Automatic segmentation of dura for quantitative analysis of lumbar stenosis: A deep learning study with 518 CT myelograms.

BACKGROUND: The diagnosis of lumbar spinal stenosis (LSS) can be challenging because radicular pain is not often present in the culprit-level localization. Accurate segmentation and quantitative analysis of the lumbar dura on radiographic images are key to the accurate differential diagnosis of LSS. The aim of this study is to develop an automatic dura-contouring tool for radiographic quantification on computed tomography myelogram (CTM) for patients with LSS. METHODS: A total of 518 CTM cases with or without lumbar stenosis were included in this study. A deep learning (DL) segmentation algorithm 3-dimensional (3D) U-Net was deployed. A total of 210 labeled cases were used to develop the dura-contouring tool, with the ratio of the training, independent testing, and external validation datasets being 150:30:30. The Dice score (DCS) was the primary measure to evaluate the segmentation performance of the 3D U-Net, which was subsequently developed as the dura-contouring tool to segment another unlabeled 308 CTM cases with LSS. Automatic masks of 446 slices on the stenotic levels were then meticulously reviewed and revised by human experts, and the cross-sectional area (CSA) of the dura was compared. RESULTS: The mean DCS of the 3D U-Net were 0.905 ± 0.080, 0.933 ± 0.018, and 0.928 ± 0.034 in the five-fold cross-validation, the independent testing, and the external validation datasets, respectively. The segmentation performance of the dura-contouring tool was also comparable to that of the second observer (the human expert). With the dura-contouring tool, only 59.0% (263/446) of the automatic masks of the stenotic slices needed to be revised. In the revised cases, there were no significant differences in the dura CSA between automatic masks and corresponding revised masks (p = 0.652). Additionally, a strong correlation of dura CSA was found between the automatic masks and corresponding revised masks (r = 0.805). CONCLUSIONS: A dura-contouring tool was developed that could automatically segment the dural sac on CTM, and it demonstrated high accuracy and generalization ability. Additionally, the dura-contouring tool has the potential to be applied in patients with LSS because it facilitates the quantification of the dural CSA on stenotic slices.

Green and efficient extraction of flavonoids from Perilla frutescens (L.) Britt. leaves based on natural deep eutectic solvents: Process optimization, component identification, and biological activity.

In this study, an ultrasonic-assisted natural deep eutectic solvent (NaDES) was used to extract flavonoids from Perilla frutescens (L.) Britt. leaves. Of 10 tested NaDESs, that comprising D-(+)-glucose and glycerol exhibited the best total flavonoid extraction rate. Response surface methodology (RSM) was used for extraction modeling and optimization, and the total flavonoid content reached 87.48 ± 1.61 mg RE/g DW, which was a significant increase of 5.36% compared with that of 80% ethanol extraction. Morphological changes in P. frutescens leaves before and after extraction were analyzed by scanning electron microscopy (SEM), and the mechanism of NaDES formation was studied by Fourier transform infrared (FT-IR) spectroscopy. Furthermore, 10 flavonoids were identified by UPLC-Q-TOF-MS. In addition, the NaDES extract had better biological activity according to five kinds of antioxidant capacity measurements, cyclooxygenase-2 (COX-2) and hyaluronidase (Hyal) inhibition experiments. Moreover, the stability test revealed that the total flavonoid loss rate of the NaDES extract after four weeks was 37.75% lower than that of the ethanol extract. These results indicate that the NaDES can effectively extract flavonoids from P. frutescens leaves and provide a reference for further applications in the food, medicine, health product and cosmetic industries.

Establishment of an induced pluripotent stem cell (iPSC) line (INNDSUi004-A) from a patient with Congenital Nemaline Myopathy.

We used a non-integrated reprogramming approach to establish a human induced pluripotent stem cell (hiPSC) line (INNDSUi004-A) from the skin fibroblasts of a 13-year-old female individual with Congenital Nemaline Myopath. The cells obtained have typical characteristics of embryonic stem cells, show expression of specific pluripotency markers, and can differentiate into three germ layers in vitro. This iPSC cell line has the genetic information of the patient and is a good model for studying disease mechanisms and developing novel therapies.

Correlation of meniscus tear type with synovial inflammation and the therapeutic potential of docosapentaenoic acid.

