Development and validation of a highly sensitive UPLC-MS/MS method for the determination of Huperzine A in rat plasma.

Huperzine A is a reversible and selective cholinesterase inhibitor and has been approved for the treatment of Alzheimer's diseases. In this study, we developed a highly sensitive and specific ulta-high-performance liquid chromatography-tandem mass spectrometry method for the determination of Huperzine A in rat plasma. An aliquot of 50 µL of rat plasma sample was pretreated with 200 µL of acetonitrile-methanol (v/v; 1:1) containing 0.2% formic acid followed by solid phase extraction. The resulting sample was separated on a Waters ACQUITY BEH C18 column using acetonitrile and water containing 0.2% formic acid as mobile phase, at a flow rate of 0.3 mL/min. Multiple-reaction monitoring (MRM) mode was used for quantitative analysis of Huperzine A in positive electrospray ionization. In the concentration range of 0.01-10 ng/mL, Huperzine A showed excellent linearity with correlation coefficient > 0.998. The intra- and inter-day RSD% were less than 9.7%, while the RE% ranged from -6.7% to 10.0%. The mean recovery was >84.5%. The validated method was demonstrated to be selective, sensitive, and reliable, which has been successfully applied to pharmacokinetic study of Huperzine A in rat plasma. Huperzine A displayed a long half-life in rat plasma and high oral bioavailability.

Simvastatin induces ferroptosis and activates anti-tumor immunity to sensitize anti-PD-1 immunotherapy in microsatellite stable gastric cancer.

BACKGROUND: Gastric cancer (GC), especially the case with microsatellite stability (MSS) phenotype, has limited efficacy for immune checkpoint blockade (ICB) therapy. Metabolism reprogramming is newly recognized to affect tumor immune microenvironment (TIME). However, the relationship between metabolism reprogramming and immunotherapy for MSS GC has not been reported. METHODS: A metabolic stratification for GC was developed based on the glycolysis/cholesterol synthesis axis using the R package "ConsensusClusterPlus". The T cell inflamed score was used to define "immune-hot" and "immune-cold" phenotypes in MSS GC. The anti-tumor and immunological effects of simvastatin were explored using in vitro and in vivo experiments. RESULTS: Three metabolic subtypes were identified in GC patients, including cholesterol, glycolysis and quiescent subtypes. The cholesterol subtype was associated with poorer clinical features and higher tumor purity. Correspondingly, we demonstrated that simvastatin, a specific inhibitor of cholesterol synthesis, significantly inhibited the proliferation, migration, and induced ferroptosis in GC cells. Interestingly, simvastatin markedly inhibited tumor growth in immunocompetent mice, while no significant effect in immunodeficient mice. Upregulation of chemokines and increased recruitment of CD8+ T cells were observed after simvastatin treatment. Consistently, the cholesterol subtype exhibited a less inflamed TIME and coincided significantly with the "immune-cold" phenotype of MSS GC. Finally, we confirmed simvastatin enhanced PD-1 blockade efficacy via modulating the TIME and activating anti-tumor immunity in tumor-bearing mice. CONCLUSION: Our data revealed the significance of cholesterol synthesis in GC and demonstrated simvastatin served as a promising sensitizer for ICB therapy by inducing ferroptosis and anti-tumor immunity in MSS GC patients.

Vibrational Analysis of Composite Conical-Cylindrical Shells with Functionally Graded Coatings in Thermal Environments.

This article studies the vibrational behavior of composite conical-cylindrical shells (CCSs) with functionally graded coatings (FGCs) in thermal environments using the first-order shear deformation theory. Firstly, the equivalent material parameters, fundamental frequency, and resonant displacement responses of the CCSs with FGCs are derived using the mixture principle, complex modulus method, and transfer function approach. Then, detailed thermal vibration tests are performed on CCS structures with and without coatings to assess the reliability of the proposed model, revealing that the current model accurately forecasts the thermal vibration behavior of the CCSs with FGCs. Finally, the effect of key parameters on the vibrational properties of the CCSs with FGCs is investigated. The results demonstrate that increasing the functionally graded index, coating thickness, and Young's modulus ratio can greatly enhance the vibration suppression capability of the structure.

Impact of the nail insertion angle on the wedge effect in intramedullary nail fixation of intertrochanteric hip fractures.

