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Fibrous 3D scaffold with small fiber diameter has the similar topographic and structural characteristics of native extracellular matrix (ECM), which provides the beneficial microenvironment for cell adhesion, growth, migration, proliferation. However, the pore structure of the biopolymer scaffold is crucial for cell regulation and tissue regeneration in practical application. In this report, we proposed a nanofiber induced silk fibroin nanofibers/silk fibroin (SFNF/SF) fibrous scaffold with homogeneous micron pores using fast freeze-drying technology under − 196 °C. The physical, chemical and biological performance of the scaffold was investigated. Ethanol post treatment of the scaffold led to the conformation transition of silk fibroin from random coil (silk I) to beta-sheet (silk II) and increase of the crystallinity of the scaffold, which greatly improved the stability of the scaffold in water. Scaffolds made from 2 to 6% SFNF/SF solution with SFNF/SF ratio ranging from 1:1 to 1:8 exhibited three dimensional (3D) fibrous structure with porosity of 80–85% and pore size ranging from 5 to 15 μm due to the entanglement of the nanofibers. And the fibrous structure of the scaffolds can be adjusted by controlling the concentration of the SFNF/SF solution and the SFNF/SF ratio. Cell culture suggested that the 3D fibrous network structure with micron pores showed advantages for cell migration comparing with the lamella structure scaffold. After 7 day’s culture, cells migrated to about 240 μm inside the 6% 1:1 scaffold, while only about 160 μm inside the 6% 1:16 scaffold. The nanofiber induced micro porous SFNF/SF scaffolds by fast freeze-drying technology is potential for preparation of micron porous scaffold.

Post-crosslinking treatment is essential for improving the water tolerance of the electrospinning keratin/Poly(ethylene oxide) (PEO) nanofiber membrane to meet the requirement of the biomedical application. In this study, three ecofriendly low-cost methods, hot air, pure oxygen, and ultraviolet irradiation were employed as the post-crosslinking treatment to prepare the electrospun keratin/PEO (90/10) nanofiber membrane with good water tolerant. A comparative study between the performances of the nanofiber prepared by different cross-linking methods were carried out. The results showed the three post-crosslinking methods were all effective for transforming the water-soluble keratin/PEO nanofiber membranes to the water insoluble membranes. However, the mechanical property, water sorption and swelling rate, molecular structure, thermal property, and crystallinity of the nanofiber membranes were all different due to the different post-crosslinking methods. After heat treatment, the tensile strength of the nanofiber membrane can reach 2.29 MPa, while that of the oxygen crosslinking and ultraviolet crosslinking are 0.99 and 1.68 MPa, respectively. The water absorption and swelling of the oxygen and ultraviolet crosslinking membranes are relatively large, and the swelling rate is about 21%. The oxygen crosslinking membrane possessed higher hydrophilicity and the contact angle is only 21°. In vitro cell culture studies showed that the post-crosslinked nanofiber membrane all presented excellent biocompatibility and supported cell adhesion and proliferation. The three ecofriendly low-cost post-crosslinking treatments are all reliable and safe to prepare keratin/PEO nanofiber membrane with good water tolerant, which is potential for tissue engineering and biomedical applications.

The epidermal growth factor receptor (EGFR) plays crucial roles in several important biological functions such as embryogenesis, epithelial tissue development, and cellular regeneration. However, in multiple solid tumor types overexpression and/or activating mutations of the EGFR gene frequently occur, thus hijacking the EGFR signaling pathway to promote tumorigenesis. Non-small cell lung cancer (NSCLC) tumors in particular often contain prevalent and shared EGFR mutations that provide an ideal source for public neoantigens (NeoAg). Studies in both humans and animal models have confirmed the immunogenicity of some of these NeoAg peptides, suggesting that they may constitute viable targets for cancer immunotherapies. Peptide vaccines targeting mutated EGFR have been tested in multiple clinical trials, demonstrating an excellent safety profile and encouraging clinical efficacy. For example, the CDX-110 (rindopepimut) NeoAg peptide vaccine derived from the EGFRvIII deletion mutant in combination with temozolomide and radiotherapy has shown efficacy in treating EGFRvIII-harboring glioblastoma multiforme (GBM) patients undergone surgery in multiple Phase I and II clinical trials. Furthermore, pilot clinical trials that have administered personalized NeoAg peptides for treating advanced-stage NSCLC patients have shown this approach to be a feasible and safe method to increase antitumor immune responses. Amongst the vaccine peptides administered, EGFR mutation-targeting NeoAgs induced the strongest T cell-mediated immune responses in patients and were also associated with objective clinical responses, implying a promising future for NeoAg peptide vaccines for treating NSCLC patients with selected EGFR mutations. The efficacy of NeoAg-targeting peptide vaccines may be further improved by combining with other modalities such as tyrosine kinase or immune checkpoint inhibitor (ICI) therapy, which are currently being tested in animal models and clinical trials. Herein, we review the most current basic and clinical research progress on EGFR-targeted peptide vaccination for the treatment of NSCLC and other solid tumor types.

