustrating a large number of SCSIs inferred based on well-established method and (c) collecting experimentally-determined subcellular locations for the DNAs/RNAs/proteins of diverse species. Given the essential physiological/pathological role of SCSIs, the SubCELL is highly expected to have great implications for modern molecular biological study, which can be freely accessed with no login requirement at: https://idrblab.org/subcell/.

A survival nomogram involving nutritional-inflammatory indicators for cervical cancer patients receiving adjuvant radiotherapy.

Objective: The combined impact of nutritional and inflammatory status on survival of cervical cancer patients remained unclear. This study aimed to construct a survival nomogram involving both nutritional and inflammatory indicators and evaluate their potential correlation. Methods: This retrospective study included 325 cervical cancer patients who received adjuvant radiotherapy between September 2010 and September 2020. Baseline nutritional indicators such as body mass index (BMI), controlling nutritional status (CONUT) and serum albumin were assessed. Inflammatory indicators of platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR), systemic immune inflammation index (SII) and system inflammation response index (SIRI) were evaluated respectively. The LASSO regression and Cox regression models were applied for variable selection and nomogram building. The predictive accuracy and superiority of prognostic model were assessed by area under curve (AUC), C-index, decision curve analysis (DCA), integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Results: Patients with high inflammatory indicators (PLR, NLR and SII) and poor nutritional status (CONUT scores > 2) suffered poorer prognosis compared to these with well nutritional status and lower inflammation levels. Our study unveiled a positive correlation between malnutrition and hyperinflammation. Even after accounting for baseline inflammatory level, malnutrition remained a significant risk factor for patients. Notably, the inflammatory level and nutritional status were further modulated by the clinical features of patients. Patients with poorer nutritional status exhibited higher levels of PLR, NLR, SII and SIRI, particularly for those in advanced clinical stages and with non-squamous cell carcinoma. In addition, our study found elevated levels of circulating basophil and serum carbohydrate antigen 125 (CA125) were associated with the poor prognosis. The prognostic nomogram which incorporated the nutritional-inflammatory indicators of PLR and CONUT showed a favorable performance with the AUC value of 0.76 at 5-year survival prediction. The DCA, IDI and NRI consistently demonstrated the favorable superiority of the model. Moreover, the nomogram-based risk stratification system could effectively classify patients into three mortality risks subgroups. Conclusions: Poorer nutritional and high inflammatory status collectively contributed to the poorer prognosis. The prognostic nomogram which incorporated nutritional-inflammatory indicators significantly improved the prediction of long-term outcomes of cervical cancer patients undergoing adjuvant radiotherapy.

Deciphering the roles of bacterial and fungal communities in the formation and quality of agarwood.

Aquilaria sinensis is a significant resin-producing plant worldwide that is crucial for agarwood production. Agarwood has different qualities depending on the method with which it is formed, and the microbial community structures that are present during these methods are also diverse. Furthermore, the microbial communities of plants play crucial roles in determining their health and productivity. While previous studies have investigated the impact of microorganisms on agarwood formation, they lack comprehensiveness, particularly regarding the properties of the microbial community throughout the entire process from seedling to adult to incense formation. We collected roots, stems, leaves, flowers, fruits and other tissues from seedlings, healthy plants and agarwood-producing plants to address this gap and assess the dominant bacterial species in the microbial community structures of A. sinensis at different growth stages and their impacts on growth and agarwood formation. The bacteria and fungi in these tissues were classified and counted from different perspectives. The samples were sequenced using the Illumina sequencing platform, and sequence analyses and species annotations were performed using a range of bioinformatics tools to assess the plant community compositions. An additional comparison of the samples was conducted using diversity analyses to assess their differences. This research revealed that Listeria, Kurtzmanomyces, Ascotaiwania, Acinetobacter, Sphingobium, Fonsecaea, Acrocalymma, Allorhizobium, Bacillus, Pseudomonas, Peethambara, and Debaryomyces are potentially associated with the formation of agarwood. Overall, the data provided in this article help us understand the important roles played by bacteria and fungi in the growth and agarwood formation process of A. sinensis, will support the theoretical basis for the large-scale cultivation of A. sinensis, and provide a basis for further research on microbial community applications in agarwood production and beyond.

Effects of Virtual Reality on Preoperative Anxiety in Adult Patients: An Updated Meta-analysis.

PURPOSE: To determine the effectiveness of virtual reality (VR) on preoperative anxiety in adult patients. DESIGN: A systematic review and meta-analysis of randomized controlled trials. METHODS: A systematic search was carried out using PubMed, Web of Science, the Cochrane Library, Embase, CINAHL, Scopus, PsycINFO, China National Knowledge Infrastructure (CNKI), WANFANG DATA, Chinese Science and Technology Periodical Database (VIP), and Sino-Med from inception to December 18, 2022. All eligible randomized controlled trials published were included (published in English and Chinese). The Cochrane Collaboration "Risk of Bias" tool was used to assess the methodological quality of the included studies. Review Manager software 5.4 was used for data analysis. FINDINGS: Nine studies with sample sizes ranging from 72 to 255 and 1,046 participants were identified. The results of the meta-analysis showed that VR significantly reduced preoperative anxiety in adults (standardized mean difference = -0.48, 95% CI: -0.93 to -0.03, P = .04). Our results suggested that VR improved postoperative satisfaction scores more effectively compared with control care (mean difference = 15.29, 95% CI: 6.25 to 24.33, P = .0009). CONCLUSIONS: Study results support that VR has a positive effect in reducing preoperative anxiety in adults. VR can also significantly improve patients' satisfaction after surgery. However, the results need to be further assessed due to the small sample sizes and high heterogeneity.

