Ultrasound-responsive microfibers promoted infected wound healing with neuro-vascularization by segmented sonodynamic therapy and electrical stimulation.

Bacteria-infected wounds pose challenges to healing due to persistent infection and associated damage to nerves and vessels. Although sonodynamic therapy can help kill bacteria, it is limited by the residual oxidative stress, resulting in prolonged inflammation. To tackle these barriers, novel 4 octyl itaconate-coated Li-doped ZnO/PLLA piezoelectric composite microfibers are developed, offering a whole-course "targeted" treatment under ultrasound therapy. The inclusion of Li atoms causes the ZnO lattice distortion and increases the band gap, enhancing the piezoelectric and sonocatalytic properties of the composite microfibers, collaborated by an aligned PLLA conformation design. During the infection and inflammation stages, the piezoelectric microfibers exhibit spatiotemporal-dependent therapeutic effects, swiftly eliminating over 94.2 % of S. aureus within 15 min under sonodynamic therapy. Following this phase, the microfibers capture reactive oxygen species and aid macrophage reprogramming, restoring mitochondrial function, achieving homeostasis, and shortening inflammation cycles. As the wound progresses through the healing stages, bioactive Zn2+ and Li + ions are continuously released, improving cell recruitment, and the piezoelectrical stimulation enhances wound recovery with neuro-vascularization. Compared to commercially available dressings, our microfibers accelerate the closure of rat wounds (Φ = 15 mm) without scarring in 12 days. Overall, this "one stone, four birds" wound management strategy presents a promising avenue for infected wound therapy.

Insights from Structure-Based Simulations into the Persulfidation of Uridine Diphosphate-Glycosyltransferase71c5 Facilitating the Reversible Inactivation of Abscisic Acid.

The action of abscisic acid (ABA) is closely related to its level in plant tissues. Uridine diphosphate-glycosyltransferase71c5 (UGT71C5) was characterized as a major UGT enzyme to catalyze the formation of the ABA-glucose ester (ABA-GE), a reversible inactive form of free ABA in Arabidopsis thaliana (thale cress). UGTs function in a mode where the catalytic base deprotonates an acceptor to allow a nucleophilic attack at the anomeric center of the donor, achieving the transfer of a glucose moiety. The proteomic data revealed that UGT71C5 can be persulfidated. Herein, an experimental method was employed to detect the persulfidation site of UGT71C5, and the computational methods were further used to identify the yet unknown molecular basis of ABA glycosylation as well as the regulatory role of persulfidation in this process. Our results suggest that the linker and the U-shaped loop are regulatory structural elements: the linker is associated with the binding of uridine diphosphate glucose (UPG) and the U-shaped loop is involved in binding both UPG and ABA.It was also found that it is through tuning the dynamics of the U-shaped loop that is accompanied by the movement of tyrosine (Y388) that the persulfidation of cysteine (C311) leads to the catalytic residue histidine (H16) being in place, preparing for the deprotonation of ABA, and then reorientates UPG and deprotonated ABA closer to the 'Michaelis' complex, facilitating the transfer of a glucose moiety. Ultimately, the persulfidation of UGT71C5 is in favor of ABA glycosylation. Our results provide insights into the molecular details of UGT71C5 recognizing substrates and insights concerning persulfidation as a possible mechanism for hydrogen sulfide (H2S) to modulate the content of ABA, which helps us understand how modulating ABA level strengthens plant tolerance.

Neoadjuvant chemotherapy for primary invasive ductal carcinoma of the nipple: A case report.

Breast cancer typically arises from the terminal duct-lobular unit of the mammary gland and rarely from the ducts inside the nipple. The present paper reports a rare case of primary invasive ductal carcinoma of the papilla, which was a locally advanced triple-negative breast cancer that was treated with 6 cycles of neoadjuvant chemotherapy with a nab-paclitaxel, epirubicin and cyclophosphamide regimen. Surgical pathology confirmed that a pathological complete response was achieved and adjuvant radiotherapy was performed postoperatively. No recurrence or metastasis occurred as of April 2024. A review of previous similar cases revealed that primary invasive breast cancer of the nipple has several manifestations. Changes in the nipple should be treated cautiously and a pathological biopsy should be performed in a timely manner. Breast cancer occurring in the nipple can be treated with reference to the same type of common breast cancer, and neoadjuvant chemotherapy can also be performed first if neoadjuvant chemotherapy is indicated.

