Mechanism of Zhenwu Decoction modulating TLR4/NF-κB/HIF-1α loop through miR-451 to delay renal fibrosis in type 2 CRS.

BACKGROUND: Type 2 cardiorenal syndrome (CRS) is a progressive renal insufficiency in patients with chronic heart failure, but its pathophysiology is still unclear. The Chinese medicine Zhenwu Decoction plays an important role in the prevention and treatment of 2-CRS, however, its mechanism of action remains unknown. PURPOSE: The aim of this study was to investigate whether the ameliorative effect of ZWD on 2-CRS renal fibrosis is related to the modulation of miR-451 expression and thus mediating the TLR4/NF-κB/HIF-1α loop. STUDY DESIGN AND METHODS: A type 2 CRS rat model was constructed using ligation of the left anterior descending branch of the coronary artery + 3/4 nephrectomy, and randomly divided into Control, Sham, Model, Captopril, ZWD-L, ZWD-M and ZWD-H groups.After 4 weeks of ZWD intervention, its effects on cardiac and renal functions of type 2 CRS rats were observed by hematuria and cardiac ultrasonography. Changes in kidney tissue morphology were observed by HE, Masson and PASM staining. The protein and mRNA expression of TLR4, NF-κB, HIF-1α and IκBα in kidney tissues were detected by immunohistochemistry and qPCR. Immunofluorescence was used to detect the protein expression of NF-κB and HIF-1α in renal tissues. Western blot and qPCR were used to detect the protein expression of MCP-1, ICAM-1, IL-1ß, IL-6, TGF-ß, α-SMA, FN, Smad2, Smad3, and E-cadherin in renal tissues. PCR was used to detect the protein expression of miR-451mRNA expression level in kidney tissues. RESULTS: In this study, we found that ZWD was able to reduce the expression of Scr, BUN, NT-proBNP, and 24-hour quantitative urine protein, elevate LVEF, FS, CO, and reduce the level of LVIDS in type 2 CRS rats, as well as attenuate renal interstitial fibrosis and improve tubular swelling. In addition, Zhenwu Decoction up-regulated the expression of miR-451 in renal tissues and inhibited the expression of TLR4, NF-κB, and HIF-1α proteins and genes, which in turn inhibited the expression of inflammatory factors and fibrosis-related factors. CONCLUSION: ZWD was able to up-regulate the expression of miR-451 in renal tissues, inhibit the TLR4/NF-κB/HIF-1α response loop, and then inhibit the expression of inflammatory factors and fibrosis-related factors, improve renal fibrosis, and delay the pathological process of type 2 CRS.

DNA Framework-Guided Self-Limiting Aggregation for Highly Luminescent Metal Cluster Nanoaggregates.

The photoluminescent properties of atomically precise metal nanoclusters (MCs) have garnered significant attention in the fields of chemical sensing and biological imaging. However, the limited brightness of single-component nanoclusters hinders their practical applications, and the conventional ligand engineering approaches have proven insufficient in enhancing the emission efficiency of MCs. Here, we present a DNA framework-guided strategy to prepare highly luminescent metal cluster nanoaggregates. Our approach involves an amphiphilic DNA framework comprising a hydrophobic alkyl core and a rigid DNA framework shell, serving as a nucleation site and providing well-defined nanoconfinements for the self-limiting aggregation of MCs. Through this method, we successfully produced homogeneous MC nanoaggregates (10.1 ± 1.2 nm) with remarkable nanoscale precision. Notably, this strategy proves adaptable to various MCs, leading to a substantial enhancement in emission and quantum yield, up to 3011- and 87-fold, respectively. Furthermore, our investigation using total internal reflection fluorescence microscopy at the single-particle level uncovered a more uniform photon number distribution and higher photostability for MC nanoaggregates compared to template-free counterparts. This DNA-templating strategy introduces a conceptually innovative approach for studying the photoluminescent properties of aggregates with nanoscale precision and holds promise for constructing highly luminescent MC nanoparticles for diverse applications.

