Tight focusing of the vector optical field with polarization varying along complex curves of the Poincaré sphere.

Different from the scalar optical field with spatially uniform polarization, the vector optical field exhibits inhomogeneous distribution of polarization on the cross section. Manipulating the variation of polarization in a single optical beam is important to acquire a flexible and controllable focused optical field. Previous studies mainly focused on the vector optical field with its polarization varying along a circular trajectory of the Poincaré sphere. Here, we demonstrate the tight focusing behaviors of the vector optical field with the polarization varying along complex curves of the Poincaré sphere, which is generated by the joint modulation of azimuthal phase and amplitude distributions of orthogonally polarized components. The longitudinal polarization component with a multipolar pattern in rotational symmetry can be achieved with similar distribution of the total focused field. The transverse and longitudinal spin angular momentum distributions in the focal space are discussed. Approximately pure transverse spin angular momentum can be constructed and manipulated in the focal space, which provides the possibility to manipulate the 3D spin flux for the applications of nano and spin photonics.

Optimization of chaotic light output in semiconductor laser systems based on multi-objective optimization algorithm.

Aiming at the weak performance of chaotic light output in semiconductor laser systems, the study designed a power control algorithm for semiconductor laser drive systems based on linear self-disturbance rejection control. Then the optimization parameters and scope were determined, and multi-objective optimization and direction preference algorithms were introduced. A chaotic optical performance optimization model based on improved multi-objective genetic algorithm was constructed using adaptive functions as evaluation indicators. These results confirmed that the larger the bandwidth of the controller, the faster the response speed of the resonant converter, but the stability was poor. When the input voltage underwent a sudden change, the current ripple coefficient of the PID algorithm was 0.55%. The linear active disturbance rejection control algorithm could ensure that the voltage and current maintained at the set values, and the output current of the algorithm was more stable when the load underwent sudden changes. The directional preference algorithm could further provide more valuable solutions on the basis of adaptive genetic algorithms. When the peak value of the autocorrelation function was equal to 0.2, the delay characteristics of chaotic light were effectively suppressed, having strong signal bandwidth and complexity. In summary, the constructed model has good application effects in optimizing chaotic optical performance and has certain positive significance for communication security.

KLF5 promotes the ossification process of ligamentum flavum by transcriptionally activating CX43.

BACKGROUND: Ossification of ligamentum flavum (OLF) is a prevalent degenerative spinal disease, typically causing severe neurological dysfunction. Kruppel-like factor 5 (KLF5) plays an essential role in the regulation of skeletal development. However, the mechanism KLF5 plays in OLF remains unclear, necessitating further investigative studies. METHODS: qRT-PCR, immunofluorescent staining and western blot were used to measure the expression of KLF5. Alkaline Phosphatase (ALP) staining, Alizarin red staining (ARS), and the expression of Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) were used to evaluate the osteogenic differentiation. Luciferase activity assay and ChIP-PCR were performed to investigate the molecular mechanisms. RESULTS: KLF5 was significantly upregulated in OLF fibroblasts in contrast to normal ligamentum flavum (LF) fibroblasts. Silencing KLF5 diminished osteogenic markers and mineralized nodules, while its overexpression had the opposite effect, confirming KLF5's role in promoting ossification. Moreover, KLF5 promotes the ossification of LF by activating the transcription of Connexin 43 (CX43), and overexpressing CX43 could reverse the suppressive impact of KLF5 knockdown on OLF fibroblasts' osteogenesis. CONCLUSION: KLF5 promotes the OLF by transcriptionally activating CX43. This finding contributes significantly to our understanding of OLF and may provide new therapeutic targets.

piRNA loading triggers MIWI translocation from the intermitochondrial cement to chromatoid body during mouse spermatogenesis.