A new strategy for the treatment of intracerebral hemorrhage: Ferroptosis.

Intracerebral hemorrhage, is a cerebrovascular disease with high morbidity, mortality, and disability. Due to the lack of effective clinical treatments, the development of new drugs to treat intracerebral hemorrhage is necessary. In recent years, ferroptosis has been found to play an important role in the pathophysiological process of intracerebral hemorrhage, which can be treated by inhibiting ferroptosis and thus intracerebral hemorrhage. This article aims to explain the mechanism of ferroptosis and its relationship to intracerebral hemorrhage. In the meantime, it briefly discusses the molecules identified to alleviate intracerebral hemorrhage by inhibiting ferroptosis, along with other clinical agents that are expected to treat intracerebral hemorrhage through this mechanism. In addition, a brief overview of the morphological alterations of different forms of cell death and their role in ICH is provided. Finally, the challenges that may arise in translating ferroptosis inhibitors from basic research to clinical use are presented. This article serves as a reference and provides insights to aid in the treatment of intracerebral hemorrhage in the clinic.

Emerging trends and hotspots in peptic ulcer from 2008 to 2023: A bibliometric analysis.

Peptic ulcer (PU) is a common digestive disorder in the gastroduodenal. Although bibliometrics has become very popular in the medical field, a bibliometric analysis of research related to PU has yet to be reported. Therefore, this research aims to analyze the trends and hotspots of PU in the last 15 years. Literature data related to PU retrieved from the Web of Science Core Collection database from 2008 to 2023 were visualized and analyzed using CiteSpace 6.1.6.msi, VOSviewer 1.6.19, and SCImago Graphica Beta 1.0.35. Six thousand four hundred ninety-one papers were collected based on inclusion and exclusion criteria. The country with the highest number of publications was China. The institution with the highest number of publications was Baylor College of Medicine. The most prolific author was Yamaoka Yoshio. Malfertheiner Peter had the highest number of citations. The journal with the most publications is World Journal of Gastroenterology. The most cited Journal is Gastroenterology. The most cited reference was published by Marshall B. J. et al in 1984. The article with the highest burst strength was published in 2012 by Malfertheiner Peter. The keyword with the highest burst strength was "oxidative stress." Our research provides a bibliometric analysis of PU research to reveal the trends and hotspots of PU for 2008 to 2023. Our findings will help researchers to quickly understand the current state of research and provide a reference for in-depth studies in this area to foster the development of PU research.

Accurate de novo design of heterochiral protein-protein interactions.

Abiotic D-proteins that selectively bind to natural L-proteins have gained significant biotechnological interest. However, the underlying structural principles governing such heterochiral protein-protein interactions remain largely unknown. In this study, we present the de novo design of D-proteins consisting of 50-65 residues, aiming to target specific surface regions of L-proteins or L-peptides. Our designer D-protein binders exhibit nanomolar affinity toward an artificial L-peptide, as well as two naturally occurring proteins of therapeutic significance: the D5 domain of human tropomyosin receptor kinase A (TrkA) and human interleukin-6 (IL-6). Notably, these D-protein binders demonstrate high enantiomeric specificity and target specificity. In cell-based experiments, designer D-protein binders effectively inhibited the downstream signaling of TrkA and IL-6 with high potency. Moreover, these binders exhibited remarkable thermal stability and resistance to protease degradation. Crystal structure of the designed heterochiral D-protein-L-peptide complex, obtained at a resolution of 2.0 Å, closely resembled the design model, indicating that the computational method employed is highly accurate. Furthermore, the crystal structure provides valuable information regarding the interactions between helical L-peptides and D-proteins, particularly elucidating a novel mode of heterochiral helix-helix interactions. Leveraging the design of D-proteins specifically targeting L-peptides or L-proteins opens up avenues for systematic exploration of the mirror-image protein universe, paving the way for a diverse range of applications.

Construction of a prognostic model for ovarian cancer based on a comprehensive bioinformatics analysis of cuproptosis-associated long non-coding RNA signatures.

