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.

Investigation of fullerene and non-fullerene materials in organic photocatalysts on the efficiency of photocatalytic degradation of polychlorinated biphenyls.

The photocatalytic degradation of polychlorinated biphenyls (PCBs) is advancing, yet the efficiency of degradation within the visible spectral range continues to encounter significant challenges. In this study, two biochar-based organic semiconductor photocatalysts, Active Carbon@PTQ10 (5,8-Dibromo-6,7-difluoro-2-(2-hexyldecoxy)quinoxaline; trimethyl-(5-trimethylstannylthiophen-2-yl)stannane): ITIC-Th (Propanedinitrile,2,2'-[[6,6,12,12-tetrakis(5-hexyl-2-thienyl)-6,12-dihydrodithieno[2,3-d: 2',3'-d'] -s-indaceno[1,2-b:5,6-b'] dithiophene-2,8-diyl] bis[methylidyne(3-oxo-1H-indene-2,1(3H)-diylidene)]] bis-) (AC@PI) and Active Carbon@PTQ10: PC71BM (6,6)-phenyl C71 butyric acid methyl ester), were synthesized using a wide bandgap material, PTQ10, as the electron donor, along with a non-fullerene material, ITIC-Th, and a fullerene material, PC71BM, as the acceptors, respectively. Under optimized conditions, AC@PI degraded 93.4 % of 2,2 ',4,4 '-tetrachlorobiphenyl (PCB 47) within 60 min. By incorporating a non-fullerene acceptor (ITIC-Th), AC@PI exhibits a larger surface photopressure, a lower hole-electron transfer ratio, a broader absorption spectrum (400 - 1000 nm), and enhanced structural stability. AC@PI can generate photogenerated electrons and holes, as well as superoxide anions (O2-) and hydroxyl radicals (OH), through type II heterojunctions, which contributes to its exceptional properties. This study synthesized novel organic semiconductor catalysts that offer a green, efficient, and non-toxic method for the degradation of aromatic pollutants, such as polychlorinated biphenyls.

De novo design of mini-protein binders broadly neutralizing Clostridioides difficile toxin B variants.

Clostridioides difficile toxin B (TcdB) is the key virulence factor accounting for C. difficile infection-associated symptoms. Effectively neutralizing different TcdB variants with a universal solution poses a significant challenge. Here we present the de novo design and characterization of pan-specific mini-protein binders against major TcdB subtypes. Our design successfully binds to the first receptor binding interface (RBI-1) of the varied TcdB subtypes, exhibiting affinities ranging from 20 pM to 10 nM. The cryo-electron microscopy (cryo-EM) structures of the mini protein binder in complex with TcdB1 and TcdB4 are consistent with the computational design models. The engineered and evolved variants of the mini-protein binder and chondroitin sulfate proteoglycan 4 (CSPG4), another natural receptor that binds to the second RBI (RBI-2) of TcdB, better neutralize major TcdB variants both in cells and in vivo, as demonstrated by the colon-loop assay using female mice. Our findings provide valuable starting points for the development of therapeutics targeting C. difficile infections (CDI).

CCL4 as a potential serum factor in differential diagnosis of central nervous system inflammatory diseases and gliomas.

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are commonly utilized to detect brain gliomas and central nervous system inflammation diseases. However, there are instances where depending solely on medical imaging for a precise diagnosis may result in unsuitable medications or treatments. Pathological analysis is regarded as the definitive method for diagnosing brain gliomas or central nervous system inflammation diseases. To achieve this, a craniotomy or stereotaxic biopsy is necessary to collect brain tissue, which can lead to complications such as cerebral hemorrhage, neurological deficits, cerebrospinal fluid leaks, and cerebral edema. Consequently, the advancement of non-invasive or minimally invasive diagnostic techniques is currently a high priority. This study included samples from four glioma patients and five patients with central nervous system inflammatory diseases, comprising both serum and paired cerebrospinal fluid (CSF). A total of 40 human cytokines were identified in these samples. We utilized a receiver operating characteristic (ROC) analysis to assess the sensitivity and specificity for distinguishing central nervous system inflammation diseases and gliomas. Additionally, we examined the correlation of these factors between serum and CSF in the patients. Ultimately, the identified factors were validated using serum from patients with clinically confirmed gliomas and central nervous system inflammation diseases followed by detection and statistical analysis through ELISA. The levels of serum factors IL-4, IFN-α, IFN-γ, IL-6, TNF-α, CCL4, CCL11, and VEGF were found to be significantly higher in gliomas compared with inflammatory diseases of the central nervous system (p < 0.05). Furthermore, a strong correlation was observed between the levels of CCL4 in serum and CSF, with a correlation coefficient of r = 0.92 (95% CI = 0.20-0.99, p = 0.027). We gathered more clinical samples to provide further validation of the abundance of CCL4 expression. A clinical study analyzing serum samples from 19 glioma patients and 22 patients with central nervous system inflammation diseases revealed that CCL4 levels were notably elevated in the inflammatory group compared with the glioma group (p < 0.001). These results suggest that assessing serum CCL4 levels may be useful in distinguishing those patients for clinical diagnostic purposes.

