Global research hotspots and trends in constraint-induced movement therapy in rehabilitation over the past 30 years: a bibliometric and visualization study.

Background: Stroke is a cerebrovascular disease with high prevalence and mortality, and upper limb hemiparesis is a major factor limiting functional recovery in stroke patients. Improvement of motor function in stroke patients through various forms of constraint-induced movement therapy (CITM) has been recognized as safe and effective in recent years. This research field lacks a comprehensive systematic and clear vein combing analysis, analyzing the literature research of CIMT in the field of rehabilitation in the past three decades, summarizing the research hotspots and cutting-edge trends in this field, in an effort to offer ideas and references for subsequent researchers. Methods: Relevant literature on CIMT in rehabilitation was collected from 1996 to 2024 within the Web of Science database's core dataset by using CiteSpace6.1, VOSviewer1.6.18, R-bibliometrix4.6.1, Pajek5.16, Scimago Graphica 1.0.26 software for visualization and analysis. Results: There were 970 papers in all United States was ranked first with 401 papers. Alabama Univ was ranked first for institutions with 53 papers. Neurorehabilitation and Neural Repair was ranked first for journals with 78 papers, and Taub E was ranked first for author publications with 64 papers. Research keywords were CIMT, stroke rehabilitation, upper extremity function, lower extremity gait balance, randomized controlled trials, physical therapy techniques (transcranial magnetic stimulation and sensory amplitude electrical stimulation), primary motor cortex plasticity, lateral dominance (spatial behaviors), cerebral vascular accidents, activities of daily living, hand function, disability, functional restoration, bimanual training, aphasia, acquired invalidity, type A Botulinum toxin and joystick riding toys. Conclusion: The current state of research shows that CIMT still has a vast potential for development in the field of rehabilitation research. The research hotspots are the clinical efficacy of CIMT combined with other therapies (botulinum toxin type A, transcranial direct current stimulation, virtual reality, mirror therapy, robotic-assisted) to enhance the functionality of upper limb hemiparesis in stroke patients, the mechanism of CIMT to improve the plasticity of the motor cortex through electrophysiological and imaging methods, and improvement of lower limb gait balance function in stroke patients and aphasia applications, the optimal intervention time and dose, and exploration of CIMT in new settings such as robot-assisted, telemedicine, and home rehabilitation.

Discovery of first-in-class PROTACs targeting maternal embryonic leucine zipper kinase (MELK) for the treatment of Burkitt lymphoma.

Maternal embryonic leucine zipper kinase (MELK) is a novel target for the treatment of various kinds of B-cell malignancies. However, the toxicity of inhibitors of MELK has led to clinical failures in cancer treatments. Moreover, inactivation of MELK catalytic domain is insufficient for achieving cancer cell apoptosis. To further confirm the role of MELK in Burkitt lymphoma treatment, we describe herein a structure-guided design of PROTACs targeting MELK. Through design, computer-assisted optimization and SAR studies, we developed the first-in-class MELK-targeting PROTAC MGP-39, which promoted a rapid and potent degradation of MELK in RAMOS cells. Additionally, the newly designed MELK degrader induced significant cell cycle arrest and apoptosis in cancer cells. Notably, compared to MELK inhibitors, MGP-39 has better anti-cancer activity and lower toxicity, indicating the practical role of PROTACs in avoiding the side effects of traditional inhibitors. More importantly, our results show that the use of a PROTAC can be adopted as a general and effective strategy for targeted cancer therapy.

Comparative analysis of bioaerosol emissions: Seasonal dynamics and exposure risks in hospital vs. municipal wastewater treatment systems.