Ovarian cancer (OCa) is a common malignancy in women, and the role of cuproptosis and its related genes in OCa is unclear. Using the GSE14407 dataset, we analyzed the expression and correlation of cuproptosis-related genes (CRGs) between tumor and normal groups. From the TCGA-OV dataset, we identified 20 cuproptosis-related long non-coding RNAs (CuLncs) associated with patient survival through univariate Cox analysis. OCa patients were divided into early-stage and late-stage groups to analyze CuLncs expression. Cluster analysis classified patients into two clusters, with Cluster1 having a poorer prognosis. Significant differences in "Lymphatic Invasion" and "Cancer status" were observed between clusters. Seven CRGs showed significant expression differences, validated using the human protein atlas (HPA) databases. Immune analysis revealed a higher ImmuneScore in Cluster1. GSEA identified associated signaling pathways. LASSO regression included 11 CuLncs to construct and validate a survival prediction model, classifying patients into high-risk and low-risk groups. Correlations between riskScore, Cluster phenotype, ImmuneScore, and immune cell infiltration were explored. Cell experiments showed that knocking down AC023644.1 decreases OCa cell viability. In conclusion, we constructed an accurate prognostic model for OCa based on 11 CuLncs, providing a basis for prognosis assessment and potential immunotherapy targets.

Design and Motion Control of Master-Slave Control Endotracheal Intubation Robot.

BACKGROUND: Master-slave remote control technology allows patients to be treated promptly during transport and also reduces the risk of contagious infections. Endotracheal intubation, guided by endoscopy and a master-slave system, enables doctors to perform the procedure efficiently and accurately. METHODS: In this paper, we present the development of a master-slave controlled endotracheal intubation robot (EIR). It is based on operation incremental mapping, a weighted recursive average filtering method to reduce vibration, and a virtual fixture designed to reduce mishandling in minimally invasive surgery. RESULTS: Simulation analysis of the master-slave control demonstrates that the weighted recursive average filtering method effectively reduces vibration, while the virtual fixture assists in confining the operator's movement within a delimited area. Experimental validation confirms the validity of the robot's structural design and control method. CONCLUSIONS: The developed robot successfully achieves the necessary motion for endotracheal intubation surgery through master-slave control.

Diagnostic and prognostic value of double-negative T cells in colorectal cancer.

Objective: To evaluate the T-lymphocyte subset distribution and the diagnostic and prognosis value of double-negative T (DNT) cells in colorectal cancer (CRC). Methods: This retrospective study compared the T-lymphocyte subsets and DNT of 114 patients with CRC with those of 107 healthy controls (HC). The diagnostic potential of DNT and T-lymphocyte subsets was assessed using the receiver operating characteristic (ROC) curve, and prognostic values were evaluated using the Kaplan-Meier curve and the Cox regression model. Results: The percentages of CD8+ T cells and DNT cells, and value of carcinoembryonic antigen (CEA), were remarkably higher in patients with CRC than in those with HC, but the ratio of CD4+/CD8+ was decreased. Using ROC curve analysis, DNT cell percentage, CEA, and CD4+/CD8+ ratio all had good diagnostic efficacy, with areas under the curve (AUCs) of 0.865, 0.786 and 0.624, respectively. The combination of DNT cell percentage and CEA had an AUC of 0.905, which was significantly higher than that of any single biomarker (p < 0.05). In univariate analysis, the Tumor Node Metastasis (TNM) clinical stage, CD4+/CD8+ ratio, and DNT cell percentage were significantly associated with overall survival (OS) (p < 0.05). In multivariate analysis, TNM clinical staging (HR = 2.37, 95 % CI: 1.15-4.90), a decreased CD4+/CD8+ ratio (HR = 0.33, 95 % CI: 0.15-0.74), and an increased DNT cell percentage (HR = 2.29, 95 % CI: 1.11-4.73) were independent prognostic factors for CRC. Conclusion: The percentage of DNT cells may be useful as an evaluation index for CRC diagnosis and prognosis, which was even better when combined with serum CEA.

Highly efficient AlGaN-based deep-ultraviolet light-emitting diodes: from bandgap engineering to device craft.

