Flexible, high‐strength titanium nanowire for scaffold biomimetic periodontal membrane

Abstract A layer of micro‐sized periodontal membrane can buffer most chewing forces to protect the interface between the natural tooth root and alveolar bone. Artificial dental implants usually direct contact onto the alveolar bone without a buffer layer, which increases the risk of surface damage. The main purpose of this work was the bionic design of a flexible layer of nanowire scaffold on a titanium implant surface according to the function of the periodontal membrane. Millions of nanowires were woven into a superhydrophilic layer of porous scaffold. The evolution of mechanical properties displayed that the biomimetic nanowire scaffold could absorb a maximum of about 1.59 KJ energy per square centimeter by low‐speed impact. The minimum tensile strength of one nanowire was 2 GPa. A biomimetic flexible periodontal membrane connection functioning between the natural tooth root and alveolar bone has great potential value for developing advanced artificial dental implants for dental restorations

Fruquintinib plus oxaliplatin combined with S-1 (SOX) as neoadjuvant therapy for locally advanced gastric cancer (GC) or gastro-oesophageal junction adenocarcinoma (GEJ): a multicentre, phase II, single-arm, open-label clinical trial (FRUTINEOGA) protocol

Introduction Curing locally advanced gastric cancer (GC) or gastro-oesophageal junction adenocarcinoma (GEJ) with surgery alone is challenging. Neoadjuvant chemotherapy (NCT) has become the standard treatment for patients with locally advanced GC/GEJ, and SOX is the most common neoadjuvant regimen in China. The generally good tolerability in patients and fruquintinib’s low potential for drug–drug interaction suggest that it may be highly suitable for combinations with other antineoplastic therapies. A combination of fruquintinib, S-1 and oxaliplatin can be a promising neoadjuvant treatment for locally advanced GC/GEJ. In this phase II study, we aim to investigate the efficacy and toxicity of fruquintinib plus SOX as neoadjuvant treatment for locally advanced GC/GEJ.Methods and analysis The FRUTINEOGA trial is a prospective, multicentre, phase II, single-arm, open-label clinical trial that will enrol 54 patients. Eligible patients will be registered, enrolled and receive 2–4 cycles of fruquintinib plus SOX, after which surgery will be performed and tumour regression will be evaluated. The primary endpoint is the pathological remission rate, and the secondary endpoints are disease-free survival, overall survival, objective response rate, major pathological response rate and R0 resection rate.Ethics and dissemination Written informed consent will be required from all patients enrolled, and it will be provided by them. The study protocol received approval from the independent ethical review committee of Guangxi Medical University Cancer Hospital, Wuming Hospital of Guangxi Medical University and Wuzhou Red Cross Hospital, Wuzhou Gongren Hospital (approval number: CS2021(96)). We will submit the finalised paper for publication on completing the analyses. This study will provide valuable insights to clinicians regarding the safety and efficacy of incorporating fruquintinib into SOX as neoadjuvant treatment for locally advanced GC/GEJ. The findings have the potential to inform future research proposals and may guide the use of fruquintinib in the neoadjuvant setting for locally advanced GC/GEJ.Trial registration number NCT05122091

Realgar Alleviated Neuroinflammation Induced by High Protein and High Calorie Diet in Rats via the Microbiota-Gut-Brain Axis

Purpose: Gastrointestinal heat retention syndrome (GHRS) often occurs in adolescents, resulting into nervous system injury. Realgar, an arsenic mineral with neuroprotective effect, has been widely used to treat GHRS. However, its mechanism of action remains unknown. Methods: A GHRS rat model was established using a high protein and high calorie diet. We performed macroscopic characterization by assessing bowel sounds, hot/cold preference, anal temperature, and fecal features. Atomic fluorescence spectroscopy was employed to evaluate brain arsenic level while hippocampal ultrastructural changes were analyzed using transmission electron microscopy. In addition, inflammatory cytokines and BBB breakdown were analyzed by western blotting, immunofluorescence assays, and immunohistochemistry staining. We also evaluated hippocampal metabolites by LC-MS while fecal microorganisms were assessed by 16S rDNA sequencing. Results: Our data showed that the high protein and high calorie diet induced GHRS. The rat model depicted decreased bowel sounds, increased fecal characteristics score, preference for low temperature zone, and increased anal temperature. In addition, there was increase in inflammatory factors IL-6, Iba-1, and NF-κB p65 as well as reduced BBB structural protein Claudin-5 and Occludin. The data also showed appearance of hippocampus metabolites disorder and fecal microbial imbalance. Realgar treatment conferred a neuroprotective effect by inhibiting GHRS-specific characteristics, neuroinflammatory response, BBB impairment, metabolites disorder, and microbial imbalance in the GHRS rat model. Conclusion: Taken together, our analysis demonstrated that realgar confers a neuroprotective effect in GHRS rats through modulation of the microbiota-gut-brain axis

