The application effect of the optimized scheduling model of virtual power plant participation in the new electric power system.

To build a comprehensive framework for virtual power plant (VPP) development aligned with market dynamics and to devise effective strategies to foster its growth, this study undertakes several key steps. Firstly, it constructs a VPP development framework based on market conditions, to drive the evolution of new power systems and facilitating energy transformation. Secondly, through a blend of theoretical analysis and model construction, the fundamental principles of VPP are systematically elucidated, and a decision model for the VPP development framework, focusing on price demand response, is formulated. Lastly, an optimal scheduling model for the new power system is developed, with its efficacy validated across three distinct scenarios. The findings underscore the critical importance of integrating energy storage technologies, particularly pumped storage hydropower systems, for achieving balance and optimization within new power systems. Model verification reveals that the incorporation of energy storage power stations significantly enhances system stability and efficiency, particularly in addressing the volatility associated with renewable energy sources. Additionally, the analysis indicates that while the adoption of energy storage technologies may marginally increase overall power generation costs, the total power generation cost declines with the integration of battery storage and pumped storage hydropower stations. This suggests that leveraging energy storage technologies not only enhances system operational reliability but also contributes to reducing the overall cost of power production to a certain extent. In summary, this study presents an economic and environmentally sustainable scheduling model for new power systems within the context of market trading environments. By offering both theoretical insights and practical guidance, it aims to support sustainable development and energy transformation initiatives. Ultimately, the study is poised to foster the adoption of clean energy, facilitate the establishment of smart grids, and bolster the sustainable utilization of energy resources, thereby advancing environmental conservation efforts.

Key periodontal pathogens may mediate potential pathogenic relationships between periodontitis and crohn's disease.

BACKGROUND: Crohn's disease (CD)-associated periodontitis is common. However, the role of periodontal pathogens in the Coexistence of CD and periodontal disease remains unclear. METHODS: To investigate the potential relationship mediated by periodontal pathogens between periodontitis and CD, we collected salivary samples from healthy participants (H group, n = 12), patients with CD (Ch group, n = 10), patients with periodontitis (Ps group, n = 12), and patients with Coexistence of CD and periodontal disease (Cp group, n = 12) and analyzed them by 16 S rRNA sequencing. RESULTS: Patients with Coexistence of CD and periodontal disease had increased levels of Fusobacterium, Actinomyces, Leptotrichia, and Prevotella, which correlated with the severity of periodontitis. Conversely, the levels of Streptococcus, Neisseria, Haemophilus, and Gemella, which decreased in Coexistence of CD and periodontal disease, were negatively correlated with the severity of periodontitis. To further investigate the role of periodontal pathogens in CD development, representative periodontal pathogens causing periodontitis, Porphyromonas gingivalis and Fusobacterium nucleatum, were administered to mice. These pathogens migrate to, and colonize, the gut, accelerating CD progression and aggravating colitis, and even systemic inflammation. In vitro experiments using a Caco-2/periodontal pathogen coculture revealed that P. gingivalis and F. nucleatum increased intestinal permeability by directly disrupting the tight junctions of intestinal epithelial cells. CONCLUSION: Our findings strongly suggest that periodontal pathogens play a role in the relationship between periodontitis and CD. These results provide a basis for understanding the pathogenesis of Coexistence of CD and periodontal disease and may lead to the development of novel therapeutic strategies.

An Improved Synchrosqueezing S-Transform and Its Application in a GPR Detection Task.