AlGaN-based light-emitting diodes (LEDs) operating in the deep-ultraviolet (DUV) spectral range (210-280 nm) have demonstrated potential applications in physical sterilization. However, the poor external quantum efficiency (EQE) hinders further advances in the emission performance of AlGaN-based DUV LEDs. Here, we demonstrate the performance of 270-nm AlGaN-based DUV LEDs beyond the state-of-the-art by exploiting the innovative combination of bandgap engineering and device craft. By adopting tailored multiple quantum wells (MQWs), a reflective Al reflector, a low-optical-loss tunneling junction (TJ) and a dielectric SiO2 insertion structure (IS-SiO2), outstanding light output powers (LOPs) of 140.1 mW are achieved in our DUV LEDs at 850 mA. The EQEs of our DUV LEDs are 4.5 times greater than those of their conventional counterparts. This comprehensive approach overcomes the major difficulties commonly faced in the pursuit of high-performance AlGaN-based DUV LEDs, such as strong quantum-confined Stark effect (QCSE), severe optical absorption in the p-electrode/ohmic contact layer and poor transverse magnetic (TM)-polarized light extraction. Furthermore, the on-wafer electroluminescence characterization validated the scalability of our DUV LEDs to larger production scales. Our work is promising for the development of highly efficient AlGaN-based DUV LEDs.

Cost-effectiveness of sotorasib as a second-line treatment for non-small cell lung cancer with KRASG12C mutation in China and the United States.

Purpose: To evaluate the cost-effectiveness of sotorasib versus docetaxel in non-small cell lung cancer (NSCLC) patients with KRASG12C mutation from the China and United States'social perspective. Materials and Methods: A Markov model that included three states (progression-free survival, post-progression survival, and death) was developed. Incremental cost-effectiveness ratio (ICER), quality-adjusted life-year (QALY), and incremental QALY were calculated for the two treatment strategies. One-way sensitivity analysis was used to investigate the factors that had a greater impact on the model results, and tornado diagrams were used to present the results. Probabilistic sensitivity analysis was performed with 1,000 Monte Carlo simulations. Assume distributions based on parameter types and randomly sample all parameter distributions each time., The results were presented as cost-effectiveness acceptable curves. Results: This economic evaluation of data from the CodeBreak 200 randomized clinical trial. In China, sotorasib generated 0.44 QAYL with a total cost of $84372.59. Compared with docetaxel, the ICER value of sotorasib was $102701.84/QALY, which was higher than willingness to pay (WTP), so sotorasib had no economic advantage. In the US, sotorasib obtained 0.35 QALY more than docetaxel, ICER was $15,976.50/QALY, which was more than 1 WTP but less than 3 WTP, indicating that the increased cost of sotorasib was acceptable. One-way sensitivity analysis showed that the probability of sotorasib having economic benefits gradually increased when the cost of follow-up examination was reduced in China. And there was no influence on the conclusions within the range of changes in China. When the willingness to pay (WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%. Conclusion: Sotorasib had a cost effect from the perspective in the United States. However, sotorasib had no cost effect from the perspective in China, and only when the WTP exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%.

A Flexible Temperature Sensor Integrated at Needle Tip for In Situ Acupoint Temperature Monitoring.

Temperature can reflect vital activities, and researchers have attempted to guide Chinese medicine diagnosis and treatment by observing acupoint temperature changes. Integrating a temperature sensor at the needle tip enables in situ acupoint temperature measurement. However, the sensor needles for acupoint temperature monitoring designed in previous studies were fabricated by manually soldering thermistor beads and metal wires, making mass production difficult. In this work, using MEMS manufacturing technology, a flexible temperature sensor that can be integrated at the needle tip is proposed and can be mass-produced on silicon wafers. The sensor uses a Pt thermistor as the temperature-sensing element and has a slender flexible structure with dimensions of 125 µm width by 3.2 cm length. As the sensor is inserted into a hollow needle, the Pt thermistor is glued to the needle tip. In the temperature range of 30 °C to 50 °C, the fabricated temperature sensor has a sensitivity of 5.00 Ω∙°C-1, a nonlinearity of ±0.39%FS, and a repeatability error of ±2.62%FS. Additionally, the sensor has been applied to in vivo acupoint temperature monitoring experiments in rats and demonstrated good performance, suggesting its promise for future research on acupoint temperature.

Joint effect of black carbon deriving from wheat straw burning and plastic mulch film debris on the soil biochemical properties, bacterial and fungal communities.