A panoramic driving perception fusion algorithm based on multi-task learning.

With the rapid development of intelligent connected vehicles, there is an increasing demand for hardware facilities and onboard systems of driver assistance systems. Currently, most vehicles are constrained by the hardware resources of onboard systems, which mainly process single-task and single-sensor data. This poses a significant challenge in achieving complex panoramic driving perception technology. While the panoramic driving perception algorithm YOLOP has achieved outstanding performance in multi-task processing, it suffers from poor adaptability of feature map pooling operations and loss of details during downsampling. To address these issues, this paper proposes a panoramic driving perception fusion algorithm based on multi-task learning. The model training involves the introduction of different loss functions and a series of processing steps for lidar point cloud data. Subsequently, the perception information from lidar and vision sensors is fused to achieve synchronized processing of multi-task and multi-sensor data, thereby effectively improving the performance and reliability of the panoramic driving perception system. To evaluate the performance of the proposed algorithm in multi-task processing, the BDD100K dataset is used. The results demonstrate that, compared to the YOLOP model, the multi-task learning network performs better in lane detection, drivable area detection, and vehicle detection tasks. Specifically, the lane detection accuracy improves by 11.6%, the mean Intersection over Union (mIoU) for drivable area detection increases by 2.1%, and the mean Average Precision at 50% IoU (mAP50) for vehicle detection improves by 3.7%.

Integrating Image Analysis and Machine Learning for Moisture Prediction and Appearance Quality Evaluation: A Case Study of Kiwifruit Drying Pretreatment.

The appearance of dried fruit clearly influences the consumer's perception of the quality of the product but is a subtle and nuanced characteristic that is difficult to quantitatively measure, especially online. This paper describes a method that combines several simple strategies to assess a suitable surrogate for the elusive quality using imaging, combined with multivariate statistics and machine learning. With such a convenient tool, this study also shows how one can vary the pretreatments and drying conditions to optimize the resultant product quality. Specifically, an image batch processing method was developed to extract color (hue, saturation, and value) and morphological (area, perimeter, and compactness) features. The accuracy of this method was verified using data from a case study experiment on the pretreatment of hot-air-dried kiwifruit slices. Based on the extracted image features, partial least squares and random forest models were developed to satisfactorily predict the moisture ratio (MR) during drying process. The MR of kiwifruit slices during drying could be accurately predicted from changes in appearance without using any weighing device. This study also explored determining the optimal drying strategy based on appearance quality using principal component analysis. Optimal drying was achieved at 60 °C with 4 mm thick slices under ultrasonic pretreatment. For the 70 °C, 6 mm sample groups, citric acid showed decent performance.

Ceria Quantum Dot Filler-Modified Polymer Electrolytes for Three-Dimensional-Printed Sodium Solid-State Batteries.

Solid polymer electrolytes have been considered as promising candidates for solid-state batteries (SSBs), owing to their excellent interfacial compatibility and high mechanical toughness; however, they suffer from intrinsic low ionic conductivity (lower than 10-6 S/cm) and large thickness (usually surpassed over 100 µm or even 500 µm), which has a negative influence on the interface resistance and ionic migration. In this work, ceria quantum dot (CQD)-modified composite polymer electrolyte (CPE) membranes with a thickness of 20 µm were successfully manufactured via 3D printing technology. The CQD fillers can reduce the crystallinity of the polymer, and the oxygen vacancies on CQDs can facilitate the dissociation of ion pairs in the NaTFSI salt to release more free Na+, improving the ionic conductivity. Meanwhile, tailoring the thickness of the CPE-CQDs membrane via 3D printing can further promote the migration and transport of Na+. Furthermore, the printed NNM//CPE-CQDs//Na SSB exhibited outstanding rate capability and cycling stability. The combination of CQD modification and thickness tailoring through 3D printing paves a new avenue for achieving high performance solid electrolyte membranes for practical application in Na SSBs.

Chlorine-Rich Na6-xPS5-xCl1+x: A Promising Sodium Solid Electrolyte for All-Solid-State Sodium Batteries.