BACKGROUND: Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and the key inflammatory mediators of synovium induced by different types of meniscal tears remain unclear. METHODS: Magnetic resonance imaging (MRI) was employed to identify the type of meniscus tear, and the quantification of synovial inflammation was assessed through H&E staining assay. Transcription and expression levels of IL-1ß and IL-6 were evaluated using bioinformatics, ELISA, RT-qPCR, and IHC of CD68 staining assays. The therapeutic potential of Docosapentaenoic Acid (DPA) was determined through network pharmacology, ELISA, and RT-qPCR assays. The safety of DPA was assessed using colony formation and EdU staining assays. RESULTS: The results indicate that both IL-1ß and IL-6 play pivotal roles in synovitis pathogenesis, with distinct expression levels across various subtypes. Among tested meniscus tears, oblique tear and bucket handle tear induced the most severe inflammation, followed by radial tear and longitudinal tear, while horizontal tear resulted in the least inflammation. Furthermore, in synovial inflammation induced by specific meniscus tears, the anterior medial tissues exhibited significantly higher local inflammation than the anterior lateral and suprapatellar regions, highlighting the clinical relevance and practical guidance of anterior medial tissues' inflammatory levels. Additionally, we identified the essential omega-3 fatty acid DPA as a potential therapeutic agent for synovitis, demonstrating efficacy in blocking the transcription and expression of IL-1ß and IL-6 with minimal side effects. CONCLUSION: These findings provide valuable insights into the nuanced nature of synovial inflammation induced by various meniscal tear classifications and contribute to the development of new adjunctive therapeutic agents in the management of synovitis.

Lysosomal dysfunction and overload of nucleosides in thymidine phosphorylase deficiency of MNGIE.

Inherited deficiency of thymidine phosphorylase (TP), encoded by TYMP, leads to a rare disease with multiple mitochondrial DNA (mtDNA) abnormalities, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). However, the impact of TP deficiency on lysosomes remains unclear, which are important for mitochondrial quality control and nucleic acid metabolism. Muscle biopsy tissue and skin fibroblasts from MNGIE patients, patients with m.3243 A > G mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and healthy controls (HC) were collected to perform mitochondrial and lysosomal functional analyses. In addition to mtDNA abnormalities, compared to controls distinctively reduced expression of LAMP1 and increased mitochondrial content were detected in the muscle tissue of MNGIE patients. Skin fibroblasts from MNGIE patients showed decreased expression of LAMP2, lowered lysosomal acidity, reduced enzyme activity and impaired protein degradation ability. TYMP knockout or TP inhibition in cells can also induce the similar lysosomal dysfunction. Using lysosome immunoprecipitation (Lyso- IP), increased mitochondrial proteins, decreased vesicular proteins and V-ATPase enzymes, and accumulation of various nucleosides were detected in lysosomes with TP deficiency. Treatment of cells with high concentrations of dThd and dUrd also triggers lysosomal dysfunction and disruption of mitochondrial homeostasis. Therefore, the results provided evidence that TP deficiency leads to nucleoside accumulation in lysosomes and lysosomal dysfunction, revealing the widespread disruption of organelles underlying MNGIE.

Real-time crash prediction on express managed lanes of Interstate highway with anomaly detection learning.

To facilitate efficient transportation, I-4 Express is constructed separately from general use lanes in metropolitan area to improve mobility and reduce congestion. As this new infrastructure would undoubtedly change the traffic network, there is a need for more understanding of its potential safety impact. Unfortunately, many advanced real-time crash prediction models encounter an important challenge in their applicability due to their demand for a substantial volume of data for direct modeling. To tackle this challenge, we proposed a simple yet effective approach - anomaly detection learning, which formulates model as an anomaly detection problem, solves it through normality feature recognition, and predicts crashes by identifying deviations from the normal state. The proposed approach demonstrates significant improvement in the Area Under the Curve (AUC), sensitivity, and False Alarm Rate (FAR). When juxtaposed with the prevalent direct classification paradigm, our proposed anomaly detection learning (ADL) consistently outperforms in AUC (with an increase of up to 45%), sensitivity (experiencing up to a 45% increase), and FAR (reducing by up to 0.53). The most performance gain is attained through the combination of Convolutional Neural Network (CNN) and Long Short-Term Memory (LSTM) in an ensemble, resulting in a 0.78 AUC, 0.79 sensitivity, and a 0.22 false alarm rate. Furthermore, we analyzed model features with a game-theoretic approach illustrating the most correlated features for accurate prediction, revealing the attention of advanced convolution neural networks to occupancy features. This provided crucial insights into improving crash precaution, the findings from which not only benefit private stakeholders but also extend a promising opportunity for governmental intervention on the express lane. This work could promote express lane with more efficient resource allocation, real-time traffic management optimization, and high-risk area prioritization.

Efficient red thermally activated delayed fluorescence emitters achieved through precise control of excited state energy levels.

The variety of highly efficient red/near-infrared (NIR) materials with thermally activated delayed fluorescence (TADF) feature is extremely limited so far, and it is necessary to expand the candidate pool of excellent red/deep-red emitters. However, how to control the energy level alignment of the 1CT (singlet charge transfer) state and the 3LE (triplet local excitation) state to improve the emission efficiency of materials remains a challenge. Herein, based on our previously reported green fluorescent material 67dTPA-FQ, three new donor-acceptor type TADF materials (TQ-oMeOTPA, TsQ-oMeOTPA and SQ-oMeOTPA) were designed by introducing 4,4'-dimethoxy triphenylamine (MeOTPA) as the donor, and introduced S atoms on the acceptors to enhance the spin-orbit coupling (SOC) and CT effects. The theoretical calculations showed that the newly introduced MeOTPA and S atom successfully enhanced the CT effect of the materials, not only shifting the luminescence peak to the deep red region but also effectively adjusting the energy level alignment of the excited state, accelerating the reverse intersystem crossing process. Finally, the organic light-emitting diodes based on SQ-oMeOTPA exhibit an external quantum efficiency of 19.1%, with an emission peak at 619 nm. This work not only expands the candidate inventory of red TADF materials, but also proves the feasibility of designing emitters by adjusting the excited state energy levels, greatly broadening the diversity of TADF emitters in design, and providing a powerful means for rapidly screening efficient emitters in the future.

Bulbil initiation: a comprehensive review on resources, development, and utilisation, with emphasis on molecular mechanisms, advanced technologies, and future prospects.

Bulbil is an important asexual reproductive structure of bulbil plants. It mainly grows in leaf axils, leaf forks, tubers and the upper and near ground ends of flower stems of plants. They play a significant role in the reproduction of numerous herbaceous plant species by serving as agents of plant propagation, energy reserves, and survival mechanisms in adverse environmental conditions. Despite extensive research on bulbil-plants regarding their resources, development mechanisms, and utilisation, a comprehensive review of bulbil is lacking, hindering progress in exploiting bulbil resources. This paper provides a systematic overview of bulbil research, including bulbil-plant resources, identification of development stages and maturity of bulbils, cellular and molecular mechanisms of bulbil development, factors influencing bulbil development, gene research related to bulbil development, multi-bulbil phenomenon and its significance, medicinal value of bulbils, breeding value of bulbils, and the application of plant tissue culture technology in bulbil production. The application value of the Temporary Immersion Bioreactor System (TIBS) and Terahertz (THz) in bulbil breeding is also discussed, offering a comprehensive blueprint for further bulbil resource development. Additionally, additive, seven areas that require attention are proposed: (1) Utilization of modern network technologies, such as plant recognition apps or websites, to collect and identify bulbous plant resources efficiently and extensively; (2) Further research on cell and tissue structures that influence bulb cell development; (3) Investigation of the network regulatory relationship between genes, proteins, metabolites, and epigenetics in bulbil development; (4) Exploration of the potential utilization value of multiple sprouts, including medicinal, ecological, and horticultural applications; (5) Innovation and optimization of the plant tissue culture system for bulbils; (6) Comprehensive application research of TIBS for large-scale expansion of bulbil production; (7) To find out the common share genetics between bulbils and flowers.

Ultralow-Loading Ruthenium-Iridium Fuel Cell Catalysts Dispersed on Zn-N Species-Doped Carbon.