The S-transform is a fundamental time-frequency (T-F) domain analysis method in ground penetrating radar (GPR) data processing and can be used for identifying targets, denoising, extracting thin layers, and high-resolution imaging. However, the S-transform spectrum experiences energy leakage near the instantaneous frequency. This phenomenon causes frequency components to erroneously spread over a wider range, impacting the accuracy and precision of GPR data processing. Synchrosqueezing is an effective method to prevent spectrum leakage. In this work, we introduce the synchrosqueezing generalized phase-shifting S-transform (SS-GPST). Initially, it resolves the compatibility issue between the S-transform and the synchrosqueezing strategy through phase-shifting. Subsequently, the SS-GPST accomplishes spectral energy focusing and resolution enhancement via a generalized parameter and synchrosqueezing. A synthetic signal test shows that the SS-GPST excels over other methods at focusing degree, spectral resolution, and signal reconstruction accuracy and speed. In actual GPR tunnel detection data processing, we assess the adaptability of the SS-GPST from three aspects: spectral energy distribution, thin layer identification, and data denoising. The results indicate: (1) compared to other methods, the SS-GPST accurately expresses spectral components with a strong focusing degree and fewer interference components; (2) high-frequency slices of the SS-GPST accurately detect the top and bottom interfaces of a 3.0-3.5 cm reinforcement protection layer; and (3) due to fewer interference components in the SS-GPST spectrum, reconstructing GPR profiles through the SS-GPST inverse transform is an efficient denoising technique. The SS-GPST demonstrates adaptability to different data processing purposes, offers high-resolution T-F spectra, and shows potential to supersede the S-transform.

Decision model for durable clinical benefit from front- or late-line immunotherapy alone or with chemotherapy in non-small cell lung cancer.

BACKGROUND: Predictive biomarkers and models of immune checkpoint inhibitors (ICIs) have been extensively studied in non-small cell lung cancer (NSCLC). However, evidence for many biomarkers remains inconclusive, and the opaqueness of machine learning models hinders practicality. We aimed to provide compelling evidence for biomarkers and develop a transparent decision tree model. METHODS: We consolidated data from 3,288 ICI-treated patients with NSCLC across real-world multicenter, public cohorts and the Choice-01 trial (ClinicalTrials.gov: NCT03856411). Over 50 features were examined for predicting durable clinical benefits (DCBs) from ICIs. Noteworthy biomarkers were identified to establish a decision tree model. Additionally, we explored the tumor microenvironment and peripheral CD8+ programmed death-1 (PD-1)+ T cell receptor (TCR) profiles. FINDINGS: Multivariate logistic regression analysis identified tumor histology, PD-ligand 1 (PD-L1) expression, tumor mutational burden, line, and regimen of ICI treatment as significant factors. Mutation subtypes of EGFR, KRAS, KEAP1, STK11, and disruptive TP53 mutations were associated with DCB. The decision tree (DT10) model, using the ten clinicopathological and genomic markers, showed superior performance in predicting DCB in the training set (area under the curve [AUC] = 0.82) and consistently outperformed other models in test sets. DT10-predicted-DCB patients manifested longer survival, an enriched inflamed tumor immune phenotype (67%), and higher peripheral TCR diversity, whereas the DT10-predicted-NDB (non-durable benefit) group showed an enriched desert immune phenotype (86%) and higher peripheral TCR clonality. CONCLUSIONS: The model effectively predicted DCB after front-/subsequent-line ICI treatment, with or without chemotherapy, for squamous and non-squamous lung cancer, offering clinicians valuable insights into efficacy prediction using cost-effective variables. FUNDING: This study was supported by the National Key R&D Program of China.

Evaluation of first-line and salvage therapies for unresectable malignant mesothelioma: A systematic review and network meta-analysis.

BACKGROUND: Randomized controlled trials (RCTs) of systemic therapies for unresectable malignant mesothelioma have reported conflicting results. It is crucial and urgent to find optimal treatment options for this malignancy, which currently has a poor prognosis. METHODS: Databases PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and major international conferences were searched until February 29, 2024. The main outcomes of interest were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs). RESULTS: We analyzed 16 RCTs with a total of 5018 patients. Among first-line therapies, nivolumab and ipilimumab significantly increased OS and resulted in fewer grade ≥3 TRAEs. Bevacizumab plus chemotherapy significantly increased PFS. Among salvage therapies, ramucirumab and chemotherapy was associated with the best OS and PFS, but resulted in more grade ≥3 TRAEs. Subgroup analysis by histologic types suggested that in first-line settings, bevacizumab and chemotherapy increase OS the most for epithelioid type, while the nivolumab plus ipilimumab treatment increases OS the most for non-epithelioid type. In salvage therapies, ramucirumab and chemotherapy increase OS for both epithelioid and non-epithelioid types. CONCLUSION: Nivolumab plus ipilimumab was associated with the best OS among first-line treatments. Ramucirumab and chemotherapy was associated with the best clinical outcomes in salvage settings. Treatment for malignant mesothelioma should be tailored based on different clinicopathological characteristics.