BACKGROUND: The wedge effect is known to be influenced by the insertion of the proximal femoral intramedullary nail through the fracture line and the large proximal diameter of the nail. However, the impact of the nail insertion angle (NIA) on the wedge effect remains unclear. This study aimed to investigate: (1) how to evaluate the NIA intraoperatively, (2) whether the NIA is associated with the wedge effect, (3) whether the NIA can serve as a reliable predictor of the wedge effect, (4) which factors affect the NIA, and (5) which surgical techniques can prevent the occurrence of the wedge effect associated with the NIA. HYPOTHESIS: We hypothesized that an excessive NIA is related to the wedge effect and that lateral deviation of the entry point is associated with an excessive NIA. PATIENTS AND METHODS: Intraoperative fluoroscopy images of patients who underwent intramedullary nail fixation for intertrochanteric hip fractures between 2013 and 2023 were analyzed. NIA and insertion point distance (IPD) were measured on hip anteroposterior radiographs with the guidewire inserted. Femoral shaft lateralization (FSL) and neck-shaft angle (NSA) were measured on hip anteroposterior radiographs before and after nail insertion; differences in FSL and NSA were calculated. A negative difference in FSL combined with a positive difference in NSA indicated the occurrence of the wedge effect. Pearson's correlation test was used to determine relationships between continuous variables (NIA, FSL, NSA, and IPD). Binary logistic regression analyzed the association between NIA and the wedge effect. Receiver operating characteristic (ROC) curve analysis was used to determine the threshold value of NIA, with predictive performance assessed using the area under the ROC curve (AUC). Other potential factors influencing the wedge effect were also examined. RESULTS: A total of 408 patients were included. The mean NIA was 15.61 ± 4.49 °. Post-nail insertion, the average increase in FSL was 3.20 mm, and the average decrease in NSA was 1.90 °. Pearson's correlation test revealed that NIA was negatively correlated with the difference in FSL (R = 0.565, P < 0.001) and positively correlated with the difference in NSA (R = 0.509, P < 0.001). Binary logistic regression showed a significant correlation between NIA and the wedge effect (P < 0.001). ROC analysis indicated that the AUC for NIA was 0.813, with an optimal cutoff point of 14.85 °. IPD was positively correlated with NIA (R = 0.519, P < 0.001). Unstable fractures were associated with increased lateralization of the femoral shaft after nail insertion (P = 0.003). DISCUSSION: The NIA is positively correlated with the wedge effect in intramedullary nail fixation of intertrochanteric hip fractures. The wedge effect tends to occur when the NIA is >14.85 °, particularly in unstable fractures. Lateral deviation of the entry point is associated with an excessive NIA. Adducting the affected limb, moving the entry point slightly medial and using a medial pusher may help control the NIA to less than 14.85 ° to reduce the wedge effect. LEVEL OF EVIDENCE: III.

The incidence and risk factors of perioperative recurrent stroke in elderly patients with previous ischemic stroke receiving hip fracture surgery.

BACKGROUND: Data are currently lacking regarding perioperative stroke recurrence in hip fracture patients with previous stroke. We aimed to analyze the incidence and risk factors of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery. METHODS: We used 2019 and 2020 data from the United States National Inpatient Sample database. We identified elderly patients with previous ischemic stroke who had undergone hip fracture surgery to analyze the incidence of stroke recurrence. A 1:4 propensity score matching was used to balance confounding factors related to demographic data and matched the control group with the stroke recurrence group. Risk factors for stroke recurrence were determined using univariate and multivariate logistic analysis. RESULTS: The incidence of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery was 5.7% (51/882). Multivariate logistic regression analysis showed that intertrochanteric fracture (odds ratio 2.24, 95% confidence interval 1.14-4.57; p = 0.021), hypertension (odds ratio 2.49, 95% confidence interval 1.26-5.02; p = 0.009), and postoperative pneumonia (odds ratio 4.35, 95% confidence interval 1.59-11.82; p = 0.004) were independently associated with stroke recurrence. CONCLUSIONS: The perioperative stroke recurrence rate in elderly hip fracture patients with previous stroke was 5.7%. Intertrochanteric fracture, hypertension, and postoperative pneumonia were identified as factors significantly associated with stroke recurrence in this study. Adequate systemic support post-fracture, effective blood pressure management, and proactive infection prevention may help reduce stroke recurrence, especially in patients with intertrochanteric fractures.

Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate Colitis.