Developing argyrodite-type, chlorine-rich, sodium-ion, solid-state electrolytes with high conductivity is a long-term challenge that is crucial for the advancement of all-solid-state batteries (ASSBs). In this study, chlorine-rich, argyrodite-type Na6-xPS5-xCl1+x solid solutions were successfully developed with a solid solution formation range of 0 ≤ x ≤ 0.5. Na5.5PS4.5Cl1.5 (x = 0.5), displaying a highest ionic conductivity of 1.2 × 10-3 S/cm at 25 °C, which is more than a hundred times higher than that of Na6PS5Cl. Cyclic voltammetry and electrochemical impedance spectroscopy results demonstrated that the rich chlorine significantly enhanced the ionic conductivity and electrochemical stability, in addition to causing a reduction in activation energy. The Na5.5PS4.5Cl1.5 composite also showed the characteristics of a pure ionic conductor without electronic conductivity. Finally, the viability of Na5.5PS4.5Cl1.5 as a sodium electrolyte for all-solid-state sodium batteries was checked in a lab-scale ASSB, showing stable battery performance. This study not only demonstrates new composites of sodium-ionic, solid-state electrolytes with relatively high conductivity but also provides an anion-modulation strategy to enhance the ionic conductivity of argyrodite-type sodium solid-state ionic conductors.

Analysis of Changes of Ang-2 and TNF-α Levels in Patients with AMI Complicated with Pulmonary Infection and Drug Resistance of Infectious Pathogens.

Objective: This study aimed to investigate the changes in angiopoietin-2 and tumor necrosis factor α levels in patients with acute myocardial infarction complicated with pulmonary infection. Methods: Retrospective selection was conducted on 61 patients with acute myocardial infarction complicated with pulmonary infection and 122 patients with simple acute myocardial infarction. A comparison was made between the two groups regarding general information and serum myocs. The distribution and drug resistance of pathogenic bacteria were also explored. Results: The study showed significant differences in the duration of alcohol consumption, the proportion of diabetes mellitus, and levels of certain markers (serum cardiac troponin T, creatine kinase isoenzyme, myoglobin, angiopoietin-2, tumor necrosis factor α) between the two groups (P < .05). Logistic regression analysis identified elevated levels of serum angiopoietin-2 and tumor necrosis factor α, along with diabetes mellitus, as independent risk factors for acute myocardial infarction complicated with pulmonary infection (P < .05). Pearson correlation analysis demonstrated a positive correlation between serum angiopoietin-2 and tumor necrosis factor α levels and CPI scores in patients (P < .05). ROC curve analysis indicated that combined diagnosis of serum angiopoietin-2 and tumor necrosis factor α had an AUC of 0.867, with a sensitivity of 85.25% and specificity of 77.87% for detecting acute myocardial infarction complicated with pulmonary infection. Among the sputum culture specimens, gram-negative bacteria accounted for 55.34%, gram-positive bacteria for 39.81%, and fungi for 4.85%. Gram-negative bacteria like Klebsiella pneumoniae and Escherichia coli showed high resistance to various antibiotics, while gram-positive bacteria like Streptococcus pneumoniae and Staphylococcus aureus had relatively low resistance to specific antibiotics. Conclusion: Gram-negative bacteria were the main pathogens and exhibited resistance to several antibiotics. Increased levels of angiopoietin-2 and tumor necrosis factor α were observed. Early detection of these markers can assist in the clinical diagnosis and guide the appropriate use of antibiotics.

Global research trends and emerging opportunities for integrin adhesion complexes in cardiac repair: a scientometric analysis.