Black carbon (BC) formed after straw burning remains in farmland soil and coexists with plastic mulch film (PMF) debris. It is unclear how BC influences soil multifunctionality in the presence of PMF debris. In this study, we determined the joint effects of BC and PMF debris on soil biochemical properties and microbial communities. We conducted a soil microcosm experiment by adding BC formed by direct burning of wheat straw and PMF debris (polyethylene (PE) and biodegradable PMF (BP)) into soil at the dosages of 1 %, and soils were sampled on the 15th, 30th, and 100th day of soil incubation for high-throughput sequencing. The results showed that the degradation of PMF debris was accompanied by the release of microplastics (MPs). BC decreased NH4+-N (PE: 68.63 %; BP: 58.97 %) and NO3--N (PE: 12.83 %; BP: 51.37 %) and increased available phosphorus (AP) (PE: 79.12 %; BP: 26.09 %) in soil containing PMF debris. There were significant differences in enzyme activity among all the treatments. High-throughput sequencing indicated that BC reduced bacterial and fungal richness and fungal diversity in PMF debris-exposed soil, whereas PMF debris and BC resulted in significant changes in the proportion of dominant phyla and genera of bacteria and fungi, which were affected by incubation time. Furthermore, BC affected microorganisms by influencing soil properties, and pH and N content were the main influencing factors. In addition, FAPRPTAX analysis indicated that BC and PMF debris affected soil C and N cycling. These findings provide new insights into the response of soil multifunctionality to BC and PMF debris.

Genomic and single-cell analyses reveal genetic signatures of swimming pattern and diapause strategy in jellyfish.

Jellyfish exhibit innovative swimming patterns that contribute to exploring the origins of animal locomotion. However, the genetic and cellular basis of these patterns remains unclear. Herein, we generated chromosome-level genome assemblies of two jellyfish species, Turritopsis rubra and Aurelia coerulea, which exhibit straight and free-swimming patterns, respectively. We observe positive selection of numerous genes involved in statolith formation, hair cell ciliogenesis, ciliary motility, and motor neuron function. The lineage-specific absence of otolith morphogenesis- and ciliary movement-related genes in T. rubra may be associated with homeostatic structural statocyst loss and straight swimming pattern. Notably, single-cell transcriptomic analyses covering key developmental stages reveal the enrichment of diapause-related genes in the cyst during reverse development, suggesting that the sustained diapause state favours the development of new polyps under favourable conditions. This study highlights the complex relationship between genetics, locomotion patterns and survival strategies in jellyfish, thereby providing valuable insights into the evolutionary lineages of movement and adaptation in the animal kingdom.

Effects of CYP3A4 genetic polymorphisms on the pharmacokinetics and efficacy of perampanel in Chinese pediatric patients with epilepsy.

OBJECTIVE: This study was the first to evaluate the effect of CYP3A4 gene polymorphisms on the plasma concentration and effectiveness of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 102 patients for this investigation. The steady-state concentration was determined after patients maintained a consistent PER dosing regimen for at least 21 days. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final check-up. RESULTS: The CYP3A4×10 GC phenotype exhibited the highest average plasma concentration of PER at 491.1 ±â€¯328.1 ng/mL, in contrast to the CC phenotype at 334.0 ±â€¯161.1 ng/mL. The incidence of adverse events was most prominent in the CYP3A4×1 G TT and CYP3A4×10 GC groups, with rates of 77.8 % (7 of 9 patients) and 50.0 % (46 of 92 patients), respectively. Moreover, the percentage of patients for whom PER was deemed ineffective was least in the CYP3A4×1 G TT and CYP3A4×10 CC groups, recorded at 11.1 % (1 of 9 patients) and 10.0 % (1 of 10 patients), respectively. There was a significant correlation between PER plasma concentration and either exposure or toxicity (both with p < 0.05). We suggest a plasma concentration range of 625-900 ng/mL as a suitable reference for PER in Chinese patients with epilepsy. CONCLUSION: The CYP3A4×10 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A4 genetic phenotype should be factored in when prescribing PER to patients with epilepsy.

Expanding the Spectrum of NUTM1 -Rearranged Sarcoma : A Clinicopathologic and Molecular Genetic Study of 8 Cases.