The precise mechanism underlying the therapeutic effects of dihydroartemisinin (DHA) in alleviating colitis remains incompletely understood. A strong correlation existed between the elevation of glial fibrillary acidic protein (GFAP)+/S100 calcium binding protein B (S100ß)+ enteric glial cells (EGCs) in inflamed colonic tissues and the disruption of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) observed in chronic colitis. DHA demonstrated efficacy in restoring the functionality of the dual gut barrier while concurrently attenuating intestinal inflammation. Mechanistically, DHA inhibited the transformation of GFAP+ EGCs into GFAP+/S100ß+ EGCs while promoting the differentiation of GFAP+/S100ß+ EGCs back into GFAP+ EGCs. Furthermore, DHA induced apoptosis in GFAP+/S100ß+ EGCs by inducing cell cycle arrest at the G0/G1 phase. The initial mechanism is further validated that DHA regulates EGC heterogeneity by improving dysbiosis in colitis. These findings underscore the multifaceted therapeutic potential of DHA in ameliorating colitis by improving dysbiosis, modulating EGC heterogeneity, and preserving gut barrier integrity, thus offering promising avenues for novel therapeutic strategies for inflammatory bowel diseases.

Ubiquitin-Specific Protease 52 as a Prognostic Biomarker Correlates with Tumor Microenvironment and Therapy Response in Colorectal Cancer.

INTRODUCTION: As the primary members of the deubiquitinase family, ubiquitin-specific proteases can regulate the efficacy of immunotherapy and mediate immune evasion. However, further research is needed to explore the influence of USP52 on the prognosis of colorectal cancer (CRC), the tumor immune microenvironment, and therapeutic response. METHODS: The differential expression of USP52 between CRC and normal tissues was analyzed using multiple public databases. The relationship between USP52 with the prognosis and clinicopathological characteristics of CRC patients was evaluated, and a nomogram was constructed to predict patient survival based on USP52 expression. Subsequently, gene set variation analysis (GSVA) was used to explore the potential biological functions of USP52 in CRC. The impact of USP52 on the tumor microenvironment (TME) was estimated. Moreover, the effect of USP52 on the response to immunotherapy and chemotherapeutic drugs in CRC was investigated. Finally, the correlation between tumor mutation burden (TMB)/microsatellite instability (MSI) status and USP52 was explored. RESULTS: The expression of USP52 was markedly upregulated in CRC, correlating with a poor prognosis in patients. GSVA uncovered a strong association between high USP52 and immune suppression. Furthermore, high USP52 was found to be correlated with a non-inflamed TME, resulting in reduced immune cell infiltration levels. Additionally, it was observed that patients with high USP52 exhibited low sensitivity to both immunotherapy and chemotherapeutic drugs. Lastly, high USP52 was negatively associated with high TMB and MSI. CONCLUSION: This study revealed the significance of USP52 in TME, efficacy of therapy, and clinical prognosis in CRC, offering novel insights for the therapeutic advancements in CRC.

Clinical Characteristics and Prognosis of Herpes Zoster Laryngitis With Vocal Fold Immobility.

OBJECTIVE: To investigate the clinical characteristics and prognosis of herpes zoster laryngitis with vocal fold immobility. STUDY DESIGN: Retrospective study. METHODS: Clinical characteristics, laryngeal signs on strobolaryngoscopy, imaging examination findings, and outcomes of patients were analyzed retrospectively. RESULTS: This study included 17 patients (11 males [64.7%] and six females [35.3%]), with a mean age of 63.3 ± 6.7 years. The primary symptoms were hoarseness (94.1%), dysphagia (76.5%), pharyngalgia on one side (76.5%), and aspiration (70.6%). No patient had skin herpes of the head and neck. The duration of symptoms was 5-30 days (median: 10 days). Twelve patients (70.6%) were in an immunocompromised state before the disease. Strobolaryngoscopy showed congestion and swelling of the mucosa on one side of the larynx, with whitish eruptions on the supraglottic mucosa and ipsilateral vocal fold immobility. Five patients (29.4%) exhibited signs of ipsilateral accessory nerve injury. The imaging examination showed supraglottic inflammatory changes in 12 patients (70.6%). Among the 14 patients whose treatment could be clearly described, only one patient received antiviral treatment, whereas others received neurotrophic and symptomatic treatment. Notably, all patients demonstrated good outcomes because their symptoms eventually returned to normal. CONCLUSION: Herpes zoster laryngitis is caused by varicella-zoster virus infection of the vagus nerve. It is characterized by laryngeal herpetic changes on one side and unilateral vocal fold immobility. The inducement of the disease tends to be associated with the abnormal immune state of patients. It can be easily misdiagnosed because of the absence of skin herpetic changes. Regardless of antiviral therapy, patients generally exhibit a favorable outcome.