Hospital wastewater is known to contain various pathogenic microorganisms and harmful substances. During the hospital wastewater treatment process, the bioaerosols released may encapsulate these pathogens, leading to human infection. This study undertook an investigation to compare the dispersion characteristics and seasonal variations of bioaerosols from hospital and municipal sewage. The results indicated that the airborne bacterial concentration from hospital sewage (119 ± 118 CFU/m3) was higher than municipal sewage (46 ± 19 CFU/m3), with the highest concentration observed in summer. The dominant bacterial genera present in bioaerosols from both sewages were alike, with the proportions varied by sewage types and the structure mainly influenced by seasonal factors. Bacteroides, Escherichia-Shigella and Streptococcus were identified as the most prevalent pathogenic genera in spring, summer and winter bioaerosols, respectively, while Pseudomonas and Acinetobacter were abundant in autumn. Although the non-carcinogenic risk associated with bioaerosols was low (<1), the presence of pathogenic species and their potential synergistic interactions elevated the overall exposure risk. The diffusion modeling results demonstrated that bioaerosol emissions from the surface of hospital sewage can reach up to 10570 CFU/m3 in summer and can spread more than 300 m downwind. The potential pathogenicity of bioaerosols was also highest in summer, which may pose a health hazard to populations located downwind. Therefore, the management and control of bioaerosols from sewage should be strengthened, especially in summer.

Carbon Nanotube-Doped 3D-Printed Silicone Electrode for Manufacturing Multilayer Porous Plasticized Polyvinyl Chloride Gel Artificial Muscles.

Plasticized polyvinyl chloride (PVC) gel has large deformation under an applied external electrical field and high driving stability in air and is a candidate artificial muscle material for manufacturing a flexible actuator. A porous PVC gel actuator consists of a mesh positive pole, a planar negative pole, and a PVC gel core layer. The current casting method is only suitable for manufacturing simple 2D structures, and it is difficult to produce multilayer porous structures. This study investigated the feasibility of a 3D-printed carbon nanotube-doped silicone electrode for manufacturing multilayer porous PVC gel artificial muscle. Carbon nanotube-doped silicone (CNT-PDMS) composite inks were developed for printing electrode layers of PVC gel artificial muscles. The parameters for the printing plane and mesh electrodes were explored theoretically and experimentally. We produced a CNT-PDMS electrode and PVC gel via integrated printing to manufacture multilayer porous PVC artificial muscle and verified its good performance.

Development of Preladenant-Based Radiotracers for Imaging A2AR in Tumors.

Activation of the adenosine 2A receptor (A2AR) can lead to tumor immunosuppression, which results in poor prognosis of immunotherapy. The aim of this study was to design novel 18F-labeled probes ([18F]F-PFP2 and [18F]F-PFP4) to visualize A2AR in the tumor. The uptake of radioprobes in A2AR-negative 4T1 breast tumor was lower than that of A2AR-positive B16F10 melanoma at 1 h p.i. (1.22 ± 0.36% ID/g vs 2.80 ± 0.72% ID/g), 2 h p.i. (1.09 ± 0.20% ID/g vs 2.93 ± 0.76% ID/g) and 3 h p.i. (0.89 ± 0.27% ID/g vs 2.73 ± 0.58% ID/g), respectively. B16F10 lung metastasis models were employed to expand the application scenarios, observing significantly higher uptake of [18F]F-PFP2 in metastatic lesions compared to normal lung tissue (5.55 ± 2.18% ID/g vs 1.89 ± 0.65% ID/g, tumor/lung ratio ∼3). It is given that [18F]F-PFP2 might lay the foundation for establishing an A2AR-targeted imaging evaluation system for tumors, which will provide more precise guidance for personalized treatment.

Mechanisms of conjugative transfer of antibiotic resistance genes induced by extracellular polymeric substances: Insights into molecular diversities and electron transfer properties.

Dissemination of antibiotic resistance genes (ARGs) has become a critical threat to public health. Activated sludge, rich in extracellular polymeric substances (EPS), is an important pool of ARGs. In this study, mechanisms of conjugation transfer of ARGs induced by EPS, including tightly bound EPS (TBEPS), soluble EPS (SEPS), and loosely bound EPS (LBEPS), were explored in terms of molecular diversities and electron transfer properties of EPS. Conjugation transfer frequency was increased by 9.98-folds (SEPS), 4.21-folds (LBEPS), and 15.75-folds (TBEPS) versus the control, respectively. Conjugation-related core genes involving SOS responses (9 genes), membrane permeability (18 genes), intercellular contact (17 genes), and energy metabolism pathways (13 genes) were all upregulated, especially in the presence of TBEPS. Carbohydrates and aliphatic substances in SEPS and LBEPS were contributors to ARG transfer, via influencing reactive oxygen species (ROS) formation (SEPS) and ROS and adenosine triphosphate (ATP) production (LBEPS). TBEPS had the highest redox potential and greatest lability and facilitated electron transfer and alternated respiration between cells, thus promoting ARG transfer by producing ATP. Generally, the chemical molecular characteristics and redox properties of EPS facilitated ARG transfer mainly by influencing lipid peroxidation and ATP, respectively.