The intermitochondrial cement (IMC) and chromatoid body (CB) are posited as central sites for piRNA activity in mice, with MIWI initially assembling in the IMC for piRNA processing before translocating to the CB for functional deployment. The regulatory mechanism underpinning MIWI translocation, however, has remained elusive. We unveil that piRNA loading is the trigger for MIWI translocation from the IMC to CB. Mechanistically, piRNA loading facilitates MIWI release from the IMC by weakening its ties with the mitochondria-anchored TDRKH. This, in turn, enables arginine methylation of MIWI, augmenting its binding affinity for TDRD6 and ensuring its integration within the CB. Notably, loss of piRNA-loading ability causes MIWI entrapment in the IMC and its destabilization in male germ cells, leading to defective spermatogenesis and male infertility in mice. Collectively, our findings establish the critical role of piRNA loading in MIWI translocation during spermatogenesis, offering new insights into piRNA biology in mammals.

Mycobacterium tuberculosis inhibits METTL14-mediated m6A methylation of Nox2 mRNA and suppresses anti-TB immunity.

Internal N6-methyladenosine (m6A) modifications are among the most abundant modifications of messenger RNA, playing a critical role in diverse biological and pathological processes. However, the functional role and regulatory mechanism of m6A modifications in the immune response to Mycobacterium tuberculosis infection remains unknown. Here, we report that methyltransferase-like 14 (METTL14)-dependent m6A methylation of NAPDH oxidase 2 (Nox2) mRNA was crucial for the host immune defense against M. tuberculosis infection and that M. tuberculosis-secreted antigen EsxB (Rv3874) inhibited METTL14-dependent m6A methylation of Nox2 mRNA. Mechanistically, EsxB interacted with p38 MAP kinase and disrupted the association of TAB1 with p38, thus inhibiting the TAB1-mediated autophosphorylation of p38. Interaction of EsxB with p38 also impeded the binding of p38 with METTL14, thereby inhibiting the p38-mediated phosphorylation of METTL14 at Thr72. Inhibition of p38 by EsxB restrained liquid-liquid phase separation (LLPS) of METTL14 and its subsequent interaction with METTL3, preventing the m6A modification of Nox2 mRNA and its association with the m6A-binding protein IGF2BP1 to destabilize Nox2 mRNA, reduce ROS levels, and increase intracellular survival of M. tuberculosis. Moreover, deletion or mutation of the phosphorylation site on METTL14 impaired the inhibition of ROS level by EsxB and increased bacterial burden or histological damage in the lungs during infection in mice. These findings identify a previously unknown mechanism that M. tuberculosis employs to suppress host immunity, providing insights that may empower the development of effective immunomodulators that target M. tuberculosis.

Precisely modulating the chromatin tracker via substituent engineering: reporting pathological oxidative stress during mitosis.

An in-depth understanding of cancer-cell mitosis presents unprecedented advantages for solving metastasis and proliferation of tumors, which has aroused great interest in visualizing the behavior via a luminescence tool. We developed a fluorescent molecule CBTZ-yne based on substituent engineering to acquire befitting lipophilicity and electrophilicity for anchoring lipid droplets and the nucleus, in which the low polarity environment and nucleic acids triggered a "weak-strong" fluorescence and "short-long" fluorescence-lifetime response. Meaningfully, CBTZ-yne visualized chromatin condensation, alignment, pull-push, and separation as well as lipid droplet dynamics, for the first time, precisely unveiling the asynchronous cellular mitosis processes affected by photo-generation reactive oxygen species according to the subtle change of fluorescence-lifetime. Our work suggested a new guideline for tracking the issue of the proliferation of malignant tumors in photodynamic therapy.

CDKL1 potentiates the antitumor efficacy of radioimmunotherapy by binding to transcription factor YBX1 and blocking PD-L1 expression in lung cancer.