Comprehensive analysis of the relationship between ubiquitin-specific protease 21 (USP21) and prognosis, tumor microenvironment infiltration, and therapy response in colorectal cancer.

BACKGROUND: Ubiquitin-specific proteases family is crucial to host immunity against pathogens. However, the correlations between USP21 and immunosurveillance and immunotherapy for colorectal cancer (CRC) have not been reported. METHODS: The differential expression of USP21 between CRC tissues and normal tissues was analyzed using multiple public databases. Validation was carried out in clinical samples through qRT-PCR and IHC. The correlation between USP21 and the prognosis, as well as clinical pathological characteristics of CRC patients, was investigated. Moreover, cell models were established to assess the influence of USP21 on CRC growth and progression, employing CCK-8 assays, colony formation assays, and wound-healing assays. Subsequently, gene set variation analysis (GSVA) was used to explore the potential biological functions of USP21 in CRC. The study also examined the impact of USP21 on cytokine levels and immune cell infiltration in the tumor microenvironment (TME). Finally, the effect of USP21 on the response to immunotherapy and chemotherapy in CRC was analyzed. RESULTS: The expression of USP21 was significantly upregulated in CRC. High USP21 is correlated with poor prognosis in CRC patients and facilitates the proliferation and migration capacities of CRC cells. GSVA indicated an association between low USP21 and immune activation. Moreover, low USP21 was linked to an immune-activated TME, characterized by high immune cell infiltration. Importantly, CRC with low USP21 exhibited higher tumor mutational burden, high PD-L1 expression, and better responsiveness to immunotherapy and chemotherapeutic drugs. CONCLUSION: This study revealed the role of USP21 in TME, response to therapy, and clinical prognosis in CRC, which provided novel insights for the therapeutic application in CRC.

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

Turning Ultra-Low Coercivity and Ultra-High Temperature Stability Within 897 K via Continuous Crystal Ordering Fluctuations.

High-performance soft magnetic materials are important for energy conservation and emission reduction. One challenge is achieving a combination of reliable temperature stability, high resistivity, high Curie temperature, and high saturation magnetization in a single material, which often comes at the expense of intrinsic coercivity-a typical trade-off in the family of soft magnetic materials with homogeneous microstructures. Herein, a nanostructured FeCoNiSiAl complex concentrated alloy is developed through a hierarchical structure strategy. This alloy exhibits superior soft magnetic properties up to 897 K, maintaining an ultra-low intrinsic coercivity (13.6 A m-1 at 297 K) over a wide temperature range, a high resistivity (138.08 µΩ cm-1 at 297 K) and the saturation magnetization with only a 16.7% attenuation at 897 K. These unusual property combinations are attributed to the dual-magnetic-state nature with exchange softening due to continuous crystal ordering fluctuations at the atomic scale. By deliberately controlling the microstructure, the comprehensive performance of the alloy can be tuned and controlled. The research provides valuable guidance for the development of soft magnetic materials for high-temperature applications and expands the potential applications of related functional materials in the field of sustainable energy.

A New Strategy for the High-Throughput Characterization of Materials' Mechanical Homogeneity Based on the Effect of Isostatic Pressing on Surface Microstrain.

A new strategy for the high-throughput characterization of the mechanical homogeneity of metallurgical materials is proposed. Based on the principle of hydrostatic transmission and the synergistic analysis of the composition, microstructure, defects, and surface profile of the chosen material, the microstrain characteristics and changes in surface roughness after isostatic pressing were analyzed. After isostatic pressing, two types of microstrains were produced: low microstrain (surface smoothening with decreasing roughness) and large microstrain (surface roughening with increasing roughness). Furthermore, the roughness of the roughened microregions could be further classified based on the strain degree. The phenomenon of weak-interface damage with a large microstrain (plastic deformation, cleavage fracture, and tearing near nonmetallic inclusions) indicated that the surface microstrain analysis could be a new method of high-throughput characterization for microregions with relatively poor micromechanical properties. In general, the effect of isostatic pressing on the surface microstrain of heat-resistant steel provides a promising strategy for achieving high-throughput screening and statistically characterizing microregions with poor micromechanical properties, such as microregions containing microcracks, nonmetallic inclusions, pores, and other surface defects.