Characterization of lncRNA and mRNA profiles in the process of repairing peripheral nerve defects with cell-matrixed nerve grafts.

BACKGROUND: Decellularized extracellular matrix (dECM) is an intriguing natural biomaterial that has garnered significant attention due to its remarkable biological properties. In our study, we employed a cell-matrixed nerve graft for the repair of sciatic nerve defects in rats. The efficacy of this approach was assessed, and concurrently, the underlying molecular regulatory mechanisms were explored to elucidate how such grafts facilitate nerve regeneration. Long noncoding RNAs (lncRNAs) regulate mRNA expression via multiple mechanisms, including post-transcriptional regulation, transcription factor effects, and competitive binding with miRNAs. These interactions between lncRNAs and mRNAs facilitate precise control of gene expression, allowing organisms to adapt to varying biological environments and physiological states. By investigating the expression profiles and interaction dynamics of mRNAs and lncRNAs, we can enhance our understanding of the molecular mechanisms through which cell-matrixed nerve grafts influence neural repair. Such studies are pivotal in uncovering the intricate networks of gene regulation that underpin this process. RESULTS: Weighted gene co-expression network analysis (WGCNA) utilizes clustering algorithms, such as hierarchical clustering, to aggregate genes with similar expression profiles into modules. These modules, which potentially correspond to distinct biological functions or processes, can subsequently be analyzed for their association with external sample traits. By correlating gene modules with specific conditions, such as disease states or responses to treatments, WGCNA enables a deeper understanding of the genetic architecture underlying various phenotypic traits and their functional implications. We identified seven mRNA modules and five lncRNA modules that exhibited associations with treatment or time-related events by WGCNA. We found the blue (mRNAs) module which displayed a remarkable enrichment in "axonal guidance" and "metabolic pathways", exhibited strong co-expression with multiple lncRNA modules, including blue (related to "GnRH secretion" and "pyrimidine metabolism"), green (related to "arginine and proline metabolism"), black (related to "nitrogen metabolism"), grey60 (related to "PPAR signaling pathway"), and greenyellow (related to "steroid hormone biosynthesis"). All of the top 50 mRNAs and lncRNAs exhibiting the strongest correlation were derived from the blue module. Validation of key molecules were performed using immunohistochemistry and qRT-PCR. CONCLUSION: Revealing the principles and molecular regulatory mechanisms of the interaction between materials and biological entities, such as cells and tissues, is a direction for the development of biomimetic tissue engineering technologies and clinically effective products.

Co-delivery of Liposomal Ketoconazole and Bevacizumab for Synergistical Inhibition of Angiogenesis Against Endometrial Cancer.

In this study, we designed a novel formulation based on liposomes for the co-delivery of cancer-derived exosome inhibitor (ketoconazole, Keto) and angiogenesis inhibitor (bevacizumab, mAb). The designed Combo-Lipo formulation was systematically characterized, exhibiting a uniform average particle size of 100 nm, as well as excellent serum and long-term physical stabilities. The cell viability assay revealed that Combo-Lipo treatment significantly reduced the viability of cancer cells compared to free drugs. Moreover, liposomes effectively inhibited angiogenic mediators and reduced tumor immune suppressive factors. The Combo-Lipo formulation demonstrated potent downregulation of angiogenic factors and synergistic effects in suppressing their production. Furthermore, liposomes inhibited tumor-associated macrophages (TAMs), leading to decreased expression of tumor-promoting factors. Together, these findings highlighted the promising characteristics of Combo-Lipo as a therapeutic formulation, including optimal particle size, serum stability, and potent anti-cancer effects, as well as inhibition of angiogenic mediators and TAMs toward treating endometrial cancer.

An accurate haplotyping method using multiplex pyrosequencing with AS-PCR to detect ABCB1 haplotypes associated with rivaroxaban-derived hemorrhagic events.

In clinical practice, owing to the comprehensive genetic insights they offer, haplotypes have attracted greater attention than individual single nucleotide polymorphisms (SNPs). Due to the long distances across SNP locations, detecting the haplotype using genomic DNA is challenging. Current haplotyping methods are either expensive and labor-intensive (high-throughput DNA sequencing), or haplotyping a single clinical sample (computational approach) is impossible. Herein, we propose using mRNA as a haplotyping target to minimize the distance among SNPs and employing allele-specific PCR (AS-PCR) to pick up a desired haplotype, followed by multiplex pyrosequencing to type the alleles at the SNP location of interest. AS-PCR was improved by combining an additional 3'-phosphorylated modified probe to achieve the specific separation of two closely similar templates. Only the sample with more than two heterozygotes needs to be haplotyped; therefore, we propose a stratification strategy to screen the samples for further haplotyping. This method was evaluated by associating ABCB1 haplotypes with the rivaroxaban-derived side effect in a cohort of 505 patients with nephrotic syndrome, focusing on the SNPs of ABCB1: rs1236C > T, rs2677G > T/A, and rs3435C > T. We successfully identified five bleeding-related haplotypes: rs1236T-rs2677T-rs3435T, rs1236C-rs2677G-rs3435T, rs1236T-rs2677G-rs3435C, rs1236C-rs2677G-rs3435C, and rs1236T-rs2677T-rs3435C. We compared the results with those from the conventional computational algorithm PHASE and observed that PHASE results dismissed the impact of rs1236C-rs2677G-rs3435C and rs1236C-rs2677G-rs3435T on bleeding risk and erroneously suggested a false positive association of rs1236C-rs2677A-rs3435T with increased bleeding risk.