Developing low-loading platinum-group-metal (PGM) catalysts is one of the key challenges in commercializing anion-exchange-membrane-fuel-cells (AEMFCs), especially for hydrogen oxidation reaction (HOR). Here, ruthenium-iridium nanoparticles being deposited on a Zn-N species-doped carbon carrier (Ru6Ir/Zn-N-C) are synthesized and used as an anodic catalyst for AEMFCs. Ru6Ir/Zn-N-C shows extremely high mass activity (5.87 A mgPGM -1) and exchange current density (0.92 mA cm-2), which is 15.1 and 3.9 times that of commercial Pt/C, respectively. Based on the Ru6Ir/Zn-N-C AEMFCs achieve a peak power density of 1.50 W cm-2, surpassing the state-of-the-art commercial PtRu catalysts and the power ratio of the normalized loading is 14.01 W mgPGM anode -1 or 5.89 W mgPGM -1 after decreasing the anode loading (87.49 µg cm-2) or the total PGM loading (0.111 mg cm-2), satisfying the US Department of Energy's PGM loading target. Moreover, the solvent and solute isotope separation method is used for the first time to reveal the kinetic process of HOR, which shows the reaction is influenced by the adsorption of H2O and OH-. The improvement of the hydrogen bond network connectivity of the electric double layer by adjusting the interfacial H2O structure together with the optimized HBE and OHBE is proposed to be responsible for the high HOR activity of Ru6Ir/Zn-N-C.

Effects of tacrolimus on proteinuria in Chinese and Indian patients with idiopathic membranous nephropathy: the results of machine learning study.

PURPOSE: The present study aims to explore the effects of tacrolimus on proteinuria in patients with idiopathic membranous nephropathy (IMN) and recommend an appropriate dosage schedule via machine learning method. METHODS: The Emax model was constructed to analyze the effects of tacrolimus on proteinuria in patients with IMN. Data were mined from published literature and machine learning was built up with Emax model, among which the efficacy indicator was proteinuria change rates from baseline. 463 IMN patients were included for modeling, and tacrolimus therapeutic window concentrations were 4-10 ng/ml. RESULTS: In machine learning model, the Emax from tacrolimus effecting proteinuria in IMN patients was -72.7%, the ET50 was 0.43 months, and the time to achieving 25% Emax, 50% Emax, 75% Emax, and 80% (plateau) Emax of tacrolimus on proteinuria in patients with IMN were 0.15, 0.43, 1.29, and 1.72 months, respectively. CONCLUSION: For achieving better therapeutic effects from tacrolimus on proteinuria in patients with IMN, tacrolimus concentration range need to be maintained at 4-10 ng/ml for at least 1.72 months.

The Impact of Spironolactone Co-administration on Cyclosporin Initial Dosage Optimization for Pediatric Refractory Nephrotic Syndrome.

OBJECTIVES: Cyclosporin has been used for the treatment of pediatric refractory nephrotic syndrome (PRNS). However, the narrow therapeutic window and large pharmacokinetic variability make it difficult to individualize cyclosporin administration. Meanwhile, spironolactone has been reported to affect cyclosporin metabolism in PRNS patients. This study aims to explore the initial dosage optimization of cyclosporin in PRNS based on the impact of spironolactone co-administration. METHODS: Monte Carlo simulation based on a previously established cyclosporin population pharmacokinetic model for PRNS was used to design cyclosporin dosing regimen. RESULTS: In this study, the probability of drug concentration reaching the target and the convenience of times of administration were considered comprehensively. The optimal administration regimen in PRNS without spironolactone was 6, 5, 4 and 3 mg/kg cyclosporin split into two doses for the body weight of 5-8, 8-18, 18-46 and 46-70 kg, respectively. The optimal administration regimen in PRNS with spironolactone was 4, 3, 2 mg/kg cyclosporin split into two doses for body weight of 5-14, 14-65, and 65-70 kg, respectively. CONCLUSION: The cyclosporin dosing regimen for PRNS based on Monte Carlo simulation was systematically developed and the initial dosage optimization of cyclosporin in PRNS was recommended for the first time.

Ultrafast restricted intramolecular rotation in molecules with aggregation induced emission.

In this work, the ultrafast intramolecular rotation behavior of 1,1,2,3,4,5-hexaphenylsilole has been investigated in several solutions with different viscosities using femtosecond transient absorption spectroscopy combined with density functional theory and time-dependent density functional theory calculations. It is demonstrated that the nonradiative process, which competes with radiative decay, involves two main stages, namely the restricted intramolecular rotation and internal conversion processes. The intramolecular rotation depends on viscosity and presents a significant restriction. The restricted rotational rate is determined to be dozens of picoseconds. The following nonradiative process is strongly dominated by intramolecular rotation. The nonradiative decay rate will decrease with the increase in viscosity, leading to a rise in the radiative probability and photoluminous yield. These results have borne out the mechanism of ultrafast restricted intramolecular rotation of aggregation induced emission and provided a detailed photophysical picture of nonradiative processes.

The formation of unsaturated IrOx in SrIrO3 by cobalt-doping for acidic oxygen evolution reaction.

Electrocatalytic water splitting is a promising route for sustainable hydrogen production. However, the high overpotential of the anodic oxygen evolution reaction poses significant challenge. SrIrO3-based perovskite-type catalysts have shown great potential for acidic oxygen evolution reaction, but the origins of their high activity are still unclear. Herein, we develop a Co-doped SrIrO3 system to enhance oxygen evolution reaction activity and elucidate the origin of catalytic activity. In situ experiments reveal Co activates surface lattice oxygen, rapidly exposing IrOx active sites, while bulk Co doping optimizes the adsorbate binding energy of IrOx. The Co-doped SrIrO3 demonstrates high oxygen evolution reaction electrocatalytic activity, markedly surpassing the commercial IrO2 catalysts in both conventional electrolyzer and proton exchange membrane water electrolyzer.

Targeting CXCR4/CXCL12 axis via [177Lu]Lu-DOTAGA.(SA.FAPi)2 with CXCR4 antagonist in triple-negative breast cancer.

PURPOSE: Radiopharmaceutical therapies targeting fibroblast activation protein (FAP) have shown promising efficacy against many tumor types. But radiopharmaceuticals alone in most cases are insufficient to completely eradicate tumor cells, which can partially be attributed to the protective interplay between tumor cells and cancer-associated fibroblasts (CAFs). The C-X-C chemokine receptor type 4/C-X-C motif chemokine 12 (CXCR4/CXCL12) interaction plays an important role in orchestrating tumor cells and CAFs. We hereby investigated the feasibility and efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2, a FAP-targeting radiopharmaceutical, in combination with AMD3100, a CXCR4 antagonist, in a preclinical murine model of triple-negative breast cancer (TNBC). METHODS: Public database was first interrogated to reveal the correlation between CAFs' scores and the prognosis of TNBC patients, as well as the expression levels of FAP and CXCR4 in normal tissues and tumors. In vitro therapeutic efficacy regarding cell proliferation, migration, and colony formation was assessed in BALB/3T3 fibroblasts and 4T1 murine breast cancer cells. In vivo therapeutic efficacy was longitudinally monitored using serial 18F-FDG, [18F]AlF-NOTA-FAPI-04, and [68Ga]Ga-DOTA-Pentixafor PET/CT scans and validated using tumor sections through immunohistochemical staining of Ki-67, α-SMA, CXCR4, and CXCL12. Intratumoral abundance of myeloid-derived suppressive cells (MDSCs) was analyzed using flow cytometry in accordance with the PET/CT schedules. Treatment toxicity was evaluated by examining major organs including heart, lung, liver, kidney, and spleen. RESULTS: CAFs' scores negatively correlated with the survival of TNBC patients (p < 0.05). The expression of CXCR4 and FAP was both significantly higher in tumors than in normal tissues. The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 significantly suppressed cell proliferation, migration, and colony formation in cell culture, and exhibited synergistic effects in 4T1 tumor models along with a decreased number of MDSCs. PET/CT imaging revealed lowest tumor accumulation of 18F-FDG and [18F]AlF-NOTA-FAPI-04 on day 13 and day 14 after treatment started, both of which gradually increased at later time points. A similar trend was observed in the IHC staining of Ki-67, α-SMA, and CXCL12. CONCLUSION: The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 is a feasible treatment against TNBC with minimal toxicity in main organs.

Resection or Biopsy: The Efficacy of Different Surgical Approaches for Primary Central Nervous System Lymphoma.