Comprehensive analyses of solute carrier family members identify SLC12A2 as a novel therapy target for colorectal cancer.

As the largest transporter family impacting on tumor genesis and development, the prognostic value of solute carrier (SLC) members has not been elucidated in colorectal cancer (CRC). We aimed to identify a prognostic signature from the SLC members and comprehensively analyze their roles in CRC. Firstly, we downloaded transcriptome data and clinical information of CRC samples from GEO (GSE39582) and TCGA as training and testing dataset, respectively. We extracted the expression matrix of SLC genes and established a prognostic model by univariate and multivariate Cox regression. Afterwards, the low-risk and high-risk group were identified. Then, the differences of prognosis traits, transcriptome features, clinical characteristics, immune infiltration and drug sensitivity between the two groups were explored. Furthermore, molecular subtyping was also implemented by non-negative matrix factorization (NMF). Finally, we studied the expression of the screened SLC genes in CRC tumor tissues and normal tissues as well as investigated the role of SLC12A2 by loss of function and gain of function. As a result, we developed a prognostic risk model based on the screened 6-SLC genes (SLC39A8, SLC2A3, SLC39A13, SLC35B1, SLC4A3, SLC12A2). Both in the training and testing sets, CRC patients in the high-risk group had the poorer prognosis and were in the more advanced pathological stage. What's more, the high-risk group were enriched with CRC progression signatures and immune infiltration. Two groups showed different drug sensitivity. On the other hand, two distinct subclasses (C1 and C2) were identified based on the 6 SLC genes. CRC patients in the high-risk group and C1 subtype had a worse prognosis. Furthermore, we found and validated that SLC12A2 was steadily upregulated in CRC. A loss-of-function study showed that knockdown of SLC12A2 expression restrained proliferation and stemness of CRC cells while a gain-of-function study showed the contrary results. Hence, we provided a 6-SLC gene signature for prognosis prediction of CRC patients. At the same time, we identified that SLC12A2 could promote tumor progression in CRC, which may serve as a potential therapeutic target.

MuRF-1 is Involved in Laryngeal Muscle Denervation Atrophy by Regulating G-Actin Ubiquitination.

OBJECTIVE: Muscle RING-finger protein-1 (MuRF-1), an E3 ubiquitin ligase, has been reported to aggravate skeletal muscle denervated atrophy by mediating the ubiquitination degradation of multiple proteins, whereas the molecular mechanism underlying MuRF-1-mediated internal laryngeal muscle denervated atrophy remains unknown. METHODS: A rat unilateral recurrent laryngeal nerve (RLN) transection model was established to evaluate denervated muscle atrophy of the larynx. The expression of MuRF-1, G- and F-actin in thyroarytenoid muscle (TA) myocytes before and after RLN injury was analyzed by immunofluorescence and Western blotting. Coimmunoprecipitation experiments detected molecular interactions between MuRF-1 and G-actin. Immunoprecipitation tested MuRF-1-mediated ubiquitination of G-actin in denervated and innervated TA muscle tissues. The shRNA-MuRF-1 AAV was used to suppress MuRF-1 expression in denervated TA muscles in vivo. RESULTS: First, MuRF-1 expression was significantly elevated in denervated TA muscle compared to innervated TA muscle (p < 0.001). Second, there was a progressive increase in the G/F-actin ratio in TA myocytes from day 3 to 14 after RLNI (p < 0.01). Furthermore, colocalization of MuRF-1 and G-actin in denervated TA myocytes was observed. Moreover, the upregulation of MuRF-1 was closely associated with the ubiquitination of G-actin in denervated TA myocytes and muscle tissues. Knockdown of MuRF-1 decelerated the degree of TA muscle atrophy compared with that in the Blank and NC groups (p < 0.001) but seemed to promote the compensatory movement of the healthy side. CONCLUSION: Collectively, we illustrate a novel molecular mechanism underlying MuRF-1-mediated internal laryngeal muscle denervated atrophy in that MuRF-1 could promote disequilibrium of the G/F-actin ratio by regulating G-actin ubiquitination. LEVEL OF EVIDENCE: NA Laryngoscope, 134:855-864, 2024.

