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Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments. Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood‒tumor barrier (BTB). BTB activates its Wnt signaling to maintain barrier properties, e.g., Mfsd2a-mediated BTB low transcytosis. Here, we reported VCAM-1-targeting nano-wogonin (W@V-NPs) as an adjuvant of nano-orlistat (O@V-NPs) to intensify drug delivery and inhibit lipogenesis of brain metastases. W@V-NPs were proven to be able to inactivate BTB Wnt signaling, downregulate BTB Mfsd2a, accelerate BTB vesicular transport, and enhance tumor accumulation of O@V-NPs. With the ability to specifically kill cancer cells in a lipid-deprived environment with IC50 at 48 ng/mL, W@V-NPs plus O@V-NPs inhibited the progression of brain metastases with prolonged survival of model mice. The combination did not induce brain edema, cognitive impairment, and systemic toxicity in healthy mice. Targeting Wnt signaling could safely modulate the BTB to improve drug delivery and metabolic therapy against brain metastases.

This is an article in the field of ceramics and composites. In order to improve the impermeability and microstructure of the impermeable wall materials, four kinds of calcium-based bentonite modified and filling material with different dosages were prepared under the action of alkali excitation reaction. The modified and filling material samples in the curing process were tested by flexible wall penetration (FWPT), nuclear magnetic resonance (NMR) scanning and electron microscope scanning (SEM). The results show that the permeability coefficient of filling material samples decreases first and then increases with the increase of bentonite content, and reaches a minimum value when the content of bentonite is 4%. The relaxation time (T2) distribution curves of the filled material specimens after curing from 1 to 28 d were all bimodal, with more than 80% of the peaks representing small pores, and the percentage of the peaks representing large pores decreasing with the increase of curing time. According to SEM images, it can be seen that a certain amount of calcium bentonite can promote the occurrence of hydration reaction, and the porosity of the material is significantly reduced. At 4% phosphate slag, the cementitious filler has the best compactness and better impermeability and strength. Accordingly, it can be determined that the better dosage of phosphate slag modified cementitious filler is 4%.

Gastric cancer (GC) is a common malignant tumor that is pernicious to the health of patients. Proteasome activator subunit 3 (PSME3) has been shown to exhibit higher expression and aggravate tumorigenesis in cancer progression. A major finding is that PSME3 is also highly expressed in GC tissues, which results in a worse prognosis. Nevertheless, the regulatory functions of PSME3 in GC progression remain unclear. This study aimed to investigate the impacts of PSME3 and related regulatory pathways on GC progression. From the Gene Expression Profiling Interactive Analysis (GEPIA) database, it was noted that PSME3 expression was up-regulated in GC tissues. Our findings suggested that in GC, PSME3 showed higher expression, resulting in a worse prognosis. Functional experiments revealed that PSME3 accelerates cell growth, migration and abnormal glycolysis in GC. PSME3 stimulates the epidermal growth factor receptor (EGFR)/c-myc pathway. In conclusion, GC cells exhibited higher PSME3 expression, which modulated the EGFR/c-myc pathway to facilitate glycolysis and migration. PSME3 might be an effective bio-target for GC treatment.

Nano-particles demonstrating excellent anticancer properties have gradually found application in cancer therapy. However, their widespread use is impeded by their potential toxicity, high cost, and the complexity of the preparation process. In this study, we achieved exosome-like Centella asiatica-derived nanovesicles (ADNVs) through a straightforward juicing and high-speed centrifugation process. We employed transmission electron microscopy and nanoparticle flow cytometry to characterize the morphology, diameter, and stability of the ADNVs. We evaluated the in vitro anticancer effects of ADNVs using Cell Counting Kit-8 and apoptosis assays. Through sequencing and bicinchoninic acid protein analysis, we discovered the abundant presence of proteins and microRNAs in ADNVs. These microRNAs can target various diseases such as cancer and infection. Furthermore, we demonstrated the effective internalization of ADNVs by HepG2 cells, resulting in an increase in reactive oxygen species levels, mitochondrial damage, cell cycle arrest at the G1 phase, and apoptosis. Finally, we analyzed changes in cellular metabolites post-treatment using cell metabolomics techniques. Our findings indicated that ADNVs primarily influence metabolic pathways such as amino acid metabolism and lipid biosynthesis, which are closely associated with HepG2 treatment. Our results demonstrate the potential utility of ADNVs as anticancer agents.

Abstract Near‐infrared (NIR)‐II fluorescence imaging‐guided photothermal therapy (PTT) has attracted great research interest, and constructing donor‐acceptor (D‐A) electronic configurations has become an established approach to lower bandgap and realize NIR‐II emission. However, very few π‐conjugated phototheranostic agents can realize efficient NIR‐II guided PTT using a clinically safe laser power density, implying that sufficient photothermal performance is still desired. In addition to the continuously refreshed photothermal conversion efficiency levels, the strategies that focus on enhancing light absorptivity have been rarely discussed and endow a new direction for enhancing PTT. Herein, a dimerization π‐extension strategy is raised to synthesize π‐conjugated dimers with A‐D‐A monomers. We observe that the light absorptivity (ε) of the dimers is strengthened three times owing to the enhanced electronic coupling effect as a result of the π‐conjugation extension, thereby surpassing the 2‐fold increase in chromophore numbers from the monomer to dimers. Thanks to the enhancement in light absorption, the dimers could generate much more photothermal heat than the monomer in in vivo PTT treatments. Therefore, an efficient anti‐tumor outcome has been fulfilled by using dimers under a low laser power (0.3 W/cm2). Moreover, the dimers with extended π‐conjugation structures become more favorable to the radiative excited state decay, thus exhibiting a distinguishing improvement in NIR‐II imaging compared with monomer. Collectively, due to the improved light absorptivity, the dimers can gain superior NIR‐II fluorescence brightness and photothermal performance over the recently reported material, which goes beyond the monomer in double doses for in vivo applications. All these results prove that dimerization is an effective strategy for designing high‐performance phototheranostic materials.

This study aimed to investigate the role of miR-558 in tumor angiogenesis by targeting heparinase (HPSE) in tongue squamous cell carcinoma (TSCC)-derived exosomes. In the present study, the role of exosome miR-558 in angiogenesis in vitro and in vivo was investigated by cell proliferation, migration, tube formation, subcutaneous tumor formation in mice, and in vivo Matrigel plug assay. The target genes of miR-558 were detected by means of dual luciferase assay. It was found that TSCC cells secrete miR-558 into the extracellular environment, with exosome as the carrier. Human umbilical vein endothelial cells (HUVEC) ingested exosomes, which not only increased the expression level of miR-558, but also enhanced their proliferation, migration, and tube formation functions. In vivo Matrigel plug assay demonstrated that TSCC cell-derived exosome miR-558 promoted neovascularization in vivo. Compared with negative control cells, TSCC cells overexpressing miR-558 formed subcutaneous tumors in nude mice, with larger volume, heavier mass, and more vascularization. Dual luciferase assay confirmed that HPSE was the direct target gene regulated by miR-558. HPSE promoted the proliferation, migration, and tube formation of HUVECs, and the knockout of HPSE could downregulate the pro-angiogenic effect of miR-558. In summary, miR-558 in TSCC exosomes promotes the proliferation, migration, and tube formation of HUVECs by targeting HPSE, and enhancing tumor angiogenesis.