AIM: To analyze the efficacy of surgical resection versus brain biopsy combined with postoperative chemotherapy for primary central nervous system lymphoma (PCNSL) and to discuss a clinically standardized treatment protocol. MATERIAL AND METHODS: Patients with a pathological diagnosis of PCNSL and subsequent chemotherapy between 2016 and 2021 at Northern Jiangsu People?s Hospital were selected and divided into groups according to whether they underwent microsurgical resection or stereotactic needle biopsy. Statistical analyses were performed to compare efficacy and safety in the two groups. RESULTS: A total of 21 patients with PCNSL were identified, of whom 12 underwent resection and 9 underwent diagnostic stereotactic biopsy only. Compared with the resection group, the biopsy group had a higher proportion of deep tumors (55.6% vs. 8.3%, p=0.016), and the mean intraoperative bleeding was significantly reduced (13.33 ± 6.61 mL vs. 170.83 ± 101.04 ml, p < 0.001). In addition, the mean survival time of patients who died during the postoperative follow-up period was shorter (6.83 ± 1.60 vs. 18.56 ± 10.20 months, p=0.016), and the one-year survival rate was lower (33.3% vs. 83.3%, p=0.032). There was no significant difference between the two groups in terms of the mean progression-free survival time or new functional impairment after surgery. CONCLUSION: For PCNSL, patients who undergo surgical resection have a better outcome than those who undergo biopsy only, suggesting that when the tumor is located at a surgically resectable site, surgical resection should be actively chosen; when the tumor is located at a deep and unresectable site, brain biopsy should be chosen.

Effect of early peri-operative arterial lactate concentration level ratios on post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF. METHODS: The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (< 1). We compared the differences in morbidity rates between the two groups. Utilized logistic regression analysis to identify the risk factors associated with PHLF development and ROC curves to compare the predictive value of lactate ratio and other liver function indicators for PHLF. RESULTS: A total of 203 patients were enrolled in the study. Overall morbidity and severe morbidity occurred in 64.5 and 12.8 per cent of patients respectively. 39 patients (19.2%) met the criteria for PHLF, including 15 patients (7.4%) with clinically relevant Post-hepatectomy liver failure (CR-PHLF). With a significantly higher incidence of PHLF observed in the lactate ratio ≥ 1 group compared to the lactate ratio < 1 group (n = 34, 26.8% vs. n = 5, 6.6%, P < 0.001). Multivariable logistic regression analysis revealed that a lactate ratio ≥ 1 was an independent predictor for PHLF (OR: 3.239, 95% CI 1.097-9.565, P = 0.033). Additionally, lactate ratio demonstrated good predictive efficacy for PHLF (AUC = 0.792). CONCLUSIONS: Early assessment of peri-operative arterial lactate concentration level ratios may provide experience in early intervention of complications in patients with hepatocellular carcinoma, which can reduce the likelihood of PHLF occurrence and improve patient prognosis.

Sonodynamic-chemotherapy synergy with chlorin e6-based carrier-free nanoparticles for non-small cell lung cancer.

Sonodynamic therapy (SDT), an emerging cancer treatment with significant potential, offers the advantages of non-invasiveness and deep tissue penetrability. The method involves activating sonosensitizers with ultrasound to generate reactive oxygen species (ROS) capable of eradicating cancer cells, addressing the challenge faced by photodynamic therapy (PDT) where conventional light sources struggle to penetrate deep tissues, impacting treatment efficacy. This study addresses prevalent challenges in numerous nanodiagnostic and therapeutic agents, such as intricate synthesis, poor repeatability, low stability, and high cost, by introducing a streamlined one-step assembly method for nanoparticle preparation. Specifically, the sonosensitizer Chlorin e6 (Ce6) and the chemotherapy drug erlotinib are effortlessly combined and self-assembled under sonication, yielding carrier-free nanoparticles (EC-NPs) for non-small cell lung cancer (NSCLC) treatment. The resulting EC-NPs exhibit optimal drug loading capacity, a simplified preparation process, and robust stability both in vitro and in vivo, owing to their carrier-free characteristics. Under the synergistic treatment of sonodynamic therapy and chemotherapy, EC-NPs induce an excess of reactive oxygen in tumor tissue, prompting apoptosis of cancer cells and reducing their proliferative capacity. Both in vitro and in vivo experiments demonstrate superior therapeutic effects of EC-NPs under ultrasound conditions compared to free Ce6. In summary, our research findings highlight that the innovatively designed carrier-free sonosensitizer EC-NPs present a therapeutic option with commendable efficacy and minimal side effects.