In this study, a novel prefabricated light-steel beam–column connection consisting of a thin-walled rectangular hollow section column and two cold-formed steel truss beams is proposed and investigated by carrying out experimental tests. Eight cruciform beam–column connection specimens with different configurations are fabricated and tested to failure under monotonic static loading. First, failure mode and the loading–displacement curve of each specimen are investigated. Consequently, the effect of three variables, including truss-beam configuration, truss-beam type, and with or without sleeve tube reinforcing the column, on the static bearing capacity of the proposed connection and the deflection of the truss beams are investigated. It is found that plug welding the sleeve to the column can significantly increase the static bearing capacity of the proposed connection. In addition, fillet welding connecting the column and the channel connectors to accommodate the end of the truss beams is crucial to the static bearing capacity of the proposed beam–column connection. Because beam–column connections with single-truss beams have a higher load-bearing capacity and require less material and assembly work, it is recommended to adopt this type of configuration for the proposed connection.

Lymphocytes are effector cells that fight cancer by killing tumor cells. Here, we aim to explore the prognostic significance of both peripheral and tumor-infiltrating lymphocytes (TILs) in newly diagnosed stage III/IV non-small-cell lung cancer (NSCLC). In total, 105 cases of newly diagnosed stage III/IV NSCLC from July 2017 to October 2022 at the Tianjin Beichen Hospital were retrospectively investigated. Peripheral blood samples at the time of diagnosis and tumor tissue slices from these patients were collected. General peripheral blood cell composition and TILs were measured and analyzed via an automatic blood analyzer and immunofluorescence staining analysis. The overall survival (OS) time of all patients was also obtained and analyzed. The median overall survival (mOS) of all patients is 12 months. The 1-, 2-, and 3-year overall survival rates were 60.5, 28.4, and 18.6%, respectively. Peripheral lymphocyte and neutrophil percentages, serum C-reactive protein (CRP) expression, tumor size, and tumor pathology are the prognostic factors of OS for newly diagnosed stage III/IV NSCLC patients. Moreover, patients with high tumor CD4+ and CD8+ T cell infiltration survived significantly longer compared to patients with low tumor CD4+ and CD8+ T cell infiltration (  < 0.0001 and  = 0.011, respectively). Compared to low tumor CD33+ cell infiltration, high tumor CD33+ cell infiltration was associated with worse OS (  = 0.018). High tumor CD8+ T cell infiltration was associated with lower peripheral lymphocyte number, lower serum CRP expression, smaller tumor size, and better tumor pathology (  = 0.012,  = 0.040,  = 0.012, and  = 0.029, respectively). Increased numbers of peripheral lymphocytes, CD33+ cells, CD4+ TILs, and CD8+ TILs were significantly associated with OS in newly diagnosed stage III/IV NSCLC patients, which were positively associated with several basic clinical factors.

Malignant glioma is refractory to conventional treatment, highlighting a need to develop novel efficacious therapies. Biguanides, a class of oral antidiabetic drug, have been thought to inhibit proliferation and metastasis in a variety of cancers. The objective of this study was to investigate the affections of biguanides, phenformin (Phen) and metformin (Met), on growth and migration of glioma cells LN229 in vitro and in vivo. Glioma cells LN229 were treated with Phen or Met, then cell proliferation and death were evaluated by MTT assay and PI stain, and cell cycle were evaluated using flow cytometric analysis, meantime wound healing assay and transwell migration assay were performed to detect cell migration ability. In addition, LN229 were injected in thigh of nude mice, and the mice were treated with Phen or Met to detect the effect of Phen and Met in vivo. Phen and Met could significantly inhibit cell growth through inhibiting cell proliferation, promoting cell death and disturbing cell cycle, and these drugs also could inhibit cell colony formation in glioma cells LN229 in vitro. Meanwhile, both Phen and Met could significantly inhibit cell migration of LN229 in vitro, through effecting the expression of E-cadherin and Vimentin. In addition, both Phen and Met inhibited the growth and migration of LN229 in a tumor xenograft model. Furthermore, Phen and Met were associated with the increased level of ROS of cell mitochondrial, and ROS inhibitor NAC could significantly rescue the cell death induced by Phen and Met. Phen and Met displayed powerful antitumor effects of LN229, and our findings powerfully suggest the possibility of Phen and Met being used as an adjuvant agent in the treatment of glioma patients.

Tumor-infiltrating lymphocytes (TILs) therapy is one of the most promising adoptive T cell therapies, which has shown great clinical efficacy against several solid malignancies. Nevertheless, clinical response to TILs mono-therapy in Asian patients with recurrent cervical cancer has not been well reported. Here, we report two patients who were diagnosed with metastatic cervical cancer and tumor progression following multiple conventional treatments. In particular, one of the patients has a history of severe myelosuppression after chemotherapy. The patients received lymphodepletion therapy, which consisted of cyclophosphamide (30mg/kg) for 2 days, followed by Fludarabine (25mg/m ) for 5 days, approximately 24 hr before receiving intravenous autologous TILs infusion. These two patients then received high doses of IL-2 for 10 days with the purpose of maintaining T cell survival and proliferation. Patient 1 experienced clinical partial response (PR) at 6 weeks post TILs infusion and a 33% tumor shrinkage at 12 weeks follow-up, and patient 2 was evaluated as stable disease (SD) at 6 weeks post treatment. Mild and manageable adverse events were observed and soon subsided after the TILs treatment. A time-course study examining the peripheral blood cell count and cytokine secretion demonstrated the persistence of infused TILs and long-term immune response. These results suggest that TILs mono-therapy can be a promising treatment strategy for Asian patients with late-stage metastatic cervical cancer even with severe myelosuppression. TILs infusion can induce persistence and a long-term systematic immune response that reversed peripheral CD4+T and CD8+T percentages implying that TILs infusion increased cytotic T cell responses, which is consistent with clinical responses in these patients. Trial registration number: NCT05366478.