BackgroundPheochromocytoma is one of the most hereditary human tumors with at least 20 susceptible genes undergoing germline and somatic mutations, and other mutations less than 1% -2%. In recent years, other rare mutations have gradually been discovered to be possibly related to the pathogenesis and metastasis of pheochromocytoma. Most patients with pheochromocytoma experience common symptoms like headaches, palpitations, and sweating, while some may have less common symptoms. The diversity of symptoms, genetic mutations, and limited treatment options make management challenging.Case presentationA 53-year-old woman was hospitalized after experiencing episodic epigastric pain for one month. A mass was found in her right adrenal gland and she underwent robot-assisted laparoscopic surgery, revealing a pheochromocytoma. At the 16-month follow-up, multiple metastatic lesions consistent with metastatic pheochromocytoma were found. A germline mutation in the dihydrolipoamide succinyltransferase (DLST) gene (c.330 + 14A>G) was detected, and despite trying chemotherapy and adjuvant therapy, the patient had a limited response with an overall survival of 27 months.ConclusionsDLST mutation is one of the rare pheochromocytoma-related mutated genes, and genetic sequencing is crucial for effective clinical management.

Abstract Aim To investigate the relationship between chemoresistance in pancreatic cancer patients receiving postoperative gemcitabine adjuvant therapy and specific clinical/pathological characteristics, as well as its impact on patient prognosis. Methods From June 2018 to June 2021, clinical and pathological data of 148 pancreatic cancer patients were collected, and 101 patients were followed up for tumor recurrence/metastasis and survival status. The correlation between chemoresistance and specific clinical/pathological characteristics or patient prognosis was retrospectively analyzed. Results Of the 148 patients, 78 were in the chemoresistance group and 70 in the non‐chemoresistance group. Univariate analysis showed that the development of chemoresistance may be related to patient age, combined diabetes, preoperative CA19‐9 level, tumor size, AJCC stage, vascular invasion, and positive lymph node ratio. Furthermore, subsequent multivariate analysis incorporating these variables indicated that tumor size may be a key factor influencing chemoresistance (p 3 cm). Conclusions Patients with pancreatic cancer receiving postoperative gemcitabine adjuvant therapy are more likely to develop chemoresistance when their tumor sizes are larger (diameter >3 cm). Development of chemoresistance exacerbates the prognosis of patients with pancreatic cancer, and larger tumor size is also a risk factor for poor prognosis in these patients.

Abstract Controversy surrounds the role of serum uric acid and whether treatment intervention is favorable in retarding the progression of chronic kidney disease (CKD). The association of serum uric acid levels and CKD patient mortality risk needs to be further determined by large sample cohort studies. The National Health and Nutrition Examination Survey participants with CKD from 1998 to 2017 were enrolled in the study. Multivariable Cox regression models were used to reveal the association of serum uric acid concentrations and CKD mortality risks. A total of 9891 CKD patients were enrolled in the study, and 3698 individuals died during the follow-up. Increasing serum uric acid levels are independently relevant to higher mortality risks of CKD patients (HR per SD increase). A restricted cubic spline curve showed a nonlinear association between serum uric acid and CKD mortality risks (p for nonlinearity = 0.046). CKD patients with higher levels of serum uric acid (≥ 5.900 mg/dL) show a significant increase in mortality risks (HR = 1.102, 95% CI 1.043–1.165). Sensitivity analysis demonstrated that the results were stable and robust. High serum uric acid levels (≥ 5.900 mg/dL) may be associated with increased mortality risks in CKD patients.

Groundwater plays an essential role in stabilizing underground structures. However, hydrostatic uplift forces from groundwater can create safety hazards. This paper obtained the groundwater buoyancy reduction coefficients of 36 types of clays through model tests and conducted a finite element simulation to obtain the buoyancy reduction coefficients of additional clays with varying soil properties. Machine learning methods, including extreme gradient boosting (XGBoost) and random forest (RF) algorithms, were used to analyze and identify the soil parameters that have a significant impact on the reduction of groundwater buoyancy. It was found that the permeability coefficient and saturation are the primary factors that influence the reduction of groundwater buoyancy. Additionally, the prediction models developed by XGBoost and RF were compared, and their accuracy was evaluated. These research findings can serve as a reference for designing underground structures that can withstand the potential risk of buoyancy in clay.

Abstract Aim To investigate the relationship among emotional intelligence (EI), resilience and academic procrastination (AP), and provide suggestions for the development of targeted intervention strategies and lowering of AP level of nursing undergraduates. Design A cross‐sectional study. Methods Three provincial universities offering nursing courses in China were investigated in this study. A convenience sample of 256 nursing undergraduates from May 2021 to September 2021 were recruited, with a response rate of 91.4%. Data were collected using face‐to‐face interviews. The survey tools included the General Information Questionnaire, Academic Procrastination Scale, Emotional Intelligence Scale and Resilience Scale. IBM SPSS v19.0 and Amos 22.0 were used for data analysis. Results The AP of sampled nursing undergraduates was at the middle level (54.4 ± 21.5). The AP of nursing undergraduates was negatively correlated with EI and resilience. Moreover, the analysis on the mediating role of resilience via structural equation model showed a good fit, with χ2/df = 2.34, RMSEA = 0.07, CFI = 0.99, GFI = 0.95, TLI = 0.98. Patient or Public Contribution No patient or public contribution.

Abstract Background Combination of chidamide and anti‐PD‐L1 inhibitor produce synergistic anti‐tumor effect in advanced NSCLC patients resistant to anti‐PD‐1 treatment. However, the effect of chidamide plus envafolimab has not been reported. Aims This study aimed to evaluate the efficacy of chidamide plus envafolimab in advanced NSCLC patients resistant toanti‐PD‐1 treatment. Materials and Methods Eligible advanced NSCLC patients after resistant to anti‐PD‐1 therapy received chidamide and envafolimab. The primary endpoint was objective response rate (ORR). The secondary end points included disease control rate (DCR), progression‐free survival (PFS), and safety. The expression of histone deacetylase 2 (HDAC2), PD‐L1, and blood TMB (bTMB) was also analyzed. Results After a median follow‐up of 8.1 (range: 7.6–9.2) months, only two patients achieved partial response. The ORR was 6.7% (2/30), DCR was 50% (15/30), and median PFS (mPFS) was 3.5 (95% confidence interval: 1.9–5.5) months. Biomarker analysis revealed that patients with high‐level HDAC2 expression had numerically superior ORR (4.3% vs. 0), DCR (52.2% vs. 0) and mPFS (3.7 vs. 1.4m). Patients with negative PD‐L1 had numerically superior DCR (52.2% vs. 33.3%) and mPFS (3.7m vs. 1.8m), so were those with low‐level bTMB (DCR: 59.1% vs. 16.7%, mPFS: 3.8 vs.1.9m). Overall safety was controllable. Discussion High HDAC2patients showed better ORR, DCR, and PFS. In addition, patient with negative PD‐L1 and low‐level bTMB had better DCR and PFS. This may be related to the epigenetic function of chidamide. However, the sample size was not big enough, so it is necessary to increase sample size to confirm the conclusion. Conclusion Combination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.

Abstract Deep NIR organic phototheranostic molecules generally have large π‐conjugation structures and show highly hydrophobic properties, thus, forming strong π–π stacking in the aqueous medium, which will affect the phototheranostic performance. Herein, an end‐group strategy is developed to lift the performance of NIR‐II emitting photosensitizers. Extensive characterizations reveal that the hydrogen‐bonding interactions of the hydroxyl end group can induce a more intense π–π electronic coupling than the chlorination‐mediated intermolecular forces. The results disclose that π–π stacking will lower fluorescence quantum yield but significantly benefit the photodynamic therapy (PDT) efficiency. Accordingly, an asymmetrically substituted derivative (BTIC‐δOH‐2Cl) is developed, which shows balanced phototheranostic properties with excellent PDT efficiency (14.6 folds of ICG) and high NIR‐II fluorescence yield (2.27%). It proves the validity of the end‐group strategy on controlling the π–π interactions and rational tuning the performance of NIR‐II organic phototheranostic agents.

Abstract Background To examine the expression characteristics of single nucleotide polymorphisms (SNPs) in the SRD5A2 gene and investigate their potential association with differences in the clinical characteristics between sexes in patients with chronic hepatitis B virus (HBV) infection. Methods A total of 30 loci in six genes primarily involved in the metabolism and signaling of sex hormones/sex hormone receptors, namely AKR1C2, AKR1C3, HSD17B6, SRD5A1, SRD5A2, and ESR1, were genotyped in 1007 patients from eight counties (cities) in Northeastern China with chronic HBV infection and 1040 healthy controls, and their association with viral replication characteristics and the differences in disease severity between sexes was assessed. Western blotting was conducted to determine the hepatic SRD5A2 protein level and its relationship with the inflammatory activity and fibrosis degree in male and female patients. Results Two SNP loci in the SRD5A2 gene (rs12470143 and rs7594951) exhibited significant differences in genotype and allele frequencies between sexes, with the proportion of T alleles significantly higher in males than in females. It was found that the incidence and severity of HBV-related liver fibrosis were significantly higher in patients with the T/T genotype in SRD5A2 rs12470143 and rs7594951 than those with the non-T/T genotype. Additionally, serum HBV DNA levels were significantly elevated in T/T patients compared to non-T/T patients. Female patients exhibited significantly lower serum DNA levels compared to male patients. Western blot analysis indicated that greater hepatic SRD5A2 protein levels were associated with higher METAVIR inflammation and fibrosis scores. Furthermore, multivariate analysis showed that the two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T), together with the male sex, age > 50 years old, HBeAg positive status, elevated serum HBsAg load, high serum HBV DNA load, and HBV genotype C, were independent risk factors for HBV-related liver fibrosis. Conclusions This study demonstrated that two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T) are associated with sex differences in the clinical characteristics of patients with chronic HBV infection.

Abstract Background Glioblastoma (GBM) is the most malignant glioma, with poor survival rates and prognosis. Several studies have reported the abnormal expression of circular RNAs (circRNAs) and their functions in the malignant biological behavior of GBM. However, such research is still in the preliminary stages, and further study is needed to confirm the therapeutic potential of circRNAs in GBM. Methods RNA-seq was performed using four tumor tissues from patients with GBM and their adjacent non-tumor brain tissues to screen differentially expressed circRNAs. Fluorescence in situ hybridization assay was used to examine the location of circ_0021350 in glioma cells. In addition, a series of biological function assays were employed to verify the oncogenic role of circ_0021350 in GBM. Quantitative reverse transcription PCR was used to examine circular, micro- (miRNA), and messenger RNA (mRNA) levels. Furthermore, dual-luciferase reporter, RNA pull-down, and RNA binding protein immunoprecipitation assays were applied to verify the interaction between circ_0021350 and its downstream effectors. Results Circ_0021350 was significantly elevated in GBM tissues and glioma cells. Overexpression of circ_0021350 promoted glioma cell proliferation and metastatic ability; silencing of circ_0021350 had the opposite effect. Mechanistic analysis revealed that circ_0021350 sponged miR-1207-3p to regulate PIK3R3, whose overexpression reversed the reduction in the malignant biological behavior of glioma cells caused by silencing circ_0021350. Conclusion Our findings suggest that circ_0021350 is an oncogenic circRNA in GBM, and the circ_0021350/miR-1207-3p/PIK3R3 axis may serve as a potential therapeutic target in GBM treatment.

Lung cancer stands as one of the most prevalent malignancies worldwide, bearing the highest morbidity and mortality rates among all malignant tumors. The treatment of lung cancer primarily encompasses surgical procedures, radiotherapy, and chemotherapy, which are fraught with significant side effects, unfavorable prognoses, and a heightened risk of metastasis and relapse. Although targeted therapy and immunotherapy have gradually gained prominence in lung cancer treatment, diversifying the array of available methods, the overall recovery and survival rates for lung cancer patients remain suboptimal. Presently, with a holistic approach and a focus on syndrome differentiation and treatment, Traditional Chinese Medicine (TCM) has emerged as a pivotal player in the prognosis of cancer patients. TCM possesses characteristics such as targeting multiple aspects, addressing a wide range of concerns, and minimizing toxic side effects. Research demonstrates that Traditional Chinese Medicine can significantly contribute to the treatment or serve as an adjunct to chemotherapy for lung cancer and other lung-related diseases. This is achieved through mechanisms like inhibiting tumor cell proliferation, inducing tumor cell apoptosis, suppressing tumor angiogenesis, influencing the cellular microenvironment, regulating immune system function, impacting signal transduction pathways, and reversing multidrug resistance in tumor cells. In this article, we offer an overview of the advancements in research concerning Traditional Chinese Medicine extracts for the treatment or adjunctive chemotherapy of lung cancer and other lung-related conditions. Furthermore, we delve into the challenges that Traditional Chinese Medicine extracts face in lung cancer treatment, laying the foundation for the development of diagnostic, prognostic, and therapeutic targets.

Rheumatoid arthritis (RA) is a self-immune inflammatory disease characterized by joint damage. A series of cytokines are involved in the development of RA. Oncostatin M (OSM) is a pleiotropic cytokine that primarily activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and other physiological processes such as cell proliferation, inflammatory response, immune response, and hematopoiesis through its receptor complex. In this review, we first describe the characteristics of OSM and its receptor, and the biological functions of OSM signaling. Subsequently, we discuss the possible roles of OSM in the development of RA from clinical and basic research perspectives. Finally, we summarize the progress of clinical studies targeting OSM for the treatment of RA. This review provides researchers with a systematic understanding of the role of OSM signaling in RA, which can guide the development of drugs targeting OSM for the treatment of RA.

Abstract Background To describe an ultrastructure in the vitreous base (VB) and its micro-anatomical characteristics by multimodal imaging. Methods Light and transmission electron microscopy of the VB were performed on specimens from post-trauma eyes and one healthy donor eye. Intra-operative fundus images associated with VB abnormalities were captured from 4 cases, including 2 retinal detachment (RD) with PVR eyes and 2 post-trauma eyes. Images during micro-anatomical observation of the three specimens were analyzed along with the fundus images obtained during vitrectomy. Results Densely packed collagen fibers were observed by light microscopy between the pigment epithelium layer and uveal tissue within the ora serrata region in specimen 1 and the post-mortem healthy eye, respectively. A similar structure was also observed by transmission electron microscopy interior to the pigment epithelium layer and exposed to the vitreous cavity in specimen 2. The collagen fibers, which were termed ciliary body-choroid-retina (CB-C-R) connector, connects to the vitreous fibers interiorly, ciliary epithelium anteriorly, peripheral retina posteriorly, and uveal tissue exteriorly. The three different RD boundaries related to the posterior edge of the VB, ora serrata, and ciliary epithelium are demonstrated with the micro-anatomical characteristics of the CB-C-R connector. Conclusion The CB-C-R connector exists deep in the VB.

Abstract A stable and reliable clock synchronization system that transfers reference clocks to nodes is essential for telecom networks. Mainly, the clock synchronization of telecom networks is carried out through satellite links. However, for the evolving ubiquitous wireless communications, especially in some harsh environments, such as underground and trenches, the satellite-based clock synchronization scheme bears inevitable obstacles, which may cause strategic risks for the telecom networks, since no control and manipulation can be imposed on the satellite systems. Therefore, to ensure the robust operation of telecom networks with performance guarantees, some auxiliary means are desirable to assist clock synchronization that is solely based on satellite links. In this article, we report a phase-stabilized frequency signal transmission on branching optical fiber for clock synchronization for telecom networks. Particularly, the phase fluctuation due to optical carriers separation link and fiber link is compensated by a feedback network, which employs a high-precision voltage-controlled oscillator in the phase-locked loop to drive the acousto-optic frequency shifter for fast phase correction. Furtherly, the factors that cause performance limitations of the frequency distribution system are analyzed. Eventually, the experiment results obtained show that a stabilized fiber-optic frequency transfer scheme can be used as a reliable method for clock synchronization with high accuracy.

Abstract Objective To investigate the efficacy of the minimally invasive clamp reduction technique via the anterior approach in the treatment of irreducible intertrochanteric femoral fractures. Methods From January 2015 to January 2021, 115 patients (48 males and 67 females) with irreducible intertrochanteric femoral fractures were treated. The average age of the patients was 78.7 (45–100 years old). The types of injuries were falls (91 cases), traffic accidents (12 cases), smashing (6 cases), and high falling (6 cases). The duration between injury and surgery ranged from 1 to 14 days, with an average of 3.9 days. The distribution of AO classification was as follows: 31-A1 in 15 cases, type 31-A2 in 67 cases and 31-A3 in 33 cases. Results All patients achieved good reduction, with fracture reduction times ranging from 10 to 32 min (mean of 18 min), and were followed up for 12–27 months after surgery (mean of 17.9 months). Two patients with pronation displacement of the proximal fracture segment died of infection or hypostatic pneumonia after internal fixation failure; one patient with failed internal fixation switched to joint replacement. After internal fixation, the lateral wall of six reversed intertrochanteric femoral fractures showed repronation and abduction displacement, but all fractures achieved bony healing. The rest of the patients did not lose fracture reduction, and all fractures achieved bony healing with a healing time ranging from 3 to 9 months (mean of 5.7 months). While two patients died and one patient exhibited failed internal fixation and thus switched to joint replacement, 91 of the remaining 112 patients had an excellent Harris score of the hip joint function at the final follow-up, while 21 patients had a good Harris score. Conclusion The minimally invasive clamp reduction technique via the anterior approach for the treatment of irreducible intertrochanteric femoral fractures is simple, effective and minimally invasive. In the case of irreducible intertrochanteric femoral fractures associated with lateral wall displacement, the lateral wall needs to be strengthened after clamp reduction and intramedullary nail fixation to avoid loss of reduction and failure of internal fixation.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, of which the leading cause of death is cardiovascular disease (CVD). The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) in RA decrease especially under hyperinflammatory conditions. It is conflictive with the increased risk of CVD in RA, which is called “lipid paradox”. The systemic inflammation may explain this apparent contradiction. The increased systemic proinflammatory cytokines in RA mainly include interleukin-6(IL-6)、interleukin-1(IL-1)and tumor necrosis factor alpha(TNF-α). The inflammation of RA cause changes in the subcomponents and structure of HDL particles, leading to a weakened anti-atherosclerosis function and promoting LDL oxidation and plaque formation. Dysfunctional HDL can further worsen the abnormalities of LDL metabolism, increasing the risk of cardiovascular disease. However, the specific mechanisms underlying lipid changes in RA and increased CVD risk remain unclear. Therefore, this article comprehensively integrates the latest existing literature to describe the unique lipid profile of RA, explore the mechanisms of lipid changes, and investigate the impact of lipid changes on cardiovascular disease.

Background: Fibrotic extracellular matrix (ECM) remodeling characterized different types of pulmonary fibrosis, and its regulation could be a potential shared treatment strategy for pulmonary fibrosis. Purpose: We aimed to investigate the effect of triptolide on pulmonary fibrosis through the inhibition of several important aspects of fibrotic ECM remodeling. Methods: Bleomycin-induced pulmonary fibrosis mice and TGF-β1-induced primary lung fibroblasts were used. The effect of triptolide on pulmonary fibrosis was detected using histopathology, immunostaining, RT-qPCR, western blotting, ELISA, and protein activity assay. Results: Triptolide significantly alleviated bleomycin-induced pulmonary fibrosis in mice. It inhibited the expression of fibrotic genes α-SMA, collagen I, fibronectin, and vimentin and blocked the TGF-β-SMAD signaling pathway both in vivo and in vitro. In addition, triptolide regulated the expression and activity of MMPs during fibrosis. Interestingly, it suppressed the expression of lysyl oxidase, which was responsible for matrix cross-linking and elevated ECM stiffness. Furthermore, triptolide blocked the biomechanical stress transduction pathway integrin-β1-FAK-YAP signaling and attenuated the pro-fibrotic feedback of fibrotic ECM on fibroblasts via integrin inhibition. Conclusion: These findings show that triptolide prevents the key linkages of fibrotic ECM remodeling, including deposition, degradation, cross-linking, and pro-fibrotic feedback and, therefore, has potential therapeutic value for pulmonary fibrosis.