Prediction performance comparison of biomarkers for response to immune checkpoint inhibitors in advanced non-small cell lung cancer.

BACKGROUND: The aim of the present study was to compare the predictive accuracy of PD-L1 immunohistochemistry (IHC), tissue or blood tumor mutation burden (tTMB, bTMB), gene expression profile (GEP), driver gene mutation, and combined biomarkers for immunotherapy response of advanced non-small cell lung cancer (NSCLC). METHODS: In part 1, clinical trials involved with predictive biomarker exploration for immunotherapy in advanced NSCLC were included. The area under the curve (AUC) of the summary receiver operating characteristic (SROC), sensitivity, specificity, likelihood ratio and predictive value of the biomarkers were evaluated. In part 2, public datasets of immune checkpoint inhibitor (ICI)-treated NSCLC involved with biomarkers were curated (N = 871). Odds ratio (OR) of the positive versus negative biomarker group for objective response rate (ORR) was measured. RESULTS: In part 1, the AUC of combined biomarkers (0.75) was higher than PD-L1 (0.64), tTMB (0.64), bTMB (0.68), GEP (0.67), and driver gene mutation (0.51). Combined biomarkers also had higher specificity, positive likelihood ratio and positive predictive value than single biomarkers. In part 2, the OR of combined biomarkers of PD-L1 plus TMB (PD-L1 cutoff 1%, 0.14; cutoff 50% 0.13) was lower than that of PD-L1 (cutoff 1%, 0.33; cutoff 50% 0.24), tTMB (0.28), bTMB (0.48), EGFR mutation (0.17) and KRAS mutation (0.47), for distinguishing ORR of patients after immunotherapy. Furthermore, positive PD-L1, tTMB-high, wild-type EGFR, and positive PD-L1 plus TMB were associated with prolonged progression-free survival (PFS). CONCLUSION: Combined biomarkers have superior predictive accuracy than single biomarkers for immunotherapy response of NSCLC. Further investigation is warranted to select optimal biomarkers for various clinical settings.

"Three-in-One" Multifunctional Hollow Nanocages with Colorimetric Photothermal Catalytic Activity for Enhancing Sensitivity in Biosensing.

Immunochromatographic assays (ICAs) have been widely used in the field detection of mycotoxin contaminants. Nevertheless, the lack of multisignal readout capability and the ability of signaling tags to maintain their biological activity while efficiently loading antibodies remain a great challenge in satisfying diverse testing demands. Herein, we proposed a novel three-in-one multifunctional hollow vanadium nanomicrosphere (high brightness-catalytic-photothermal properties)-mediated triple-readout ICA (VHMS-ICA) for sensitive detection of T-2. As the key to this biosensing strategy, vanadium was used as the catalytic-photothermal characterization center, and natural polyphenols were utilized as the bridging ligands for coupling with the antibody while self-assembling with formaldehyde cross-linking into a hollow nanocage-like structure, which offers the possibility of realizing a three-signal readout strategy and improving the coupling efficiency to the antibody while preserving its biological activity. The constructed sensors showed a detection limit (LOD) of 2 pg/mL for T-2, which was about 345-fold higher than that of conventional gold nanoparticle-based ICA (0.596 ng/mL). As anticipated, the detection range of VHMS-ICA was extended about 8-fold compared with the colorimetric signal alone. Ultimately, the proposed immunosensor performed well in maize and oat samples, with satisfactory recoveries. Owing to the synergistic and complementary interactions between distinct signaling modes, the establishment of multimodal immunosensors with multifunctional tags is an efficient strategy to satisfy diversified detection demands.

