A review on associated factors and management measures for sarcopenia in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia, insulin resistance, and insufficient insulin secretion. Sarcopenia, as a new complication of diabetes, is characterized by the loss of muscle mass and the progressive decline of muscle strength and function in T2DM patients, which has a serious impact on the physical and mental health of patients. Insulin resistance, mitochondrial dysfunction, and chronic inflammation are common mechanisms of diabetes and sarcopenia. Reasonable exercise training, nutrition supplement, and drug intervention may improve the quality of life of patients with diabetes combined with sarcopenia. This article reviews the relevant factors and management measures of sarcopenia in T2DM patients, in order to achieve early detection, diagnosis, and intervention.

TIE1 promotes cervical cancer progression via Basigin-matrix metalloproteinase axis.

Background: Tyrosine kinase with immunoglobulin and EGF-like domains 1 (TIE1) is known as an orphan receptor prominently expressed in endothelial cells and participates in angiogenesis by regulating TIE2 activity. Our previous study demonstrated elevated TIE1 expression in cervical cancer cells. However, the role of TIE1 in cervical cancer progression, metastasis and treatment remains elusive. Methods: Immunohistochemistry staining for TIE1 and Basigin was performed in 135 human cervical cancer tissues. Overexpressing vectors and siRNAs were used to manipulate gene expression in tumor cells. Colony formation, wound healing, and transwell assays were used to assess cervical cancer cell proliferation and migration in vitro. Subcutaneous xenograft tumor and lung metastasis mouse models were established to examine tumor growth and metastasis. Co-Immunoprecipitation and Mass Spectrometry were applied to explore the proteins binding to TIE1. Immunoprecipitation and immunofluorescence staining were used to verify the interaction between TIE1 and Basigin. Cycloheximide chase assay and MG132 treatment were conducted to analyze protein stability. Results: High TIE1 expression was associated with poor survival in cervical cancer patients. TIE1 overexpression promoted the proliferation, migration and invasion of cervical cancer cells in vitro, as well as tumor growth and metastasis in vivo. In addition, Basigin, a transmembrane glycoprotein, was identified as a TIE1 binding protein, suggesting a pivotal role in matrix metalloproteinase regulation, angiogenesis, cell adhesion, and immune responses. Knockdown of Basigin or treatment with the Basigin inhibitor AC-73 reversed the tumor-promoting effect of TIE1 in vitro and in vivo. Furthermore, we found that TIE1 was able to interact with and stabilize the Basigin protein and stimulate the Basigin-matrix metalloproteinase axis. Conclusion: TIE1 expression in cervical cells exerts a tumor-promoting effect, which is at least in part dependent on its interaction with Basigin. These findings have revealed a TIE2-independent mechanism of TIE1, which may provide a new biomarker for cervical cancer progression, and a potential therapeutic target for the treatment of cervical cancer patients.

[Spinal cord electrical stimulation with neurophysiological monitoring for treatment of high-risk diabetic foot].

OBJECTIVE: To evaluate the clinical efficacy of a single-session implantation of spinal cord electrical stimulation with neurophysiological monitoring a spinal cord electrical stimulator under general anesthesia with neurophysiological monitoring for the treatment of high-risk diabetic foot. METHODS: The clinical data of seven patients with high-risk diabetic foot who underwent spinal cord electrical stimulation in neurosurgery ward nine of Tianjin Huanhu Hospital from May 2022 to May 2023 were collected. The operation was performed under general anesthesia with the "C" arm X ray machine guidance and neurophysiological monitoring. The arterial diameter and peak flow rate of lower extremity, lower extremity skin temperature (calf skin temperature, foot skin temperature), visual analog scale (VAS), continuous distance of movement, blood glucose level and toe wound were compared between patients before and after surgery. RESULTS: A total of seven patients with high-risk diabetic foot were included. The diameters and peak flow rates of femoral artery, popliteal artery, anterior tibial artery, posterior tibial artery and dorsal foot artery in both lower limbs were significantly improved after surgery. All patients had different degrees of lower limb pain before operation. After operation, VAS score decreased significantly (1.1±0.9 vs. 6.8±3.4), the pain was significantly relieved, and the calf skin temperature and foot skin temperature were significantly higher than those before surgery [calf skin temperature (centigrade): 33.3±0.9 vs. 30.9±0.7, foot skin temperature (centigrade): 31.4±0.8 vs. 29.1±0.6], fasting blood glucose and postprandial blood glucose were significantly lower than those before surgery [fasting blood glucose (mmol/L): 7.6±1.4 vs. 10.5±1.2, postprandial blood glucose (mmol/L): 9.3±2.3 vs. 13.5±1.1], the differences were statistically significant (all P < 0.01). The lower limb movement of all seven patients was significantly improved after surgery, including one patient who needed wheelchair travel before surgery, and one patient who had intermittent claudication before surgery. Among them, one patient needed wheelchair travel and one patient had intermittent claudication before surgery. All patients could walk normally at 2 weeks after operation. Among the seven patients, two patients had the diabetic foot wound ulceration before surgery, which could not heal for a long time. One month after surgery, blood flow around the foot wound recovered and the healing was accelerated. The wound was dry and crusted around the wound, and the wound healed well. CONCLUSIONS: For diabetic high-risk foot patients who are intolerant to diabetic peripheral neuralgia and local anesthesia spinal cord electrical stimulation test, one-time implantation of spinal cord electrical stimulator under general anesthesia under neurophysiological monitoring can effectively alleviate peripheral neuralgia and other diabetic foot related symptoms, improve lower limb blood supply, and reduce the risk of toe amputation. Clinical practice has proved the effectiveness of this technique, especially for the early treatment of diabetic high-risk foot patients.

PBRM1 presents a potential ctDNA marker to monitor response to neoadjuvant chemotherapy in cervical cancer.

Neoadjuvant chemotherapy (NACT) is a therapeutic option for locally advanced cervical cancer (LACC) patients. This study was aimed to identify potential liquid biopsy biomarkers to monitor the NACT response. Through targeted next-generation sequencing (NGS) analysis of circulating tumor DNA (ctDNA) and tumor tissue DNA (ttDNA) taken from LACC patients undergoing platinum-based NACT, 64 genes with mutations emerge during NACT in the non-responders but none in the responders. Among them, the PBRM1, SETD2, and ROS1 mutations were frequently detected in the ctDNA and ttDNA of the non-responders, and mutant PBRM1 was associated with poorer survival of patients. In vitro, PBRM1 knockdown promoted resistance to cisplatin through boosting STAT3 signaling in cervical cancer cells, while it sensitized tumor cells to poly-ADP-ribose-polymerase inhibitor olaparib. These findings suggest that mutant PBRM1 is a potential ctDNA marker of emerging resistance to NACT and of increased sensitivity to olaparib, which warrants further clinical validation.

Tumor-derived small extracellular vesicles facilitate omental metastasis of ovarian cancer by triggering activation of mesenchymal stem cells.

BACKGROUND: Omental metastasis is the major cause of ovarian cancer recurrence and shortens patient survival, which can be largely attributed to the dynamic evolution of the fertile metastatic microenvironment driven by cancer cells. Previously, we found that adipose-derived mesenchymal stem cells (ADSCs) undergoing a phenotype shift toward cancer-associated fibroblasts (CAFs) participated in the orchestrated omental premetastatic niche for ovarian cancer. Here, we aim to elucidate the underlying mechanisms. METHODS: Small extracellular vesicles were isolated from ovarian cancer cell lines (ES-2 and its highly metastatic subline, ES-2-HM) and patient ascites using ultracentrifugation. Functional experiments, including Transwell and EdU assays, and molecular detection, including Western blot, immunofluorescence, and RT-qPCR, were performed to investigate the activation of ADSCs in vitro. High-throughput transcriptional sequencing and functional assays were employed to identify the crucial functional molecules inducing CAF-like activation of ADSCs and the downstream effector of miR-320a. The impact of extracellular vesicles and miR-320a-activated ADSCs on tumor growth and metastasis was assessed in subcutaneous and orthotopic ovarian cancer xenograft mouse models. The expression of miR-320a in human samples was evaluated using in situ hybridization staining. RESULTS: Primary human ADSCs cocultured with small extracellular vesicles, especially those derived from ES-2-HM, exhibited boosted migration, invasion, and proliferation capacities and elevated α-SMA and FAP levels. Tumor-derived small extracellular vesicles increased α-SMA-positive stromal cells, fostered omental metastasis, and shortened the survival of mice harboring orthotopic ovarian cancer xenografts. miR-320a was abundant in highly metastatic cell-derived extracellular vesicles, evoked dramatic CAF-like transition of ADSCs, targeted the 3'-untranslated region of integrin subunit alpha 7 and attenuated its expression. miR-320a overexpression in ovarian cancer was associated with omental metastasis and shorter survival. miR-320a-activated ADSCs facilitated tumor cell growth and omental metastasis. Depletion of integrin alpha 7 triggered CAF-like activation of ADSCs in vitro. Video Abstract CONCLUSIONS: miR-320a in small extracellular vesicles secreted by tumor cells targets integrin subunit alpha 7 in ADSCs and drives CAF-like activation, which in turn facilitates omental metastasis of ovarian cancer.

ITGA7 loss drives the differentiation of adipose-derived mesenchymal stem cells to cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAFs) represent a major cellular component of the tumor (pre-)metastatic niche and play an essential role in omental dissemination of ovarian cancer. The omentum is rich in adipose, and adipose-derived mesenchymal stem cells (ADSCs) have been identified as a source of CAFs. However, the molecular events driving the phenotype shift of ADSCs remain largely unexplored. In this research, we focus on integrins, transmembrane receptors that have been widely involved in cellular plasticity. We found that integrin α7 (ITGA7) was the only member of the integrin family that positively correlated with both overall survival and progression-free survival in ovarian cancer through GEPIA2. The immunohistochemistry signal of ITGA7 was apparent in the tumor stroma, and a lower omental ITGA7 level was associated with metastasis. Primary ADSCs were isolated from the omentum of patients with ovarian cancer and identified by cellular morphology, biomarkers, and multilineage differentiation. The conditional medium of ovarian cancer cells induced ITGA7 expression decrease and phenotypic changes in ADSCs. Downregulation of ITGA7 in primary omental ADSCs led to decrease in stemness properties and emerge of characteristic morphology and biomarkers of CAFs. Moreover, the conditioned medium of ADSCs with ITGA7 depletion exhibited enhanced abilities to improve the migration and invasion of ovarian cancer cells in vitro. Overall, these findings indicate that loss of ITGA7 may induce the differentiation of ADSCs to CAFs that contribute to a tumor-supportive niche.

Multicargo-loaded inverse opal gelatin hydrogel microparticles for promoting bacteria-infected wound healing.

Nowadays, many strategies have been developed to design biomaterials to accelerate bacteria-infected wound healing. Here, we presented a new type of multicargo-loaded inverse opal hydrogel microparticle (IOHM) for regulating oxidative stress, antibiosis, and angiogenesis of the bacteria-infected wound. The methacrylate acylated gelatin (GelMA)-based inverse opal hydrogel microparticles (IOHMs) were obtained by using the colloidal crystal microparticles as templates, and fullerol, silver nanoparticles (Ag NPs), and vascular endothelial growth factor (VEGF) were loaded in IOHMs. The developed multicargo-loaded IOHMs displayed good size distribution and biocompatibility, and when they were applied in cell culture, bacteria culture, and animal experiments, they exhibited excellent anti-oxidative stress properties, antibacterial properties, and angiogenesis. These characteristics of the developed multicargo-loaded IOHMs make them ideal for bacteria-infected wound healing.

Heme Metabolism-Related Gene TENT5C is a Prognostic Marker and Investigating Its Immunological Role in Colon Cancer.