AimsTo explore the clinical characteristics of patients with symptomatic duodenal diverticula and to generalize how to make appropriate treatment choices for this group of patients.Materials and methodsFrom January 2010 to September 2020, a total of 647 patients with duodenal diverticula (DD) were included in this study. 345 of them with relevant symptoms were divided into the symptomatic group and the other 302 patients were in the asymptomatic group.ResultsAmong all patients, most DD were located in the periampullary area,

During the spaceborne inverse synthetic aperture ladar (ISAL) imaging, the radial velocity between the piggyback satellite of ladar and the observed satellite is usually relatively large, which will introduce the inner-pulse Doppler that cannot be ignored in the echo. In this case, the traditional “stop-and-go” assumption will no longer hold, and the compressed result along the range direction would be seriously broaden. Therefore, to obtain a well-focused ISAL image, this article proposed a spaceborne ISAL imaging algorithm for high-speed moving targets based on the inner-pulse Doppler compensation and residue video phase (RVP) correction. In the article, the estimate method of the radial velocity, the inner-pulse Doppler compensation method, and the RVP correction method are given. After inner-pulse Doppler compensation, RVP correction and translational motion compensation, the range-compressed result under the “stop-and-go” assumption can be obtained, and the target can then be imaged by the traditional ISAL imaging algorithm. The simulation results demonstrate the effectiveness of the proposed algorithm.

Meningioma, one of the most common primary central nervous system tumors, are classified into three grades by the World Health Organization (WHO) based on histopathology. The gold-standard treatment, surgical resection, is hampered by issues such as incomplete resection in some cases and a high recurrence rate. Alongside genetic alterations, DNA methylation, plays a crucial role in progression of meningiomas in the occurrence and development of meningiomas. The epigenetic landscape of meningioma is instrumental in refining tumor classification, identifying robust molecular markers, determining prognosis, guiding treatment selection, and innovating new therapeutic strategies. Existing classifications lack comprehensive accuracy, and effective therapies are limited. Methylated DNA markers, exhibiting differential characteristics across varying meningioma grades, serve as invaluable diagnostic tools. Particularly, combinatorial methylated markers offer insights into meningioma pathogenesis, tissue origin, subtype classification, and clinical outcomes. This review integrates current research to highlight some of the most promising DNA and promoter methylation markers employed in meningioma diagnostics. Despite their promise, the development and application of DNA methylation biomarkers for meningioma diagnosis and treatment are still in their infancy, with only a handful of DNA methylation inhibitors currently clinically employed for meningioma treatment. Future studies are essential to validate these markers and ascertain their clinical utility. Combinatorial methylated DNA markers for meningiomas have broad implications for understanding tumor development and progression, signaling a paradigm shift in therapeutic strategies for meningiomas.

Abstract Water-conducting fractured zones in a rock mass can cause problems in mining. Attempts have been made to monitor their development using microseismic signals. However, due to the lack of prior information, it is difficult to filter out mixed low-frequency interference with traditional denoising methods. In this work, the proposed adaptive filtering algorithm is applied after the wavelet packets are decomposed. It is based on a cross-correlation analysis. The algorithm takes a high-quality signal in the common source waveform as prior information and applies the corresponding correlation coefficients between subbands as a threshold. The algorithm was verified with simulations. The results show that low-frequency interference can be effectively suppressed by filtering. For single-frequency interference, the signal-to-noise ratio increased from − 10.18 to 13.97, and the root-mean-square error was 43.88. For multi-frequency interference, it increased from − 10.01 and − 2.63 to 13.50 and 7.99. The root-mean-square errors were 46.31 and 138.07. The narrower the main frequency band of the interference signal and the less the overlap of the main frequency band of the interference signal and the effective signal, the better the filtering effect. When the algorithm was applied to microseismic data collected in the field, the number of effective channels increased and the accuracy improved. The development of a water-conducting fractured zone in the field was consistent with the microseismic location obtained after interference was removed by the algorithm, which indicates that it is feasible to monitor a water-conducting fractured zone by analyzing microseismic waveforms with the adaptive filtering algorithm.

Seismic responses of utility tunnel-soil system were studied via shaking table model tests with considerations of two kinds of double box utility tunnels: with and without joint connections. These two testing utility tunnel models were made of galvanized iron wire and micro-concrete, and the ground was simulated by the dry standard sand through layered tamping treatment. The utility tunnel-soil system was subjected to horizontal vibration in uniaxial direction perpendicular to the longitudinal direction of tunnel model. Via instrumentations of earth pressure gauges, accelerometers and strain gauges, the earth pressure response, acceleration response and bending moment response were measured. The testing results show that the joint connections in the utility tunnel along the longitudinal direction play an important role in determining the characteristic of earth pressure response and bending moment response, whereas the effect of joint connections on acceleration response is less significant. In addition, the partition wall exhibits the consistent acceleration response with the side-wall of double box utility tunnel model under seismic condition. Based on the testing results, it is suggested that the joint connection should be taken reasonably into consideration during design and construction for engineering practice.

Slope stability prediction plays a significant role in landslide disaster prevention and mitigation. This study develops an ensemble learning-based method to predict the slope stability by introducing the random forest (RF) and extreme gradient boosting (XGBoost). As an illustration, the proposed approach is applied to the stability prediction of 786 landslide cases in Yunyang County, Chongqing, China. For comparison, the predictive performance of RF, XGBoost, support vector machine (SVM), and logistic regression (LR) is systematically investigated based on the well-established confusion matrix, which contains the known indices of recall rate, precision, and accuracy. Furthermore, the feature importance of the 12 influencing variables is also explored. Results show that the accuracy of the XGBoost and RF for both the training and testing data is superior to that of SVM and LR, revealing the superiority of the ensemble learning models (i.e. XGBoost and RF) in the slope stability prediction of Yunyang County. Among the 12 influencing factors, the profile shape is the most important one. The proposed ensemble learning-based method offers a promising way to rationally capture the slope status. It can be extended to the prediction of slope stability of other landslide-prone areas of interest.

Abstract The master integrals for the mixed QCD-QED two-loop virtual corrections to the charged-current Drell-Yan process q q ¯ $$ q\overline{q} $$ ′ → ℓν are computed analytically by using the differential equation method. A suitable choice of master integrals makes it successful to cast the differential equation system into the canonical form. We keep the dependence on charged lepton mass in the building of differential equations and then expand the system against the ratio of small charged lepton mass to large W-boson mass. In such a way the final results will contain large logarithms of the form log( m ℓ 2 $$ {m}_{\ell}^2 $$ / m W 2 $$ {m}_W^2 $$ ). Finally, all the canonical master integrals are given as Taylor series around d = 4 spacetime dimensions up to order four, with coefficients expressed in terms of Goncharov polylogarithms up to weight four.