Objective: Cardiac regenerative medicine has gained significant attention in recent years, and integrins are known to play a critical role in mediating cardiac development and repair, especially after an injury from the myocardial infarction (MI). Given the extensive research history and interdisciplinary nature of this field, a quantitative retrospective analysis and visualization of related topics is necessary. Materials and methods: We performed a scientometric analysis of published papers on cardiac integrin adhesion complexes (IACs), including analysis of annual publications, disciplinary evolution, keyword co-occurrence, and literature co-citation. Results: A total of 2,664 publications were finally included in the past 20 years. The United States is the largest contributor to the study and is leading this area of research globally. The journal Circulation Research attracts the largest number of high-quality publications. The study of IACs in cardiac repair/regenerative therapies involves multiple disciplines, particularly in materials science and developmental biology. Keywords of research frontiers were represented by Tenasin-C (2019-2023) and inflammation (2020-2023). Conclusion: Integrins are topics with ongoing enthusiasm in biological development and tissue regeneration. The rapidly emerging role of matricellular proteins and non-protein components of the extracellular matrix (ECM) in regulating matrix structure and function may be a further breakthrough point in the future; the emerging role of IACs and their downstream molecular signaling in cardiac repair are also of great interest, such as induction of cardiac proliferation, differentiation, maturation, and metabolism, fibroblast activation, and inflammatory modulation.

The Phenotypic and Genotypic Spectrum of CSF1R-Related Disorder in China.

BACKGROUND: Colony-stimulating factor 1 receptor (CSF1R)-related disorder (CRD) is a rare autosomal dominant disease. The clinical and genetic characteristics of Chinese patients have not been elucidated. OBJECTIVE: The objective of the study is to clarify the core features and influence factors of CRD patients in China. METHODS: Clinical and genetic-related data of CRD patients in China were collected. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Sundal MRI Severity Score were evaluated. Whole exome sequencing was used to analyze the CSF1R mutation status. Patients were compared between different sexes, mutation types, or mutation locations. RESULTS: A total of 103 patients were included, with a male-to-female ratio of 1:1.51. The average age of onset was (40.75 ± 8.58). Cognitive impairment (85.1%, 86/101) and parkinsonism (76.2%, 77/101) were the main clinical symptoms. The most common imaging feature was bilateral asymmetric white matter changes (100.0%). A total of 66 CSF1R gene mutants (22 novel mutations) were found, and 15 of 92 probands carried c.2381 T > C/p.I794T (16.30%). The MMSE and MoCA scores (17.0 [9.0], 11.90 ± 7.16) of female patients were significantly lower than those of male patients (23.0 [10.0], 16.36 ± 7.89), and the white matter severity score (20.19 ± 8.47) of female patients was significantly higher than that of male patients (16.00 ± 7.62). There is no statistical difference in age of onset between male and female patients. CONCLUSIONS: The core manifestations of Chinese CRD patients are progressive cognitive decline, parkinsonism, and bilateral asymmetric white matter changes. Compared to men, women have more severe cognitive impairment and imaging changes. c.2381 T > C/p.I794T is a hotspot mutation in Chinese patients. © 2024 International Parkinson and Movement Disorder Society.

Clinical and Genetic Spectrum in a Large Cohort of Hereditary Spastic Paraplegia.

BACKGROUND: Next-generation sequencing-based molecular assessment has benefited the diagnosis of hereditary spastic paraplegia (HSP) subtypes. However, the clinical and genetic spectrum of HSP due to large fragment deletions/duplications has yet to be fully defined. OBJECTIVE: We aim to better characterize the clinical phenotypes and genetic features of HSP and to provide new thoughts on diagnosis. METHODS: Whole-exome sequencing (WES) was performed in patients with clinically suspected HSP, followed by multiple ligation-dependent probe amplification (MLPA) sequentially carried out for those with negative findings in known causative genes. Genotype-phenotype correlation analyses were conducted under specific genotypes. RESULTS: We made a genetic diagnosis in 60% (162/270) of patients, of whom 48.9% (132/270) had 24 various subtypes due to point mutations (SPG4/SPG11/SPG35/SPG7/SPG10/SPG5/SPG3A/SPG2/SPG76/SPG30/SPG6/SPG9A/SPG12/SPG15/SPG17/SPG18/SPG26/SPG49/SPG55/SPG56/SPG57/SPG62/SPG78/SPG80). Thirty patients were found to have causative rearrangements by MLPA (11.1%), among which SPG4 was the most prevalent (73.3%), followed by SPG3A (16.7%), SPG6 (3.3%), SPG7 (3.3%), and SPG11 (3.3%). Clinical analysis showed that some symptoms were often related to specific subtypes, and rearrangement-related SPG3A patients seemingly had later onset. We observed a presumptive anticipation among SPG4 and SPG3A families due to rearrangement. CONCLUSIONS: Based on the largest known Asian HSP cohort, including the largest subgroup of rearrangement-related pedigrees, we gain a comprehensive understanding of the clinical and genetic spectrum of HSP. We propose a diagnostic flowchart to sequentially detect the causative genes in practice. Large fragment mutations account for a considerable proportion of HSP, and thus, MLPA screening acts as a beneficial supplement to routine WES. © 2024 International Parkinson and Movement Disorder Society.

