Enhanced ophthalmic bioavailability and stability of atropine sulfate via sustained release particles using polystyrene sulfonate resin.

Atropine sulfate (ATS) eye drops at low concentrations constitute a limited selection for myopia treatment, with challenges such as low ophthalmic bioavailability and inadequate stability. This study proposes a novel strategy by synthesizing ophthalmic sodium polystyrene sulfonate resin (SPSR) characterized by a spherical shape and uniform size for cationic exchange with ATS. The formulation of ATS@SPSR suspension eye drops incorporates xanthan gum and hydroxypropyl methylcellulose (HPMC) as suspending agents. In vitro studies demonstrated that ATS@SPSR suspension eye drops exhibited sustained release characteristics, and tropic acid, its degradation product, remained undetected for 30 days at 40 °C. The ATS levels in the tear fluids and aqueous humor of New Zealand rabbits indicated a significant increase in mean residence time (MRT) and area under the drug concentration-time curve (AUC0-12h) for ATS@SPSR suspension eye drops compared to conventional ATS eye drops. Moreover, safety assessment confirmed the non-irritating nature of ATS@SPSR suspension eye drops in rabbit eyes. In conclusion, the cation-responsive sustained-release ATS@SPSR suspension eye drops enhanced the bioavailability and stability of ATS, offering a promising avenue for myopia treatment.

Comparative study of percutaneous endoscopic lumbar decompression and traditional revision surgery in the treatment of symptomatic adjacent segment degeneration.

OBJECTIVE: The objective of this study is to evaluate and compare the surgical outcomes and complications of Percutaneous Endoscopic Lumbar Decompression (PELD) and traditional revision surgery in treating symptomatic Adjacent Segment Degeneration (ASD). This comparison aims to delineate the advantages and disadvantages of these methods, assisting spine surgeons in making informed surgical decisions. METHODS: 66 patients with symptomatic ASD who failed conservative treatment for more than 1 month and received repeated lumbar surgery were retrospectively collected in the study from January 2015 to November 2018, with the average age of 65.86 ± 11.04 years old. According to the type of surgery they received, all the patients were divided in 2 groups, including 32 patients replaced the prior rod in Group A and 34 patients received PELD at the adjacent level in Group B. Patients were followed up routinely and received clinical and radiological evaluation at 3, 6, 12 months and yearly postoperatively. Complications and hospital costs were recorded through chart reviews. RESULTS: The majority of patients experienced positive surgical outcomes. However, three cases encountered complications. Notably, Group B patients demonstrated superior pain relief and improved postoperative functional scores throughout the follow-up period, alongside reduced hospital costs (P < 0.05). Additionally, significant reductions in average operative time, blood loss, and hospital stay were observed in Group B (P < 0.05). Notwithstanding these benefits, three patients in Group B experienced disc re-herniation and underwent subsequent revision surgeries. CONCLUSIONS: While PELD offers several advantages over traditional revision surgery, such as reduced operative time, blood loss, and hospital stay, it also presents a higher likelihood of requiring subsequent revision surgeries. Future studies involving a larger cohort and extended follow-up periods are essential to fully assess the relative benefits and drawbacks of these surgical approaches for ASD.

Lutein Loaded in ß-Cyclodextrin Metal-Organic Frameworks for Stability and Solubility Enhancements.

Lutein (Lut) is a recognized nutritional supplement known for its antioxidative and anti-inflammatory properties, crucial in mitigating ocular disease. However, enhancements to Lut stability and solubility remain challenges to be addressed in the healthcare industry. Herein, we fabricated and evaluated a food-grade highly porous ß-cyclodextrin metal-organic framework (ß-CD-MOF) for its ability to encapsulate Lut. Lut stability considerably improved when loaded into ß-CD-MOF to form a Lut@ß-CD-MOF complex, which exhibited better stability than Lut loaded into the γ-cyclodextrin metal-organic framework (Lut@γ-CD-MOF), Lut@ß-CD, and commercial product (Blackmores™) at 40°C, 60°C, and 70°C, respectively. The solubility of Lut@ß-CD-MOF in water increased by 26.8-fold compared to raw Lut at 37°C. Lut@ß-CD-MOF exhibited greater hydrophilicity, as determined by measuring the water contact angle. Molecular docking and other characterizations of Fourier transform infrared spectroscopy and powder X-ray diffraction confirmed that Lut was successfully encapsulated in the chamber formed by the three cyclodextrins in ß-CD-MOF. Thermogravimetric analysis and Raman spectroscopy demonstrated that Lut distributed in the ß-CD-MOF cavity deeply improved Lut stability and solubility. In conclusion, our findings underscored the function of ß-CD-MOF in enhancing Lut stability and solubility for formulation applications.