Micro X-ray fluorescence (µ-XRF) methodology for quantitative elemental imaging of Al-Zn-Mg-Cu alloys with varying chemical compositions.

The preparation and characterization of Al-Zn-Mg-Cu alloys with varying chemical compositions are helpful for rapid screening of the optimal compositions in the research and development of new materials. The traditional testing methods cannot accurately determine the composition gradient in samples because they have a low spatial resolution or are semi-quantitative and time-consuming. The micro X-ray fluorescence (µ-XRF) methodology has been used for the elemental imaging of Al-Zn-Mg-Cu alloys with varying chemical compositions. The experimental conditions, including testing voltages, testing currents and the dwell time for each pixel, were optimized systematically to improve the repeatability and accuracy of the µ-XRF methodology. The quantitative elemental imaging of an Al-Zn-Mg-Cu alloy rod sample using µ-XRF was performed, and the results were validated by conducting spark optical emission spectroscopy. The limits of detection of µ-XRF for Zn, Mg, and Cu were 0.007 wt%, 0.068 wt%, and 0.002 wt%, respectively. This versatile elemental imaging technique provided an effective means for the component analysis and process evaluation of alloy samples with a composition gradient and thus for research and development of new materials.

Chlamydospore dormancy and predatory activity of nematophagous fungus Duddingtonia flagrans.

The chlamydospores of Duddingtonia flagrans are an essential survival and reproductive structure and also an effective ingredient for the biocontrol of parasitic nematodes in livestock. In this study, entering and exiting dormancy conditions and predatory activity of the fungal chlamydospores were conducted. During this fungal growth process, the cultivation time is negatively correlated with spore germination rates. After the spores were processed by vacuum drying for 168 h, their germination rate dropped to 0.94%. In contrast, the percentage of living spores remained 54.82%, suggesting that the spores entered structural dormancy in the arid environment. Meanwhile, the efficacies of the spore against Haemonchus contortus larvae were 93.05% (0 h), 92.19% (16 h), 92.77% (96 h), and 86.45% (168 h), respectively. After dormant spores were stored at 4°C, -20°C, and 28°C (RH90 ~ 95%) for 7 days, their germination rate began to increase significantly (p < 0.05). For in vitro predation assay under the condition of 28°C (RH90 ~ 95%), the predation rate was significantly higher on the 7th day after incubation than that on the 3rd day (p < 0.05). During the period when spores were stored at room temperature for 8 months, their germination rate decreased in the first 5 months and then increased slowly to reach a peak in the 7th month. However, the reduction rate of H. contortus L3 in feces captured by spores remained above 71% for the first 7 months. These results will help us increase the end products yield and the quality of biological control of parasitic nematodes in livestock.

Quantitative Characterization of Elemental Segregation in Inconel 718 Superalloy by Micro-Beam X-ray Fluorescence Spectroscopy and Its Correlation Study.

Inconel 718 (IN718) nickel-based superalloy is widely used in aerospace and nuclear applications owing to its excellent comprehensive mechanical properties, oxidation resistance, and hot corrosion resistance. However, the elemental segregation caused by heterogeneous solidification during casting has great influence on the mechanical properties. Therefore, accurately characterizing the segregation behavior is necessary. Traditional quantitative characterization of elemental segregation uses various sampling methods, in which only macroscopic segregation results are obtained. In this study, micro-beam X-ray fluorescence (µ-XRF) is used for the quantitative characterization of element micro-segregation in IN718 superalloy. The concentration distributions of Cr, Fe, Mo, Nb, and Ti in IN718 alloy are determined with optimized testing parameters, and the degree of elemental segregation in different regions of the analytical area is calculated. It is found that the segregation degree of Nb and Ti in the testing area is larger than other alloying elements. The correlation between the microstructure distribution and the segregation degree of Nb and Ti has been studied using scanning electron microscopy (SEM) combined with energy-dispersive spectrometry (EDS). There is severe segregation of Nb and Ti in areas where Nb-containing precipitates are accumulated. The distribution of abnormal signals of Nb with a high fluorescence intensity has a close relationship with the area of precipitates-enriched Nb.

Comprehensive analysis of the relationship between cuproptosis-related gene GCSH and prognosis, tumor microenvironment infiltration, and therapy response in endometrial cancer.

BACKGROUND: Cuproptosis, a novel form of cell death regulated by protein lipoylation and implicated in mitochondrial metabolism. However, the impact of the cuproptosis-related gene γ-glutamylcysteine synthetase (GCSH) on endometrial cancer (EC) prognosis, tumor immune microenvironment, and therapeutic response remains to be further researched. METHODS: The differential expression of GCSH between endometrial cancer and normal tissues was analyzed using multiple public databases. Additionally, cancer and adjacent tissues were prospectively collected from 17 EC patients, and immunohistochemical analysis was performed to further investigate GCSH expression differences. The relationship between GCSH and the prognosis and clinicopathological characteristics of EC patients was evaluated, and a nomogram was constructed to predict patient survival based on GCSH expression. Then, Gene set variation analysis (GSVA) was utilized to explore the potential biological functions of GCSH in EC. The impact of GCSH on the tumor microenvironment (TME) was estimated. Finally, the effect of GCSH on the response to immunotherapy and chemotherapeutic drugs in EC was investigated. RESULTS: The expression of GCSH was significantly upregulated in EC. High GCSH expression was associated with poor prognosis in EC patients. Enrichment analysis showed that high GCSH was associated with immune suppression. Furthermore, high GCSH was found to be associated with a non-inflamed TME, leading to decreased infiltration levels of immune cells. Finally, it was observed that patients with high GCSH were insensitive to both immunotherapy and chemotherapeutic drugs. CONCLUSION: This study revealed the role of GCSH in TME, response to therapy, and clinical prognosis in EC, which provided novel insights for the therapeutic application in EC.

Regression of a large prolapsed lumbar disc herniation achieved by conservative treatment: A case report and literature review.

A common spinal condition known as lumbar disc herniation (LDH) can result in radicular and low back discomfort. A 27-year-old man was admitted to our hospital with a 6-year history of persistent low back pain, and his low back pain had recurred with radiation to his lower extremities over the last two months. An extensive right-sided paracentral disc herniation in the L5/S1 intervertebral region, which compressed the nerve root, was discovered by magnetic resonance imaging (MRI) of his lumbar spine. After receiving conservative treatment, the patient reported that his lower back discomfort and neurogenic claudication had gradually subsided after 4 months. After one year, a follow-up MRI showed that the massive, prolapsed disc herniation at the L5/S1 level had totally disappeared. The sagittal protrusion length of the L5/S1 intervertebral disc shrank from 12.35 mm to 3.49 mm. However, there remained a chance of vertebral height loss. During the course of treatment, the height of the L5/S1 intervertebral space was still slightly reduced. The intervertebral space height declined from 7.705 mm to 7.201 mm after one year of treatment. The current case and a review of the literature demonstrate that LDH can decrease with conservative therapy over a short period of time. We stress the effectiveness of conservative treatment in very select LDH cases that lack a clear surgical justification.

Chemical Composition of Litsea pungens Essential Oil and Its Potential Antioxidant and Antimicrobial Activities.

Litsea pungens is a plant with medicinal and edible properties, where the fruits are edible and the leaves have medicinal properties. However, there is limited research on the chemical and pharmacological activities of the plant. In this study, essential oils were extracted by steam distillation and their antioxidant and antibacterial activities were further evaluated. Gas chromatography-mass spectrometry (GC-MS) was used to identify the chemical components of L. pungens fresh fruit essential oil (FREO) and L. pungens fresh flower essential oil (FLEO), rapeseed oil (RO) and commercial Litsea oil (CEO). The results showed that 12 chemical components were identified in FREO. Twelve chemical components were identified from FLEO, four chemical components were identified from CEO, and thirteen chemical components were identified from RO. Except for RO, the other three oils were mainly composed of terpenes, among which limonene is the main chemical component. In terms of antioxidant activity, FREO, FLEO, CEO and RO have antioxidant capacity, mainly reflected in the scavenging DPPH free radicals and the iron ion chelating ability, and the antioxidant activity shows a certain dose effect, but the antioxidant activity of FLEO is the weakest among the four oils. Meanwhile, under the stress of hydrogen peroxide, CEO demonstrated a significant antioxidant protective effect on cells. It is worth mentioning that compared with the positive control, the FREO exhibited a better antibacterial rate. When the concentration of essential oil is 20 mg/mL, the bacteriostatic rate can reach 100%. Therefore, it could be a promising candidate among medicinal and edible plants.