BACKGROUND: The evasion of the immune response by tumor cells through programmed death-ligand 1 (PD-L1) has been identified as a factor contributing to resistance to radioimmunotherapy in lung cancer patients. However, the precise molecular mechanisms underlying the regulation of PD-L1 remain incompletely understood. This study aimed to investigate the role of cyclin-dependent kinase-like 1 (CDKL1) in the modulation of PD-L1 expression and the response to radioimmunotherapy in lung cancer. METHODS: The tumorigenic roles of CDKL1 were assessed via cell growth, colony formation, and EdU assays and an in vivo nude mouse xenograft model. The in vitro radiosensitization effect of CDKL1 was evaluated using a neutral comet assay, γH2AX foci formation analysis, and a clonogenic cell survival assay. The protein‒protein interactions were confirmed via coimmunoprecipitation and GST pulldown assays. The regulation of PD-L1 by CDKL1 was evaluated via chromatin immunoprecipitation (ChIP), real-time quantitative PCR, and flow cytometry analysis. An in vitro conditioned culture model and an in vivo C57BL/6J mouse xenograft model were developed to detect the activation markers of CD8+ T cells and evaluate the efficacy of CDKL1 overexpression combined with radiotherapy (RT) and an anti-PD-L1 antibody in treating lung cancer. RESULTS: CDKL1 was downregulated and suppressed the growth and proliferation of lung cancer cells and increased radiosensitivity in vitro and in vivo. Mechanistically, CDKL1 interacted with the transcription factor YBX1 and decreased the binding affinity of YBX1 for the PD-L1 gene promoter, which consequently inhibits the expression of PD-L1, ultimately leading to the activation of CD8+ T cells and the inhibition of immune evasion in lung cancer. Moreover, the combination of CDKL1 overexpression, RT, and anti-PD-L1 antibody therapy exhibited the most potent antitumor efficacy against lung cancer. CONCLUSIONS: Our findings demonstrate that CDKL1 plays a crucial role in regulating PD-L1 expression, thereby enhancing the antitumor effects of radioimmunotherapy. These results suggest that CDKL1 may be a promising therapeutic target for the treatment of lung cancer.

MRPS16 promotes lung adenocarcinoma growth via the PI3K/AKT/Frataxin signalling axis.

Although MRPS16 is involved in cancer development, its mechanisms in developing LAUD remain unclear. Herein, qRT-PCR, WB and IHC were utilized for evaluating MRPS16 expression levels, while functional assays besides animal experiments were performed to measure MRPS16 effect on LAUD progression. Using WB, the MRPS16 effect on PI3K/AKT/Frataxin signalling pathway was tested. According to our study, MRPS16 was upregulated in LAUD and was correlated to the advanced TNM stage as well as poor clinical outcomes, which represent an independent prognostic factor. Based on functional assays, MRPS16 is involved in promoting LAUD growth, migration and invasion, which was validated further in subsequent analyses through PI3K/AKT/Frataxin pathway activation. Moreover, MRPS16-knockdown-mediated Frataxin overexpression was shown to restore the reduction in tumour cells proliferation, migration and invasion. Our results revealed that MRPS16 caused an aggressive phenotype to LAUD and was a poor prognosticator; thus, targeting MRPS16 may be effectual in LAUD treatment.

Bruceantinol targeting STAT3 exerts promising antitumor effects in in vitro and in vivo osteosarcoma models.

Bruceantinol (BOL) is a quassinoid compound found in the fruits of Brucea javanica. Previous research has highlighted the manifold physiological and pharmacological activities of BOL. Notably, BOL has demonstrated antitumor cytotoxic and antibacterial effects, lending support to its potential as a promising therapeutic agent for various diseases. Despite being recognized as a potent antitumor inhibitor in multiple cancer types, its efficacy against osteosarcoma (OS) has not been elucidated. In this work, we investigated the antitumor properties of BOL against OS. Our findings showed that BOL significantly decreased the proliferation and migration of OS cells, induced apoptosis, and caused cell death without affecting the cell cycle. We further confirmed that BOL potently suppressed tumor growth in vivo. Mechanismly, we discovered that BOL directly bound to STAT3, and prevent the activation of STAT3 signaling at low nanomolar concentrations. Overall, our study demonstrated that BOL potently inhibited the growth and metastasis of OS, and efficiently suppressed STAT3 signaling pathway. These results suggest that BOL could be a promising therapeutic candidate for OS.

Enhancing the antioxidant properties and compatibility of protein/sodium alginate film by incorporating Zanthoxylum bungeanum essential oil Pickering emulsion.

Zanthoxylum bungeanum essential oil (ZBEO) Pickering emulsion was incorporated into rice protein (RP)/sodium alginate (SA)-based film to enhance the antioxidant activity and compatibility. With increasing ZBEO content from 2 % to 4 %, the average size of ZBEO Pickering emulsion ranged from 124.28 to 165.65 nm. The best mechanical property with a tensile strength of 14.56 MPa and hydrophobicity with a water vapor permeability of 2.11 × 10-12 g⋅cm-1⋅s-1⋅Pa-1 of emulsion film were achieved with 0.8 % ZBEO. In addition, the loss of ZBEO in the emulsion films was reduced by 11-14 %. The DPPH radical scavenging activity of emulsion film with 1.2 % ZBEO was 65.54 % in 95 % ethanol. The results of Fourier transform infrared spectroscopy and molecular dynamics simulation showed that electrostatic interactions played a leading role in film formation. Overall, ZBEO Pickering emulsion is an effective method to enhance the antioxidant activity, mechanical strength and hydrophobicity of RP/SA film.

Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation.

Cytosine base editing achieves C•G-to-T•A substitutions and can convert four codons (CAA/CAG/CGA/TGG) into STOP-codons (induction of STOP-codons, iSTOP) to knock out genes with reduced mosaicism. iSTOP enables direct phenotyping in founders' somatic cells, but it remains unknown whether this works in founders' germ cells so as to rapidly reveal novel genes for fertility. Here, we initially establish that iSTOP in mouse zygotes enables functional characterization of known genes in founders' germ cells: Cfap43-iSTOP male founders manifest expected sperm features resembling human "multiple morphological abnormalities of the flagella" syndrome (i.e., MMAF-like features), while oocytes of Zp3-iSTOP female founders have no zona pellucida. We further illustrate iSTOP's utility for dissecting the functions of unknown genes with Ccdc183, observing MMAF-like features and male infertility in Ccdc183-iSTOP founders, phenotypes concordant with those of Ccdc183-KO offspring. We ultimately establish that CCDC183 is essential for sperm morphogenesis through regulating the assembly of outer dynein arms and participating in the intra-flagellar transport. Our study demonstrates iSTOP as an efficient tool for direct reproductive disease modeling and phenotyping in germ cells of the founder generation, and rapidly reveals the essentiality of Ccdc183 in fertility, thus providing a time-saving approach for validating genetic defects (like nonsense mutations) for human infertility.

Regulating Lipid Metabolism via Mitochondrial Dynamics in Tongue Squamous Cell Carcinoma Cancer Stem Cells.