A Novel Bifunctional Protein TNFR2-Fc-IL-1ra (TFI): Expression, Purification and its Neutralization Activity of Inflammatory Factors

Tumor necrosis factor receptor (TNF) and internleukin-1 (IL-1) are the most potent proinflammatory cytokines involving in autoimmune and inflammatory human diseases. Many anti-inflammatory agents have been exploited for anti-inflammation treatments by targeting cytokines including TNF and IL-1. Theoretically, simultaneously neutralizing or blocking two important inflammatory mediators may achieve a synergistic therapeutic effect. We have developed a recombinant fusion protein, TNFR2-Fc-IL-1ra (TFI), which consists of a TNF-neutralizing domain that specifically binds to TNF-alpha, an IL-1 receptor antagonist domain, and a dimerization Fc portion of human IgG1, for bifunctional inflammatory inhibitor. Recombinant DNA expressing the sequence of this fusion protein was expressed in CHO-S cells. The protein product was purified using a two-step purification protocol and the identity of the protein was confirmed by western blot analysis. The purified recombinant protein had a purity of about 98 % as determined by HPLC, and a molecular mass of 164.6 kDa as determined by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The results of cell binding inhibition indicate that TFI was able to strongly neutralize TNF activity and antagonize IL-1r activity, suggesting that TFI may be used as a bifunctional ligand with enhanced anti-inflammatory effect. The result obtained in this study may provide a platform for extending bifunctional anti-inflammatory drug development

The gypsy Insulator of Drosophila melanogaster, Together With Its Binding Protein Suppressor of Hairy-Wing, Facilitate High and Precise Expression of Transgenes in Arabidopsis thaliana

The variation of expression pattern exhibited by a transgene as a result of random integration, known as position effect, is, among other mechanisms, a particular challenge to reverse genetics. We present a strategy to counteract position effect in Arabidopsis thaliana by flanking the transgenes with the gypsy insulator from Drosophila melanogaster. In addition, Suppressor of Hairy-wing [Su(Hw)], the binding protein of the gypsy insulator, was coexpressed. Results indicated that the gypsy insulators could efficiently improve the expression levels of reporter genes driven by various kinds of promoters by 8- to 13-fold. Coexpression of the Su(Hw) protein led to a more uniform expression level of transgenes, as the coefficient of variation of expression levels was reduced further. The gypsy-Su(Hw) system enhanced expression levels, but did not alter the specificity of promoter activities, as experimentally evidenced by the promoters of the PIN and the AFB gene families. Interestingly, the gypsy insulator was also able to improve the expression of a selectable marker gene outside the insulated region, which facilitated the screen of transformants. Our system will likely decrease the number of lines that experimenters need to create and examine for a given transgene by contributing to relatively high and precise expression of transgenes in plants. Certain features of the gypsy insulator in Arabidopsis also provide new perspectives on the insulator field

High‐Performance and Stable Dopant‐Free Silicon Solar Cells with Magnesium Acetylacetonate Electron‐Selective Contacts

One of the challenges in fabricating high‐performance n‐type crystalline silicon (n‐type c‐Si) solar cells is the high‐quality n‐type c‐Si/metal contact. Schottky barriers are commonly found on the n‐type c‐Si/metal contact, which suppresses electron transportation. Herein, novel stacks of magnesium acetylacetonate (Mg(Acac)2)/magnesium (Mg)/silver (Ag) to form electron‐selective contacts for n‐type c‐Si solar cells are presented, which enables a dopant‐free process. An ohmic contact on n‐type c‐Si is formed using the Mg(Acac)2/Mg/Ag stacks. The transmission spectrum and ultraviolet photoelectron spectroscopy measurements show negligible conduction‐band offset and large valence‐band offset between Mg(Acac)2 and n‐type c‐Si, which indicates the electron‐transporting and hole‐blocking properties of Mg(Acac)2/n‐type c‐Si heterocontacts. Moreover, the contact resistivities (ρ c ) between the Mg(Acac)2/Mg/Ag electron‐selective heterocontacts and n‐type c‐Si substrates are lower than 10 mΩ cm2, which demonstrates the good electrode properties of the Mg(Acac)2/Mg/Ag stacks. The Mg(Acac)2/Mg/Ag electron‐selective stacks are applied on n‐type c‐Si solar cells with partial rear contact, and >20% efficiency is achieved, which is higher than that in a reference cell with only Ag contact. The stability of the n‐type c‐Si solar cell performance equipped with Mg(Acac)2/Mg/Ag contacts is verified under ambient conditions. This novel low‐temperature contact technique offers a reliable alternative for high‐performance n‐type c‐Si solar cells

Engineered human spinal cord-like tissues with dorsal and ventral neuronal progenitors for spinal cord injury repair in rats and monkeys

Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host's ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair