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Objective: Baicalin has antioxidative, antiviral, and anti-inflammatory properties. However, its ability to alleviate oxidative stress (OS) and DNA damage in liver cells exposed to aflatoxin B1 (AFB1), a highly hepatotoxic compound, remains uncertain. In this study, the protective effects of baicalin on AFB1-induced hepatocyte injury and the mechanisms underlying those effects were investigated. Methods: Stable cell lines expressing CYP3A4 were established using lentiviral vectors to assess oxidative stress levels by conducting assays to determine the content of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Additionally, DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) and comet assays. Transcriptome sequencing, molecular docking, and in vitro experiments were conducted to determine the mechanisms underlying the effects of baicalin on AFB1-induced hepatocyte injury. In vivo, a rat model of hepatocyte injury induced by AFB1 was used to evaluate the effects of baicalin. Results: In vitro, baicalin significantly attenuated AFB1-induced injury caused due to OS, as determined by a decrease in ROS, MDA, and SOD levels. Baicalin also considerably decreased AFB1-induced DNA damage in hepatocytes. This protective effect of baicalin was found to be closely associated with the TP53-mediated ferroptosis pathway. To elaborate, baicalin physically interacts with P53, leading to the suppression of the expression of GPX4 and SLC7A11, which in turn inhibits ferroptosis. In vivo findings showed that baicalin decreased DNA damage and ferroptosis in AFB1-treated rat liver tissues, as determined by a decrease in the expression of γ-H2AX and an increase in GPX4 and SLC7A11 levels. Overexpression of TP53 weakened the protective effects of baicalin. Conclusions: Baicalin can alleviate AFB1-induced OS and DNA damage in liver cells via the TP53-mediated ferroptosis pathway. In this study, a theoretical foundation was established for the use of baicalin in protecting the liver from the toxic effects of AFB1.

Summary: The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Abstract Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. HCC with liver fluke infection could harbor unique biological behaviors. This study was aimed at investigating radiomics features of HCC with liver fluke infection and establishing a model to predict the expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) as well as prognosis at the same time. A total of 134 HCC patients were included. Gadoxetic acid-enhanced magnetic resonance imaging (MRI) images of all patients were acquired. Radiomics features of the tumor were extracted and then data dimensionality was reduced. The radiomics model was established to predict liver fluke infection and the radiomics score (Radscore) was calculated. There were 11 features in the four-phase combined model. The efficiency of the combined model increased significantly compared to each single-phase MRI model. Radscore was an independent predictor of liver fluke infection. It was also significantly different between different expression of CK7/ CK19. Meanwhile, liver fluke infection was associated with CK7/CK19 expression. A cut-off value was set up and all patients were divided into high risk and low risk groups of CK7/CK19 positive expression. Radscore was also an independent predictor of these two biomarkers. Overall survival (OS) and recurrence free survival (RFS) of negative liver fluke infection group were significantly better than the positive group. OS and RFS of negative CK7 and CK19 expression were also better, though not significantly. Positive liver fluke infection and CK19 expression prediction groups harbored significantly worse OS and RFS, survival of positive CK7 expression prediction was unsatisfying as well. A radiomics model was established to predict liver fluke infection among HCC patients. This model could also predict CK7 and CK19 expression. OS and RFS could be foreseen by this model at the same time.

Abstract Objective To assess the diagnostic value and clinical significance of nucleoporin 107 (NUP107) in hepatocellular carcinoma (HCC), and explore the possible mechanisms. Methods The transcriptomic and clinical data of HCC patients were retrieved from The Cancer Genome Atlas (TCGA) and GEO databases. Tissue specimens were collected from HCC patients in the Guangxi area. According to the expression levels and prognostic characteristics of NUP107, ROC curves and nomogram models were constructed using the R package. Results NUP107 was highly expressed in 26 human cancers including HCC, and was associated with advanced HCC staging and worse prognosis. NUP107 showed satisfactory ability to predict the prognosis of HCC patients (AUC >0.8). Results of gene set enrichment analysis (GSEA) further showed that NUP107 was mainly associated with cell cycle‐related pathways such as the cell cycle, DNA replication, G2M checkpoint, E2F target, and mitotic spindle. In addition, NUP107 was also associated with immune infiltration in HCC and showed significant positive correlation with immune checkpoints (PD‐L1 and TIM‐3).