Background: There is a strong correlation between consuming high amounts of heme and an elevated risk of developing various types of cancer, including colorectal cancer. However, the role of heme metabolism-related genes (HRGs) in colorectal cancer remains unclear. Our study aimed to identify prognostic markers for colorectal cancer patients based on these genes. Methods: The heme metabolism score was assessed using gene set variation analysis (GSVA). Potential prognostic HRGs were identified from the TCGA-COAD dataset using LASSO and COX regression analyses. The expression level of TENT5C was validated in the GEO database and clinical samples. To explore the association between TENT5C expression and immune cell infiltrations, we performed ESTIMATE and single-sample gene set enrichment analysis (ssGSEA). Results: The low level of heme metabolism score was associated with a poor prognosis in colorectal cancer patients. TENT5C is a prognostic gene and an independent prognostic biomarker for overall survival. Its expression was confirmed in multiple datasets and clinical samples, showing a positive correlation with immune cells and immune score. GSEA results suggested TENT5C's significant role in regulating immune and inflammatory responses in colorectal cancer. Conclusion: TENT5C can be used as a biomarker in colorectal cancer. Additionally, TENT5C is associated with both prognosis and immune infiltration. These findings lay a strong groundwork for future research to delve into the specific role of TENT5C in the development and advancement of colorectal cancer.

Hypertension and hyperglycaemia are positively correlated with local invasion of early cervical cancer.

Background: Metabolic disorders are involved in the development of numerous cancers, but their association with the progression of cervical cancer is unclear. This study aims to investigate the association between metabolic disorders and the pathological risk factors and survival in patients with early cervical cancer. Methods: Patients with FIGO IB1 (2009) primary cervical cancer who underwent radical hysterectomy and systematic pelvic lymph node dissection at our institution from October 2014 to December 2017 were included retrospectively. Clinical data regarding the metabolic syndrome and surgical pathology of the patient were collected. The correlations between metabolic disorders (hypertension, hyperglycemia, and obesity) and clinicopathological characteristics as well as survival after surgery were analyzed. Results: The study included 246 patients with clinical IB1 cervical cancer, 111 (45.1%) of whom had at least one of the comorbidities of hypertension, obesity, or hyperglycemia. Hypertension was positively correlated with parametrial invasion and poorly differentiated histology; hyperglycemia was positively correlated with stromal invasion; obesity was negatively associated with lymph node metastasis; but arbitrary disorder did not show any correlation with pathologic features. Hypertension was an independent risk factor for parametrial invasion (OR=6.54, 95% CI: 1.60-26.69); hyperglycemia was an independent risk factor for stromal invasion (OR=2.05, 95% CI: 1.07-3.95); and obesity was an independent protective factor for lymph node metastasis (OR=0.07, 95% CI: 0.01-0.60). Moreover, the patients with hypertension had a significantly lower 5-year OS rate (70.0% vs. 95.3%, P<0.0001) and a significantly lower 5-year PFS rate than those without hypertension (70.0% vs. 91.2%, P=0.010). Conclusion: Hypertension and hyperglycemia are positively associated with local invasion of early cervical cancer, which need to be verified in multi-center, large scale studies.

Corrigendum: Assessing the causal relationship between genetically determined inflammatory biomarkers and low back pain risk: a bidirectional two-sample Mendelian randomization study.

[This corrects the article DOI: 10.3389/fimmu.2023.1174656.].

Method for testing freeform surfaces based on a Shack-Hartmann sensor with plane wavefront scanning and stitching.

Currently, the surface error measurement technology for freeform faces a significant contradiction between measurement accuracy and dynamic range. The study proposes a non-null testing method for measuring freeform surfaces by utilizing a Shack-Hartmann wavefront sensor to emit a small aperture parallel beam and scan along the normal direction at the center of subapertures for stitching (SHPSS). A mathematical model based on ray tracing and the reflection theorem is established to calculate the sampling points on an ideal freeform surface, the reference spot array on CCD, and the corresponding relationship between microlens array and spots. An algorithm is proposed to iteratively calculate the wavefront aberration and gradually approach the actual sampling points using the established model. Theoretical analysis and numerical simulation results indicate that SHPSS can increase the dynamic range and improve the accuracy of wavefront reconstruction. The error analysis of the SHPSS method is carried out, the measurement accuracy of full aperture freeform surface is 11.45 nm. A testing system is set up and experiments are conducted on a 100 mm aperture freeform reflective mirror. The RMS of the SHPSS test results is less than λ/30 (λ=635 nm) compared to the interferometric test results. By analyzing five groups of repeated measurement experiments, the repeatability accuracy of SHPSS method is less than 1/80 λ (RMS). This demonstrates the feasibility and measurement capabilities of the method for freeform surface testing.