Optimization design of battery bracket for new energy vehicles based on 3D printing technology.

Nowadays, what captures consumers' primary attention is how to purchase electric vehicles with long range and desirable price. Lightweight construction stands as one of the most effective approaches for prolonging range and lowering costs. As a consequence, it is particularly imperative to undertake lightweight design optimization for the battery bracket of new energy vehicles by applying 3D printing technology. To actualize this goal, Rhino software was initially employed for 3D modeling to design the battery bracket system for a pure electric vehicle in China. Subsequently, topology optimization design of the battery bracket was carried out by adopting Altair Inspire software. Last but not least, manufacturing and assembly inspection were completed using a 3D printer. The results show that the maximum displacement of the battery lower tray bracket after topology optimization is 3.20 mm, which is slightly higher than before, but still relatively small. The maximum Mises equivalent stress rose to 240.7 MPa post-optimization, but brought about a uniform stress distribution at the bottom of the bracket. In comparison, the minimum factor of safety met design requirements at 1. The mass was lessened to 0.348 kg, representing a 49.2% decrease in comparison with pre-optimization levels. The 3D-printed bracket was fabricated by employing a 3D printer, thereby achieving the aforementioned mass abatement. The battery pack parts exhibited a bright surface with low roughness and no discernible warping or deformation defects. As revealed by the assembly results, the components of the battery pack bracket are tightly coordinated with each other, with no evident assembly conflicts, revealing that the dimensional accuracy and fit of the completed parts meet production requirements. These findings lay solid groundwork for the mass production of high-performance battery pack brackets.

An efficient visual servo tracker for herd monitoring by UAV.

It is a challenging and meaningful task to carry out UAV-based livestock monitoring in high-altitude (more than 4500 m on average) and cold regions (annual average - 4 °C) on the Qinghai Tibet Plateau. The purpose of artificial intelligence (AI) is to execute automated tasks and to solve practical problems in actual applications by combining the software technology with the hardware carrier to create integrated advanced devices. Only in this way, the maximum value of AI could be realized. In this paper, a real-time tracking system with dynamic target tracking ability is proposed. It is developed based on the tracking-by-detection architecture using YOLOv7 and Deep SORT algorithms for target detection and tracking, respectively. In response to the problems encountered in the tracking process of complex and dense scenes, our work (1) Uses optical flow to compensate the Kalman filter, to solve the problem of mismatch between the target bounding box predicted by the Kalman filter (KF) and the input when the target detection in the current frame is complex, thereby improving the prediction accuracy; (2) Using a low confidence trajectory filtering method to reduce false positive trajectories generated by Deep SORT, thereby mitigating the impact of unreliable detection on target tracking. (3) A visual servo controller has been designed for the Unmanned Aerial Vehicle (UAV) to reduce the impact of rapid movement on tracking and ensure that the target is always within the field of view of the UAV camera, thereby achieving automatic tracking tasks. Finally, the system was tested using Tibetan yaks on the Qinghai Tibet Plateau as tracking targets, and the results showed that the system has real-time multi tracking ability and ideal visual servo effect in complex and dense scenes.

Ni-based catalysts supported on Hbeta zeolite for the hydrocracking of waste polyolefins.