Abstract Background Clear aligner (CA) treatment has been gaining popularity, but the biomechanical effects of CAs in bimaxillary dentition have not been thoroughly investigated. Direct and indirect strong anchorages are two common anchorage control methods, but the underlying biomechanical mechanism has not yet been elucidated. This study aimed to investigate the different biomechanical effects of CAs in closing the bimaxillary space under different anchorage controls, further instructing the compensation strategies design and strong anchorage choice in clinical practice. Methods Three-dimensional (3D) bimaxillary models of different anchorage controls were created based on cone-beam computed tomography and intraoral scan data. Four first premolars were extracted using 3D modeling software. Finite element analysis was conducted to simulate the space closure process of the CAs. Results In the two strong anchorage groups, the bimaxillary dentition presented different movement patterns during the space closure process, and the lower dentition was more vulnerable to elastic force. From the vertical view, direct strong anchorage with elastic force had the advantage of flattening the longitudinal occlusal curve and resisting the roller-coaster effects, whereas indirect strong anchorage could lead to a deep longitudinal occlusal curve. From the sagittal view, indirect strong anchorage with metallic ligaments had a greater instantaneous anchorage protection effect, particularly in the lower dentition, which reduced the mesial movement of the posterior teeth by nearly four times that of the direct anchorage group. In addition, indirect strong anchorage presented better anterior teeth torque/tipping control, while direct strong anchorage could aggravate lingual tipping of the upper central incisors. Due to the differences in anterior–posterior anchorage and arch shape, compared with the upper dentition, anchorage preservation and vertical control effects were amplified in the lower dentition. Conclusions The biomechanical effects of CAs differed between the two strong anchorage groups. Due to the differences in dentition morphology, anterior–posterior anchorage, and dental arch shape, CAs present different biomechanical effects in bimaxillary space closure. Orthodontists should consider the corresponding mechanical compensation according to specific anchorage control methods and dentitions.

Abstract Background As cancer is one of the main leading causes of mortality, a series of monotherapies such as chemotherapy, gene therapy and radiotherapy have been developed to overcome this thorny problem. However, a single treatment approach could not achieve satisfactory effect in many experimental explorations. Results In this study, we report the fabrication of cyclic RGD peptide (cRGD) modified Au4-iron oxide nanoparticle (Au4-IO NP-cRGD) based on aggregation-induced emission (AIE) as a multifunctional theranostic system. Besides Au4 cluster-based fluorescence imaging and enhanced radiotherapy, iron oxide (IO) nanocluster could realize magnetic resonance (MR) imaging and Fenton reaction-based chemotherapy. Abundant toxic reactive oxygen species generated from X-ray irradiation and in situ tumor-specific Fenton reaction under acidic microenvironment leads to the apoptotic and necrotic death of cancer cells. In vivo studies demonstrated good biocompatibility of Au4-IO NP-cRGD and a high tumor suppression rate of 81.1% in the synergistic therapy group. Conclusions The successful dual-modal imaging and combined tumor therapy demonstrated AIE as a promising strategy for constructing multifunctional cancer theranostic platform. Graphical Abstract

Abstract Background This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Methods A total of 112 PDAC patients from TCGA and 48 patients from GEO were included in the analysis. The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) was carried out to identify potential mechanisms of these genes affecting prognosis. Results In TCGA database, high expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway. Conclusion GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.

The purpose of this investigation was to assess the diagnostic and prognostic significance of ATP binding cassette subfamily C (ABCC) genes in hepatocellular carcinoma (HCC). The Student t-test was used to compare the expression level of ABCCs between HCC and paraneoplastic tissues. Receiver operating characteristic curve (ROC) analysis was applied for diagnostic efficiency assessment. The Kaplan–Meier method and Cox proportional hazards model were respectively applied for survival analysis. Genes with prognostic significance were subsequently used to construct prognostic models. From the perspective of genome-wide enrichment analysis, the mechanisms of prognosis-related ABCC genes were attempted to be elaborated by gene set enrichment analysis (GSEA). It was observed in the TCGA database that ABCC1, ABCC4, ABCC5, and ABCC10 were significantly upregulated in tumor tissues, while ABCC6 and ABCC7 were downregulated in HCC tissues. Receiver operating characteristic analysis revealed that ABCC7 might be a potential diagnostic biomarker in HCC. ABCC1, ABCC4, ABCC5, and ABCC6 were significantly related to the prognosis of HCC in the TCGA database. The prognostic significance of ABCC1, ABCC4, ABCC5, and ABCC6 was also observed in the Guangxi cohort. In the Guangxi cohort, both polymerase chain reaction and IHC (immunohistochemical) assays demonstrated higher expression of ABCC1, ABCC4, and ABCC5 in HCC compared to liver tissues, while the opposite was true for ABCC6. GSEA analysis indicated that ABCC1 was associated with tumor differentiation, nod-like receptor signal pathway, and so forth. It also revealed that ABCC4 might play a role in HCC by regulating epithelial-mesenchymal transition, cytidine analog pathway, met pathway, and so forth. ABCC5 might be associated with the fatty acid metabolism and KRT19 in HCC. ABCC6 might impact the cell cycle in HCC by regulating E2F1 and myc. The relationship between ABCC genes and immune infiltration was explored, and ABCC1,4,5 were found to be positively associated with infiltration of multiple immune cells, while ABCC6 was found to be the opposite. In conclusion, ABCC1, ABCC4, ABCC5, and ABCC6 might be prognostic biomarkers in HCC. The prognostic models constructed with ABCC1, ABCC4, ABCC5, and ABCC6 had satisfactory efficacy.

Esophageal squamous cell carcinoma (ESCC) is a common cancer occurring in males and females worldwide. Accumulating evidence continues to highlight the crucial roles of long non-coding RNAs (lncRNAs) in the process of tumorigenesis. However, the regulatory mechanism of lncRNAs in ESCC remains unclear. The aim of this study is to elucidate the role of lncRNA Krüppel-like factor 3 antisense RNA 1 (KLF3-AS1) in ESCC by regulating miR-185-5p and KLF3. Initially, ESCC cell spheres with stem cell-like properties were prepared by suspension culture, and subsequently characterized by assessing colony formation ability and stem cell markers. LncRNA KLF3-AS1 was found to be poorly expressed in ESCC and could upregulate the expression of KLF3 by binding to miR-185-5p. lncRNA KLF3-AS1 upregulation was observed to inhibit miR-185-5p, thereby contributing to decreased expression of SOX2 and Oct4 (octamer-binding transcription factor 4). Furthermore, enhancement of lncRNA KLF3-AS1 resulted in reduced colony formation ability, cell invasion and migration, and tumor volume in vivo while promoting cell apoptosis in ESCC through downregulation of miR-185-5p. Collectively, this study indicated that lncRNA KLF3-AS1 inhibited ESCC cell invasion and migration by impairing miR-185-5p-mediated inhibition of KLF3, highlighting a promising novel potential target for ESCC treatment.

Abstract In this paper, an anomalous spectral data of distributed Bragg reflector (DBR) quantum cascade lasers (QCLs) emitting around 7.6 μm is presented. The two-section DBR lasers, consisting of a gain section and an unpumped Bragg reflector, display an output power above 0.6 W in continuous wave (CW) mode at room temperature. The anomalous spectral data is defined as a longitudinal mode which moves toward shorter wavelengths with increasing temperature or injection current, which is unexpected. Although the longer wavelength modes are expected to start lasing when raising device temperature or injection current, occasional mode hops to a shorter wavelength are seen. These anomalous mode transitions are explained by means of modal analysis. The thermal-induced change of the refractive index implied by an increase in the temperature or injection current yields nearly periodic transitions between cavity modes.

Abstract High-power, low-threshold stable single-mode operation buried distributed feedback quantum cascade laser by incorporating sampled grating emitting at λ ~ 4.87 μm is demonstrated. The high continuous wave (CW) output power of 948 mW and 649 mW for a 6-mm and 4-mm cavity length is obtained at 20 °C, respectively, which benefits from the optimized optical field distribution of sampled grating. The single-mode yields of the devices are obviously enhanced by controlling cleaved positions of the two end facets precisely. As a result, stable single-mode emission and mode tuning linearly without any mode hopping of devices are obtained under the different heat sink temperatures or high injection currents.

Abstract Power scaling in broad area quantum cascade laser (QCL) usually leads to the deterioration of the beam quality with an emission of multiple lobes far-field pattern. In this letter, we demonstrate a tapered QCL array integrated with Talbot cavity at one side of the array. Fundamental supermode operation is achieved in the arrays with taper straight-end connected to the Talbot cavity. Lateral far-field of the fundamental supermode shows a near diffraction limited beam divergence of 2.7°. The output power of a five-element array is about three times as high as a single-ridge laser with an emission wavelength of around 4.8 μm. However, arrays with the taper-end connected to the Talbot cavity always show a high-order supermode operation whatever Talbot cavity length is.

Abstract In this work, quantum cascade lasers (QCLs) based on strain compensation combined with two-phonon resonance design are presented. Distributed feedback (DFB) laser emitting at ~ 4.76 μm was fabricated through a standard buried first-order grating and buried heterostructure (BH) processing. Stable single-mode emission is achieved under all injection currents and temperature conditions without any mode hop by the optimized antireflection (AR) coating on the front facet. The AR coating consists of a double layer dielectric of Al2O3 and Ge. For a 2-mm laser cavity, the maximum output power of the AR-coated DFB-QCL was more than 170 mW at 20 °C with a high wall-plug efficiency (WPE) of 4.7% in a continuous-wave (CW) mode.

Abstract In the present work, an ultra-low power consumption substrate-emitting distributed feedback (DFB) quantum cascade laser (QCL) was developed. The continuous-wave (CW) threshold power dissipation is reduced to 0.43 W at 25 °C by shortening the cavity length to 0.5 mm and depositing high-reflectivity (HR) coating on both facets. As far as we know, this is the recorded threshold power dissipation of QCLs in the same conditions. Single-mode emission was achieved by employing a buried second-order grating. Mode-hop free emission can be observed within a wide temperature range from 15 to 105 °C in CW mode. The divergence angles are 22.5o and 1.94o in the ridge-width direction and cavity-length direction, respectively. The maximum optical power in CW operation was 2.4 mW at 25 °C, which is sufficient to spectroscopy applications.

Abstract Very low power-consumption distributed feedback (DFB) quantum cascade lasers (QCLs) at the wavelength around 4.9 μm were fabricated by conventional process without lateral regrowth of InP:Fe or using sidewall grating. Benefitted from the optimized materials and low waveguide loss, very low threshold current density of 0.5 kA/cm2 was obtained for a device with cavity length of 2 mm. Combined with the partial-high-reflection coating, the 1-mm-long DFB QCL achieved low power-consumption continuous wave (CW) operation up to 105 °C. The CW threshold power-consumptions were 0.72 and 0.78 W at 15 and 25 °C, respectively. The maximum CW output power was over 110 mW at 15 °C and still more than 35 mW at 105 °C. At 15 °C, wall-plug efficiency of 5.5% and slope efficiency of 1.8 W/A were deduced, which were very high for low power-consumption DFB QCLs.

Skeletal stem cells (SSCs) are postnatal self-renewing, multipotent, and skeletal lineage-committed progenitors that are capable of giving rise to cartilage, bone, and bone marrow stroma including marrow adipocytes and stromal cells in vitro and in an exogenous environment after transplantation in vivo. Identifying and isolating defined SSCs as well as illuminating their spatiotemporal properties contribute to our understating of skeletal biology and pathology. In this review, we revisit skeletal stem cells identified most recently and systematically discuss their origin and distributions.