[Progress of allergic rhinitis research based on transcriptome sequencing].

Traditional studies on allergic rhinitis（AR） have mainly adopted animal models and biomolecular approaches. In addition, the advent of transcriptome sequencing technology is promoting the development of AR at the genetic level. Recently, many scholars have focused on the role of common RNA in the pathogenesis of AR, suggesting that breakthroughs have been made in the field of AR bioinformatics analysis. This review aims to summarize the research advances in AR, the development of transcriptome sequencing technology, and the application of transcriptome sequencing in AR, in order to explore potential drug targets for AR treatment and provide new insights into precision medicine.

Multi-omic dissection of the cold resistance traits of white water lily.

The white water lily (Nymphaea candida), exemplifying nature's resilience, thrives in the high-altitude terrains of Xinjiang, China, serving as an ideal model for investigating cold adaptation mechanisms in aquatic plants. This study meticulously elucidates the complex cold adaptation mechanisms of the white water lily through a comprehensive and integrated methodological approach. We discovered that the water lily undergoes ecodormancy in winter, retaining high cellular viability and growth potential. During overwintering, the white water lily demonstrates effective resource reallocation, a process facilitated by morphological adjustments, thereby strengthening its resistance to cold temperatures. This enhancement is achieved particularly through the compartmentalization of large vacuoles, the accumulation of osmoregulatory substances, and an increased antioxidant capacity. We established the first exhaustive full-length transcriptome for the white water lily. A subsequent comprehensive analysis of the transcriptome, phytohormones, and metabolome uncovered a multifaceted regulatory network orchestrating cold adaptation. Our research spotlights phytohormone signaling, amino acid metabolism, and circadian rhythms as key elements in the water lily's defense against cold. The results emphasize the critical role of nitrogen metabolism, especially amino acid-related pathways, during cold stress. Metabolite profiling revealed the importance of compounds like myo-inositol and L-proline in enhancing cold tolerance. Remarkably, our study demonstrates that the white water lily notably diminishes the utilization of unsaturated fatty acids in its temperature regulation strategies. In conclusion, this research substantially enriches our understanding of the white water lily's intricate cold adaptation mechanisms, offering new perspectives on the adaptive strategies of aquatic plants and potential applications in agricultural advancement.

Molecular, biological characterization and drug sensitivity of chidamide-resistant MCF7 cells.

Background: Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase inhibitor for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. However, drug resistance is commonly occurred after a long period of medication. This study aimed to investigate the characterization of induced resistance to CHI and explore the potential cross-resistance to chemotherapeutic agents. Methods: CHI with gradually increasing concentrations was added to breast cancer MCF7 cells to establish a CHI-resistant MCF7 (MCF7-CHI-R) cell line. Cell counting kit-8 (CCK-8) assays were performed to detect half-maximal inhibitory concentration (IC50) of CHI. Colony formation was used to determine the proliferation inhibition rate. Western blot analysis was conducted to detect expressions of protein related with cell cycle, apoptosis, ferroptosis, and histone deacetylase (HDAC). Flow cytometry was used to analyze apoptosis and cell cycle. Results: The IC50 value of CHI of MCF7-CHI-R cells was increased in comparison with MCF7 cells. And CHI led to cell cycle arrest and ferroptosis, which were not exhibited in MCF7-CHI-R cells. Moreover, HDAC activity decreased in MCF7-CHI-R cells in comparison with MCF7 cells, and HDAC1 and HDAC10 might be involved in the resistance to CHI. In addition, MCF7-CHI-R cells were resistant to gemcitabine (GEM), doxorubicin (ADM), docetaxel (DXT), albumin-bound paclitaxel (nab-PTX) and paclitaxel (PTX). Conclusions: The MCF7-CHI-R was established and the anti-ferroptosis pathway activation was involved in the resistance of MCF-CHI-R cells. Also, MCF7-CHI-R cells were resistant to GEM, ADM, DXT, nab-PTX and PTX.