Background Trees of Bombax ceiba L. could produce a large number of viable seeds in the dry-hot valleys. However, the seedling regeneration of the species is difficult in these areas as mild drought often occur repeatedly which might be followed by heat stress. However, how the repeated drought affects the subsequent drought and heat tolerance of B. ceiba is not clear. In this study, chlorophyll fluorescence, soluble sugar content and lipid metabolism were measured for the drought-treated seedlings and heat-treated seedlings with or without drought hardening. Results Neither the first nor third dehydration treatments affected the photosynthetic activity and soluble sugar content of B. ceiba seedlings. However, they differentially affected the fluidity of the local membranes and the levels of diacylglycerol and phosphatidic acid. Heat shock severely decreased the photosynthetic efficiency but drought priming reduced the effects of heat shock. Moreover, heat shock with or without drought priming had differential effects on the metabolism of soluble sugars and some lipids. In addition, the unsaturation level of membrane glycerolipids increased following heat shock for non-drought-hardened seedlings which, however, maintained for drought-hardened seedlings. Conclusions The results suggest that two cycles of dehydration/recovery can affect the metabolism of some lipids during the third drought stress and may enhance the heat tolerance of B. ceiba by adjusting lipid composition and membrane fluidity.

Background The triglyceride-glucose (TyG) index is considered a dependable biomarker for gauging insulin resistance. The atherogenic index of plasma (AIP) represents a marker reflecting atherosclerosis. However, there is currently no study specifically exploring the associations of these two biomarkers with the severity of new-onset coronary artery disease (CAD) under different glucose metabolic states. Therefore, this study aims to evaluate the correlations of these two biomarkers with CAD severity in patients newly diagnosed with CAD under various glucose metabolism conditions. Method Totally 570 subjects first administered coronary angiography were enrolled, including 431 first diagnosed CAD patients and 139 non-CAD patients. CAD severity  was gauged by the quantity of narrowed arteries (single-vessel and multi-vessel CAD). According to WHO diabetes guidelines, glucose metabolic states were divided into normal glucose regulation (NGR), pre-diabetes mellitus (Pre-DM), and diabetes mellitus (DM). The relationships of the TyG index and AIP with CAD severity were validated by logistic regression analysis, including adjustment for traditional cardiovascular risk elements and medical treatments. Their predictive efficacy for CAD was evaluated by receiver operating characteristic (ROC) curves. Result The TyG index and AIP were independently correlated with CAD in accordance with logistic regression analysis (both P < 0.05). Regardless of the glucose metabolic states, there was no statistical correlation between the TyG index and CAD severity. However, AIP in NGR patients was significantly related to CAD severity (P < 0.05). The areas under the curve of the TyG index and AIP for predicting CAD were 0.682 and 0.642 (both P < 0.001), respectively, and their optimal cut-off values were 3.210 (Youden index: 0.305) and 0.095 (Youden index:0.246), respectively. Conclusion The TyG index and AIP have significant associations with CAD. The TyG index had no association with CAD severity, regardless of glucose metabolic states. AIP exhibited a discernible link with CAD severity in NGR patients, but not in the pre-DM or DM populations. The TyG index and AIP have similar predictive values for new-onset CAD.

Infertility poses a significant burden on both global and national scales. However, the epidemiology of primary infertility among reproductive-aged couples in China remains poorly understood. Therefore, this study aimed to investigate the global infertility rate and identify factors associated with primary infertility among middle-aged couples in China. Cross-sectional data were derived from the Global Burden of Disease (GBD) study and the Chinese Health and Retirement Longitudinal Study (CHARLS), two extensive databases that examined various disease burdens and associated factors at both global and national levels. From 1990 to 2019, the global infertility population has shown a steady annual increase. In China, the age-standardized prevalence rate of infertility has remained relatively stable over the past three decades. However, this rate was notably higher than the global age-standardized infertility prevalence rate. Our analysis revealed that the prevalence of primary infertility among middle-aged Chinese couples was approximately 1.7% (947,953/56,892,517). Additionally, we identified anxiety as an associated factor with infertility, highlighting the need for increased public attention to mental health in China. Infertility continued to be a pressing issue on both global and national levels. This situation warranted widespread attention from Chinese policymakers and healthcare managers. The findings might guide future policy-making and medical interventions in China, with a particular focus on supporting the reproductive needs of middle-aged individuals.