Role of the tumor microenvironment in the lymphatic metastasis of cervical cancer (Review).

Lymphatic metastasis is the primary type of cervical cancer metastasis and is associated with an extremely poor prognosis in patients. The tumor microenvironment primarily includes cancer-associated fibroblasts, tumor-associated macrophages, myeloid-derived suppressor cells, immune and inflammatory cells, and blood and lymphatic vascular networks, which can promote the establishment of lymphatic metastatic sites within immunosuppressive microenvironments or promote lymphatic metastasis by stimulating lymphangiogenesis and epithelial-mesenchymal transformation. As the most important feature of the tumor microenvironment, hypoxia plays an essential role in lymph node metastasis. In this review, the known mechanisms of hypoxia, and the involvement of stromal components and immune inflammatory cells in the tumor microenvironment of lymphatic metastasis of cervical cancer are discussed. Additionally, a summary of the clinical trials targeting the tumor microenvironment for the treatment of cervical cancer is provided, emphasizing the potential and challenges of immunotherapy.

Hemivertebra resection after age three produces the similar results but with less complications compared to earlier surgery: a minimum of 5-year follow-up.

BACKGROUND: The optimal timing for hemivertebra resection remains controversial. Early intervention before 3 years of age seems being able to get better correction with less fusion segments. However, it was also reported that early surgery may be associated with more complications. The purpose of this study is to investigate correction outcomes and complications of delayed hemivertebra resection (between 3 and 5 years of age), in comparison with earlier surgery (before 3 years of age). METHODS: Patients who had undergone thoracolumbar hemivertebra resection at a single level before 5 years of age and had more than 5 years of follow-up were reviewed. Twenty-four patients had hemivertebra resection surgery below 3 years of age (early surgery, Group E), and 33 patients received surgery between 3 and 5 years of age (delayed surgery, Group D). Radiographs from preoperative, immediately postoperative, and the latest follow-up visits were reviewed to investigate the correction outcomes. Complications were recorded and compared between these two groups. RESULTS: The patients of Group E had shorter operation time and less blood loss than those of Group D (P = 0.003 and P = 0.006). Notably, the fusion segments were 2.3 ± 0.7 and 3.1 ± 1.2 in group E and group D (P = 0.005), respectively, indicating group E averagely saved 0.8 motion segments. At the time of surgery, group E had smaller main curve magnitude either in the coronal or in the sagittal plane than group D and experienced similar correction rates of scoliosis (83.3 ± 21.6% vs. 81.2 ± 20.1%, P = 0.707) and kyphosis (65.1 ± 23.8% vs. 71.7 ± 24.9%, P = 0.319). However, group E had relatively higher complication rates than group D and relatively greater correction loss in either coronal or sagittal plane during follow-up. CONCLUSIONS: Hemivertebra resection resulted in similar correction results in both age groups. However, the rate of complications was lower for Group D than Group E. Thus, for non-kyphotic hemivertebra, surgery may be delayed till 3 to 5 years of age.

Associations between socioeconomic status and stroke in American adults: A population-based study.

Stroke is an acute cerebrovascular disease that can lead to disability and death. This study aimed to investigate the relationship between socioeconomic status (SES) and stroke. SES was evaluated by two variables: poverty to income ratio (PIR) and education level. In this multi-subject study, we collected data from the National Health and Nutrition Examination Survey (NHANES) database between 2009 and 2018, and finally 22,792 adults (≥20 years old) were included in the study. We proceeded with weighted multivariate logistic regression analysis as well as subgroup analysis. When analyzing the effect of PIR on stroke alone, the results showed that an increase in PIR levels was associated with a decrease in stroke incidence (OR = 0.764 95% CI: (0.711, 0.820), p < 0.001). The multivariate analysis presented a decline in stroke incidence in the highest quartile PIR group compared to the lowest quartile PIR group (OR = 0.296 95% CI: (0.214, 0.409), P＜0.001). Our results indicated that PIR is a protective factor for stroke, but there are exceptions in this relationship among different people. Hence, it is imperative that policymakers, healthcare providers, and clinicians take into account the inequality distribution of SES among adults while developing and executing stroke prevention and treatment strategies.

