Impact of changes in collagen construction and molecular state on integrin - binding properties.

The interaction between the integrin and collagen is important in cell adhesion and signaling. Collagen, as the main component of extracellular matrix, is a base material for tissue engineering constructs. In tissue engineering, the collagen structure and molecule state may be altered to varying degrees in the process of processing and utilizing, thereby affecting its biological properties. In this work, the impact of changes in collagen structure and molecular state on the binding properties of collagen to integrin α2ß1 and integrin specific cell adhesion were explored. The results showed that the molecular structure of collagen is destroyed under the influence of heating, freeze-grinding and irradiation, the triple helix integrity is reduced and molecular breaking degree is increased. The binding ability of collagen to integrin α2ß1 is increased with the increase of triple helix integrity and decays exponentially with the increase of molecular breaking degree. The collagen molecular state can also influences the binding ability of collagen to cellular receptor. The collagen fibrils binding to integrin α2ß1 and HT1080 cells is stronger than to collagen monomolecule. Meanwhile, the hybrid fibril exhibits a different cellular receptor binding performance from corresponding single species collagen fibril. These findings provide ideas for the design and development of new collagen-based biomaterials and tissue engineering research.

Malaria cases in China acquired through international travel, 2013-2022.

BACKGROUND: Despite the World Health Organisation certifying China malaria-free in 2021, the risk of local transmission caused by imported malaria cases remains a significant clinical and public health issue. It is necessary to present the changing trends of malaria in China and discuss the role of travel medicine services in consolidating malaria elimination. METHODS: This study systematically reviewed articles and reports related to human malaria from 2013 to 2022 published in international and Chinese databases. Data on malaria (i.e. number of cases, Plasmodium spp., diagnostic method, country of acquisition, provinces with high risk of re-introduction and transmission) were collected and synthesised, then summarised using descriptive statistics. RESULTS: Overall, 24 758 cases of malaria (>99.5% laboratory confirmed, > 99.2% imported, 0.5% fatal) were reported in China from 2013 to 2022, with a downward trend over the years (4128 cases in 2013 compared to 843 cases in 2022; χ2 trend p-value = 0.005). The last locally acquired case was reported in 2017. P. falciparum (65.5%) was the most common species identified, followed by P. vivax (20.9%) and P. ovale (10.0%). Two Pheidole knowlesi cases were also identified in 2014 and 2017 in returned travellers from Malaysia and Indonesia, respectively. The most common countries of malaria acquisition were Ghana, Angola, and Myanmar. P. vivax was mainly detected in returned travellers from Myanmar, while P. falciparum and P. ovale were detected in travellers from Sub-Saharan Africa. Imported cases were mainly reported in Yunnan, Jiangsu, Sichuan, Guangxi, Shandong, Zhejiang, and Henan provinces, where large numbers of Chinese people travel overseas for work. CONCLUSION: Returned travellers from malaria-endemic countries pose a significant risk of malaria re-introduction to China. Travel medicine should be strengthened to improve the capacity and accessibility of both pre- and post-travel services, including malaria prophylaxis and prompt diagnosis of illness in returned travellers.

Hysteresis-Free and Bias-Stable Organic Transistors Fabricated by Dip-Coating with a Vertical-Phase-Separation Structure.

The morphology of organic films plays a pivotal role in determining the performance of transistor devices. While the dip-coating technique is capable of producing highly oriented organic films, it often encounters challenges such as limited coverage and the presence of defects in gaps between strips, adversely affecting device performance. In this study, we address these challenges by increasing solution viscosity through the incorporation of a substantial proportion of dielectric polymers, thereby enhancing the participation of additional molecules during the film formation process when pulled up. This method produces continuous and oriented organic films with a notable absence of gaps, significantly improving the carrier mobility of transistor devices by more than twofold. Importantly, the fabricated devices exhibit remarkable reliability, showing no hysteresis even after 200 cycles of measurement. Furthermore, the current and threshold voltages of the devices demonstrate exceptional stability, maintaining steady after 10,000 s of bias measurement. This approach provides a solution for the cost-effective and large-scale production of organic transistors, contributing significantly to the advancement of organic electronics.

In vitro anti-Helicobacter pylori activity and antivirulence activity of cetylpyridinium chloride.

The primary treatment method for eradicating Helicobacter pylori (H. pylori) infection involves the use of antibiotic-based therapies. Due to the growing antibiotic resistance of H. pylori, there has been a surge of interest in exploring alternative therapies. Cetylpyridinium chloride (CPC) is a water-soluble and nonvolatile quaternary ammonium compound with exceptional broad-spectrum antibacterial properties. To date, there is no documented or described specific antibacterial action of CPC against H. pylori. Therefore, this study aimed to explore the in vitro activity of CPC against H. pylori and its potential antibacterial mechanism. CPC exhibited significant in vitro activity against H. pylori, with MICs ranging from 0.16 to 0.62 µg/mL and MBCs ranging from 0.31 to 1.24 µg/mL. CPC could result in morphological and physiological modifications in H. pylori, leading to the suppression of virulence and adherence genes expression, including flaA, flaB, babB, alpA, alpB, ureE, and ureF, and inhibition of urease activity. CPC has demonstrated in vitro activity against H. pylori by inhibiting its growth, inducing damage to the bacterial structure, reducing virulence and adherence factors expression, and inhibiting urease activity.

Exploring vehicle-centric strategies for sustainable urban mobility: A theoretical framework for saving energy and reducing noise in transportation.