Monomeric CXCL12-Engineered Adipose-Derived Stem Cells Transplantation for the Treatment of Ischemic Stroke.

Adipose-derived stem cells (ASCs) possess therapeutic potential for ischemic brain injury, and the chemokine CXCL12 has been shown to enhance their functional properties. However, the cumulative effects of ASCs when combined with various structures of CXCL12 on ischemic stroke and its underlying molecular mechanisms remain unclear. In this study, we genetically engineered mouse adipose-derived ASCs with CXCL12 variants and transplanted them to the infarct region in a mice transient middle cerebral artery occlusion (tMCAO) model of stroke. We subsequently compared the post-ischemic stroke efficacy of ASC-mCXCL12 with ASC-dCXCL12, ASC-wtCXCL12, and unmodified ASCs. Neurobehavior recovery was assessed using modified neurological severity scores, the hanging wire test, and the elevated body swing test. Changes at the tissue level were evaluated through cresyl violet and immunofluorescent staining, while molecular level alterations were examined via Western blot and real-time PCR. The results of the modified neurological severity score and cresyl violet staining indicated that both ASC-mCXCL12 and ASC-dCXCL12 treatment enhanced neurobehavioral recovery and mitigated brain atrophy at the third and fifth weeks post-tMCAO. Additionally, we observed that ASC-mCXCL12 and ASC-dCXCL12 promoted angiogenesis and neurogenesis, accompanied by an increased expression of bFGF and VEGF in the peri-infarct area of the brain. Notably, in the third week after tMCAO, the ASC-mCXCL12 exhibited superior outcomes compared to ASC-dCXCL12. However, when treated with the CXCR4 antagonist AMD3100, the beneficial effects of ASC-mCXCL12 were reversed. The AMD3100-treated group demonstrated worsened neurological function, aggravated edema volume, and brain atrophy. This outcome is likely attributed to the interaction of monomeric CXCL12 with CXCR4, which regulates the recruitment of bFGF and VEGF. This study introduces an innovative approach to enhance the therapeutic potential of ASCs in treating ischemic stroke by genetically engineering them with the monomeric structure of CXCL12.

Self-Biased Magneto-Electric Antenna for Very-Low-Frequency Communications: Exploiting Magnetization Grading and Asymmetric Structure-Induced Resonance.

VLF magneto-electric (ME) antennas have gained attention for their compact size and high radiation efficiency in lossy conductive environments. However, the need for a large DC magnetic field bias presents challenges for miniaturization, limiting portability. This study introduces a self-biased ME antenna with an asymmetric design using two magneto materials, inducing a magnetization grading effect that reduces the resonant frequency during bending. Operating principles are explored, and performance parameters, including the radiation mechanism, intensity and driving power, are experimentally assessed. Leveraging its excellent direct and converse magneto-electric effect, the antenna proves adept at serving as both a transmitter and a receiver. The results indicate that, at 2.09 mW and a frequency of 24.47 kHz, the antenna has the potential to achieve a 2.44 pT magnetic flux density at a 3 m distance. A custom modulation-demodulation circuit is employed, applying 2ASK and 2PSK to validate communication capability at baseband signals of 10 Hz and 100 Hz. This approach offers a practical strategy for the lightweight and compact design of VLF communication systems.

Intracardiac metastasis of gestational choriocarcinoma: a case report and literature review.

INTRODUCTION: Gestational trophoblastic neoplasia (GTN) with intracardiac metastasis is rare, and here we reported a patient with intracardiac metastasis of high-risk and refractory gestational choriocarcinoma and reviewed relevant literatures. CASE PRESENTATION: A 37-year-old woman presented with vaginal bleeding and high level of ß-human chorionic gonadotropin (ß-hCG) at 199,060 (mIU/mL). It was clinically diagnosed with gestational choriocarcinoma. The patient initially received eight cycles of chemotherapy but unsatisfactory response was observed, and the level of ß-hCG still ranged between 5000 and 10,000. Then there was found intracardiac masses in the right atrium (2.6*1.7 cm), anterior chordae tendineae of the tricuspid valve (1.4*0.7 cm) and the right ventricle (4.1*2.9 cm) by ultrasonic cardiogram (UCG). PET/CT highly suspected the intracardiac metastasis of choriocarcinoma (SUVmax = 9.3) and no disease was found in the lung and pelvis. The patient undertook complete intracardiac masses resection. The pathology confirmed the intracardiac metastasis of disease. After a week of operation, the UCG found a 5.4*4.2 cm mass in the right atrium again. Considering the poor prognosis, the patient received palliative care and eventually died of disease progression. CONCLUSION: Intracardiac metastasis of GTN is an aggressive sign of disease. Patients can benefit from chemotherapy and surgery. Future investigation of PD-1 immunotherapy combines with chemotherapy are expected to improve the prognosis in this group of patients.

Dynamic driving risk in highway tunnel groups based on pupillary oscillations.

This study aims to understand the dynamic changes in driving risks in highway tunnel groups. Real-world driving experiments were conducted, collecting pupil area data to measure pupil size oscillations using the Percentage of Pupil Area Variable (PPAV) metric. The analysis focused on investigating relative pupil size fluctuations to explore trends in driving risk fluctuations within tunnel groups. The objective was to identify accident-prone areas and key factors influencing driving risks, providing insights for safety improvements. The findings revealed an overall "whipping effect" phenomenon in driving risk changes within tunnel groups. Differences were observed between interior tunnel areas and open sections, including adjacent, approach, and departure zones. Higher driving risks were associated with locations closer to the tail end of the tunnel group and shorter exit departure sections. Targeted safety improvement designs should consider fluctuation patterns in different directions, with attention to tunnels at the tail end. In open sections, increased travel distance and lengths of upstream and downstream tunnels raised driving risks, while longer open zones improved driving risks. Driving direction and sequence had minimal impact on risks. By integrating driver vision, tunnel characteristics, and the environment, this study identified high-risk areas and critical factors, providing guidance for monitoring and improving driving risks in tunnel groups. The findings have practical implications for the operation and safety management of tunnel groups.

Engineered exosomes mediated targeted delivery of neuroprotective peptide NR2B9c for the treatment of traumatic brain injury.

Neuroprotection is one of the core treatment strategies for brain injuries including traumatic brain injury (TBI). NR2B9c is a promising neuroprotective peptide but its clinical translation is limited because of poor brain penetrability. Exosomes are naturally occurring nanovesicles having therapeutic potential for TBI as well as an efficient drug delivery carrier to the brain. Here, we engineered exosomes with neuron targeting peptide rabies virus glycoprotein (RVG29) via bio-orthogonal click chemistry technique and loaded it with NR2B9c, developing RVG-ExoNR2B9c. RVG29 conjugated exosome had higher neuron targeting efficiency compared to naïve exosomes both in vivo and in vitro. RVG-ExoNR2B9c had great cytoprotective effect against oxygen glucose deprived Neuro2a cells. Intravenous administration of RVG-ExoNR2B9c significantly improved behavioral outcomes and reduced the lesion volume after TBI injury in a mice controlled cortical impact model. Due to their multifunctionality and significant efficacy, we anticipate that RVG-ExoNR2B9c have the potential to be translated both as therapeutic agent as well as cargo delivery system to the brain for the treatment of TBI.