Flexible, Stable, and Efficient Counter Electrode for Quantum-Dot-Sensitized Solar Cells Based on Carbon Nanotube Films.

With the rapid development in information, communication, energy, medical care, and other fields, the demand for light, strong, flexible, and stable materials continues to grow. Carbon nanotube (CNT) films possess outstanding properties, such as flexibility, good tensile properties, low density, and high electrical conductivity, making them promising materials for a wide range of applications. This paper reports an effective strategy that combines stretching treatment, laser etching, and electron beam deposition to fabricate an iron-deposited CNT film, which can serve as a counter electrode (CE) of quantum-dot-sensitized solar cells. The study also investigates the influences of processing parameters, such as stretching ratio and iron-depositing thickness on the film's stacking structure, electrical conductivity, and catalytic activity. Under optimized stretching ratios and depositing thicknesses, the catalytic activity of the reacted deposited layer and the high electrical conductivity of the flexible film basis can be fully utilized, allowing the photoelectric conversion efficiency (PCE) of the solar cells to reach approximately 4.58%. Additionally, the CE exhibits flexibility, light transmission, and good stability, with its primary properties remaining above 97% after nearly 50 days. Thus, this research provides innovative material options and development strategies for the development of electrode materials.

Analysis of Spinal-Pelvic Sagittal Plane Parameters in Patients with Lumbar Vertebral Posterior Ring Apophysis Separation.

OBJECTIVE: To investigate the characteristics of the spinal-pelvic sagittal sequence in patients with lumbar vertebral posterior ring apophysis separation (PRAS). METHODS: A retrospective analysis was conducted on 119 hospitalized patients with PRAS, and 119 adults without symptoms of low back and leg pain were selected as the control. General data and spinal-pelvic sagittal parameters were collected and analyzed. RESULTS: Compared to the control group, the pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL), and thoracic kyphosis of the PRAS group were significantly lower, while the pelvic tilt (PT), sagittal vertical axis, and PI minus LL were significantly higher. There was no significant difference in thoracolumbar kyphosis between the 2 groups. In patients with PRAS, the LL value of lumbar curvature was moderately correlated with thoracic kyphosis and SS, while PI, PT, and SS were pairwise correlated, indicating that the change in one parameter is often accompanied by simultaneous changes in other parameters if PRAS happens. The correlation between different parameters could provide guidance for the diagnosis of PRAS. In terms of LL type, the PRAS group was mainly of Roussouly type I, while the control group was mainly of type II, and the difference in the composition ratio was statistically significant. CONCLUSIONS: As reflected by the spinal-pelvic sagittal parameters, the patients with PRAS exhibited reduced thoracic and lumbar curvature, posterior PT, and fewer vertebral bodies involved in LL. These morphological characteristics indicate the changes of the mechanical structure of the spine.

Genome-wide identification of the Q-type C2H2 zinc finger protein gene family and expression analysis under abiotic stress in lotus (Nelumbo nucifera G.).

BACKGROUND: Lotus (Nelumbo nucifera G.) is an important aquatic plant with high ornamental, economic, cultural and ecological values, but abiotic stresses seriously affect its growth and distribution. Q-type C2H2 zinc finger proteins (ZFPs) play an important role in plant growth development and environmental stress responses. Although the Q-type C2H2 gene family has been identified in some plants, limited reports has been carried out it in lotus. RESULTS: In this study, we identified 45 Q-type NnZFP members in lotus. Based on the phylogenetic tree, these Q-type NnZFP gene family members were divided into 4 groups, including C1-1i, C1-2i, C1-3i and C1-4i. Promoter cis-acting elements analysis indicated that most Q-type NnZFP gene family members in lotus were associated with response to abiotic stresses. Through collinearity analyses, no tandem duplication gene pairs and 14 segmental duplication gene pairs were identified, which showed that duplication events might play a key role in the expansion of the Q-type NnZFP gene family. The synteny results suggested that 54 and 28 Q-type NnZFP genes were orthologous to Arabidopsis and rice, respectively. The expression patterns of these Q-type NnZFP genes revealed that 30 Q-type NnZFP genes were expressed in at least one lotus tissue. Nn5g30550 showed relatively higher expression levels in all tested tissues. 12 genes were randomly selected with at least one gene from each phylogenetic clade, and the expression of these selected genes were confirmed by qRT-PCR (quantitative real-time polymerase chain reaction). The results indicated that Q-type NnZFP genes were extensively involved in cadmium, drought, salt and cold stresses responses. Among them, 11 genes responded to at least three different stress treatments, especially Nn2g12894, which induced by all four treatments. CONCLUSIONS: These results could increase our understanding of the characterization of the Q-type NnZFP gene family and provide relevant information for further functional analysis of Q-type NnZFP genes in plant development, and abiotic stress tolerance in lotus.