Assessing the causal relationship between genetically determined inflammatory biomarkers and low back pain risk: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies have suggested an association between inflammatory markers and low back pain (LBP), but the causal relationship between these factors remains uncertain. Methods: We conducted a bidirectional two-sample Mendelian randomization analysis (MR) study to investigate whether there is a causal relationship between inflammatory markers and low back pain. We obtained genetic data for CRP, along with its upstream inflammatory markers IL-6, IL-8, and IL-10, as well as low back pain from publicly available genome-wide association studies (GWAS). We applied several MR methods, including inverse variance weighting, weighted median, MR-Egger, Wald Ratio, and MR-PRESSO, to test for causal relationships. Sensitivity analyses were also conducted to assess the robustness of the results. Results: Our analyses utilizing the Inverse Variance Weighted (IVW) method, the MR-Egger method, and the weighted median method indicated that IL-6 may be associated with an increased risk of LBP (Effect Size: -0.009, 95% Confidence Interval: -0.013-0.006, p = 9.16e-08); however, in the reverse direction, there was no significant causal effect of LBP on inflammatory markers. Conclusion: Our study used a Mendelian randomization approach and found that elevated IL-6 levels may reduce the risk of LBP.

Association between urinary caffeine and caffeine metabolites and stroke in American adults: a cross-sectional study from the NHANES, 2009-2014.

This study investigates the potential correlation between urinary caffeine levels and the occurrence of stroke, a serious cerebrovascular disease that can lead to disability or death. The data used in this study was obtained from the National Health and Nutrition Examination Survey conducted between 2009 and 2014. The study analyzed a total of 5,339 individuals, divided into a control group (n = 5,135) and a stroke group (n = 162). The researchers utilized multiple logistic regression and smoothed curve fitting to examine the relationship between urinary caffeine and caffeine metabolites and the incidence of stroke. The study found that higher urinary caffeine levels were associated with a lower risk of stroke in Mexican American participants (odds ratio [OR] = 0.886, 95% confidence interval [CI]: (0.791, 0.993), P = 0.037). After adjusting for certain participant characteristics, it was also found that higher urinary paraxanthine levels were associated with a lower risk of stroke incidence (OR = 0.991, 95% CI (0.984, 0.999), P = 0.027). Meanwhile, the highest urinary paraxanthine levels group had 43.7% fewer strokes than the lowest level group (OR = 0.563, 95% CI (0.341, 0.929), P = 0.025). In this study, we showed a negative link between urine paraxanthine levels and the risk of stroke. Meanwhile, urinary caffeine levels were negatively associated with the incidence of stroke in Mexican Americans, but no correlation in other populations. Our findings may have predictive and diagnostic implications in clinical practice. Further extensive prospective investigations are still needed to validate our conclusions.

Establishment of a triplex TaqMan quantitative real-time PCR assay for simultaneous detection of Cymbidium mosaic virus, Odontoglossum ringspot virus and Cymbidium ringspot virus.

Orchids are significant ornamental plants whose viral infection results in substantial economic damage. Cymbidium mosaic virus (CymMV), Odontoglossum ringspot virus (ORSV), and Cymbidium ringspot virus (CymRSV) represent three important and prevalent orchid viruses. The detection system proposed in this study uses a triplex TaqMan quantitative real-time PCR assay to identify CymMV, ORSV, and CymRSV in a simultaneous manner. We designed specific primers and probes for CymMV, ORSV, and CymRSV, with amplified sequences of 156 bp, 148 bp, and 145 bp, respectively. The minimum detection limit of the triplex qRT-PCR assay for CymMV and CymRSV was 1 copy/assay, and the minimum detection limit was 10 copies/assay for ORSV. The minimum stable detection limits for CymMV, ORSV, and CymRSV were 10, 102, and 102 copies/assay, respectively. Therefore, this system exhibited higher sensitivity (approximately 10 to 104-fold) than RT-PCR. The intra-and interassay CVs of Cq values are less than 0.55 and 0.95%, respectively, indicating that the triplex assay is highly reliable and accurate. In addition, 66 samples from five different orchid genera were analyzed using the established assay and gene chip. The detection results demonstrated that the triplex probe qRT-PCR demonstrated higher sensitivity than the gene chip, indicating that the triplex real-time PCR assay could be used for the detection of field samples. Our findings suggest that the triplex real-time RT-PCR detection system represents a rapid, simple, and accurate tool for detecting CymMV, ORSV, and CymRSV on orchids.