BACKGROUND: Cancer stem cells (CSCs) are a sub-population of cancer cells present in many kinds of malignant tumors that have the potential for self-proliferation and differentiation. These cells have been demonstrated as the main cause of tumor recurrence and metastasis. Strong evidence indicates that CSCs prefer reprogrammed fatty acid ß-oxidation over oxidative phosphorylation for sustaining energy supply. Although mitochondrial dynamics participate in the regulation of cancer stemness, the correlation between the inhibition of mitochondrial fission and the regulation of lipid metabolism in CSCs remains poorly understood. METHODS: The human tongue squamous cell carcinoma (TSCC) cell lines CAL27 and SAS were used to obtain the CSCs by 3D Spheroid Culture. Then,western blot methods, RT-PCR and flow cytometry analysis were used to identify the TSCC CSCs. Next, Immunofluorescence method, transmission electron microscopy detection and western blot methods were used to evaluate the mitochondrial morphology and the quantity of lipid droplets (LDs). Lastly, lipidomic analysis was applied to explored the lipidomic alterations of TSCC CSCs with different mitochondrial morphology. RESULTS: Here, we show that the quantity of lipid droplets containing intracellular triglyceride (TG) can be decreased by regulating mitochondrial morphology. Lipidomic analysis using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) also compared alterations in lipid metabolites in tongue squamous cell carcinoma (TSCC) CSCs, TSCC cells (non-CSCs), and CSCs with different mitochondrial morphology. Discriminant lipids of statistical significance were successfully annotated, including phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), sphingomyelins (SMs), triacylglycerols (TGs), phosphatidylglycerols (PGs), phosphatidylserines (PSs), lysophosphatidylcholines (LPCs), and lysophosphatidylethanolamines (LPEs). CONCLUSION: This study provides a deeper insight into the alterations of lipid metabolism associated with TSCC CSCs, non-CSCs and CSCs regulated by mitochondrial dynamics and thus serves as a guide toward novel targeted therapies.

Predicting survival in patients with buccal cancer: A study based on SEER database and external validation in China.

OBJECTIVE: Buccal mucosa cancer (BMC) is one of the most common oral cancers and has poor prognosis. The study aimed to develop and validate nomograms for predicting the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS) of BMC patients. METHODS: We collected and reviewed information on BMC patients diagnosed between 2004 and 2019 from the Surveillance Epidemiology and End Results database. Two nomograms were developed and validated to predict the OS and CSS based on predictors identified by univariate and multivariate Cox regression. An extra external validation was further performed using data from Sun Yat-sen Memorial Hospital (SYSMH). RESULTS: A total of 3154 BMC patients included in this study were randomly assigned to training and validation groups in a 2:1 ratio. Independent prognostic predictors were identified, confirmed, and fitted into nomograms for OS and CSS, respectively. The C-indices are 0.767 (Training group OS), 0.801 (Training group CSS), 0.763 (Validation group OS), and 0.781 (Validation group OS), respectively. Moreover, the nomograms exhibited remarkable precision in forecasting and significant clinical significance, as evidenced by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA). The final validation using our data from SYSMH also showed high accuracy and substantial clinical benefits within the nomograms. The C-indices are 0.849 (SYSMH group OS) and 0.916 (SYSMH group CSS). These indexes are better than tumor, node, and metastasis stage based on prediction results. CONCLUSIONS: The nomograms developed with great performance predicted 1-, 3-, and 5-year OS and CSS of BMC patients. Use of the nomograms in clinical practices shall bring significant benefits to BMC patients.

Analysis of the Potential Angiogenic Mechanisms of BuShenHuoXue Decoction against Osteonecrosis of the Femoral Head Based on Network Pharmacology and Experimental Validation.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease with a high disability rate. The clinical effect of BuShenHuoXue decoction (BSHX) for ONFH is satisfactory. We aimed to elucidate the potential angiogenic mechanisms of BSHX in a rat femoral osteonecrosis model and bone marrow mesenchymal stem cells (BMSCs). METHODS: With in vivo experiments, we established the steroid-induced osteonecrosis of the femoral head (SONFH) model using Sprague-Dawley (SD) rats (8-week-old). The rats were randomly divided into five group of 12 rats each and given the corresponding interventions: control, model (gavaged with 0.9% saline), BSHX low-, medium- and high-dose groups (0.132 3, 0.264 6, and 0.529 2 g/mL BSHX solution by gavage). After 12 weeks, haematoxylin and eosin (H&E) staining was preformed to evaluate rat osteonecrosis. the expression of angiogenic factors (CD31, VEGFA, KDR, VWF) in rat femoral head was detected by immunohistochemistry, qPCR and western blotting. In cell experiment, BMSCs were isolated and cultured in the femoral bone marrow cavity of 4-week-old SD rats. BMSCs were randomly divided into eight groups and intervened with different doses of BSHX-containing serum and glucocorticoids: control group (CG); BSHX low-, medium-, and high-dose groups (CG + 0.661 5, 1.323, and 2.646 g/kg BSHX gavage rat serum); dexamethasone (Dex) group; and Dex + BSHX low-, medium-, and high-dose groups (Dex + 0.661 5, 1.323, and 2.646 g/kg BSHX gavaged rat serum), the effects of BSHX-containing serum on the angiogenic capacity of BMSCs were examined by qPCR and Western blotting. A co-culture system of rat aortic endothelial cells (RAOECs) and BMSCs was then established. Migration and angiogenesis of RAOECs were observed using angiogenesis and transwell assay. Identification of potential targets of BSHX against ONFH was obtained using network pharmacology. RESULTS: BSHX upregulated the expression of CD31, VEGFA, KDR, and VWF in rat femoral head samples and BMSCs (p < 0.05, vs. control group or model group). Different concentrations of BSHX-containing serum significantly ameliorated the inhibition of CD31, VEGFA, KDR and VWF expression by high concentrations of Dex. BSHX-containing serum-induced BMSCs promoted the migration and angiogenesis of RAOECs, reversed to some extent the adverse effect of Dex on microangiogenesis in RAOECs, and increased the number of microangiogenic vessels. Furthermore, we identified VEGFA, COL1A1, COL3A1, and SPP1 as important targets of BSHX against ONFH. CONCLUSION: BSHX upregulated the expression of angiogenic factors in the femoral head tissue of ONFH model rats and promoted the angiogenic capacity of rat RAOECs and BMSCs. This study provides an important basis for the use of BSHX for ONFH prevention and treatment.

Integrated Single-cell and Bulk RNA Sequencing Analysis Cross Talk between Ferroptosis-related Genes and Prognosis in Oral Cavity Squamous Cell Carcinoma.

BACKGROUND: Ferroptosis is a new type of programmed apoptosis and plays an important role in tumour inhibition and immunotherapy. OBJECTIVE: In this study, we aimed to explore the potential role of ferroptosis-related genes (FRGs) and the potential therapeutic targets in oral cavity squamous cell carcinoma (OCSCC). METHODS: The transcription data of OCSCC samples were obtained from the Cancer Genome Atlas (TCGA) database as a training dataset. The prognostic FRGs were extracted by univariate Cox regression analysis. Then, we constructed a prognostic model using the least absolute shrinkage and selection operator (LASSO) and Cox analysis to determine the independent prognosis FRGs. Based on this model, risk scores were calculated for the OCSCC samples. The model's capability was further evaluated by the receiver operating characteristic curve (ROC). Then, we used the GSE41613 dataset as an external validation cohort to confirm the model's predictive capability. Next, the immune infiltration and somatic mutation analysis were applied. Lastly, single-cell transcriptomic analysis was used to identify the key cells. RESULTS: A total of 12 prognostic FRGs were identified. Eventually, 6 FRGs were screened as independent predictors and a prognostic model was constructed in the training dataset, which significantly stratified OCSCC samples into high-risk and low-risk groups based on overall survival. The external validation of the model using the GSE41613 dataset demonstrated a satisfactory predictive capability for the prognosis of OCSCC. Further analysis revealed that patients in the highrisk group had distinct immune infiltration and somatic mutation patterns from low-risk patients. Mast cell infiltrations were identified as prognostic immune cells and played a role in OCSCC partly through ferroptosis. CONCLUSION: We successfully constructed a novel 6 FRGs model and identified a prognostic immune cell, which can serve to predict clinical prognoses for OCSCC. Ferroptosis may be a new direction for immunotherapy of OCSCC.

Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

Niobium Oxide Anode with Lattice Structure Self-Optimization for High-Power and Nearly Zero-Degeneration Battery Operation.