Continuous blood exchange in rats as a novel approach for experimental investigation.

Blood exchange therapy, specifically Whole blood exchange (WBE), is increasingly being utilized in clinical settings to effectively treat a range of diseases. Consequently, there is an urgent requirement to establish convenient and clinically applicable animal models that can facilitate the exploration of blood exchange therapy mechanisms. Our study conducted continuous WBE in rats through femoral and tail vein catheterization using dual-directional syringe pumps. To demonstrate the applicability of continuous WBE, drug-induced hemolytic anemia (DIHA) was induced through phenylhydrazine hydrochloride (PHZ) injection. Notability, the rats of DIHA + WBE group all survived and recovered within the subsequent period. After the implementation of continuous WBE therapy day (Day 1), the DIHA + WBE group exhibited a statistically significant increase in red blood cells (RBC) (P = 0.0343) and hemoglobin (HGB) levels (P = 0.0090) compared to DIHA group. The rats in the DIHA + WBE group exhibited a faster recovery rate compared to the DIHA group, indicating the successful establishment of a continuous blood exchange protocol. This experimental approach demonstrates not just promising efficacy in the treatment of DIHA and offers a valuable tool for investigating the underlying mechanisms of blood exchange. Furthermore, it has a great potential to the advancement of biomedical research such as drug delivery exploration.

EDTA enables to alleviate impacts of metal ions on conjugative transfer of antibiotic resistance genes.

Various heavy metals are reported to be able to accelerate horizontal transfer of antibiotic resistance genes (ARGs). In real water environmental settings, ubiquitous complexing agents would affect the environmental behaviors of heavy metal ions due to the formation of metal-organic complexes. However, little is known whether the presence of complexing agents would change horizontal gene transfer due to heavy metal exposure. This study aimed to fill this gap by investigating the impacts of a typical complexing agent ethylenediaminetetraacetic acid (EDTA) on the conjugative transfer of plasmid-mediated ARGs induced by a range of heavy metal ions. At the environmentally relevant concentration (0.64 mg L-1) of metal ions, all the tested metal ions (Mg2+, Ca2+, Co2+, Pb2+, Ni2+, Cu2+, and Fe3+) promoted conjugative transfer of ARGs, while an inhibitory effect was observed at a relatively higher concentration (3.20 mg L-1). In contrast, EDTA (0.64 mg L-1) alleviated the effects of metal ions on ARGs conjugation transfer, evidenced by 11 %-66 % reduction in the conjugate transfer frequency. Molecular docking and dynamics simulations disclosed that this is attributed to the stronger binding of metal ions with the lipids in cell membranes. Under metal-EDTA exposure, gene expressions related to oxidative stress response, cell membrane permeability, intercellular contact, energy driving force, mobilization, and channels of plasmid transfer were suppressed compared with the metal ions exposure. This study offers insights into the alleviation mechanisms of complexing agents on ARGs transfer induced by free metal ions.

Ozonolysis of phospholipids at the air-water interface intervened by polyfluoroalkyl substances.

Perfluoroalkyl substances (PFASs) are ubiquitous in the environment and even accumulate in the human body associated with their excellent stability and persistence. However, the effect and reaction mechanism at the molecular level on the cell phospholipid peroxidation remained unclear. In this work, the interfacial reaction of model phospholipids (POPG) intervened by per- and polyfluoroalkyl substances (PFASs) at the air-water interface of a hanged droplet exposed to ozone (O3) was investigated. Perfluorinated carboxylates and sulfonates were evaluated. Four-carbon PFASs promoted interfacial ozonolysis, but PFASs with longer carbon skeletons impeded this chemistry. A model concerning POPG packing was proposed and it was concluded that the interfacial chemistry was mediated by chain length rather than their functional groups. Four-carbon PFASs could couple into POPG ozonolysis by mainly reacting with aldehyde products along with minor Criegee intermediates, but this was not observed for longer PFASs. This is different from that condensed-phase Criegee intermediates preferred to reacting with per-fluoroalkyl carboxylic acids. These results provide insight into the adverse health of PFASs on cell peroxidation.

Hispidin Increases Cell Apoptosis and Ferroptosis in Prostate Cancer Cells Through Phosphatidylinositol-3-Kinase and Mitogen-activated Protein Kinase Signaling Pathway.

BACKGROUND/AIM: Chemotherapy is mainly used in the clinical treatment of prostate cancer. Different anticancer mechanisms can induce cell death in various cancers. Reactive oxygen species (ROS) play crucial roles in cell proliferation, differentiation, apoptosis, and signal transduction. It is widely accepted that ROS accumulation is closely related to chemical drug-induced cancer cell death. MATERIALS AND METHODS: We utilized the MTT assay to detect changes in cell proliferation. Additionally, colony formation and wound healing assay were conducted to investigate the effect of hispidin on cell colony formation and migration ability. Fluorescence microscopy was used to detect intracellular and mitochondrial ROS levels, while western blot was used for detection of cell apoptosis. RESULTS: Hispidin treatment significantly decreased viability of PC3 and DU145 cancer cells but exhibited no cytotoxicity in WPMY-1 cells. Furthermore, hispidin treatment inhibited cell migration and colony formation and triggered cellular and mitochondrial ROS accumulation, leading to mitochondrial dysfunction and mitochondrion-dependent apoptosis. Moreover, hispidin treatment induced ferroptosis in PC3 cells. Scavenging of ROS with N-acetyl cysteine significantly inhibited hispidin-induced apoptosis by altering the expression of apoptosis-related proteins, such as cleaved caspase-3, 9, Bax, and Bcl2. Furthermore, hispidin treatment dramatically up-regulated MAPK (involving p38, ERK, and JNK proteins) and NF-kB signaling pathways while down-regulating AKT phosphorylation. Hispidin treatment also inhibited ferroptosis signaling pathways (involving P53, Nrf-2, and HO-1 proteins) in PC3 cells. In addition, inhibiting these signaling pathways via treatment with specific inhibitors significantly reversed hispidin-induced apoptosis, cellular ROS levels, mitochondrial dysfunction, and ferroptosis. CONCLUSION: Hispidin may represent a potential candidate for treating prostate cancer.

Model informed precision medicine of Chinese herbal medicines formulas-A multi-scale mechanistic intelligent model.

Recent trends suggest that Chinese herbal medicine formulas (CHM formulas) are promising treatments for complex diseases. To characterize the precise syndromes, precise diseases and precise targets of the precise targets between complex diseases and CHM formulas, we developed an artificial intelligence-based quantitative predictive algorithm (DeepTCM). DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling, molecular and theoretical levels of traditional Chinese medicine (TCM). As an example, our model simulated the optimal CHM formulas for the treatment of coronary heart disease (CHD) with depression, and through model sensitivity analysis, we calculated the balanced scoring of the formulas. Furthermore, we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions. Finally, we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice. This novel multiscale model opened up a new avenue to combine "disease syndrome" and "macro micro" system modeling to facilitate translational research in CHM formulas.

Heterogeneous hydrochlorination of lipids mediated by fatty acids in an indoor environment.

Fatty acids from cooking fumes and hypochlorous acid (HOCl) released from indoor cleaning adversely affect respiratory health, but the molecular-level mechanism remains unclear. Here, the effect of cooking oil fumes [palmitic acid (PA), oleic acid (OA), and linoleic acid (LA)] on lung model phospholipid (POPG) hydrochlorination mediated by HOCl at the air-water interface of the hanged droplets was investigated. Interfacial hydrochlorination of POPG was impeded by OA and LA, while that of POPG was facilitated by PA. The effect on POPG hydrochlorination increased with the decrease in oil fume concentration. A potential mechanism with respect to the chain length of these oil fumes, regardless of their saturation, was proposed. PA with a short carbon chain looses the POPG packing and leads to the exposure of the C=C double bonds of POPG, whereas OA and LA with a long carbon chain hinder HOCl from reaching the C=C bonds of POPG. These results for short chain and low concentration dependence suggest that the decay of oil fumes or the conversion of short-chain species by indoor interfacial chemistry might be adverse to lung health. These results provide insights into the relationship between indoor multicomponent pollutants and the respiratory system.

Efficacy and safety of gemcitabine plus raltitrexed or S-1 versus standard third-line therapies in metastatic colorectal cancer: a retrospective cohort study.

Background: After the failure of standard first- and second-line treatments, including oxaliplatin, irinotecan, and 5-fluorouracil (5-FU) combined with targeted drugs, the currently recommended third-line regimens for metastatic colorectal cancer (mCRC) include TAS-102, regorafenib, and fruquintinib. However, these regimens have the drawbacks of mediocre efficacy, substantive side effects, and high cost. Therefore, more effective, economical regimens with fewer side effects are needed in clinical practice. In this study, we assessed the efficacy and safety of gemcitabine plus raltitrexed or S-1 as a third- or later-line treatment in comparison to those of standard third-line therapies for patients with mCRC. Methods: Patients with previous failures of at least two lines of standard therapy with oxaliplatin, 5-FU, irinotecan, or capecitabine combined with targeted drugs were included. The participants received standard third-line therapies (including TAS-102, regorafenib, and fruquintinib) or gemcitabine plus raltitrexed or S-1 until disease progression, death, or intolerable toxicity arose. Imaging follow-up was performed every 3 months during their treatment. Progression-free survival (PFS) and overall survival (OS) were recorded. Cox regression analysis was used to investigate the potential predictors of survival. Results: From April 2018 to October 2022, 60 patients with mCRC were enrolled in our study. The numbers of patients in the chemotherapy, fruquintinib, regorafenib, and TAS-102 groups were 13, 15, 17, and 15, respectively; the median OS of the four groups was 7.4, 6.1, 8.3, and 6.7 months (P=0.384), respectively; the median PFS was 4.1, 3.4, 4.4, and 2.3 months (P=0.656), respectively; the overall response rate was 7.69%, 6.67%, 0.00%, and 13.33%, respectively; and the disease control rate was 61.54%, 60.00%, 70.59%, and 60.00%, respectively. Additionally, multivariate analysis revealed that primary lesion located in the rectum was adverse independent prognostic factors for OS. A typical case is presented in this article. Conclusions: The gemcitabine plus raltitrexed or S-1 regimen is a potential regimen with tolerable adverse reactions and low cost for patients with mCRC.

Rational Design and Pharmacomodulation of 18F-Labeled Biotin/FAPI-Conjugated Heterodimers.

Due to the complex heterogeneity in different cancer types, the heterodimeric strategy has been intensively practiced to improve the effectiveness of tumor diagnostics. In this study, we developed a series of novel 18F-labeled biotin/FAPI-conjugated heterobivalent radioligands ([18F]AlF-NSFB, [18F]AlF-NSFBP2, and [18F]AlF-NSFBP4), synergistically targeting both fibroblast activation protein (FAP) and biotin receptor (BR), to enhance specific tumor uptake and retention. The in vitro and in vivo biological properties of these dual-targeting tracers were evaluated, with a particular focus on positron emission tomography imaging in A549 and HT1080-FAP tumor-bearing mice. Notably, in comparison to the corresponding FAP-targeted monomer [18F]AlF-NSF, biotin/FAPI-conjugated heterodimers exhibited a high uptake in tumor and prolong retention. In conclusion, as a proof-of-concept study, the findings validated the superiority of biotin/FAPI-conjugated heterodimers and the positive influence of biotin and linker on pharmacokinetics of radioligands. Within them, the bispecific [18F]AlF-NSFBP4 holds significant promise as a candidate for further clinical translational studies.