Autologous Transplantation Tooth Guide Design Based on Deep Learning.

BACKGROUND: Autologous tooth transplantation requires precise surgical guide design, involving manual tracing of donor tooth contours based on patient cone-beam computed tomography (CBCT) scans. While manual corrections are time-consuming and prone to human errors, deep learning-based approaches show promise in reducing labor and time costs while minimizing errors. However, the application of deep learning techniques in this particular field is yet to be investigated. PURPOSE: We aimed to assess the feasibility of replacing the traditional design pipeline with a deep learning-enabled autologous tooth transplantation guide design pipeline. STUDY DESIGN, SETTING, SAMPLE: This retrospective cross-sectional study used 79 CBCT images collected at the Guangzhou Medical University Hospital between October 2022 and March 2023. Following preprocessing, a total of 5,070 region of interest images were extracted from 79 CBCT images. PREDICTOR VARIABLE: Autologous tooth transplantation guide design pipelines, either based on traditional manual design or deep learning-based design. MAIN OUTCOME VARIABLE: The main outcome variable was the error between the reconstructed model and the gold standard benchmark. We used the third molar extracted clinically as the gold standard and leveraged it as the benchmark for evaluating our reconstructed models from different design pipelines. Both trueness and accuracy were used to evaluate this error. Trueness was assessed using the root mean square (RMS), and accuracy was measured using the standard deviation. The secondary outcome variable was the pipeline efficiency, assessed based on the time cost. Time cost refers to the amount of time required to acquire the third molar model using the pipeline. ANALYSES: Data were analyzed using the Kruskal-Wallis test. Statistical significance was set at P < .05. RESULTS: In the surface matching comparison for different reconstructed models, the deep learning group achieved the lowest RMS value (0.335 ± 0.066 mm). There were no significant differences in RMS values between manual design by a senior doctor and deep learning-based design (P = .688), and the standard deviation values did not differ among the 3 groups (P = .103). The deep learning-based design pipeline (0.017 ± 0.001 minutes) provided a faster assessment compared to the manual design pipeline by both senior (19.676 ± 2.386 minutes) and junior doctors (30.613 ± 6.571 minutes) (P < .001). CONCLUSIONS AND RELEVANCE: The deep learning-based automatic pipeline exhibited similar performance in surgical guide design for autogenous tooth transplantation compared to manual design by senior doctors, and it minimized time costs.

Network pharmacology and in vivo studies reveal the neuroprotective effects of paeoniflorin on Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that has still not been effectively treated. Paeoniflorin is a traditional Chinese medicine with potential neuroprotective effects against brain injury; however, the beneficial effects and mechanisms of action in AD have not been clarified. We aimed to explore the mechanisms of action of paeoniflorin in AD using network pharmacology and experimental validation. Network pharmacology analysis revealed 30 candidate targets through the intersection of the targets of paeoniflorin and related genes in AD, which were mainly enriched in oxidative stress and inflammation. Moreover, key targets of paeoniflorin against AD, namely Nrf2 (encoded by NFE2L2) and TLR4, were screened and found to be closely related to oxidative stress and inflammation. Subsequent in vivo experiments revealed that paeoniflorin treatment improved the cognition of APP/PS1 mice by ameliorating oxidative stress and neuroinflammation, which were associated with the upregulation of Nrf2 and HO1, and the downregulation of TLR4. Collectively, the present study demonstrates that paeoniflorin alleviates cognitive impairment in AD by regulating oxidative stress and neuroinflammation, and that Nrf2, HO1, and TLR4 could be key targets.

Novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives as potential anticancer agents.