Li+ insertion-induced structure transformation in crystalline electrodes vitally influence the energy density and cycle life of secondary lithium-ion battery. However, the influence mechanism of structure transformation-induced Li+ migration on the electrochemical performance of micro-crystal materials is still unclear and the strategy to profit from such structure transformation remains exploited. Here, an interesting self-optimization of structure evolution during electrochemical cycling in Nb2 O5 micro-crystal with rich domain boundaries is demonstrated, which greatly improves the charge transfer property and mechanical strength. The lattice rearrangement activates the Li+ diffusion kinetics and hinders the particle crack, thus enabling a nearly zero-degeneration operation after 8000 cycles. Full cell paired with lithium cobalt oxides displays an exceptionally high capacity of 176 mA h g-1 at 8000 mA g-1 and excellent long-term durability at 6000 mA g-1 with 63% capacity retention over 2000 cycles. Interestingly, a unique fingerprint based on the intensity ratio of two X-ray diffraction peaks is successfully extracted as a measure of Nb2 O5 electrochemical performance. The structure self-optimization for fast charge transfer and high mechanical strength exemplifies a new battery electrode design concept and opens up a vast space of strategy to develop high-performance lithium-ion batteries with high energy density and ultra-long cycle life.

The rational dose for MaXingShiGan decoction is crucial for its clinical effectiveness in treating bronchial pneumonia: three randomized, double-blind, dose-parallel controlled clinical studies.

Objective: Evaluate the impact of adjusting the overall dose, Gypsum Fibrosum [Mineral; Gypsum] (ShiGao, SG) dose, and Prunus armeniaca L. [Rosaceae; Semen Armeniacae Amarum] (KuXingRen, KXR) dose on the efficacy of MaXingShiGan Decoction (MXSG) in treating children with bronchial pneumonia (Wind-heat Blocking the Lung), in order to provide strategy supported by high-quality evidence for the selection of rational clinical doses of MXSG. Methods: Based on the basic dose of MXSG, we conducted three randomized, double-blind, dose parallel controlled, multicenter clinical trials, involving adjustments to the overall dose, SG dose, and KXR dose, and included 120 children with bronchial pneumonia (Wind-heat Blocking the Lung) respectively. And the patients were divided into low, medium, and high dose groups in a 1:1:1 ratio, with 40 cases in each group. The intervention period lasted for 10 days. The primary outcome was the clinical cured rate, while the secondary outcomes included the effectiveness in alleviating major symptoms of bronchial pneumonia (including fever, cough, dyspnea, and phlegm congestion). And the occurrence of adverse events was recorded. Results: We first recorded and analyzed the baseline characteristics of the three studies, including age, gender, height, and so on. The results indicated that there were no significant differences among the dose groups within each study. For the study adjusting the overall dose of MXSG, the results showed that both the medium-dose group and high-dose group had significantly higher clinical cured rates compared to the low-dose group (Chi-square value 9.01, p = 0.0111). However, there was no significant benefit between the high-dose group and the medium-dose group (81.58% vs. 81.08%). Regarding phlegm congestion, excluding fever, cough, and dyspnea, both the medium-dose group and high-dose group had significantly higher clinical cured rates than the low-dose group (Chi-square value 6.31, p = 0.0426), and there was no significant benefit between the high-dose group and the medium-dose group (69.23% vs. 75.00%). A total of 5 adverse events were observed, of which only 1 case in the medium-dose group was possibly related to the experimental medication. For the study adjusted the SG dose in MXSG, the results showed that the high-dose group had the highest clinical cured rate, but the inter-group difference was not statistically significant (Chi-square value 3.36, p = 0.1864). The area under the curve (AUC) for cough in the medium-dose group was significantly lower than in the low-dose group and high-dose group (F-test value 3.14, p = 0.0471). Although no significant differences were observed in fever and dyspnea among the groups, the AUC in the high-dose group was lower than in the medium-dose and low-dose groups. In comparing the complete defervescence time, both the high-dose group (p < 0.0001) and the medium-dose group (p = 0.0015) achieved faster than the low-dose group. The high-dose group slightly outperformed the medium-dose group (0.50 (0.50, 0.80) vs. 0.80 (0.40, 1.40)), although the difference was not significant. In the medium-dose group, 1 adverse event was observed, but it was not related to the experimental medication. For the study adjusted the KXR dose in MXSG, the results showed that both the medium-dose group and high-dose group had significantly higher cured rates compared to the low-dose group (Chi-square value 47.05, p < 0.0001). However, there was no significant benefit comparing the high-dose group to the medium-dose group (90.00% vs. 92.50%). Regarding clinical symptoms, the results indicated that for cough (F-test value 3.16, p = 0.0460) and phlegm congestion (F-test value 3.84, p = 0.0243), the AUC for both the medium-dose group and high-dose group were significantly lower than in the low-dose group. Although there was benefit in the high-dose group compared to the medium-dose group, it was not statistically significant. No adverse events were observed during the study period. Conclusion: The synthesis of the three conducted clinical studies collectively indicates that for children with bronchial pneumonia (Wind-heat Blocking the Lung), the basic clinical dose of MXSG may represents an optimal intervention dose based on the accumulated clinical experience of doctors. If the dose is insufficient, the clinical effects might be compromised, but using a higher dose does not significantly enhance benefits. Concerning different symptoms, increasing the overall formula's dose has a favorable impact on improving phlegm congestion, increasing the SG is effective in improving symptoms such as fever, cough, and dyspnea, while higher dose of KXR is effective in alleviating cough and phlegm congestion. These findings suggest that for MXSG, achieving the optimal intervention dose is crucial to achieve better clinical efficacy. For the SG and KXR, if certain symptoms are more severe, increasing the dose can be considered within safe limits, can lead to significant clinical benefits in symptom improvement. This also explains why the dose of MXSG might vary among clinical doctors, while maintaining a balance between safety and effectiveness. Of course, our study is still exploratory clinical trials, and further studies are needed to confirm our findings. Clinical Trial Registration: https://www.chictr.org.cn/index.html; Identifier: ChiCTR-TRC-13003093, ChiCTR-TRC-13003099.