Polyolefin plastics are the most popular polymer materials worldwide, and the catalytic degradation of post-consumer polyolefins has attracted increased attention as a viable process. In this study, two types of Ni-based catalysts supported on Hbeta zeolite, Ni-Hbeta and NiS2-Hbeta, have been successfully synthesized for the hydrocracking of waste polyolefin. The experimental results indicated that the synergistic effect between Ni or NiS2 and the acidic sites of Hbeta zeolites can significantly enhance the tandem cracking and hydrogenation of polyolefin plastics, which suppresses the formation of gas products and coke. Ni-Hbeta employed as a catalyst can effectively degrade HDPE into high value liquid and gas products with high yield of 94% under 523 K and 3 MPa H2, while also exhibiting excellent cycle stability. In particular, Ni-Hbeta shows better catalytic performance than NiS2-Hbeta during the hydrocracking of HDPE at a relatively low temperature of 523 K. Furthermore, Ni-Hbeta catalyst also exhibits a remarkable capability for efficient depolymerization of unsorted post-consumer polyolefin plastics (HDPE, LDPE, PP) containing various additives and pollutants. These findings underscore the application potential of employing noble metal-free and recyclable catalysts for hydrocracking plastic waste, thereby facilitating the realization of a circular economy for plastics.

Identification and validation of microbial biomarkers from cross-cohort datasets using xMarkerFinder.

Microbial signatures have emerged as promising biomarkers for disease diagnostics and prognostics, yet their variability across different studies calls for a standardized approach to biomarker research. Therefore, we introduce xMarkerFinder, a four-stage computational framework for microbial biomarker identification with comprehensive validations from cross-cohort datasets, including differential signature identification, model construction, model validation and biomarker interpretation. xMarkerFinder enables the identification and validation of reproducible biomarkers for cross-cohort studies, along with the establishment of classification models and potential microbiome-induced mechanisms. Originally developed for gut microbiome research, xMarkerFinder's adaptable design makes it applicable to various microbial habitats and data types. Distinct from existing biomarker research tools that typically concentrate on a singular aspect, xMarkerFinder uniquely incorporates a sophisticated feature selection process, specifically designed to address the heterogeneity between different cohorts, extensive internal and external validations, and detailed specificity assessments. Execution time varies depending on the sample size, selected algorithm and computational resource. Accessible via GitHub ( https://github.com/tjcadd2020/xMarkerFinder ), xMarkerFinder supports users with diverse expertise levels through different execution options, including step-to-step scripts with detailed tutorials and frequently asked questions, a single-command execution script, a ready-to-use Docker image and a user-friendly web server ( https://www.biosino.org/xmarkerfinder ).

High-precision tracking and positioning for monitoring Holstein cattle.

Enhanced animal welfare has emerged as a pivotal element in contemporary precision animal husbandry, with bovine monitoring constituting a significant facet of precision agriculture. The evolution of intelligent agriculture in recent years has significantly facilitated the integration of drone flight monitoring tools and innovative systems, leveraging deep learning to interpret bovine behavior. Smart drones, outfitted with monitoring systems, have evolved into viable solutions for wildlife protection and monitoring as well as animal husbandry. Nevertheless, challenges arise under actual and multifaceted ranch conditions, where scale alterations, unpredictable movements, and occlusions invariably influence the accurate tracking of unmanned aerial vehicles (UAVs). To address these challenges, this manuscript proposes a tracking algorithm based on deep learning, adhering to the Joint Detection Tracking (JDT) paradigm established by the CenterTrack algorithm. This algorithm is designed to satisfy the requirements of multi-objective tracking in intricate practical scenarios. In comparison with several preeminent tracking algorithms, the proposed Multi-Object Tracking (MOT) algorithm demonstrates superior performance in Multiple Object Tracking Accuracy (MOTA), Multiple Object Tracking Precision (MOTP), and IDF1. Additionally, it exhibits enhanced efficiency in managing Identity Switches (ID), False Positives (FP), and False Negatives (FN). This algorithm proficiently mitigates the inherent challenges of MOT in complex, livestock-dense scenarios.

Effect of luteolin on glioblastoma's immune microenvironment and tumor growth suppression.