Abstract Purpose We built a joint replacement loosening model based on the original rabbit model of infection and evaluated the performance characteristics of 18F-FDG and 68 Ga-FAPI in evaluating infection and loosening. Methods After surgery, the rabbits were divided into four groups, with six individuals in the control group and 10 each in the aseptic loosening, S. aureus and S. epidermidis groups. PET/CT and serological examination were performed three times at two-week intervals. After the rabbits were euthanized, micro-CT, tissue pathology, pullout tests and scanning electron microscopy (SEM) were performed. Results The pullout test and SEM showed the feasibility of the aseptic loosening model. 18F-FDG showed similar performance in the control and loosening groups. The SUVmax of the S. aureus group was consistently higher than that of the S. epidermidis group. As for 68 Ga-FAPI, the SUVmax of the control group was lowest in the second week and gradually increased over subsequent weeks. The SUVmax of the loosening group began to exceed that of the control group after the second week. The SUVmax of the S. aureus group in the second week was the lowest among the four groups and increased as the number of weeks increased. The pathology results showed concordance with the performance of PET/CT. Linear regressions between SUVmax and serology showed that 18F-FDG was positively correlated with CRP and IL-6, while 68 Ga-FAPI revealed negative correlations with CRP and IL-6 in the second week and positive correlations in the sixth week. In addition, the SUVmax and MT(target)V of both 18F-FDG and 68 Ga-FAPI were negatively correlated with bone volume/trabecular volume (TV) and bone surface area/TV. Conclusion In this longitudinal observation, 68 Ga-FAPI showed greater sensitivity than 18F-FDG in detecting diseases, and 68 Ga-FAPI had no intestinal or muscular uptake. The MT(target)V of 68 Ga-FAPI was larger than that of 18F-FDG, which meant that 68 Ga-FAPI had the potential to define the scope of lesions more accurately. Finally, the SUVmax of 68 Ga-FAPI could not differentiate between loosening and infection; further study of the diagnostic criteria is warranted.

In an urbanization process, infrastructure elements such as tunnels and deep excavations are widely used to service the development of cities. Owing to the lengthy geological processes of geomaterials and the limited availability of site-specific test data, soil and rock properties exhibiting spatial variability are frequently encountered in geological and geotechnical engineering. This paper presents a comprehensive review of the application of spatial variability in tunneling and deep excavation over the past 20 years. It is found that the spatial variability is generally modeled as a random field (RF) in finite element software, based on random field theory (RFT). This model has been widely used in the design, stability evaluation, and probabilistic analysis of tunnels and excavations. Previous works have proven that the performance of tunnels and deep excavations can be better captured by considering the spatial variability, as compared with conventional deterministic analysis methods. Nonetheless, current research still faces many factual scientific problems. Therefore, this paper also identifies some research gaps, as well as recommendations for further investigations.

Rockhead profile is an important part of geological profiles and can have significant impacts on some geotechnical engineering practice, and thus, it is necessary to establish a useful method to reverse the rockhead profile using site investigation results. As a general method to reflect the spatial distribution of geo-material properties based on field measurements, the conditional random field (CRF) was improved in this paper to simulate rockhead profiles. Besides, in geotechnical engineering practice, measurements are generally limited due to the limitations of budget and time so that the estimation of the mean value can have uncertainty to some extent. As the Bayesian theory can effectively combine the measurements and prior information to deal with uncertainty, CRF was implemented with the aid of the Bayesian framework in this study. More importantly, this simulation procedure is achieved as an analytical solution to avoid the time-consuming sampling work. The results show that the proposed method can provide a reasonable estimation about the rockhead depth at various locations against measurement data and as a result, the subjectivity in determining prior mean can be minimized. Finally, both the measurement data and selection of hyper-parameters in the proposed method can affect the simulated rockhead profiles, while the influence of the latter is less significant than that of the former.

Abstract Glucagonoma is an extremely rare neuroendocrine tumor that arises from pancreatic islet alpha cells. Although glucagonoma is usually accompanied by a variety of characteristic clinical symptoms, early diagnosis is still difficult due to the scarcity of the disease. In this study, we present the cumulative experiences, clinical characteristics and treatments of seven patients diagnosed with glucagonoma during the past 10 years at the First Affiliated Hospital of Xi’an Jiaotong University. The seven patients in our cohort consisted of six females and one male with an average diagnosis age of 40.1 years (range 23–51). The average time from onset of symptoms to diagnosis of glucagonoma was 14 months (range 2–36 months). All the patients visited dermatology first for necrolytic migratory erythema (NME) 7/7 (100%), and other presenting symptoms included diabetes mellitus (DM) 4/7 (57%), stomatitis 2/7 (28%), weight loss 4/7 (57%), anemia 4/7 (57%), diarrhea 1/7 (14%), and DVT1/7 (14%). Plasma glucagon levels were increased in all patients (range 216.92–3155 pg/mL) and declined after surgery. Imaging studies revealed that four of seven patients had liver metastasis. Six of seven patients received surgical resection, and all of them received somatostatin analog therapy. Symptoms improved significantly in 6 out of 7 patients. Three of seven patients died of this disease by the time of follow-up. Our data suggest that if persistent NME is associated with DM and high glucagon levels, timely abdominal imaging should be performed to confirm glucagonoma. Once diagnosed, surgery and somatostatin analogs are effective for symptom relief and tumor control.

The interactions between T cells and B cells are essential for antibody responses and the development of autoimmune diseases. Recently, a distinct subset of T cells capable of helping B cells was established in synovial fluid, and they were termed peripheral helper T (Tph) cells. PD-1hiCXCR5−CD4+ Tph cells express high levels of CXCL13, which drives the formation of lymphoid aggregates and tertiary lymphoid structures, ultimately facilitating the local production of pathogenic autoantibodies. Tph and T follicular helper cells share some key features but can be distinguished by their surface markers, transcriptional regulation, and migration capability. We summarize recent findings on Tph cells in this review and provide a perspective on their potential roles in a range of autoimmune diseases. More clinical and in-depth mechanistic investigations of Tph cells may help to improve the understanding of pathogenesis and further provide novel therapeutic targets in autoimmune diseases.

Background: GGPS1(geranylgeranyl diphosphate synthase 1) is a member of the prenyltransferase family. Abnormal expression of GGPS1 can disrupt the balance between protein farnesylation and geranylgeranylation, thereby affecting a variety of cellular physiologic and pathological processes. However, it is still unknown how this gene could contribute to the prognosis of oral squamous cell carcinoma (OSCC). This study aimed to explore the prognostic role of GGPS1 in OSCC and its relationship with clinical features.Methods: The RNA-seq data and clinical data were obtained from TCGA. The survival analyses, Cox regression analyses, ROC curves, nomograms, calibration curves, and gene function enrichments were established by R software.Results: The results showed that the high expression of GGPS1 in OSCC is related to poor prognosis. At the same time, multivariate Cox regression analyses showed that GGPS1 could be an independent prognostic biomarker, and its gene expression level is closely related to the histological stage of cancer. GGPS1 may promote tumorigenesis because of its metabolic function.Conclusion: This study came to a conclusion that GGPS1, whose high expression has a significantly unfavorable meaning toward the prognosis of OSCC, can act as a novel independent biomarker for OSCC.

Colorectal cancer (CRC) is one of the most common malignancies worldwide and the second leading cause of cancer-related death. In recent years, the relationship between gut microbiota and CRC has attracted increasing attention from researchers. Studies reported that changes in the composition of gut microbiota, such as increase in the number of Fusobacterium nucleatum and Helicobacter hepaticus, impair the immune surveillance by affecting the intestinal mucosal immunity and increase the risk of tumor initiation and progression. The tumor microenvironment is the soil for tumor survival. Close contacts between gut microbiota and the tumor microenvironment may directly affect the progression of tumors and efficacy of antitumor drugs, thus influencing the prognosis of patients with CRC. Recently, many studies have shown that traditional Chinese medicine can safely and effectively improve the efficacy of antitumor drugs, potentially through remodeling of the tumor microenvironment by regulated gut microbiota. This article describes the effect of gut microbiota on the tumor microenvironment and possible mechanisms concerning the initiation and progression of CRC, and summarizes the potential role of traditional Chinese medicine.

The prevalence of metabolic syndrome (MetS) is drastically growing worldwide, resulting in MetS-associated kidney disease. According to traditional theories, preventing blood pressure, lipid, glycose, and obesity and improving insulin resistance (IR), a couple of medications are required for MetS. It not only lowers patients’ compliance but also elevates adverse reactions. Accordingly, we attempted to seek answers from complementary and alternative medicine. Ultimately, berberine (BBR) was chosen due to its efficacy and safety on MetS through multi-pathways and multi-targets. The effects and mechanisms of BBR on obesity, IR, diabetic nephropathy, hypertension, hyperlipidemia, and hyperuricemia were elaborated. In addition, the overall properties of BBR and interventions for various kidney diseases were also collected. However, more clinical trials are expected to further identify the beneficial effects of BBR.

Natural products are a main source of new chemical entities for use in drug and pesticide discovery. In order to discover lead compounds with high herbicidal activity, a series of new pyrido[2,3-d] pyrimidine derivatives were designed and synthesized using 2-chloronicotinic acid as the starting material. Their structures were characterized with 1H NMR, 13C NMR and HRMS, and the herbicidal activities against dicotyledonous lettuce (Lactuca sativa), field mustard (Brassica campestris), monocotyledonous bentgrass (Agrostis stolonifera) and wheat (Triticum aestivum) were determined. The results indicated that most of the pyrido[2,3-d] pyrimidine derivatives had no marked inhibitory effect on lettuce at 1 mM. However, most of the pyrido[2,3-d] pyrimidine derivatives possessed good activity against bentgrass at 1 mM. Among them, the most active compound, 3-methyl-1-(2,3,4-trifluorophenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (2o), was as active as the positive controls, the commercial herbicides clomazone and flumioxazin. Molecular simulation was performed with molecular docking and DFT calculations. The docking studies provided strong evidence that 2o acts as an herbicide by inhibition of protoporphyrinogen oxidase. However, the physiological results indicate that it does not act on this target in vivo, implying that it could be metabolically converted to a compound with a different molecular target.

Cancer is one of the most difficult diseases for human beings to overcome. Its development is closely related to a variety of factors, and its specific mechanisms have been a hot research topic in the field of scientific research. The tropomyosin family (Tpm) is a group of proteins closely related to the cytoskeleton and actin, and recent studies have shown that they play an important role in various cancers, participating in a variety of biological activities, including cell proliferation, invasion, and migration, and have been used as biomarkers for various cancers. The purpose of this review is to explore the research progress of the Tpm family in tumorigenesis development, focusing on the molecular pathways associated with them and their relevant activities involved in tumors. PubMed and Web of Science databases were searched for relevant studies on the role of Tpms in tumorigenesis and development and the activities of Tpms involved in tumors. Data from the literature suggest that the Tpm family is involved in tumor cell proliferation and growth, tumor cell invasion and migration, tumor angiogenesis, tumor cell apoptosis, and immune infiltration of the tumor microenvironment, among other correlations. It can be used as a potential biomarker for early diagnosis, follow-up, and therapeutic response of some tumors. The Tpm family is involved in cancer in a close relationship with miRNAs and LncRNAs. Tpms are involved in tumor tissue invasion and migration as a key link. On this basis, TPM is frequently used as a biomarker for various cancers. However, the specific molecular mechanism of its involvement in cancer progression has not been explained clearly, which remains an important direction for future research.

Abstract Perineural invasion (PNI) is a pathologic feature of pancreatic cancer and is associated with poor outcomes, metastasis, and recurrence in pancreatic cancer patients. However, the molecular mechanism of PNI remains unclear. The present study aimed to investigate the mechanism that HGF/c-Met pathway facilitates the PNI of pancreatic cancer. In this study, we confirmed that c-Met expression was correlated with PNI in pancreatic cancer tissues. Activating the HGF/c-Met signaling pathway potentiated the expression of nerve growth factor (NGF) to recruit nerves and promote the PNI. Activating the HGF/c-Met signaling pathway also enhanced the migration and invasion ability of cancer cells to facilitate cancer cells invading nerves. Mechanistically, HGF/c-Met signaling pathway can active the mTOR/NGF axis to promote the PNI of pancreatic cancer. Additionally, we found that knocking down c-Met expression inhibited cancer cell migration along the nerve, reduced the damage of the sciatic nerve caused by cancer cells and protected the function of the sciatic nerve in vivo. Taken together, our findings suggest a supportive mechanism of the HGF/c-Met signaling pathway in promoting PNI by activating the mTOR/NGF axis in pancreatic cancer. Blocking the HGF/c-Met signaling pathway may be an effective target for the treatment of PNI.

Abstract We propose a new observable for the measurement of the forward–backward asymmetry $$(A_{FB})$$ ( A FB ) in Drell–Yan lepton production. At hadron colliders, the $$A_{FB}$$ A FB distribution is sensitive to both the electroweak (EW) fundamental parameter $$\sin ^{2} \theta _{W}$$ sin 2 θ W , the weak mixing angle, and the parton distribution functions (PDFs). Hence, the determination of $$\sin ^{2} \theta _{W}$$ sin 2 θ W and the updating of PDFs by directly using the same $$A_{FB}$$ A FB spectrum are strongly correlated. This correlation would introduce large bias or uncertainty into both precise measurements of EW and PDF sectors. In this article, we show that the sensitivity of $$A_{FB}$$ A FB on $$\sin ^{2} \theta _{W}$$ sin 2 θ W is dominated by its average value around the Z pole region, while the shape (or gradient) of the $$A_{FB}$$ A FB spectrum is insensitive to $$\sin ^{2} \theta _{W}$$ sin 2 θ W and contains important information on the PDF modeling. Accordingly, a new observable related to the gradient of the spectrum is introduced, and demonstrated to be able to significantly reduce the potential bias on the determination of $$\sin ^{2} \theta _{W}$$ sin 2 θ W when updating the PDFs using the same $$A_{FB}$$ A FB data.

Background: The biological functions of the Frizzled gene family (FZDs), as the key node of wingless-type MMTV integration site family (Wnt) and mammalian target of rapamycin signaling pathways, have not been fully elucidated in glioma. This study aims to identify novel therapeutic targets and prognostic biomarkers for gliomas, which may help us understand the role of FZDs.Methods: RNA-sequence data were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects. Survival analyses, Cox regression analyses, nomograms, calibration curves, receiver operating characteristic (ROC) curves, gene function enrichment analyses, and immune cell infiltration analyses were conducted using R.Results: High expressions of FZDs were positively associated with the activation of mTOR signaling. FZD1/2/3/4/5/7/8 was significantly highly expressed in tumor tissues, and the high expression of FZD1/2/5/6/7/8 was significantly positively associated with poorer prognosis. FZD2 and FZD6 positively served as independent predictors of poor prognosis. Gene function analysis showed that FZDs were associated with mTOR signaling, immune response, cytokine-cytokine receptor interaction, extracellular matrix organization, apoptosis, and p53 signaling pathway.Conclusions: Our finding strongly indicated a crucial role of FZDs in glioma. FZD1/2/5/6/7/8 could be an unfavorable prognostic factor in glioma and FZD2 and FZD6 may be novel independent predictors of poor prognosis in glioma.

The past decade has witnessed unprecedented medical progress, which has translated into cardiac surgery being increasingly common and safe. However, complications such as postoperative delirium remain a major concern. Although the pathophysiological changes of delirium after cardiac surgery remain poorly understood, it is widely thought that inflammation and oxidative stress may be potential triggers of delirium. The development of delirium following cardiac surgery is associated with perioperative risk factors. Multiple interventions are being explored to prevent and treat delirium. Therefore, research on the potential role of biomarkers in delirium as well as identification of perioperative risk factors and pharmacological interventions are necessary to mitigate the development of delirium.

Prediction of the rate of penetration (ROP) is integral to drilling optimization. Many scholars have established intelligent prediction models of the ROP. However, these models face challenges in adapting to different formation properties across well sections or regions, limiting their applicability. In this paper, we explore a novel prediction framework combining feature construction and incremental updating. The framework fine-tunes the model using a pre-trained ROP representation. Our method adopts genetic programming to construct interpretable features, which fuse bit properties with engineering and hydraulic parameters. The model is incrementally updated with constant data streams, enabling it to learn the static and dynamic data. We conduct ablation experiments to analyze the impact of interpretable features’ construction and incremental updating. The results on field drilling datasets demonstrate that the proposed model achieves robustness against forgetting while maintaining high accuracy in ROP prediction. The model effectively extracts information from data streams and constructs interpretable representational features, which influence the current ROP, with a mean absolute percentage error of 7.5% on the new dataset, 40% lower than the static-trained model. This work provides a theoretical reference for the interpretability and transferability of ROP intelligent prediction models.

Crystallization often occurs in the laser welding of amorphous alloys, reducing the properties of amorphous alloys. Therefore, the research in this thesis focuses on the experimental selection of suitable welding parameters to prevent crystallization of Zr-based amorphous alloys during the laser welding process. As such, it is necessary to simulate the temperature field curve of the welding area by computer and then determine the power and laser moving speed of laser welding. In this paper, the temperature field curve of the Zr41.2Ti13.8Cu12.5Ni10Be22.5 (Vit1) amorphous alloy in laser welding is obtained by finite element analysis. The continuous heating curve (CHT) of Vit1 is fitted by the Vogel–Fulcher–Tammann (VFT) equation and the Kissinger equation. If the temperature field curve intersects with the CHT curve, crystallization occurs. The experiment results show that the VFT equation can be used to predict the crystallization of Vit1 better in laser welding. The temperature and welding time are increased by using a low welding speed. Therefore, the temperature of the weld zone cannot fall in time, resulting in the intersection of the temperature field curve and the CHT curve. Thus, crystallization can be avoided if the welding speed is controlled within a reasonable range, and the highest temperature is kept under the CHT curve. The combination of the CHT curve and the temperature field curve shows that the samples at 300 W-3 mm/s and 300 W-6 mm/s welding parameters all undergo crystallization, while the samples at 300 W-9 mm/s and 300 W-12 mm/s welding parameters do not undergo crystallization. Through the flexural test, it is found that the flexural strength of the welded interface is at its the maximum under 300 W-9 mm/s.

Blood–brain barrier (BBB) strictly controls matter exchange between blood and brain, and severely limits brain penetration of systemically administered drugs, resulting in ineffective drug therapy of brain diseases. However, during the onset and progression of brain diseases, BBB alterations evolve inevitably. In this review, we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer's disease, Parkinson's disease, epilepsy, stroke, traumatic brain injury and brain tumor. The advances on optimization of small molecules for BBB crossing and non-systemic administration routes (e.g., intranasal treatment) for BBB bypassing are not included in this review.

ObjectiveWe aimed to develop a nomogram to predict the survival and prognosis of adenosquamous carcinoma of the pancreas (ASCP).BackgroundAdenosquamous carcinoma of the pancreas (ASCP) is a relatively rare histological subtype of pancreatic exocrine neoplasms. It was reported a worse survival in ASCP than in pancreatic adenocarcinoma (PDAC). Prediction of ASCP prognosis is of great importance.MethodsHistologically confirmed ASCP patients from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program database were finally enrolled and divided into development and internal validation cohorts. Moreover, a multi-center cohort of 70 patients from China was registered as the external validation. A nomogram was developed based on independent predictors of ASCP determined in multivariable analysis.ResultsA total of 233 patients from SEER were finally included. Univariate and Multivariate analysis showed that tumor size, radiotherapy, chemotherapy, and lymph node ratio (LNR) were considered the independent prognostic indicators. We developed a nomogram according to these four parameters. The C index of the nomogram in the development cohort was 0.696. Through analysis of the area under the curve (AUC) of the different cohorts, we observed that the predictive efficacy of the nomogram for 1-, and 2-year overall survival (OS) were better than those of the American Joint Committee on Cancer (AJCC) TNM (8th) staging system both in the development and validation cohort. External validation confirmed that 1-year survival is 67.2% vs. 29.7%, similar to the internal cohort analysis.ConclusionThe nomogram showed good performance in predicting the survival of ASCP. It could help surgeons to make clinical decisions and develop further plans.

Abstract Objective To determine the role of diffusion-weighted magnetic resonance imaging (DW-MRI) and apparent diffusion coefficient (ADC) imaging to guide stereotactic biopsy for the diagnosis of intracranial angiitis. Case presentation In a 28-year-old woman who had experienced inactive headache and right limbs numbness for 4 days, preoperative magnetic resonance (MR) scanning, enhanced scanning, diffusion tensor imaging, magnetic resonance spectroscopy, diffusion-weighted imaging (DWI), and ADC image scanning were performed. Stereotactic biopsy was performed in one target where the area of edema detected with MR FLAIR, and two targets where the area shown as a high-value and a lower value area in the DWI/ADC image. Pathological examinations together with computed tomographic and enhanced MRI scans were conducted after surgery. A preoperative enhanced MRI scan showed a uniform low-intensity lesion in the patient’s left centrum semiovale, with a volume of 3.1 cm3. The DWI and ADC images showed uneven high-intensity signals and different ADC values in the lesion area, respectively. During surgery, tissues around the lesion and the lesion center were sampled at the three selected targets. The postoperative pathological diagnosis was primary angiitis of the central nervous system, and the patient was given anti-inflammatory medication and hormone therapy. The 3-year follow-up confirmed that the patient had recovered well, with a Glasgow Outcome Scale score of five. Conclusion DW-MRI and ADC images can be reliably used to determine the location of small intracranial lesions, and guide stereotactic biopsy to facilitate the diagnosis of primary vasculitis of the central nervous system.

Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.