Apart from the lethal midline carcinoma (NUT carcinoma), NUTM1 translocation has also been reported in mesenchymal tumors, but is exceedingly rare. Here, we describe a series of 8 NUTM1 -rearranged sarcomas to further characterize the clinicopathologic features of this emerging entity. This cohort included 2 males and 6 females with age ranging from 24 to 64 years (mean: 51 y; median: 56 y). Tumors occurred in the colon (2), abdomen (2), jejunum (1), esophagus (1), lung (1) and infraorbital region (1). At diagnosis, 6 patients presented with metastatic disease. Tumor size ranged from 1 to 10.5 cm (mean: 6 cm; median: 5.5 cm). Histologically, 4 tumors were composed of primitive small round cells to epithelioid cells intermixed with variable spindle cells, while 3 tumors consisted exclusively of small round cells to epithelioid cells and 1 tumor consisted predominantly of high-grade spindle cells. The neoplastic cells were arranged in solid sheets, nests, or intersecting fascicles. Mitotic activity ranged from 1 to 15/10 HPF (median: 5/10 HPF). Other features included rhabdoid phenotype (4/8), pronounced nuclear convolutions (2/8), prominent stromal hyalinization (2/8), focally myxoid stroma (1/8), foci of osteoclasts (1/8), and necrosis (1/8). By immunohistochemistry, all tumors showed diffuse and strong nuclear staining of NUT protein, with variable expression of pancytokeratin (AE1/AE3) (2/8), CK18 (1/8), CD99 (3/8), NKX2.2 (2/8), cyclin D1 (2/8), desmin (2/8), BCOR (2/8), S100 (1/8), TLE1 (1/8), and synaptophysin (1/8). Seven of 8 tumors demonstrated NUTM1 rearrangement by fluorescence in situ hybridization analysis. RNA-sequencing analysis identified MXD4::NUTM1 (3/7), MXI1::NUTM1 (3/7), and MGA::NUTM1 (1/7) fusions, respectively. DNA-based methylation profiling performed in 2 cases revealed distinct methylation cluster differing from those of NUT carcinoma and undifferentiated small round cell and spindle cell sarcomas. At follow-up (range: 4 to 24 mo), 1 patient experienced recurrence at 8.5 months, 4 patients were alive with metastatic disease (5, 10, 11, and 24 mo after diagnosis), 3 patients remained well with no signs of recurrence or metastasis (4, 6, and 12 mo after diagnosis). Our study further demonstrated that NUTM1 -rearranged sarcoma had a broad range of clinicopathologic spectrum. NUT immunohistochemistry should be included in the diagnostic approach of monotonous undifferentiated small round, epithelioid to high-grade spindle cell malignancies that difficult to classify by conventional means. DNA-based methylation profiling might provide a promising tool in the epigenetic classification of undifferentiated sarcomas.

Neuroprotective effects of total phenolics from Hemerocallis citrina Baroni leaves through the PI3K/AKT pathway.

Neurological injury, as a major pathogenic mechanism in depression, holds significant importance in the research and development of antidepressant drugs. Hemerocallis citrina Baroni (H. citrina), referred to as "Forgetting Sadness Grass," has been confirmed to possess remarkable neuroprotective effects. Studies have identified that the total phenolics in H. citrina Baroni leaves (HLTP) consist of flavonoids and phenolic acids and numerous studies have substantiated the neuroprotective effects of them. Based on this, we propose that HLTP may possess neuroprotective properties. To confirm this hypothesis, we initially employed network pharmacology techniques to predict potential targets for the neuroprotective effects of HLTP based on the Swiss Target Prediction database. GO and KEGG analyses were conducted to predict potential pathways, and a component-target-pathway network was constructed. Molecular docking experiments were then performed to analyze the binding abilities of the selected active components with the main targets. Furthermore, we validated the neuroprotective effects of HLTP and key targets selected through network pharmacology using a corticosterone-induced PC12 neuronal cell damage model. Network pharmacology research has identified that in the HLTP, Quercetin, Rutin, Apigenin, and Isoquercitrin are potential active components that may exert neuroprotective effects by modulating key targets such as AKT1, TNF, TP53, and CASP3 through crucial pathways including PI3K/AKT and apoptosis. Molecular docking revealed that 4-O-Caffeoylquinic acid, 5-O-Caffeoylshikimic acid, 4-p-Coumaroylquinic acid, and 5-O-Feruloylquinic acid exhibit low binding energies with key targets. Particularly, 4-O-Caffeoylquinic acid forms stable binding through hydrogen bonding with residues such as LYS389, GLU49, GLN47, LYS30, ASP44, and GLU40 in AKT1. PC12 cells were stimulated with 200 µmol/L Corticosterone (Cort) for 24 h, and then treated with 50, 100 and 200 µg/mL of HLTP for 24 h. The cell viability of damaged cells were significantly increased in a dose-dependent manner by 9.50%, 10.42% and 21.25%, respectively (P < 0.01). Western blot analysis confirmed that HLTP significantly (P < 0.01) increased the protein expression of PI3K and AKT by 15.24%, 30.44%, 41.03%, and 21.78%, 43.63%, 12.86%, respectively. In addition, through biochemical method, flow cytometry and WB analysis, we found that different concentrations of HLTP can all improve cell damage by reducing ROS, MDA, Ca2+, Cyt-C, Caspase-3, TNF-α and IL-1ß, and increasing SOD, CAT, MMP, Bcl-2/Bax and IL-10. In particular, the HLTP at 200 µg/mL, compared with the Model group, decreased by 140.2%, 54.66%, 51.34%, 65.26%, 40.32%, 63.87%, and 55.38%, and increased by 39.65%, 35.45%, 38.38%, 28.54%, and 39.98%, respectively. Through the above experiments, we verified that HLTP may exert neuroprotective effects by mediating the PI3K/AKT signaling pathway to counteract oxidative stress damage, improve mitochondrial dysfunction, and alleviate inflammatory injury.