Trifunctional Nanocomposites with Colorimetric Magnetic Catalytic Activities Labels in Sandwich Immunochromatographic Detection of Escherichia coli O157:H7.

The emergence of nanoenzymes has catalyzed the robust advancement of the lateral flow immunoassay (LFIA) in recent years. Among them, multifunctional nanocomposite enzymes with core-shell architectures are considered preferable for promoting the sensing ability due to their good biocompatibility, precise control over size, and surface properties etc. Herein, we developed a dual-channel ensured lateral flow immunoassay (DFLIA) platform utilizing a magnetic, colorimetric, and catalytic multifunctional nanocomposite enzyme (Fe3O4@TCPP@Pd) [TCPP, Tetrakis (4-carboxyphenyl) porphyrin] for the ultrasensitive and highly accurate rapid detection of Escherichia coli O157:H7 (E. coli O157:H7). Fe3O4@TCPP@Pd-mAb exhibits superior performance compared to traditional AuNPs, including enhanced sensitivity and an extended linear detection range, benefiting from its high brightness signal, strong magnetic separation ability, and high peroxidase activity (Vmax = 2.32 µM S1-). Moreover, the Fe3O4@TCPP@Pd-labeled mAb probe exhibited exceptional stability and high affinity toward E. coli O157:H7 (with an affinity constant of approximately 1.723 × 109 M-1), indicating its potential for the efficient capture of the pathogen. Impressively, the developed Fe3O4@TCPP@Pd-DFLIA achieved ultrasensitive detection for E. coli O157:H7 with pre- and postcatalytic naked-eye detection sensitivities of 255 cfu/mL and 77 cfu/mL, respectively, representing an approximately 41-fold improvement over the conventional AuNP-based LFIA and also possessed good specificity and reproducibility [relative standard deviation (RSD) < 10%]. Additionally, the established DFLIA exhibited satisfactory recoveries in detecting pork and milk samples, further validating the reliability of this platform for immunoassays and demonstrating its potential for utilization in bioassays and clinical diagnostics.

Effects of different extreme cold exposure on heart rate variability.

Frequent extreme cold events in recent years have brought serious threats to outdoor workers and rescuers. Changes in ambient temperature are associated with altered cardiac autonomic function. The study aims to investigate heart rate variability (HRV) and its relationship to other physiological parameters under extreme cold exposures. Twelve males underwent a 30-min preconditioning phase in a neutral environment followed by a 30-min cold exposure (-5, -10, -15, and -20 °C). Time-domain indexes(meanRR, SDNN, RMSSD, and pNN50), frequency domain indexes [Log(HF), Log(LF), and low frequency/high frequency (LF/HF)], parasympathetic nervous system (PNS), and sympathetic nervous system (SNS) were analysed. Results showed all HRV indexes of four cold exposures were significant. The decrease in temperature was accompanied by progressive PNS activation with SNS retraction. SDNN was the most sensitive HRV index and had good linear relationships with blood pressure, pulse, and hand temperature. The results are significant for formulating safety protection strategies for workers in extremely cold environments.Practitioner Summary: This study investigated heart rate variability (HRV) in 12 males during a 30-min cold exposure (-5, -10, -15, and -20 °C). Results showed all HRV indexes of four cold exposures were significant. The decrease in temperature was accompanied by progressive PNS activation with SNS retraction. SDNN was the most sensitive HRV index and had good linear relationships with blood pressure, pulse, and hand temperature.

Topical Drug Delivery of Concentrated Cabazitaxel in an α-Tocopherol and DMSO Solution.