Fibular free flap necrosis after mandibular reconstruction surgery with osteoradionecrosis: Establishment and verification of an early warning model.

OBJECTIVE: Fibular free flap necrosis (FFFN) is the most common complication in patients with osteoradionecrosis (ORN) after mandibular reconstruction surgery. However, there are no effective forecasting tools at present. This research is aimed to establish and verify a nomogram model to predict the risk of FFFN after mandibular reconstruction surgery in ORN patients. METHODS: A total of 193 ORN patients with mandibular reconstruction using fibular free flap (150 cases in the model group and 43 cases in the validation group) were enrolled in this study. In the model group, the variables were optimized by lasso regression. Then the prediction model was established by binary logistic regression analysis, and the nomogram was drawn. The bootstrap self-sampling method was used for internal verification. Moreover, 43 cases in the validation group were used for external validation. RESULTS: The results of lasso regression and binary logistic regression analysis showed that the radiotherapy interval (≤2 years), trismus, diabetes, without deep venous anastomoses, and American society of anesthesiologists (ASA) III were the independent risk factors for FFFN after mandibular reconstruction surgery in ORNJ patients (P<0.05). Based on the above-mentioned risk factors, the nomogram model was established. The AUC values of the model group and the validation group were 0.936 and 0.964, respectively. The curve analysis showed that when the probability thresholds of the model group and the validation group were 5.699%∼98.229% and 0.413%∼99.721%, respectively. So the patient's clinical net profit rate was the highest. CONCLUSION: A nomogram combining the factors of radiotherapy interval (≤2 years), trismus, diabetes, without deep venous anastomoses, and ASA III provided a comparatively effective way to predict the risk of FFFN after mandibular reconstruction surgery in ORN patients, which has distinct applied clinical value.