BACKGROUND: Glioblastoma is the most malignant and prevalent primary human brain tumor, and the immunological microenvironment controlled by glioma stem cells is one of the essential elements contributing to its malignancy. The use of medications to ameliorate the tumor microenvironment may give a new approach for glioma treatment. METHODS: Glioma stem cells were separated from clinical patient-derived glioma samples for molecular research. Other studies, including CCK8, EdU, Transwell, and others, supported luteolin's ability to treat glioma progenitor cells. Network pharmacology and molecular docking models were used to study the drug target, and qRT-PCR, WB, and IF were used to evaluate the molecular mechanism. Intracranial xenografts were examined using HE and IHC, while macrophage polarization was examined using FC. RESULTS: We originally discovered that luteolin inhibits glioma stem cells. IL6 released by glioma stem cells is blocked during medication action and inhibits glioma stem cell proliferation and invasion via the IL6/STAT3 signaling pathway. Additionally, luteolin inhibits the secretion of TGFß1, affects the polarization function of macrophages in the microenvironment, inhibits the polarization of M2 macrophages in TAM, and further inhibits various functions of glioma stem cells by affecting the IL6/STAT3 signaling pathway, luteolin crosstalk TGFß1/SMAD3 signaling pathway, and so on. CONCLUSIONS: Through the suppression of the immunological microenvironment and inhibition of the IL6/STAT3 signaling pathway, our study determined the inhibitory effect of luteolin on glioma stem cells. This medication's dual inhibitory action, which has a significant negative impact on the glioma stem cells' malignant process, makes it both a viable anti-glioma medication and a candidate for targeted glioma microenvironment therapy.

Association of Sleep Pattern and Genetic Susceptibility with Obstructive Sleep Apnea: A Prospective Analysis of the UK Biobank.

Purpose: The prevalence of obstructive sleep apnea (OSA) is high worldwide. This study aimed to quantify the relationship between the incidence of OSA and sleep patterns and genetic susceptibility. Methods: A total of 355,133 white British participants enrolled in the UK Biobank between 2006 and 2010 with follow-up data until September 2021 were recruited. We evaluated sleep patterns using a customized sleep scoring method based on the low-risk sleep phenotype, defined as follows: morning chronotype, 7-8 hours of sleep per day, never/rarely experience insomnia, no snoring, no frequent daytime sleepiness, never/rarely nap, and easily getting up early. The polygenic risk score was calculated to assess genetic susceptibility to OSA. Cox proportional hazard models were used to evaluate the associations between OSA and sleep patterns and genetic susceptibility. Results: During a mean follow-up of 12.57 years, 4618 participants were diagnosed with OSA (age: 56.83 ± 7.69 years, women: 31.3%). Compared with those with a poor sleep pattern, participants with a normal (HR: 0.42, 95% CI: 0.38-0.46), ideal (HR: 0.21, 95% CI: 0.19-0.24), or optimal (HR: 0.15, 95% CI: 0.12-0.18) sleep pattern were significantly more likely to have OSA. The genetic susceptibility of 173,239 participants was calculated, and the results showed that poor (HR: 3.67, 95% CI: 2.95-4.57) and normal (HR: 1.89, 95% CI: 1.66-2.16) sleep patterns with high genetic susceptibility can increase the risk for OSA. Conclusion: This large-scale prospective study provides evidence suggesting that sleep patterns across seven low-risk sleep phenotypes may protect against OSA in individuals with varying degrees of genetic susceptibility.

PM2.5-induced cellular senescence drives brown adipose tissue impairment in middle-aged mice.