Microbially Driven Iron Cycling Facilitates Organic Carbon Accrual in Decadal Biochar-Amended Soil.

Soil organic carbon (SOC) is pivotal for both agricultural activities and climate change mitigation, and biochar stands as a promising tool for bolstering SOC and curtailing soil carbon dioxide (CO2) emissions. However, the involvement of biochar in SOC dynamics and the underlying interactions among biochar, soil microbes, iron minerals, and fresh organic matter (FOM, such as plant debris) remain largely unknown, especially in agricultural soils after long-term biochar amendment. We therefore introduced FOM to soils with and without a decade-long history of biochar amendment, performed soil microcosm incubations, and evaluated carbon and iron dynamics as well as microbial properties. Biochar amendment resulted in 2-fold SOC accrual over a decade and attenuated FOM-induced CO2 emissions by approximately 11% during a 56-day incubation through diverse pathways. Notably, biochar facilitated microbially driven iron reduction and subsequent Fenton-like reactions, potentially having enhanced microbial extracellular electron transfer and the carbon use efficiency in the long run. Throughout iron cycling processes, physical protection by minerals could contribute to both microbial carbon accumulation and plant debris preservation, alongside direct adsorption and occlusion of SOC by biochar particles. Furthermore, soil slurry experiments, with sterilization and ferrous iron stimulation controls, confirmed the role of microbes in hydroxyl radical generation and biotic carbon sequestration in biochar-amended soils. Overall, our study sheds light on the intricate biotic and abiotic mechanisms governing carbon dynamics in long-term biochar-amended upland soils.

Characterization of dental light-curing resin composites incorporating multiple modified low-shrink monomers.

OBJECTIVE: Polymerization shrinkage poses a significant challenge in dental resin composites. The objective of this study is to introduce spiroorthocarbonate monomer 3,9-dimethylene-1,3,5,7-tetraoxa-spiro[5,5]undecane (BMSOC) and epoxy resin monomer 3,4-epoxycyclohexylmethyl-3,4-epoxycyclohexane carboxylate (ECHM-ECHC) into bisphenol-S-bis(3-methacrylato-2-hydroxy propyl)ether (BisS-GMA) based resin composites to develop composites with reduced shrinkage properties. METHODS: BMSOC and BisS-GMA were synthesized and thoroughly mixed with ECHM-ECHC, followed by inorganic fillers and photoinitiators. Based on the composition of the resin matrix, five groups of experimental composites were prepared, with traditional bisphenol A-dimethacrylate glycidyl ester (Bis-GMA)/triethylene glycol dimethacrylate (TEGDMA) based composite serving as the control. The polymerization properties, including degree of conversion (DC) and polymerization shrinkage (PS), as well as marginal microleakage, wettability, flexural strength (FS), flexural modulus (FM), and biocompatibility were evaluated. RESULTS: The results demonstrated that compared with the control group, the PS of BisS-GMA based composites containing BMSOC and ECHM-ECHC were significantly reduced (P < 0.05), and the lowest PS (0.96 ± 0.08 %) was observed when the ratio of BisS-GMA: (Epoxy + BMSOC) was 4:6. Additionally, the experimental composites also exhibited improved DC, minimal microleakage, low hydrophilicity, enhanced mechanical properties, qualified in vivo biocompatibility, and slight/moderate in vitro biocompatibility. SIGNIFICANCE: The resin composites incorporating multiple modified low-shrink monomers are promising for dental applications to prevent various clinical problems caused by PS and extend restoration longevity.