Envafolimab plus lenvatinib and transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a prospective, single-arm, phase II study.

Evidences regarding the feasibility of transcatheter arterial chemoembolization (TACE)-based therapy for unresectable hepatocellular carcinoma (uHCC) remains limited. This study aimed to investigate the efficacy and safety of TACE combined with envafolimab and lenvatinib for uHCC. Eligible patients with uHCC received envafolimab and lenvatinib after TACE until disease progression, conversion to surgery, intolerable toxicities, or death. The primary endpoint was the objective response rate (ORR) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Between March 2022 and July 2022, 38 patients were included for safety analysis, and 36 patients were included for efficacy analysis. As of the data cutoff (13 December 2023), the median follow-up was 16.9 months. The ORR was 50%, and disease control rate (DCR) was 83.3% per RECIST 1.1 (ORR and DCR of both 83.3% per modified RECIST (mRECIST)). The median progression-free survival (PFS) was 7.58 months. Of 36 patients, 17 patients were converted to resectable HCC with a surgical conversion rate of 47.2%, and 16 patients underwent surgery with R0 resection rate of 100%, pathologic complete response (pCR) rate of 31.3%. Overall incidences of treatment-related adverse events (TRAEs) of any grade was 97.4%. Grade ≥ 3 TRAEs were observed in 52.6% patients. No treatment-related deaths occurred. Image mass cytometry (IMC) analysis revealed that combined treatment improved the immune status of the tumor microenvironment, and resident macrophages had the potential to predict efficacy of this treatment. Envafolimab plus lenvatinib and TACE yielded promising survival outcomes and conversion efficiency with a tolerable safety profile. Trial registration Clinical trials: NCT05213221.

Efficient photodegradation of carbamazepine by organocatalysts incorporating a third component with a more complementary absorption spectrum.

Carbamazepine, recognized as one of the most prevalent pharmaceuticals, has attracted considerable attention due to its potential impact on ecosystems and human health. In response, this work synthesized and characterized a novel environmentally friendly and cost-effective organic semiconductor photocatalyst PM6:Y6:ITCPTC loaded with coconut shell charcoal, and then investigated its performance for photocatalytic removal. Remarkably, carbamazepine demonstrated a photodegradation efficiency exceeding 99% within a mere 20 minutes of exposure to one sunlight intensity, and also showed good effectiveness under a low light intensity of 50 W. The catalyst exhibited exceptional reusability and stability, maintaining degradation efficiency between 95-99% over 25 cycles. The high photocatalytic activity of PM6:Y6:ITCPTC is primarily attributed to the incorporation of the third component (named ITCPTC), which enhances exciton dissociation and carrier transfer, generating superoxide radicals, electrons, and holes. Furthermore, the plausible degradation pathway of carbamazepine was proposed based on the measured intermediates and density functional theory calculations.

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.

Feasibility and effectiveness of a foam rolling intervention in pregnant women requiring bed rest for foetal protection: a randomised controlled trial.

BACKGROUND: Bed rest during pregnancy can lead to reduced physical activity, impairing lower limb venous blood flow and increasing the risk of deep vein thrombosis (DVT) and muscle atrophy. We investigated the clinical efficacy of foam rolling intervention (FRI) in enhancing lower limb venous blood flow, mitigating the risk of DVT and muscle atrophy in pregnant women on bed rest. METHODS: This single-blind, randomised controlled trial enrolled 86 pregnant women with long-term bed rest for foetal protection (≥ 7 days), gestational age ≥ 20 weeks, and maternal age < 40 years. Participants were randomly assigned to a control or experimental group using a random number table. The control group received standard care, whereas the experimental group underwent FRI. Researchers and statisticians were aware of the treatment groups, however, the participants were blinded. Lower limb blood flow velocity, D-dimer levels, incidence of DVT, and the extent of lower limb muscle atrophy were assessed in both groups at baseline and post-intervention (day 7). To account for a 5% attrition rate and potential sampling error, the estimated sample size for each experimental and control group was 40. RESULTS: Before the intervention, no significant differences were observed between the experimental and control groups in peak blood flow, mean flow velocity, D-dimer values, or leg circumference (P > 0.05), however, the peak blood velocities of the popliteal veins were significantly higher in the control group (P = 0.031). On the seventh day post-intervention, the experimental group had significantly higher mean and peak blood velocities in femoral and popliteal veins, significantly (P < 0.05), lower mean D-dimer levels (P = 0.035), and a significantly smaller reduction in thigh and calf circumference (P < 0.001). Consequently, the rate of thigh muscle atrophy was significantly slower in the experimental group (P = 0.011). CONCLUSIONS: FRI is an effective intervention for improving lower limb venous blood flow, mitigating the risk of DVT and muscle atrophy in pregnant women on bed rest. TRIAL REGISTRATION: This trial was retrospectively registered with the Chinese Clinical Trial Registry on June 18, 2024 (registration number: ChiCTR2400085770).

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.

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.

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.

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.

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.

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.

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%.

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.

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.

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.