Airborne fine particulate matter (PM2.5) exposure is closely associated with metabolic disturbance, in which brown adipose tissue (BAT) is one of the main contributing organs. However, knowledge of the phenotype and mechanism of PM2.5 exposure-impaired BAT is quite limited. In the study, male C57BL/6 mice at three different life phases (young, adult, and middle-aged) were simultaneously exposed to concentrated ambient PM2.5 or filtered air for 8 weeks using a whole-body inhalational exposure system. H&E staining and high-resolution respirometry were used to assess the size of adipocytes and mitochondrial function. Transcriptomics was performed to determine the differentially expressed genes in BAT. Quantitative RT-PCR, immunohistochemistry staining, and immunoblots were performed to verify the transcriptomics and explore the mechanism for BAT mitochondrial dysfunction. Firstly, PM2.5 exposure caused altered BAT morphology and mitochondrial dysfunction in middle-aged but not young or adult mice. Furthermore, PM2.5 exposure increased cellular senescence in BAT of middle-aged mice, accompanied by cell cycle arrest, impaired DNA replication, and inhibited AKT signaling pathway. Moreover, PM2.5 exposure disrupted apoptosis and autophagy homeostasis in BAT of middle-aged mice. Therefore, BAT in middle-aged mice was more vulnerable to PM2.5 exposure, and the cellular senescence-initiated apoptosis, autophagy, and mitochondrial dysfunction may be the mechanism of PM2.5 exposure-induced BAT impairment.

Controlled release of vitamin A palmitate from crosslinked cyclodextrin organic framework for dry eye disease therapy.

Controlled release drug delivery systems of eye drops are a promising ophthalmic therapy with advantages of good patient compliance and low irritation. However, the lack of a suitable drug carrier for ophthalmic use limits the development of the aforementioned system. Herein, the crosslinked cyclodextrin organic framework (COF) with a cubic porous structure and a uniform particle size was synthesized and applied to solidify vitamin A palmitate (VAP) by using the solvent-free method. The VAP@COF suspension eye drops were formulated by screening co-solvents, suspending agents, and stabilizing agents to achieve a homogeneous state and improve stability. According to the in vitro release study, the VAP@COF suspension exhibited a controlled release of VAP within 12 h. Both the ex vivo corneal contact angle and in vivo fluorescence tracking indicated that the VAP@COF suspension prolonged the VAP residence time on the ocular surface. This suspension accelerated the recovery of the dry eye disease (DED) model in New Zealand rabbits. Furthermore, the suspension was non-cytotoxic to human corneal epithelial cells and non-irritation to rabbit eyes. In summary, the particulate COF is an eye-acceptable novel carrier that sustains release and prolongs the VAP residence time on the ocular surface for DED treatment.

First-principles studies on the electronic and contact properties of monolayer Ga2STe-metal contacts.

Monolayer (ML) Janus III-VI compounds have attracted the use of multiple competitive platforms for future-generation functional electronics, including non-volatile memories, field effect transistors, and sensors. In this work, the electronic and interfacial properties of ML Ga2STe-metal (Au, Ag, Cu, and Al) contacts are systematically investigated using first-principles calculations combined with the non-equilibrium Green's function method. The ML Ga2STe-Au/Ag/Al contacts exhibit weak electronic orbital hybridization at the interface, while the ML Ga2STe-Cu contact exhibits strong electronic orbital hybridization. The Te surface is more conducive to electron injection than the S surface in ML Ga2STe-metal contact. Quantum transport calculations revealed that when the Te side of the ML Ga2STe is in contact with Au, Ag and Cu electrodes, p-type Schottky contacts are formed. When in contact with the Al electrode, an n-type Schottky contact is formed with an electron SBH of 0.079 eV. When the S side of ML Ga2STe is in contact with Au and Al electrodes, p-type Schottky contacts are formed, and when it is in contact with Ag and Cu electrodes, n-type Schottky contacts are formed. Our study will guide the selection of appropriate metal electrodes for constructing ML Ga2STe devices.

How would autonomous vehicles behave in real-world crash scenarios?