Topical chemotherapy approaches are relevant for certain skin cancer treatments. This study observes that cabazitaxel (CTX), a broad-spectrum second-generation taxane cytotoxic agent, can be dissolved in α-tocopherol at high concentrations exceeding 100 mg mL-1 . 2D nuclear magnetic resonance (NMR) analysis and molecular dynamics (MD) are used to study this phenomenon. The addition of 30% dimethyl sulfoxide (DMSO) to the α-tocopherol/CTX solution improves its working viscosity and enhances CTX permeation through human skin in vitro (over 5 µg cm-2 within 24 h), while no detectable drug permeates when CTX is dissolved in α-tocopherol alone. In a transepidermal water loss assay, the barrier impairment induced by CTX in 30% DMSO in α-tocopherol, but not in pure DMSO, is reversible 8 h after the formulation removal from the skin surface. Antitumor efficacy of the topical CTX formulation is evaluated in nude mice bearing A431 human squamous carcinoma skin cancer xenografts. With topical application of concentrated CTX solutions (75 mg mL-1 ), tumor growth is significantly suppressed compared to lower concentration groups (0, 25, or 50 mg mL-1 CTX). Taken together, these findings show that topical delivery of CTX using a DMSO and α-tocopherol solvent warrants further study as a treatment for skin malignancies.

Formic Acid-Regulated Defect Engineering in Zr-Based Metal-Organic Frameworks toward Fluorescence Sensor for Sensitive Detection of Chlortetracycline.

The elaborate defect-engineering of luminescent metal-organic frameworks (MOFs) allows them with enhanced sensing performance. A modulator-induced defect formation strategy is adopted in this paper, and the impact of the open-metal sites on sensing process is rationalized. It is demonstrated that the defect level can be tuned to a remarkable extent by controlling the amount of modulator. When a particular defect concentration is reached, the UiO-66-xFA can be acted as highly sensitive ratiometric fluorescence probes for chlortetracycline (CTE) determination with an ultralow detection limit of 9.9 nm. Furthermore, by virtue of the obvious variation in fluorescence chromaticity of probes from blue to yellow, a sensory hydrogels-based smartphone platform is proposed for visible quantitation of CTE by identifying the RGB values. A delicate device integrated with UV lamp and dark cavity has been developed for avoiding inconsistencies of ambient light and visual errors. Finally, the sensor obtains satisfactory results in the detection of actual seafood samples, with no significant differences from those of liquid chromatography-mass spectrometry. This approach anticipates a novel route to sensitize optical sensors through the design and synthesis of moderate defects in luminescent MOFs.

Imaging of Gastrointestinal Tract Ailments.

Gastrointestinal (GI) disorders comprise a diverse range of conditions that can significantly reduce the quality of life and can even be life-threatening in serious cases. The development of accurate and rapid detection approaches is of essential importance for early diagnosis and timely management of GI diseases. This review mainly focuses on the imaging of several representative gastrointestinal ailments, such as inflammatory bowel disease, tumors, appendicitis, Meckel's diverticulum, and others. Various imaging modalities commonly used for the gastrointestinal tract, including magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT), and photoacoustic tomography (PAT) and multimodal imaging with mode overlap are summarized. These achievements in single and multimodal imaging provide useful guidance for improved diagnosis, staging, and treatment of the corresponding gastrointestinal diseases. The review evaluates the strengths and weaknesses of different imaging techniques and summarizes the development of imaging techniques used for diagnosing gastrointestinal ailments.

Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitis.

Periodontitis is an oral chronic inflammatory disease. Inhibiting tissue destruction and promoting tissue regeneration are important means for the treatment of periodontitis. Metformin not only has hypoglycemic effect but also has anti-inflammatory effect. Metformin has been shown to inhibit oxidative stress and activate autophagy through AMPK/mTOR pathway. High mobility group box 1 (HMGB1) has been implicated in the pathogenesis of many inflammatory diseases including periodontitis, it can participate in the induction of oxidative stress. HMGB1 is an autophagy regulator under oxidative stress, which can activate mTOR pathway. However, it is not clear whether metformin is related to HMGB1 and its mechanism in the process of periodontitis. Cell viability and expression of inflammatory cytokines were clarified by Cell Counting Kit-8, real-time PCR and enzyme-linked immunosorbent assay. Western blot and immunofluorescence were conducted to determine HMGB1 intracellular localization and expression of autophagy-associated proteins in vitro. Experimental periodontitis mice model was induced by administering a ligature. Immunohistochemistry was performed to detect the expression and localization of HMGB1 in vivo. The results of CCK-8, real-time PCR, enzyme-linked immunosorbent assay, Western blot and immunofluorescence showed lipopolysaccharide (LPS) treatment inhibited cell viability, and increased HMGB1 expression at a dose-independent manner. Metformin can reduce the effect of LPS. It also improves autophagy pathway inhibited by LPS and down-regulates mTOR expression. In addition, metformin attenuated alveolar bone resorption induced by ligation. This study provides new evidence for that metformin is a potential drug for the treatment of periodontitis and HMGB1 may be a potential target for periodontal intervention.

A prognostic and immunotherapeutic predictive model based on the cell-originated characterization of tumor microenvironment in lung adenocarcinoma.

Tumor microenvironment (TME) plays a crucial role in predicting prognosis and response to therapy in lung cancer. Our study established a prognostic and immunotherapeutic predictive model, the tumor immune cell score (TICS), by differentiating cell origins in lung adenocarcinoma (LUAD) based on the transcriptomic data of 2,510 patients in 14 independent cohorts, including 12 public datasets and two in-house cohorts. The high TICS was associated with prolonged overall survival (OS), especially in the early-stage LUAD. For the advanced-stage LUAD, high TICS predicted a superior OS in patients who were treated with immunotherapy instead of chemotherapy or TKI. The result suggested that TICS could serve as an indicator for the prognostic stratification management of patients in the early-stage LUAD, and as a potential guide for therapeutic decision-marking in the advanced-stage LUAD. Our findings provided an insight into prognosis stratification and potential guidance for treatment strategy selection.

Detection of MET Polysomy by Next-generation Sequencing and Its Clinical Relevance for MET Inhibitors.

Next-generation sequencing (NGS) has failed to detect mesenchymal epithelial transition factor gene (MET) polysomy in previous studies. We included three non-small cell lung cancer (NSCLC) cohorts in this retrospective study to establish new criteria for detecting MET polysomy and to explore the clinical relevance of MET polysomy. Cohort 1 included 53 patients whose tissues were available for both FISH and NGS assays. Paired plasma and tissue samples were obtained from 261 patients with NSCLC as cohort 2. Cohort 3 included 46 patients with metastatic NSCLC, who presented with MET copy-number gain assessed by NGS. ROC analysis demonstrated that a cut-off point of 2.3 copies achieved the maximum Youden index in discriminating polysomy from normal copy number. Compared with the FISH test for MET polysomy, the sensitivity, specificity, and agreement of NGS were 90%, 90%, and 96.2%, respectively. Following optimization using maximum somatic allele frequency, the sensitivity and specificity of NGS for defining polysomy using plasma samples according to different circulating tumor DNA mutation frequencies were 42% and 63%. The concordance rate between tissue and plasma samples for detecting polysomy was 85%. Regarding the response to MET inhibitor, the median progression-free survival (PFS) of the MET amplification group was significantly higher than that of the polysomy group. The median PFS was similar between the polysomy and normal groups. Our results indicated that NGS may serve as an alternative method for detecting MET polysomy in NSCLC tissues. Moreover, patients with MET polysomy may not benefit from MET inhibitors. Significance: In this study, we established a methodology to differentiate polysomy from normal copy numbers and amplification using NGS. Moreover, this study suggests that it is critical to discriminate MET polysomy from amplification, for the former may dilute the clinical benefit of MET inhibitors.

Prediction of human thermal comfort preference based on supervised learning.

Human thermal comfort is relevant to human life comfort and plays a pivotal role in occupational health and thermal safety. To ensure that intelligent temperature-controlled equipment can deliver a sense of cosiness to people while improving its energy efficiency, we designed a smart decision-making system that sets the thermal comfort adjustment preference as a label, reflecting both the human body's thermal feeling and its acceptance of the thermal environment. By training a series of supervised learning models underpinned by environmental and human features, the most appropriate adjustment mode in the current environment was predicted. To bring this design into reality, we tried six supervised learning models, and then, by comparison and evaluation, we identified that the Deep Forest's performance was the best. The model takes into account objective environmental factors and human body parameters. In this way, it can achieve high accuracy in application and good simulation and prediction results. The results can provide feasible references for feature selection and model selection in further research with the aim of testing thermal comfort adjustment preference. The model can provide recommendations for the thermal comfort preference in a specific place at a particular time, as well as guidance on human thermal comfort preference and thermal safety precautions in specific occupational groups.