Selenocompounds protect against damage to healthy cells and induce the death of tumor cells by apoptosis; for this reason, they are attractive compounds for cancer research. In the present study, two series of novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives were synthesized, and their anti-proliferation activities were evaluated. Of the 23 compounds synthesized, most showed potent anti-proliferative activity against human cancer cell lines. Specifically, compounds 3h, 3g, and 3h-2, which had a 2- or 4-position halogen substituent on 1-((phenylethynyl)selanyl)-3-phenoxypropan-2-ol, exhibited the best anti-proliferative activity against tumor cells. Flow cytometry demonstrated that 3h, 3g, and 3h-2 induced G2/M phase arrest and apoptosis in A549 cells. Cellular studies demonstrated that the induction of apoptosis by 3h correlated with changes in the expression of cell cycle-related proteins and apoptosis-related proteins. Xenograft tumor experiments in nude mice revealed that compound 3h has antitumor effects in vivo and no evident toxic effects in nude mice. In addition, compound 3h alleviated cisplatin-induced liver and kidney damage. These findings uncover the applicability of compound 3h as a novel lead compound for cancer treatment.

Bio-clickable, small extracellular vesicles-COCKTAIL therapy for ischemic stroke.

Delivering large therapeutic molecules via the blood-brain barrier to treat ischemic stroke remains challenging. NR2B9c is a potent neuroprotective peptide but it's safe and targeted delivery to the brain requires an efficient, natural, and non-immunogenic delivery technique. Small extracellular vesicles (sEVs) have shown great potential as a non-immunogenic, natural cargo delivery system; however, tailoring of its inefficient brain targeting is desired. Here, we coupled rabies virus glycoprotein 29 with sEVs surface via bio-orthogonal click chemistry reactions, followed by loading of NR2B9c, ultimately generating stroke-specific therapeutic COCKTAIL (sEVs-COCKTAIL). Primary neurons and Neuro-2a cells were cultured for in vitro and transient middle cerebral artery occlusion model was used for in vivo studies to evaluate neuron targeting and anti-ischemic stroke potential of the sEVs-COCKTAIL. Bio-clickable sEVs were selectively taken up by neurons but not glial cells. In the in vitro ischemic stroke model of oxygen-glucose deprivation, the sEVs-COCKTAIL exhibited remarkable potential against reactive oxygen species and cellular apoptosis. In vivo studies further demonstrated the brain targeting and increased half-life of bio-clickable sEVs, delivering NR2B9c to the ischemic brain and reducing stroke injury. Treatment with the sEVs-COCKTAIL significantly increased behavioral recovery and reduced neuronal apoptosis after transient middle cerebral artery occlusion. NR2B9c was delivered to neurons binding to post-synaptic density protein-95, inhibiting N-methyl-d-Aspartate receptor-mediated over production of oxidative stress and mitigating protein B-cell lymphoma 2 and P38 proteins expression. Our results provide an efficient and biocompatible approach to a targeted delivery system, which is a promising modality for stroke therapy.

Noncanonical Condensation of Nucleic Acid Chains by Hydrophobic Gold Nanocrystals.

Nucleic acid condensates are essential for various biological processes and have numerous applications in nucleic acid nanotechnology, gene therapy, and mRNA vaccines. However, unlike the in vivo condensation that is dependent on motor proteins, the in vitro condensation efficiency remains to be improved. Here, we proposed a hydrophobic interaction-driven mechanism for condensing long nucleic acid chains using atomically precise hydrophobic gold nanoclusters (Au NCs). We found that hydrophobic Au NCs could condense long single-stranded DNA or RNA to form composites of spherical nanostructures, which further assembled into bead-shaped suprastructures in the presence of excessive Au NCs. Thus, suprastructures displayed gel-like behaviors, and Au NCs could diffuse freely inside the condensates, which resemble the collective motions of condensin complexes inside chromosomes. The dynamic hydrophobic interactions between Au NCs and bases allow for the reversible release of nucleic acids in the presence of mild triggering agents. Our method represents a significant advancement toward the development of more efficient and versatile nucleic acid condensation techniques.