Objective: To investigate the expression of p16, cyclin D1, retinoblastoma tumor suppressor protein (Rb) and MIB-1 in skull base chordoma and chondrosarcoma tissues, and to determine the clinicopathological significance of the above indexes in these diseases. Methods: A total of 100 skull base chordoma, 30 chondrosarcoma, and 20 normal cartilage tissue samples were analyzed by immunohistochemistry. The expression levels of p16, cyclinD1, Rb and MIB-1 proteins were assessed for potential correlation with the clinicopathological features. Results: As compared to normal cartilage specimen (control), there was decreased expression of p16, and increased expression of cyclin D1, Rb and MIB-1 proteins, in both skull base chordoma and chondrosarcoma specimens. MIB-1 LI levels were significantly increased in skull base chordoma specimens with negative expression of p16, and positive expression of cyclin D1 and Rb (P 0.05). However, p16 and MIB-1 levels correlated with the intradural invasion, and expression of p16, Rb and MIB-1 correlated with the number of tumor foci (P

Background: To investigate the relation between serum leptin levels and cerebral infarction (CI) by meta-analysis. Materials and Methods: Scientific literature databases were searched for studies published in Chinese and English. After retrieving relevant articles through database searches and screening using predefined selection criteria, high-quality studies related to our research topic were selected for inclusion in this meta-analysis. All statistical analyses were conducted using Comprehensive Meta-Analysis 2.0 (CMA 2.0, Biostat Inc., Englewood, New Jersey, USA). Results: The study results revealed that serum leptin levels were significantly higher in CI patients as compared to normal controls. The outcomes of subgroup analysis by ethnicity suggested that the serum leptin levels in CI patients were significantly higher than normal controls in both Asian and Caucasian populations. Further, subgroup analysis based on the detection method indicated that the serum leptin levels in CI patients were significantly higher compared with normal controls when measured by radioimmunoassay (RIA) but enzyme-linked immunosorbent assay (ELISA)-based measurements did not show such statistically significant differences. Conclusion: Our meta-analysis results suggest that serum leptin levels in CI patients may be closely correlated with CI risks.

Coilia nasus, a migratory fish species found in the middle and lower reaches of the Yangtze River and along offshore areas of China, possesses considerable aquacultural and economic potential. However, the species faces challenges due to significant variation in the gonadal development rate among females, resulting in inconsistent ovarian maturation times at the population level, an extended reproductive period, and limitations on fish growth rate due to ovarian prematurity. In the present study, we combined genome-wide association study (GWAS) and comparative transcriptome analysis to investigate the potential single nucleotide polymorphisms (SNPs) and candidate genes associated with population-asynchronous ovarian development in C. nasus. Genotyping of the female population based on whole-genome resequencing yielded 2 120 695 high-quality SNPs, 39 of which were suggestively associated with ovarian development. Of note, a significant SNP peak on LG21 containing 30 suggestively associated SNPs was identified, with cpne5a determined as the causal gene of the peak. Therefore, single-marker and haplotype association analyses were performed on cpne5a, revealing four genetic markers (P<0.05) and seven haplotypes (r2>0.9) significantly associated with the phenotype. Comparative transcriptome analysis of precociously and normally maturing individuals screened out 29 and 426 overlapping differentially expressed genes in the brain and ovary, respectively, between individuals of different body sizes. Integrating the GWAS and transcriptome analysis results, this study identified genes and pathways related to hypothalamic-pituitary-gonadal axis hormone secretion, extracellular matrix, angiogenesis, and gap junctions involved in population-asynchronous ovarian development. The insights gained from this study provide a basis for a deeper understanding of the molecular mechanisms underlying ovarian development in fish and may facilitate the genetic breeding of C. nasus strains exhibiting population-synchronous ovarian development in the future. [ABSTRACT FROM AUTHOR]