In Situ Self-Assembled Formation of Nitrogen-Rich Ag@Ti3C2 Film for Sensitive Detection and Spatial Imaging of Pesticides with Laser Desorption/Ionization Mass Spectrometry (LDI-MS).

Pesticide residues are hazardous to human health; thus, developing a rapid and sensitive method for pesticide detection is an urgent need. Herein, novel nitrogen-rich Ag@Ti3C2 (Ag@N-Ti3C2) was synthesized via an ecofriendly, ultraviolet-assisted strategy, followed by in situ formation of a highly homogeneous film on target carriers via a facile water evaporation-induced self-assembly process. Ag@N-Ti3C2 shows greater surface area, electrical conductivity, and thermal conductivity than Ti3C2. This Ag@N-Ti3C2 film overcomes the limitations of conventional matrixes and allows laser desorption/ionization mass spectrometry (LDI-MS) to provide fast and high-throughput analysis of pesticides (e.g., carbendazim, thiamethoxam, propoxur, dimethoate, malathion, and cypermethrin) with ultrahigh sensitivity (detection limits of 0.5-200 ng/L), enhanced reproducibility, extremely low background, and good salt tolerance. Furthermore, the levels of pesticides were quantified with a linear range of 0-4 µg/L (R2 > 0.99). This Ag@N-Ti3C2 film was used for high-throughput analysis of pesticides spiked in traditional Chinese herbs and soft drink samples. Meanwhile, high-resolution Ag@N-Ti3C2 film-assisted LDI-MS imaging (LDI MSI) was used to successfully explore spatial distributions of xenobiotic pesticides and other endogenous small molecules (e.g., amino acids, saccharides, hormones, and saponin) in the roots of plants. This study presents the new Ag@N-Ti3C2 self-assembled film equably deposits on the ITO slides and provides a dual platform for pesticide monitoring and has the advantages of high conductivity, accuracy, simplicity, rapid analysis, minimal sample volume requirement, and an imaging function.

ITGA5 promotes tumor angiogenesis in cervical cancer.

PURPOSE: Integrins are critical to cancer progression. Integrin alpha 5 (ITGA5) is correlated with the prognosis of cervical cancer patients. However, whether ITGA5 plays an active role in cervical cancer progression or not remains unknown. METHODS: ITGA5 protein expression was detected in 155 human cervical cancer tissues by immunohistochemistry. Data from The Cancer Genome Atlas were utilized to identify risk factors for the overall survival of cervical cancer patients and ITGA5-associated differentially expressed genes. Analyses of single-cell RNA-seq based on Gene Expression Omnibus datasets were performed to show the coexpression of ITGA5 and angiogenesis factors. Tube formation assay, 3D spheroid sprout assay, qRT-PCR, Western Blotting, ELISA, and immunofluorescence were conducted to explore the angiogenic function of ITGA5 in vitro and underlying mechanisms. RESULTS: High ITGA5 level was significantly correlated with increased risk in terms of overall survival and advanced disease stage in cervical cancer patients. ITGA5-associated differentially expressed genes linked ITGA5 to angiogenesis, and immunohistochemistry showed a positive correlation between ITGA5 and microvascular density in cervical cancer tissues. Moreover, tumor cells transfected with ITGA5-targeting siRNA decreased ability to promote endothelial tube formation in vitro. ITGA5/VEGFA coexpression was observed in a tumor cell subpopulation and the decreased endothelial angiogenesis by downregulating ITGA5 could be reversed by VEGFA. Bioinformatics analysis highlighted the PI3K-Akt signaling pathway as downstream of ITGA5. Downregulation of ITGA5 in tumor cells significantly decreased p-AKT and VEGFA levels. Fibronectin (FN1) coated cells or transfected with FN1-targeting siRNA showed fibronectin may play a critical role on ITGA5-mediated angiogenesis. CONCLUSION: ITGA5 promotes angiogenesis and possibly be a potential predictive biomarker for poor survival of patients in cervical cancer.