Autonomous Vehicles (AVs) have the potential to revolutionize transportation systems by enhancing traffic safety. Safety testing is undoubtedly a critical step for enabling large-scale deployment of AVs. High-risk scenarios are particularly important as they pose significant challenges and provide valuable insights into the driving capabilities of AVs. This study presents a novel approach to assess the safety of AVs using in-depth crash data, with a particular focus on real-world crash scenarios. First, based on the high-definition video recording of the whole process prior to the crash occurrences, 453 real-world crashes involving 596 passenger cars from China In-depth Mobility Safety Study-Traffic Accident (CIMSS-TA) database were reconstructed. Pertinent static and dynamic elements needed for the construction of the testing scenarios were extracted. Subsequently, 596 testing scenarios were created via each passenger car's perspective within the simulation platform. Following this, each of the crash-involved passenger cars was replaced with Baidu Apollo, a famous automated driving system (ADS), for counterfactual simulation. Lastly, the safety performance of the AV was assessed using the simulation results. A logit model was utilized to identify the fifteen crucial scenario elements that have significant impacts on the test results. The findings demonstrated that the AV could avoid 363 real-world crashes, accounting for approximately 60.91% of the total, and effectively mitigated injuries in the remaining 233 unavoidable scenarios compared to a human driver. Moreover, the AV maintain a smoother speed in most of the scenarios. The common feature of these unavoidable scenarios is that the AV is in a passive state, and the crashes are not caused by the AV violating traffic rules, but rather caused by abnormal behavior exhibited by the human drivers. Additionally, seven specific scenarios have been identified wherein AVs are unable to avoid a crash. These findings demonstrate that, compared to human drivers, AVs can avoid crashes that are difficult for humans to avoid, thereby enhancing traffic safety.

Analysis of blood methylation quantitative trait loci in East Asians reveals ancestry-specific impacts on complex traits.

Methylation quantitative trait loci (mQTLs) are essential for understanding the role of DNA methylation changes in genetic predisposition, yet they have not been fully characterized in East Asians (EAs). Here we identified mQTLs in whole blood from 3,523 Chinese individuals and replicated them in additional 1,858 Chinese individuals from two cohorts. Over 9% of mQTLs displayed specificity to EAs, facilitating the fine-mapping of EA-specific genetic associations, as shown for variants associated with height. Trans-mQTL hotspots revealed biological pathways contributing to EA-specific genetic associations, including an ERG-mediated 233 trans-mCpG network, implicated in hematopoietic cell differentiation, which likely reflects binding efficiency modulation of the ERG protein complex. More than 90% of mQTLs were shared between different blood cell lineages, with a smaller fraction of lineage-specific mQTLs displaying preferential hypomethylation in the respective lineages. Our study provides new insights into the mQTL landscape across genetic ancestries and their downstream effects on cellular processes and diseases/traits.

Transcriptomic Analysis of PDCoV-Infected HIEC-6 Cells and Enrichment Pathways PI3K-Akt and P38 MAPK.

Porcine Deltacoronavirus (PDCoV) is a newly identified coronavirus that causes severe intestinal lesions in piglets. However, the understanding of how PDCoV interacts with human hosts is limited. In this study, we aimed to investigate the interactions between PDCoV and human intestinal cells (HIEC-6) by analyzing the transcriptome at different time points post-infection (12 h, 24 h, 48 h). Differential gene analysis revealed a total of 3560, 5193, and 4147 differentially expressed genes (DEGs) at 12 h, 24 h, and 48 h, respectively. The common genes among the DEGs at all three time points were enriched in biological processes related to cytokine production, extracellular matrix, and cytokine activity. KEGG pathway analysis showed enrichment of genes involved in the p53 signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway. Further analysis of highly expressed genes among the DEGs identified significant changes in the expression levels of BUB1, DDIT4, ATF3, GBP2, and IRF1. Comparison of transcriptome data at 24 h with other time points revealed 298 DEGs out of a total of 6276 genes. KEGG analysis of these DEGs showed significant enrichment of pathways related to viral infection, specifically the PI3K-Akt and P38 MAPK pathways. Furthermore, the genes EFNA1 and KITLG, which are associated with viral infection, were found in both enriched pathways, suggesting their potential as therapeutic or preventive targets for PDCoV infection. The enhancement of PDCoV infection in HIEC-6 was observed upon inhibition of the PI3K-Akt and P38 MAPK signaling pathways using sophoridine. Overall, these findings contribute to our understanding of the molecular mechanisms underlying PDCoV infection in HIEC-6 cells and provide insights for developing preventive and therapeutic strategies against PDCoV infection.