The brain-skin axis in vitiligo.

Vitiligo is an acquired autoimmune skin disease characterized by patchy depigmentation of the skin, often accompanied by white hair. The aetiology of vitiligo is complex and difficult to cure, and its disfiguring appearance significantly impacts patients' mental and physical health. Psychological stress is a major factor in inducing and exacerbating vitiligo, as well as affecting its treatment efficacy, though the specific mechanisms remain unclear. Increasing research on the brain-skin axis in skin immunity suggests that psychological stress can influence local skin immunity through this axis, which may play a crucial role in the pathogenesis of vitiligo. This review focuses on the role of brain-skin axis in the pathogenesis of vitiligo, and explores the possible mechanism of brain-skin axis mediating the pathogenesis of vitiligo from the aspects of sympathetic nervous system, hypothalamic-pituitary-adrenal (HPA) axis and hormones and neuropeptides, aiming to provide the necessary theoretical basis for psychological intervention in the prevention and treatment of vitiligo.

FGTN: Fragment-based graph transformer network for predicting reproductive toxicity.

Reproductive toxicity is one of the important issues in chemical safety. Traditional laboratory testing methods are costly and time-consuming with raised ethical issues. Only a few in silico models have been reported to predict human reproductive toxicity, but none of them make full use of the topological information of compounds. In addition, most existing atom-based graph neural network methods focus on attributing model predictions to individual nodes or edges rather than chemically meaningful fragments or substructures. In current studies, we develop a novel fragment-based graph transformer network (FGTN) approach to generate the QSAR model of human reproductive toxicity by considering internal topological structure information of compounds. In the FGTN model, the compound is represented by a graph architecture using fragments to be nodes and bonds linking two fragments to be edges. A super molecule-level node is further proposed to connect all fragment nodes by undirected edges, obtaining global molecular features from fragment embeddings. The FGTN model achieved an accuracy (ACC) of 0.861 and an area under the receiver operating characteristic curve (AUC) value of 0.914 on nonredundant blind tests, outperforming traditional fingerprint-based machine learning models and atom-based GCN model. The FGTN model can attribute toxic predictions to fragments, generating specific structural alerts for the positive compound. Moreover, FGTN may also have the capability to distinguish various chemical isomers. We believe that FGTN can be used as a reliable and effective tool for human reproductive toxicity prediction in contribution to the advancement of chemical safety assessment.

Physiological and gene expression responses of Protohermes xanthodes (Megaloptera: Corydalidae) larvae to imidacloprid.

Megaloptera larvae are important bioindicator species and potential resource insects. To further cultivate their economic role, their living environment must be examined in more detail. In this study, we analyzed the physiological and biochemical effects of a sublethal dose of imidacloprid, a widely used neonicotinoid insecticide, on the larvae of Protohermes xanthodes. After treatment with imidacloprid, P. xanthodes larvae exhibited clear symptoms of poisoning, including the head curling up toward the ventral surface. Additionally, the activity of acetylcholinesterase was significantly inhibited following exposure. The activities of glutathione S-transferases initially continuously increased but showed a slight decrease after 8 days. Catalase activity initially increased and then decreased following imidacloprid treatment; superoxide dismutase activity fluctuated over time, and peroxidase activity continuously increased. The expression levels of HSP70s genes were evaluated using qRT-PCR. These results indicate that P. xanthodes larvae exhibit a toxic response to imidacloprid exposure, manifested as oxidative stress, as observed through behavioral and physiological indicators.

Comprehensive hepatotoxicity prediction: ensemble model integrating machine learning and deep learning.

Background: Chemicals may lead to acute liver injuries, posing a serious threat to human health. Achieving the precise safety profile of a compound is challenging due to the complex and expensive testing procedures. In silico approaches will aid in identifying the potential risk of drug candidates in the initial stage of drug development and thus mitigating the developmental cost. Methods: In current studies, QSAR models were developed for hepatotoxicity predictions using the ensemble strategy to integrate machine learning (ML) and deep learning (DL) algorithms using various molecular features. A large dataset of 2588 chemicals and drugs was randomly divided into training (80%) and test (20%) sets, followed by the training of individual base models using diverse machine learning or deep learning based on three different kinds of descriptors and fingerprints. Feature selection approaches were employed to proceed with model optimizations based on the model performance. Hybrid ensemble approaches were further utilized to determine the method with the best performance. Results: The voting ensemble classifier emerged as the optimal model, achieving an excellent prediction accuracy of 80.26%, AUC of 82.84%, and recall of over 93% followed by bagging and stacking ensemble classifiers method. The model was further verified by an external test set, internal 10-fold cross-validation, and rigorous benchmark training, exhibiting much better reliability than the published models. Conclusion: The proposed ensemble model offers a dependable assessment with a good performance for the prediction regarding the risk of chemicals and drugs to induce liver damage.

Recent Advances in Fire-Retardant Silicone Rubber Composites.

Silicone rubber (SR), as one kind of highly valuable rubber material, has been widely used in many fields, e.g., construction, transportation, the electronics industry, automobiles, aviation, and biology, owing to its attractive properties, including high- and low-temperature resistance, weathering resistance, chemical stability, and electrical isolation, as well as transparency. Unfortunately, the inherent flammability of SR largely restricts its practical application in many fields that have high standard requirements for flame retardancy. Throughout the last decade, a series of flame-retardant strategies have been adopted which enhance the flame retardancy of SR and even enhance its other key properties, such as mechanical properties and thermal stability. This comprehensive review systematically reviewed the recent research advances in flame-retarded SR materials and summarized and introduced the up-to-date design of different types of flame retardants and their effects on flame-retardant properties and other performances of SR. In addition, the related flame-retardant mechanisms of the as-prepared flame-retardant SR materials are analyzed and presented. Moreover, key challenges associated with these various types of FRs are discussed, and future development directions are also proposed.

Identification of differentially expressed tumour-related genes regulated by UHRF1-driven DNA methylation.

Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an epigenetic regulator that plays critical roles in tumours. However, the DNA methylation alteration patterns driven by UHRF1 and the related differentially expressed tumour-related genes remain unclear. In this study, a UHRF1-shRNA MCF-7 cell line was constructed, and whole-genome bisulfite sequencing and RNA sequencing were performed. The DNA methylation alteration landscape was elucidated, and DNA methylation-altered regions (DMRs) were found to be distributed in both gene bodies and adjacent regions. The DMRs were annotated and categorized into 488 hypermethylated/1696 hypomethylated promoters and 1149 hypermethylated/5501 hypomethylated gene bodies. Through an integrated analysis with the RNA sequencing data, 217 methylation-regulated upregulated genes and 288 downregulated genes were identified, and these genes were primarily enriched in nervous system development and cancer signalling pathways. Further analysis revealed 21 downregulated oncogenes and 15 upregulated TSGs. We also showed that UHRF1 silencing inhibited cell proliferation and migration and suppressed tumour growth in vivo. Our study suggested that UHRF1 and the oncogenes or TSGs it regulates might serve as biomarkers and targets for breast cancer treatment.

The mechanism of cancer-depression comorbidity.

Cancer and depression are closely interrelated, particularly in patients with advanced cancer, who often present with comorbid anxiety and depression for various reasons. Recently, there has been a growing interest in the study of depression in cancer patients, with the aim of assessing the possible triggers, predictors, adverse events, and possible treatment options for depression in several common cancers. The objective of this narrative review is to synthesize the extant literature on the relationship between the occurrence and progression of depression in several common patient categories. The authors conducted a comprehensive review of 75 articles published in PubMed over the past five years. This review was further evaluated in the present paper. Ultimately, it was determined that depression is a prevalent and detrimental phenomenon among cancer patients, particularly those with advanced disease. Consequently, there is a pressing need to prioritize research and interventions aimed at improving the quality of life and psychosocial well-being of cancer patients, including those with advanced disease. The relationship between cancer and depression has been evolving dynamically in recent times. The current research findings indicate a strong association between cancer and depression. However, the direction of causality remains unclear. Focusing on depression in cancer patients may, therefore, be beneficial for these patients.

Rational Design of Oil-Resistant and Electrically Conductive Fluorosilicone Rubber Foam Nanocomposites for Sensitive Detectability in Complex Solvent Environments.

Recent years have witnessed the explosive development of highly sensitive smart sensors based on conductive polymer foam materials. However, the design and development of multifunctional polymeric foam composites as smart sensors applied in complex solvent and oil environments remain a critical challenge. Herein, we design and synthesize vinyl-terminated polytrifluoropropylmethylsiloxane through anionic ring-opening polymerization to fabricate fluorosilicone rubber foam (FSiRF) materials with nanoscale wrinkled surfaces and reactive Si-H groups via a green and rapid chemical foaming strategy. Based on the strong adhesion between FSiRF materials and consecutive oxidized ketjen black (OKB) nano-network, multifunctional FSiRF nanocomposites were prepared by a dip-coating strategy followed by fluoroalkylsilane modification. The optimized F-OKB@FSiRF nanocomposites exhibit outstanding mechanical flexibility in wide-temperature range (100 cycle compressions from -20 to 200 °C), structure stability (no detached particles after being immersed into various aqueous solutions for up to 15 days), surface superhydrophobicity (water contact angle of 154° and sliding angle of ∼7°), and tunable electrical conductivity (from 10-5 to 10-2 S m-1). Additionally, benefiting from the combined actions of multiple lines of defense (low surface energy groups, physical barriers, and "shielding effect"), the F-OKB@FSiRF sensor presents excellent anti-swelling property and high sensitivity in monitoring both large-deformation and tiny vibrations generated by knocking the beaker, ultrasonic action, agitating, and sinking objects in weak-polar or nonpolar solvents. This work conceivably provides a chemical strategy for the fabrication of multifunctional polymeric foam nanocomposite materials as smart sensors for broad applications.

Waterborne Intumescent Fire-Retardant Polymer Composite Coatings: A Review.

Intumescent fire-retardant coatings, which feature thinner layers and good decorative effects while significantly reducing heat transfer and air dispersion capabilities, are highly attractive for fire safety applications due to their effective prevention of material combustion and protection of materials. Particularly, the worldwide demand for improved environmental protection requirements has given rise to the production of waterborne intumescent fire-retardant polymer composite coatings, which are comparable to or provide more advantages than solvent-based intumescent fire-retardant polymer composite coatings in terms of low cost, reduced odor, and minimal environmental and health hazards. However, there is still a lack of a comprehensive and in-depth overview of waterborne intumescent fire-retardant polymer composite coatings. This review aims to systematically and comprehensively discuss the composition, the flame retardant and heat insulation mechanisms, and the practical applications of waterborne intumescent fire-retardant polymer composite coatings. Finally, some key challenges associated with waterborne intumescent fire-retardant polymer composite coatings are highlighted, following which future perspectives and opportunities are proposed.

SARS-CoV-2 Vaccination Improves Semen Quality in Men Recovered From COVID-19: A Retrospective Cohort Study.

Coronavirus disease 2019 (COVID-19) has been reported to decrease semen quality in reproductive-age men. Semen quality in vaccinated men after SARS-CoV-2 infection remains unclear. We recruited reproductive-age Chinese men scheduled for COVID-19 vaccination from December 2022 to March 2023. Among 1,639 vaccinated participants, an upward trend was found in sperm concentration (p < .001), progressive motility (p < .001), total motility (p < .001), total motile sperm count (TMSC) (p < .001), and normal morphology (p = .01) over time following COVID-19 recovery. Among men with an SARS-CoV-2 infection that lasted less than 30 days, men who received an inactivated vaccine booster had higher sperm progressive (p = .006) and total motility (p = .005) as well as TMSC (p = .008) than those without a booster vaccine, whereas no difference was found in semen parameters among men who received a recombinant protein vaccine. Similarly, an upward trend in semen quality was found among 122 men who provided semen samples before and after COVID-19. Higher risks of asthenozoospermia (odds ratio [OR] = 2.23, p < .001) and teratozoospermia (OR = 2.09, p = .03) were found among men who had an SARS-CoV-2 infection that lasted less than 30 days than among those without COVID-19. Collectively, after receiving SARS-CoV-2 vaccination, adverse but reversible semen parameters were observed in men recovering from COVID-19 over time. Recombinant protein vaccines and inactivated vaccine boosters should be recommended to all reproductive-age men.

ABL1-mediated phosphorylation promotes FOXM1-related tumorigenicity by Increasing FOXM1 stability.

The transcription factor FOXM1, which plays critical roles in cell cycle progression and tumorigenesis, is highly expressed in rapidly proliferating cells and various tumor tissues, and high FOXM1 expression is related to a poor prognosis. However, the mechanism responsible for FOXM1 dysregulation is not fully understood. Here, we show that ABL1, a nonreceptor tyrosine kinase, contributes to the high expression of FOXM1 and FOXM1-dependent tumor development. Mechanistically, ABL1 directly binds FOXM1 and mediates FOXM1 phosphorylation at multiple tyrosine (Y) residues. Among these phospho-Y sites, pY575 is indispensable for FOXM1 stability as phosphorylation at this site protects FOXM1 from ubiquitin-proteasomal degradation. The interaction of FOXM1 with CDH1, a coactivator of the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C), which is responsible for FOXM1 degradation, is significantly inhibited by Y575 phosphorylation. The phospho-deficient FOXM1(Y575F) mutant exhibited increased ubiquitination, a shortened half-life, and consequently a substantially decreased abundance. Compared to wild-type cells, a homozygous Cr-Y575F cell line expressing endogenous FOXM1(Y575F) that was generated by CRISPR/Cas9 showed obviously delayed mitosis progression, impeded colony formation and inhibited xenotransplanted tumor growth. Overall, our study demonstrates that ABL1 kinase is involved in high FOXM1 expression, providing clear evidence that ABL1 may act as a therapeutic target for the treatment of tumors with high FOXM1 expression.

Friction heat-driven robust self-lubricity of n-alkanols/epoxy resin coatings enabled by solid-liquid phase transition.

Due to the inherent damage effect, friction heat is commonly undesirable yet inevitable in moving components. Hence, obtaining robust running of mechanical assemblies under high sliding velocity is challenging. Herein, we report an alternative strategy to design robust self-healing lubricity materials by taking advantage of friction heat-driven solid-liquid phase transition employing facile coatings of n-alkanols/epoxy resin. The lubricity performance of composite coatings increased with sliding velocity, leading to a low friction coefficient (0.066) and wear rate (1.968 × 10-7 mm3 N-1 m-1) under 5000 rpm. The low friction was mainly attributed to the controlled phase-transition characteristics of n-alkanols, which absorbed friction heat to release liquid n-alkanols for maintaining intelligent shear interfaces. The low wear was ascribed to the high load-bearing capacity and self-healing property of composite coatings. Our study may guide a common framework to rationally design self-healing lubricant materials via solid-liquid phase transition by utilizing the undesirable (yet inevitable) friction heat. Our approach could achieve the robust, ultralow friction and wear of moving components under harsh working conditions.

Mix and Shake: A Mild Way to Drug-Loaded Lysozyme Nanoparticles.

Biocompatible nanoparticles as drug carriers can improve the therapeutic efficiency of hydrophobic drugs. However, the synthesis of biocompatible and biodegradable polymeric nanoparticles can be time-consuming and often involves toxic solvents. Here, a simple method for protein-based stable drug-loaded particles with a narrow polydispersity is introduced. In this process, lysozyme is mixed with hydrophobic drugs (curcumin, ellipticine, and dasatinib) and fructose to prepare lysozyme-based drug particles of around 150 nm in size. Fructose is mixed with the drug to generate nanoparticles that serve as templates for the lysozyme coating. The effect of lysozyme on the physicochemical properties of these nanoparticles is studied by transmission electron microscopy (TEM) and scattering techniques (e.g., dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS)). We observed that lysozyme significantly stabilized the curcumin fructose particles for 7 days. Moreover, additional drugs, such as ellipticine and dasatinib, can be loaded to form dual-drug particles with narrow polydispersity and spherical morphology. The results also reveal that lysozyme dual ellipticine/dasatinib curcumin particles enhance the cytotoxicity and uptake on MCF-7 cells, RAW 264.7 cells, and U-87 MG cells due to the larger and rigid hydrophobic core. In summary, lysozyme in combination with fructose and curcumin can serve as a powerful combination to form protein-based stable particles for the delivery of hydrophobic drugs.

Identification and immunological characteristics of anoikis-associated molecular clusters in lung adenocarcinoma.

Anoikis plays a crucial role in the progression, prognosis, and immune response of lung adenocarcinoma (LUAD). However, its specific impact on LUAD remains unclear. In this study, we investigated the intricate interplay of nesting apoptotic factors in LUAD. By analyzing nine key nesting apoptotic factors, we categorized LUAD patients into two distinct clusters. Further examination of immune cell profiles revealed that Cluster A exhibited greater infiltration of innate immune cells than did Cluster B. Additionally, we identified two genes closely associated with prognosis and developed a predictive model to differentiate patients based on molecular clusters. Our findings suggest that the loss of specific anoikis-related genes could significantly influence the prognosis, tumor microenvironment, and clinical features of LUAD patients. Furthermore, we validated the expression and functional roles of two pivotal prognostic genes, solute carrier family 2 member 1 (SLC2A1) and sphingosine kinase 1 (SPHK1), in regulating tumor cell viability, migration, apoptosis, and anoikis. These results offer valuable insights for future mechanistic investigations. In conclusion, this study provides new avenues for advancing our understanding of LUAD, improving prognostic assessments, and developing more effective immunotherapy strategies.

Analytical Perspectives on Cement Sheath Integrity: A Comprehensive Review of Theoretical Research.

The cement sheath, serving as the primary element of well barriers, plays a crucial role in maintaining zonal isolation, protecting the casing from corrosion, and providing mechanical support. As the petroleum industry shifts from conventional to deep unconventional resources, the service environment for cement sheaths has become increasingly complex. High temperatures, high pressures, cyclic loading, and thermal stresses in downhole conditions have significantly increased the risk of cement sheath failure. A growing trend toward theoretical analysis of stress distribution, failure modes, and control mechanisms within the casing-cement sheath-formation system is evident. This paper comprehensively reviews theoretical research on cement sheath integrity from four key perspectives: (1) the concept of cement sheath integrity failure, (2) cement sheath constitutive models, (3) analytical models of the cement sheath-casing-formation system, and (4) numerical simulations of the cement sheath-casing-formation system. Through these discussions, this review provides profound insights into cement sheath integrity failure and offers valuable guidance for future research and practices.

A 2-order additive fuzzy measure identification method based on hesitant fuzzy linguistic interaction degree and its application in credit assessment.

To reflect both fuzziness and hesitation in the evaluation of interactivity between attributes in the identification process of 2-order additive fuzzy measure, this work uses the hesitant fuzzy linguistic term set (HFLTS) to describe and depict the interactivity between attributes. Firstly, the interactivity between attributes is defined by the supermodular game theory. According to this definition, a linguistic term set is established to characterize the interactivity between attributes. Under the linguistic term set, the experts employ linguistic expressions generated by context-free grammar to qualitatively describe the interactivity between attributes. Secondly, through the conversion function, the linguistic expressions are transformed into the hesitant fuzzy linguistic term sets (HFLTSs). The individual evaluation results of all experts were further aggregated with the defined hesitant fuzzy linguistic weighted power average operator (HFLWPA). Thirdly, based on the standard Euclidean distance formula of the hesitant fuzzy linguistic elements (HFLEs), the hesitant fuzzy linguistic interaction degree (HFLID) between attributes is defined and calculated by constructing a piecewise function. As a result, a 2-order additive fuzzy measure identification method based on HFLID is proposed. Based on the proposed method, using the Choquet fuzzy integral as nonlinear integration operator, a multi-attribute decision making (MADM) process is then presented. Taking the credit assessment of the big data listed companies in China as an application example, the analysis results of application example prove the feasibility and effectiveness of the proposed method. This work successfully reflects both the fuzziness and hesitation in evaluating the interactivity between attributes in the identification process of 2-order additive fuzzy measure, enriches the theoretical framework of 2-order additive fuzzy measure, and expands the applicability and methodology of 2-order additive fuzzy measure in multi-attribute decision making.

Association Between Baseline Echocardiographic Parameters and Acute Coronavirus Disease 2019 Infection in Hospitalized Patients.

Background The current study aimed to examine the association between baseline clinical and echocardiographic parameters with new-onset coronavirus disease 2019 (COVID-19) infection. Methodology We retrospectively enrolled consecutive hospitalized patients from our center during the national outbreak of the COVID-19 pandemic in China. Overall, 100 patients were enrolled, including 38 patients with COVID-19 infection. Results Compared with those without infection, patients with COVID-19 infection were more likely male (63.2% vs. 35.5%, p = 0.008), were older (59.08 vs. 52.35 years, p = 0.022), had higher heart failure (31.6% vs. 11.3%, p = 0.018) and hypertension (52.6% vs. 30.6%, p = 0.036) rates, had lower left ventricular ejection fraction (LVEF) (61.16% vs. 65.76%, p = 0.018), had higher A-wave velocity (86.84 vs. 73.63 cm/s, p = 0.003), and had and lower E/A ratio (0.85 vs 1.04, p = 0.015). On univariate and multivariate analysis, baseline echocardiographic parameters (LVEF and A-wave velocity) were independent risk factors for COVID-19 infection. There were no significant changes in echocardiographic parameters during the one-month follow-up period in patients infected and not infected with COVID-19. Conclusions In conclusion, baseline echocardiographic parameters were significantly associated with acute COVID-19 infection.

The PKA-CREB1 axis regulates coronavirus proliferation by viral helicase nsp13 association.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a worldwide threat in the past 3 years. Although it has been widely and intensively investigated, the mechanism underlying the coronavirus-host interaction requires further elucidation, which may contribute to the development of new antiviral strategies. Here, we demonstrated that the host cAMP-responsive element-binding protein (CREB1) interacts with the non-structural protein 13 (nsp13) of SARS-CoV-2, a conserved helicase for coronavirus replication, both in cells and in lung tissues subjected to SARS-CoV-2 infection. The ATPase and helicase activity of viral nsp13 were shown to be potentiated by CREB1 association, as well as by Protein kinase A (PKA)-mediated CREB1 activation. SARS-CoV-2 replication is significantly suppressed by PKA Cα, cAMP-activated protein kinase catalytic subunit alpha (PRKACA), and CREB1 knockdown or inhibition. Consistently, the CREB1 inhibitor 666-15 has shown significant antiviral effects against both the WIV04 strain and the Omicron strain of the SARS-CoV-2. Our findings indicate that the PKA-CREB1 signaling axis may serve as a novel therapeutic target against coronavirus infection. IMPORTANCE: In this study, we provide solid evidence that host transcription factor cAMP-responsive element-binding protein (CREB1) interacts directly with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) helicase non-structural protein 13 (nsp13) and potentiate its ATPase and helicase activity. And by live SARS-CoV-2 virus infection, the inhibition of CREB1 dramatically impairs SARS-CoV-2 replication in vivo. Notably, the IC50 of CREB1 inhibitor 666-15 is comparable to that of remdesivir. These results may extend to all highly pathogenic coronaviruses due to the conserved nsp13 sequences in the virus.

Nomogram to Predict the Outcome of Ventriculoperitoneal Shunt Among Patients with Non-HIV Cryptococcal Meningitis.

BACKGROUND: The ventriculoperitoneal (VP) shunt is widely acknowledged as a treatment option for managing intracranial hypertension resulting from non-human immunodeficiency virus (HIV) cryptococcal meningitis (CM). Nonetheless, there is currently no consensus on the appropriate surgical indications for this procedure. Therefore, it is crucial to conduct a preoperative evaluation of patient characteristics and predict the outcome of the VP shunt to guide clinical treatment effectively. METHODS: A retrospective analysis was conducted on data from 85 patients with non-HIV CM who underwent VP shunt surgery at our hospital. The analysis involved studying demographic data, preoperative clinical manifestations, cerebrospinal fluid (CSF) characteristics, and surgical outcomes and comparisons between before and after surgery. A nomogram was developed and evaluated. RESULTS: The therapy outcomes of 71 patients improved, whereas 14 cases had worse outcomes. Age, preoperative cryptococcus count, and preoperative CSF protein levels were found to influence the surgical outcome. The nomogram exhibited exceptional predictive performance (area under the curve = 0.896, 95% confidence interval: 0.8292-0.9635). Internal validation confirmed the nomogram's excellent predictive capabilities. Moreover, decision curve analysis demonstrated the nomogram's practical clinical utility. CONCLUSIONS: The surgical outcome of VP shunt procedures patients with non-HIV CM was associated with age, preoperative cryptococcal count, and preoperative CSF protein levels. We developed a nomogram that can be used to predict surgical outcomes in patients with non-HIV CM.

Maximizing Aqueous Drug Encapsulation: Small Nanoparticles Formation Enabled by Glycopolymers Combining Glucose and Tyrosine.

Highly potent heterocyclic drugs are frequently poorly water soluble, leading to limited or abandoned further drug development. Nanoparticle technology offers a powerful delivery approach by enhancing the solubility and bioavailability of hydrophobic therapeutics. However, the common usage of organic solvents causes unwanted toxicity and process complexity, therefore limiting the scale-up of nanomedicine technology for clinical translation. Here, we show that an organic-solvent-free methodology for hydrophobic drug encapsulation can be obtained using polymers based on glucose and tyrosine. An aqueous solution based on a tyrosine-containing glycopolymer is able to dissolve solid dasatinib directly without adding an organic solvent, resulting in the formation of very small nanoparticles of around 10 nm loaded with up to 16 wt % of drug. This polymer is observed to function as both a drug solubilizer and a nanocarrier at the same time, offering a simple route for the delivery of insoluble drugs.