Choice of Mandarin Spatial Demonstratives in Distant Interaction.

Scholars are divided on whether the Speaker's (S') choice of spatial demonstratives in verbal interaction is ego-centric or not. We studied the choice of "zhe (here)/ na (there)" by a Mandarin S instructing Hearer (H) from a few to dozens of meters. Using within-group and between-group experiments in a picture-description paradigm, we found that both S- and H- distance (Ds and Dh) to the Referent constantly influence S' demonstrative choice, and the social relation as a variable (Relation) between S and H also exerts some influence. Our findings support the idea that spatial reference in verbal interaction is somewhat non-egocentric.

Current development of cabazitaxel drug delivery systems.

The second-generation taxane cabazitaxel has been clinically approved for the treatment of metastatic castration-resistant prostate cancer after docetaxel failure. Compared with the first-generation taxanes paclitaxel and docetaxel, cabazitaxel has potent anticancer activity and is less prone to drug resistance due to its lower affinity for the P-gp efflux pump. The relatively high hydrophobicity of cabazitaxel and the poor aqueous colloidal stability of the commercial formulation, following its preparation for injection, presents opportunities for new cabazitaxel formulations with improved features. This review provides an overview of cabazitaxel drug formulations and hydrophobic taxane drug delivery systems in general, and particularly focuses on emerging cabazitaxel delivery systems discovered in the past 5 years. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Analysis of the spatiotemporal patterns and decoupling effects of China's water resource spatial equilibrium.

The significance of water resource spatial equilibrium (WRSE) research is to maximally remove the spatial restrictions of water on regional development, including social development, economic development and eco-environmental maintenance. Although great achievements have been made, national-scale WRSE research is rare; besides, the spatiotemporal patterns and decoupling effects of WRSE have been poorly studied in current research. Thus, the aim of this research is to measure the WRSE in China for the period 2008-2019 by using an improved coupling coordination model and to empirically analyse its distribution dynamics and decoupling effects. The results show that the WRSE status of China's 31 provincial administrative regions from 2008 to 2019 is at a moderate level. Based on the spatiotemporal patterns and decoupling effects analysis, areas in urgent need of improving WRSE status are identified, and tailored countermeasures are provided for each area. To our knowledge, this paper is the first nationwide study of the spatiotemporal patterns and decoupling effects of WRSE.

Bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration.

Diabetes mellitus (DM) aggravates periodontitis, resulting in accelerated periodontal bone resorption. Disordered glucose metabolism in DM causes reactive oxygen species (ROS) overproduction resulting in compromised bone healing, which makes diabetic periodontal bone regeneration a major challenge. Inspired by the natural bone healing cascade, a mesoporous silica nanoparticle (MSN)-incorporated PDLLA (poly(dl-lactide))-PEG-PDLLA (PPP) thermosensitive hydrogel with stepwise cargo release is designed to emulate the mesenchymal stem cell "recruitment-osteogenesis" cascade for diabetic periodontal bone regeneration. During therapy, SDF-1 quickly escapes from the hydrogel due to diffusion for early rat bone marrow stem cell (rBMSC) recruitment. Simultaneously, slow degradation of the hydrogel starts to gradually expose the MSNs for sustained release of metformin, which can scavenge the overproduced ROS under high glucose conditions to reverse the inhibited osteogenesis of rBMSCs by reactivating the AMPK/ß-catenin pathway, resulting in regulation of the diabetic microenvironment and facilitation of osteogenesis. In vitro experiments indicate that the hydrogel markedly restores the inhibited migration and osteogenic capacities of rBMSCs under high glucose conditions. In vivo results suggest that it can effectively recruit rBMSCs to the periodontal defect and significantly promote periodontal bone regeneration under type 2 DM. In conclusion, our work provides a novel therapeutic strategy of a bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration.