Spatial immune landscapes of SARS-CoV-2 gastrointestinal infection: macrophages contribute to local tissue inflammation and gastrointestinal symptoms.

Background: In some patients, persistent gastrointestinal symptoms like abdominal pain, nausea, and diarrhea occur as part of long COVID-19 syndrome following acute respiratory symptoms caused by SARS-CoV-2. However, the characteristics of immune cells in the gastrointestinal tract of COVID-19 patients and their association with these symptoms remain unclear. Methodology: Data were collected from 95 COVID-19 patients. Among this cohort, 11 patients who exhibited gastrointestinal symptoms and underwent gastroscopy were selected. Using imaging mass cytometry, the gastrointestinal tissues of these patients were thoroughly analyzed to identify immune cell subgroups and investigate their spatial distribution. Results: Significant acute inflammatory responses were found in the gastrointestinal tissues, particularly in the duodenum, of COVID-19 patients. These alterations included an increase in the levels of CD68+ macrophages and CD3+CD4+ T-cells, which was more pronounced in tissues with nucleocapsid protein (NP). The amount of CD68+ macrophages positively correlates with the number of CD3+CD4+ T-cells (R = 0.783, p < 0.001), additionally, spatial neighborhood analysis uncovered decreased interactions between CD68+ macrophages and multiple immune cells were noted in NP-positive tissues. Furthermore, weighted gene coexpression network analysis was employed to extract gene signatures related to clinical features and immune responses from the RNA-seq data derived from gastrointestinal tissues from COVID-19 patients, and we validated that the MEgreen module shown positive correlation with clinical parameter (i.e., Total bilirubin, ALT, AST) and macrophages (R = 0.84, p = 0.001), but negatively correlated with CD4+ T cells (R = -0.62, p = 0.004). By contrast, the MEblue module was inversely associated with macrophages and positively related with CD4+ T cells. Gene function enrichment analyses revealed that the MEgreen module is closely associated with biological processes such as immune response activation, signal transduction, and chemotaxis regulation, indicating its role in the gastrointestinal inflammatory response. Conclusion: The findings of this study highlight the role of specific immune cell groups in the gastrointestinal inflammatory response in COVID-19 patients. Gene coexpression network analysis further emphasized the importance of the gene modules in gastrointestinal immune responses, providing potential molecular targets for the treatment of COVID-19-related gastrointestinal symptoms.

Anti-seasonal flooding drives substantial alterations in riparian plant diversity and niche characteristics in a unique hydro-fluctuation zone.

Human-induced disturbances such as dam construction and regulation have led to widespread alterations in hydrological processes and thus substantially influence plant characteristics in the hydro-fluctuation zones (HFZs). To reveal utilization of limited resources and mechanisms of inter-specific competition and species co-existence of plant communities based on niche breadth and overlap under the different HFZs of the Three Gorges Reservoir (TGR) in China, we conducted a field investigation with 368 quadrats on the effects of hydrological alterations on plant diversity and niche characteristics. The results showed anti-seasonal flooding precipitated the gradual disappearance of the original diverse niches, resulting in the reduction of plant species richness and functional diversity and more obvious competition among plant species with similar resource requirements. Annuals, perennials and shrubs accounted for 71.23%, 27.39% and 1.37%, respectively, suggesting that annuals and flood-tolerant riparian herbs were favored under such novel flooding conditions. A consistent increase in species number, Shannon-Wiener diversity index and Simpson dominance index with altitude was inconsistent with hump-shaped diversity-disturbance relationship of the intermediate disturbance hypothesis, while the opposite trend was observed for the Pielou evenness index. This species distribution pattern might be caused by several synergetic attributes (e.g., the submergence depth, plant tolerant capacity to flooding, life form, dispersal mode and inter-specific competition). Vegetation types shifted from xerophytes to mesophytes and eventually to hygrophytes with the increasing flooding time in the HFZs. Hydrological alterations proved to be the paramount driver of vegetation distribution in the different HFZs. The niche analysis provided the first insights on the mechanisms of resource utilization and inter-specific competition, of which annuals could germinate quickly after soil drainage to achieve the greatest competitive advantages and occupy a larger niche space than other plants. Vegetation was still in the early stage of primary succession in the novel riparian forests. Therefore, vegetation restoration strategies should be biased towards herbaceous plants, due to annuals with better environmental adaptability, supplemented by shrubs and small trees. To establish a complete reference system for vegetation restoration, natural vegetation monitory plots in the different succession stages should be established in the different HFZs of the TGR, and their environmental conditions, community structures and inter-specific relationships further analyzed.

Adjusting the charging behavior of TiO2 with basic surfactants in an apolar medium for electrophoretic displays.

Electrophoretic displays (EPDs) are attracting attention as potential candidates for information display due to their eye-friendly nature, environmental friendliness and bistability. However, their response speed, which is closely related to the charging behavior of electrophoretic particles, is still inadequate for practical applications. Herein, five basic surfactants were employed to adjust the particle charge of titanium dioxide (TiO2) in the apolar medium Isopar L. Particle charge is strongly related to the effective surfactant coverage on surface sites, dominated by the interaction between anchoring groups and solvation chains. As a result, the electrophoretic mobility of TiO2 could be tuned between -8.09 × 10-10 and +2.26 × 10-10 m2 V-1 s-1. Due to the increased particle charge, TiO2 particles could be well dispersed in Isopar L with the assistance of S17000, T151 and T154. A black-white dual particle electrophoretic system with 2.0% (w/v) S17000 was constructed to obtain EPD devices. The EPD device gained a maximum white-and-black-state reflectivity of 41.79%/0.56% and a peak contrast ratio of 74.15. Its response time could be reduced to as low as 166.7 ms, which outperforms the majority of other black-white EPD devices.

Self-Floating Polydopamine/Polystyrene Composite Porous Structure via a NaCl Template Method for Solar-Driven Interfacial Water Evaporation.

Solar energy, as a clean and renewable energy source, holds significant promise for addressing water shortages. Utilizing solar energy for water evaporation is seen as an effective solution in this regard. While many existing interfacial photothermal water evaporation systems rely on nanoparticles or graphene as photothermal or support materials, this study introduced polydopamine (PDA) as a photothermal material due to its environmental friendliness and excellent photon absorption characteristics that closely match the solar spectrum. Polystyrene (PS) was also introduced as a support material for its porous structure and density similar to water, enabling it to float on water. The resulting PS-PDA composite porous structure solar evaporator exhibited a photothermal conversion efficiency comparable to nanoparticles (over 75%), yet with lower production costs and minimal environmental impact. This innovative approach offers a scalable solution for water-scarce regions, providing a cost-effective and efficient means to address water scarcity. The use of PDA and PS in this context highlights the potential for utilizing common materials in novel ways to meet pressing environmental challenges.

Chemical Recycling of Poly(cyclohexene carbonate)s via Synergistic Catalysis.

Chemical recycling of polymers to the corresponding monomers offers a valuable solution to address the current plastics crisis for creating an ideal and circular polymer economy. Here, we present a bimetallic synergistic depolymerization of the widely studied CO2-based polycarbonates, poly(cyclohexene carbonate)s, to epoxide monomers efficiently. The bimetallic CrIII-complex-mediated highly selective depolymerization and repolymerization was achieved via the regulation of reaction temperature, thus closing the circular loop of poly(cyclohexene carbonate)s in situ. Mechanistic investigation has revealed that the formation of epoxides undergoes a direct chain-end unzipping process. A bimetallic catalysis involving a nucleophilic attack of the metal-alkoxide species toward the methine carbon atom bound with an adjacent carbonyl that is activated by the other metal center features a lower energy barrier in DFT calculations, which promotes the epoxide extrusion.

CTHRC1 modulates cell proliferation and invasion in hepatocellular carcinoma by DNA methylation.

BACKGROUND: Collagen triple helix repeat containing-1 (CTHRC1), an extracellular matrix protein, is highly expressed in hepatocellular carcinoma (HCC) and linked to poor prognosis. Nevertheless, the precise mechanism of CTHRC1 in HCC is unclear. METHODS: Agena MassARRAY® Methylation Analysis assessed the methylation level of CTHRC1 in the promoter region. Functional assays were conducted to investigate the effects of CTHRC1 knockdown in Hep3B2.1 cells. RNA sequencing identified differentially expressed genes and lncRNAs associated with angiogenesis after CTHRC1 knockdown. Furthermore, differential alternative splicing (AS) and gene fusion events were analyzed using rMATS and Arriba. RESULTS: In HCC cell lines, CTHRC1 was highly expressed and associated with hypomethylation. Downregulation of CTHRC1 inhibited Hep3B2.1 cell proliferation, migration, and invasion, blocked cells in the G1/S phase, and promoted apoptosis. We obtained 34 mRNAs and 7 lncRNAs differentially expressed between the NC and CTHRC1 inhibitor groups. Additionally, we found 4 angiogenesis-related mRNAs and lncRNAs significantly correlated with CTHRC1. RT-qPCR results showed that knockdown of CTHRC1 in Hep3B2.1 cells resulted in significantly aberrant expression of CXCL6, LINC02127, and AC020978.8. Moreover, the role of CTHRC1 in HCC development may be associated with events, like 12 AS events and 5 pairs of fusion genes. CONCLUSIONS: High expressed CTHRC1 is associated with hypomethylation and may promote HCC development, involving events like angiogenesis, alternative splicing, and gene fusion.

Association of accelerated biological aging with brain volumes: A cross-sectional study.

BACKGROUND: Multiple epidemiological studies have observed the connection between aging and brain volumes. The concept of accelerated biological aging (BA) is more powerful for observing the degree of aging of an individual than chronologic age (CA). The objective of this study is to explore the relationship between BA and brain volumes. METHODS: BA was measured from clinical traits using two blood-chemistry algorithms, the Klemera-Doubal method (KDM) and the PhenoAge. The two age acceleration biomarkers were calculated by the residuals from regressing CA, termed "KDM-acceleration" and "PhenoAge-acceleration". Brain volumes were from brain magnetic resonance imaging (MRI) data. After adjustment for confounding factors, general linear regression models were used to examine associations between KDM-acceleration and PhenoAge-acceleration and brain volumes, respectively. Additionally, we stratified participants by sex, age, and the four quartiles of the Townsend Deprivation Index (TDI) for extra subgroup analysis. RESULTS: 14,725 participants with available information were enrolled. After full adjustment, we observed negative associations between KDM-acceleration and brain volumes, such as gray matter (ß = -0.029), white matter (ß = -0.021), gray and white matter (ß = -0.026), and hippocampus (ß = -0.011 for left and ß = -0.014 for right). There were also negative associations between PhenoAge-acceleration and brain volumes, such as white matter (ß = -0.008), gray and white matter (ß = -0.010), thalamus (ß = -0.011 for left and ß = -0.010 for right). In the subgroup analysis stratified by sex, age, and the four quartiles of TDI, the association between KDM-acceleration and PhenoAge-acceleration and brain volumes still existed. In subgroup analyses, the variation in associations suggests that socioeconomic and biological factors may differentially influence brain aging. CONCLUSIONS: Our research indicated that more advanced BA was associated with less brain tissue.

Influence of reduced-port laparoscopic surgery on perioperative indicators, postoperative recovery, and serum inflammation in patients with colorectal carcinoma.

BACKGROUND: Conventional five-port laparoscopic surgery, the current standard treatment for colorectal carcinoma (CRC), has many disadvantages. AIM: To assess the influence of reduced-port laparoscopic surgery (RPLS) on perioperative indicators, postoperative recovery, and serum inflammation indexes in patients with CRC. METHODS: The study included 115 patients with CRC admitted between December 2019 and May 2023, 52 of whom underwent conventional five-port laparoscopic surgery (control group) and 63 of whom underwent RPLS (research group). Comparative analyses were performed on the following dimensions: Perioperative indicators [operation time (OT), incision length, intraoperative blood loss (IBL), and rate of conversion to laparotomy], postoperative recovery (first postoperative exhaust, bowel movement and oral food intake, and bowel sound recovery time), serum inflammation indexes [high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)], postoperative complications (anastomotic leakage, incisional infection, bleeding, ileus), and therapeutic efficacy. RESULTS: The two groups had comparable OTs and IBL volumes. However, the research group had a smaller incision length; lower rates of conversion to laparotomy and postoperative total complication; and shorter time of first postoperative exhaust, bowel movement, oral food intake, and bowel sound recovery; all of which were significant. Furthermore, hs-CRP, IL-6, and TNF-α levels in the research group were significantly lower than the baseline and those of the control group, and the total effective rate was higher. CONCLUSION: RPLS exhibited significant therapeutic efficacy in CRC, resulting in a shorter incision length and a lower conversion rate to laparotomy, while also promoting postoperative recovery, effectively inhibiting the inflammatory response, and reducing the risk of postoperative complications.

Ablation apprentices and their first experience of pulmonary vein isolation procedure on paroxysmal atrial fibrillation with different sheaths.

OBJECTIVES: This study aimed at exploring how using different kinds of sheaths will affect the very first ablation procedure of apprentices. METHODS: 15 patients with paroxysmal atrial fibrillation were randomized to used fixed-curve, conventional steerable or visualized steerable sheath, and received complete isolation of pulmonary veins. All ablations were the very first procedure performed by 15 ablation apprentices. The use of fluoroscopy and catheter stability during the PVI were analyzed. RESULTS: Procedure duration was much longer in the fixed-curve group (116.8 ± 27 vs. 62.2 ± 17 vs. 60.4 ± 17, p < 0.001). X-ray exposure was lowest with visualized sheath (17.6 ± 5 vs. 18.6 ± 6 vs. 5.2 ± 6, p < 0.001). CF SD differed significantly, especially at the anterior aspect of LSPV (7.90 ± 2.90 vs. 5.04 ± 2.18 vs. 4.52 ± 2.40, p < 0.001) and posterior aspect of RSPV (6.84 ± 2.79 vs. 3.42 ± 2.04 vs. 3.50 ± 2.30, p < 0.001) in the fixed-curve group. Impedance drop was significantly smaller in the fixed-curve group at the anterior aspect of LSPV (8.74 ± 3.02 vs. 11.49 ± 5.48 vs. 12.57 ± 5.96, p = 0.005). CONCLUSION: Even for the very first ablation procedure of an ablation apprentice, the use of steerable sheaths will significantly reduce the procedure duration and improve the catheter stability, but only visualized steerable sheath can reduce fluoroscopic time.

Micronutrient-Associated Single Nucleotide Polymorphism and Mental Health: A Mendelian Randomization Study.

PURPOSE: Previous studies have demonstrated the link between micronutrients and mental health. However, it remains uncertain whether this connection is causal. We aim to investigate the potential causal effects of micronutrients on mental health based on linkage disequilibrium score (LDSC) regression and Mendelian randomization (MR) analysis. METHODS: Utilizing publicly available genome-wide association study (GWAS) summary datasets, we performed LDSC and MR analysis to identify candidate micronutrients with potential causal effects on mental health. Single nucleotide polymorphisms (SNPs) significantly linked with candidate micronutrients with a genome-wide significance level (p < 5 × 10-8) were selected as instrumental variables (IVs). To estimate the causal effect of candidate micronutrients on mental health, we employed inverse variance weighted (IVW) regression. Additionally, two sensitivity analyses, MR-Egger and weighted median, were performed to validate our results. RESULTS: We found evidence supporting significant causal associations between micronutrients and mental health. LDSC detected several candidate micronutrients, including serum iron (genetic correlation = -0.134, p = 0.032) and vitamin C (genetic correlation = -0.335, p < 0.001) for attention-deficit/hyperactivity disorder (ADHD), iron-binding capacity (genetic correlation = 0.210, p = 0.037) for Alzheimer's disease (AD), and vitamin B12 (genetic correlation = -0.178, p = 0.044) for major depressive disorder (MDD). Further MR analysis suggested a potential causal relationship between vitamin B12 and MDD (b = -0.139, p = 0.009). There was no significant heterogeneity or pleiotropy, indicating the validity of the findings. CONCLUSION: In this study, we identified underlying causal relationships between micronutrients and mental health. Notably, more research is necessary to clarify the underlying biological mechanisms by which micronutrients affect mental health.

Receptive Field Space for Point Cloud Analysis.

Similar to convolutional neural networks for image processing, existing analysis methods for 3D point clouds often require the designation of a local neighborhood to describe the local features of the point cloud. This local neighborhood is typically manually specified, which makes it impossible for the network to dynamically adjust the receptive field's range. If the range is too large, it tends to overlook local details, and if it is too small, it cannot establish global dependencies. To address this issue, we introduce in this paper a new concept: receptive field space (RFS). With a minor computational cost, we extract features from multiple consecutive receptive field ranges to form this new receptive field space. On this basis, we further propose a receptive field space attention mechanism, enabling the network to adaptively select the most effective receptive field range from RFS, thus equipping the network with the ability to adjust granularity adaptively. Our approach achieved state-of-the-art performance in both point cloud classification, with an overall accuracy (OA) of 94.2%, and part segmentation, achieving an mIoU of 86.0%, demonstrating the effectiveness of our method.

Mapping the current trends and hotspots of adult hippocampal neurogenesis from 2004-2023: a bibliometric analysis.

Objective: We utilized bibliometric and data visualization techniques to discern the primary research domains and emerging frontiers in the field of adult hippocampal neurogenesis (AHN). Methods: We systematically searched the Web of Science database for AHN-related articles published between 2004 and 2023. The retrieved articles were filtered based on publication types (articles and reviews) and language (English). We employed CiteSpace, VOSviewer, and the online bibliometric platform (bibliometric.com) to visualize and analyze the collected data. Results: In total, 1,590 AHN-related publications were discovered, exhibiting a steady increase in yearly publications over time. The United States emerged as the leading contributor in AHN research in terms of both publication quantity and national influence. Among all research institutions in the field of AHN, the University of California System exhibited the highest impact. Kempermann, Gerd was the most active author. The publications of the top three active authors primarily focused on the functions of AHN, and reversing hippocampal damage and cognitive impairment by improving AHN. An analysis of reference co-citation clustering revealed 8 distinct research clusters, and the notable ones included "adult hippocampal neurogenesis," "neurogenesis," "hippocampus," "dentate gyrus," "neural stem cell," and "depression." Additionally, a burst keyword detection indicated that 'anxiety' is a current research hotspot in the field of AHN. Conclusion: This in-depth bibliographic assessment of AHN offers a deeper insight into the present research hotspots in the field. The association between AHN and cognitive diseases, such as Alzheimer's disease (AD) and anxiety, has emerged as a prominent research hotspot.

Cell-Cultured Fish Meat via Scale-Up Expansion of Carassius auratus Skeletal Muscle Cells Using Edible Porous Microcarriers and Quality Evaluation.

Emerging technologies for cell-cultured fish meat as an environmentally friendly protein source for humans still have many obstacles, including large-scale production of high-quality cells, differentiation and bioassembly of cellular material, and improvement of the quality of meat products. Here, we used edible porous microcarriers as scaffolds to support scalable skeletal muscle cell expansion to prepare centimeter-scale cell-cultured fish (CCM) of Carassius auratus for the first time. The quality of CCM was assessed by analyzing the texture, nutrition, flavor, and safety. The results indicated that CCM demonstrated a softer texture than natural fish due to a high moisture content. CCM contained higher protein and lower fat contents, with no significant difference in energy from natural golden crucian carp meat (NGM). CCM had better digestible properties, and 17 volatile components were identified in CCM, ten cocontained compared to NGM. ELISA quantified penicillin, streptomycin, vitamin D, and insulin residues as risk factors in CCM. In conclusion, we utilized edible porous microcarriers to scale-up the expansion of Carassius auratus skeletal muscle cells and bioassembled high-quality CCM of Carassius auratus for the first time, which represents a state-of-the-art protocol applicable to different fish species and even to other economic animals and provides a theoretical basis for scaling up cell-cultured meat production.

Preparation and in vivo and ex vivo studies of sirolimus nano-in-situ gel ophthalmic formulation.

Sirolimus (SR) is a macrolide with antifungal and antitumor immunosuppressant properties, classified as a selective inhibitor of mammalian target of rapamycin (mTOR). In this study, an ionic in situ gel of SR (SR-SUS-ISG) was formulated using gellan gum, exhibiting stability regardless of temperature and pH variations, causing minimal irritation. Harnessing the physiological conditions of the eye, SR-SUS-ISG underwent gelation upon contact with ions, increasing drug viscosity and prolonging retention on the ocular surface. Concurrently, SR-SUS-ISG displayed favorable shear dilution properties, reducing viscosity at ambient temperature, enhancing fluidity, and facilitating convenient packaging and transport. Biocompatibility assessments on both human corneal epithelial cells and rabbit eyes demonstrated that SR-SUS-ISG could well be tolerated. Pharmacokinetic investigations in rabbit ocular aqueous humor revealed sustained release, improved corneal penetration, and enhanced bioavailability. Additionally, in a rat corneal alkali burn model, SR-SUS-ISG exhibited inhibitory effects on corneal neovascularization, associated with decreased levels of the inflammatory factors VEGF and MMPs. These findings suggested that SR-SUS-ISG held promise as an effective ocular drug delivery system.

Low storage temperature affects quality and volatile compounds in fresh tomatoes.

To investigate the impact of low temperature on the quality and flavor of ripe red tomatoes, we analyzed transcriptomes and volatile metabolomes of ripe red fruits stored at 0 °C and 20 °C for 8 days. The results showed that 0 °C maintained the sugar content by increasing the expression of sucrose synthetase (SUS) and sucrose transporter (SUT). Low expression of aroma synthesis-related genes, such as alcohol dehydrogenase 1 (ADH1), amino acid decarboxylase 1 A (AADC1A), and branched-chain amino acid aminotransferase 2 (BCAT2), were associated with reduced levels of pentanal, hexanal, 3-methylbutanal, 2-methylbutanal, and 2-phenylethanol. Additionally, the expression of pectinesterase (PE), beta-galactosidase (ß-GAL), and beta-glucosidase (ß-Glu), as well as phytoene synthase1 (PSY1) involved in carotenoid synthesis, was inhibited, thereby maintaining fruits texture and color. Furthermore, storage at 0 °C induced the expression of numerous genes regulating antioxidant and heat shock proteins, which further preserved the postharvest quality of tomatoes.

Synthesis of Hexabenzocoronene-cored Graphdiyne Nanosheets through Dehydrogenative Coupling on Au(111) Surface.

Thermally-induced dehydrogenative coupling of polyphenylenes on metal surfaces is an important technique to synthesize 𝜋-conjugated carbon nanostructures with atomic precision. However, this protocol has rarely been utilized to fabricate structurally defined carbon nanosheets composed of sp- and sp2-hybridized carbon atoms. Here, we present the synthesis of butadiyne-linked hexabenzocoronenes (HBCs) on Au(111) surfaces as core-expanded graphdiynes. The reaction started from hexa(4-ethylphenyl)benzene, which undergoes dehydrogenation toward hexa(4-vinylphenyl)benzene, followed by planarization to hexabenzocoronene, coupling between the vinyl groups, and further dehydrogenation. In addition to butadiyne linkages, benzene groups were also found as another type of linker. The reaction sequences were monitored by scanning tunneling microscopy and bond-resolved non-contact atomic force microscopy, which disclose the structures of intermediates and final products. In combination with density functional theory simulations, the key steps from ethyl substituents to butadiyne and benzene linkers were elucidated. This is a new on-surface synthesis of core-expanded graphdiynes with unprecedented electronic properties.

The efficacy of and user satisfaction with different antiandrogens in Chinese transgender women.

Objective: Cyproterone acetate (CPA) and spironolactone (SPL) are different antiandrogens in gender-affirming hormone therapy (GAHT) for transgender women. Few studies have evaluated their efficacy and user satisfaction, especially among East Asians. This study aimed to evaluate these aspects in Chinese transgender women. Methods: Data were collected retrospectively from transgender women visiting the Peking University Third Hospital from 2012 to 2021. From 639 people identified as transgender women, 151 of them (80 using CPA and 71 using SPL, 16 to 40-year-old) under stable GAHT ≥6 months were enrolled. Total testosterone levels and visual analogue scale (VAS)-based satisfaction scores were evaluated. Results: No difference was observed in age between the CPA and SPL groups (median [IQR], 22 [20-24] years and 23 [20-26] years, respectively). The duration of GAHT was longer in CPA group than in SPL group (18 [10-32] months vs. 12 [8-21] months, p = 0.009). Total testosterone levels were significantly lower with CPA treatment (25 mg/d) than with SPL treatment (100 mg/d) (median [IQR]: 0.7 [0.7-2.1] nmol/L vs. 13.0 [6.0-17.8] nmol/L, p < 0.001). The proportion of total testosterone levels reaching the recommended range was significantly higher in CPA group than in SPL group (75.0% vs. 11.3%, p < 0.001). VAS-based satisfaction scores for erection decreased and figure feminization were higher in CPA group than in SPL group, which remained unchanged after adjusting for age, treatment duration, estradiol dose, and comorbid mental disorders (p < 0.05). The prolactin levels were higher in CPA group than in SPL group (18.9 [11.8-28.1] ng/ml vs. 11.8 [7.9-18.4] ng/ml, p < 0.001). No severe safety events were reported in both groups. Conclusion: In Chinese transgender women, CPA was more effective than SPL in lowering testosterone levels. Additionally, VAS scores indicated greater satisfaction with erection decreased and figure feminization using CPA compared to SPL.

Ultrasound-Activated PROTAC Prodrugs Overcome Immunosuppression to Actuate Efficient Deep-Tissue Sono-Immunotherapy in Orthotopic Pancreatic Tumor Mouse Models.

The degradation of oncoproteins mediated by proteolysis-targeting chimera (PROTAC) has emerged as a potent strategy in cancer therapy. However, the clinical application of PROTACs is hampered by challenges such as poor water solubility and off-target adverse effects. Herein, we present an ultrasound (US)-activatable PROTAC prodrug termed NPCe6+PRO for actuating efficient sono-immunotherapy in a spatiotemporally controllable manner. Specifically, US irradiation, which exhibits deep-tissue penetration capability, results in Ce6-mediated generation of ROS, facilitating sonodynamic therapy (SDT) and inducing immunogenic cell death (ICD). Simultaneously, the generated ROS cleaves the thioketal (TK) linker through a ROS-responsive mechanism, realizing the on-demand activation of the PROTAC prodrug in deep tissues. This prodrug activation results in the degradation of the target protein BRD4, while simultaneously reversing the upregulation of PD-L1 expression associated with the SDT process. In the orthotopic mouse model of pancreatic tumors, NPCe6+PRO effectively suppressed tumor growth in conjunction with US stimulation.

Trend of albumin nanoparticles in oncology: a bibliometric analysis of research progress and prospects.

Background: Delivery systems based on albumin nanoparticles (NPs) have recently garnered substantial interest in anti-tumor drug development. However, systematic bibliometric analyses in this field remain lacking. This study aimed to analyze the current research status, hotspots, and frontiers in the application of albumin NPs in the field of oncology from a bibliometric perspective. Methods: Using the Web of Science Core Collection (WOSCC) as the data source, retrieved articles were analyzed using software, such as VOSviewer 1.6.18 and CiteSpace 6.1.6, and the relevant visualization maps were plotted. Results: From 1 January 2000, to 15 April 2024, 2,262 institutions from 67 countries/regions published 1,624 articles related to the application of albumin NPs in the field of oncology. The USA was a leader in this field and held a formidable academic reputation. The most productive institution was the Chinese Academy of Sciences. The most productive author was Youn YS, whereas Kratz F was the most frequently co-cited author. The most productive journal was the International Journal of Nanomedicine, whereas the Journal of Controlled Release was the most co-cited journal. Future research hotspots and frontiers included "rapid and convenient synthesis methods predominated by self-assembly," "surface modification," "construction of multifunctional NPs for theranostics," "research on natural active ingredients mainly based on phenolic compounds," "combination therapy," and "clinical applications." Conclusion: Based on our bibliometric analysis and summary, we obtained an overview of the research on albumin NPs in the field of oncology, identified the most influential countries, institutions, authors, journals, and citations, and discussed the current research hotspots and frontiers in this field. Our study may serve as an important reference for future research in this field.