Protective Mechanism of Rosa roxburghii Tratt Fermentation Broth against Ultraviolet-A-Induced Photoaging of Human Embryonic Skin Fibroblasts.

This study takes the fruit of Rosa roxburghii Tratt (RRT) as a fermentation substrate and carries out a quantitative visual analysis of the domestic and foreign literature on screenings of five different lactic acid bacteria to obtain a fermentation broth. Systemic anti-photoaging effects are analyzed at the biochemical, cellular, and molecular biological levels. DPPH and ABTS free radical scavenging activities are used to verify the antioxidant capacity of the RRT fruit fermentation broth in vitro. Human embryonic skin fibroblasts (HESs) are used to establish a UVA damage model, and the antioxidant capacity of the RRT fruit fermentation broth is verified in terms of intracellular reactive oxygen species (ROS) and antioxidant enzyme activity. RT-qPCR and ELISA are used to detect the expression of TGF-ß/Smad, MMPs, and the MAPK/AP-1 and Nrf2/Keap-1 signaling pathways in order to explore the anti-oxidation and anti-photoaging effects of the RRT fruit fermentation broth by regulating different signaling pathways. The results show that an RRT fruit fermentation broth can effectively protect cells from oxidative stress caused by UVA and has significant anti-photoaging effects, with the co-cultured Lactobacillus Yogurt Starter LYS-20297 having the highest overall effect.

Protective Effect of Panax notoginseng Extract Fermented by Four Different Saccharomyces cerevisiae Strains on H2O2 Induced Oxidative Stress in Skin Fibroblasts.

Purpose: To produce Panax notoginseng extract as a cosmetic ingredient through Saccharomyces cerevisiae fermentation. Methods: We first compared the total sugar content, polysaccharide content, reducing sugar content, total phenolic content, total saponin content, DPPH free radical, ABTS free radical, hydroxyl free radical scavenging ability and ferric reducing antioxidant power (FRAP) of Panax notoginseng fermented extract (pnFE) and unfermented extract (pnWE). Their potential correlations were analyzed by Pearson's correlation analysis. Then, the oxidative stress model of H2O2-induced MSFs was used to evaluate the effects of different pnFE on MSF viability, reactive oxygen species (ROS), malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) to explore their protective effects on MSFs subjected to H2O2-induced cellular oxidative damage. Finally, their safety and stability were evaluated by using the red blood cell (RBC) test and hen's egg test-chorioallantoic membrane (HET-CAM) assay, and changes in pH and content of soluble solids, respectively. Results: Compared with pnWE, pnFE has more active substances and stronger antioxidant capacity. In addition, pnFE has a protective effect on H2O2-induced oxidative stress in MSFs with appropriate safety and stability. Conclusion: PnFE has broad application prospects in the field of cosmetics.

Effects of Aripiprazole on Olanzapine Population Pharmacokinetics and Initial Dosage Optimization in Schizophrenia Patients.

Objective: Olanzapine has already been used to treat schizophrenia patients; however, the initial dosage recommendation when multiple drugs are used in combination, remains unclear. The purpose of this study was to explore the drug-drug interaction (DDI) of multiple drugs combined with olanzapine and to recommend the optimal administration of olanzapine in schizophrenia patients. Methods: In this study, we obtained olanzapine concentrations from therapeutic drug monitoring (TDM) database. In addition, related medical information, such as physiological, biochemical indexes, and concomitant drugs was acquired using medical log. Sixty-five schizophrenia patients were enrollmented for analysis using population pharmacokinetic model by means of nonlinear mixed effect (NONMEM). Results: Weight and combined use of aripiprazole significantly affected olanzapine clearance. Without aripiprazole, for once-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40-70, and 70-100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40-60, and 60-100 kg schizophrenia patients, respectively. With aripiprazole, for once-daily olanzapine administration dosages, 0.4, 0.3 mg/kg/day were recommended for 40-53, and 53-100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.4 mg/kg/day was recommended for 40-100 kg schizophrenia patients, respectively. Conclusion: Aripiprazole significantly affected olanzapine clearance, and when schizophrenia patients use aripiprazole, the olanzapine dosages need adjust. Meanwhile, we firstly recommended the optimal initial dosages of olanzapine in schizophrenia patients.