Adopting energy-saving and noise-reducing technologies in vehicle transportation has the potential to mitigate urban traffic pollution and promote sustainable urban mobility. However, a universal analytical framework for obtaining the combined energy savings and noise reduction patterns in vehicles is still lacking. This study addresses this gap by integrating a fundamental traffic noise model with a vehicle energy conservation equation. A theoretical framework was constructed that establishes the relationship between vehicle noise and energy consumption, with the theoretical origins of this framework explained. By summarizing a substantial body of classical literature, the typical model's properties are analyzed through the principle of optimality, and the noise interval for combined vehicle energy-saving and noise-reducing is determined. Subsequently, a rigorous vehicle experiment was conducted to validate the proposed framework's effectiveness, utilizing synchronized data on energy consumption and noise. The findings indicate that vehicles can achieve unconstrained combined energy-saving and noise-reducing in four driving states and conditional combined energy-saving and noise-reducing in five driving states. The Recall index demonstrates a verification rate exceeding 0.62 for the combined energy-saving and noise-reducing rules. This research provides valuable insights to support energy-saving and noise-reducing measures in urban traffic.

Effect of Celastrus Orbiculatus Extract on proliferation and apoptosis of human Burkitt lymphoma cells.

The lymphoma incidence rate is on the rise, with invasive forms particularly prone to relapse following conventional treatment, posing a significant threat to human life and wellbeing. Numerous studies have shown that traditional Chinese botanical drug medicine offers promising therapeutic benefits for various malignancies, with previous experimental findings indicating that Celastrus orbiculatus extract effectively combats digestive tract tumors. However, its impact on lymphoma remains unexplored. This study aims to investigate the impact and underlying mechanisms of COE on the proliferation and apoptosis of Burkitt lymphoma cells. We diluted COE in RPMI-1640 medium to create various working concentrations and introduced it to human Burkitt lymphoma Raji and Ramos cells. To evaluate cell viability, we used the CCK-8 assay, and we observed morphological changes using HE staining. We also conducted Annexin V-PI and JC-1 staining experiments to assess apoptosis. By combining the cell cycle experiment with the EDU assay, we gained insights into the effects of COE on DNA replication in lymphoma cells. Using Western blotting, we detected alterations in apoptosis-related proteins. In vivo experiments revealed that following COE intervention, tumor volume decreased, survival time was prolonged, spleen size reduced, and the expression of tumor apoptosis-related proteins changed. Our findings indicate that COE effectively inhibits lymphoma cell proliferation and promotes apoptosis by regulating these apoptosis-related proteins.

Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

Improvement of roughness in ultrasonic assisted magnetorheological finishing of small titanium alloy nuts by orthogonal test method.

Titanium alloy with high corrosion resistance, high strength-to-density ratio, and excellent biocompatibility has a wide range of applications in the field of biomedical implants. Polishing experiments of titanium alloy with a small size and complex shapes were investigated using an ultrasonic assisted magnetorheological finishing (UMRF) device excited by a three-pole magnetic field generator. The models of the normal force and the shear force were first proposed based on the Preston equation to analyze the mechanism of material removal in the UMRF process. Subsequently, the single-factor experiments using titanium alloy nuts (M3) and the MR polishing fluid with silicon carbide abrasives were carried out. Furthermore, to improve the surface roughness and the change rate of surface roughness of nuts, orthogonal tests with a standard L9(34) orthogonal array were designed and performed based on the optimized process parameters obtained from the single-factor experiment. The results indicated the effect on surface roughness and change rate of surface roughness as applied current > roller speed > ultrasonic amplitude > spindle speed and applied current > roller speed > spindle speed > ultrasonic amplitude, respectively. Moreover, the surface roughness was improved from an initial 1.247 µm to a final 0.104 µm after the polishing for 80 min under these optimal process parameters.

Two New Phenylpropanoid Compounds from Lilium Brownii and Their Anti-monoamine Oxidase Activity.

Baihe is a commonly used Chinese medicine for the treatment of neurological disorders. Clinically, the bulbs of Lilium brownii are used to act as Baihe. In the study, two new phenylpropanoid compounds including 3-O-acetyl-1-O-caffeoylglycerol (1) and 3-O-acetyl-1-O-p-coumaroylglycerol (2) were isolated from the bulbs of L. brownii. Their structures were identified by spectroscopic method and the effect on monoamine oxidase activity was determined using an enzyme labeling method. The results show 1 and 2 have anti-monoamine oxidase activity with 20.96% and 22.31% inhibition rates at 50 µg/ml, respectively.

Pediatric Ménière's disease with disassociated cochlear and vestibular symptoms: a case report.

Background: Typical Ménière's disease (MD) rarely occurs in childhood. Compared to adults, age-associated changes in vestibular function can occur during infancy and childhood. Previous case reports may have lacked some audiovestibular tests in children. It is worthwhile to follow a child with MD to observe how vertigo and hearing loss could progress under an insufficient vestibular system. Case Description: A 14-year-old pediatric patient with disassociated episodes between vertigo and hearing loss was finally diagnosed with MD. He was diagnosed with probable MD due to lack of objective evidence of hearing loss in his first two admissions. However, in his third admission, he had hearing loss even without attack of vertigo and was finally diagnosed. By listing the patient's audiovestibular auxiliary tests in a chronological order, we might follow the progress of pediatric MD. Gadolinium-enhanced magnetic resonance imaging (Gd-MRI) might be sensitive to reflect endolymphatic hydrops (EH). Medications including corticosteroids might be effective for both hearing loss and vertigo. Conclusions: In pediatric MD, vestibular and cochlear symptoms may occur and progress independently. Audiovestibular evaluation, especially caloric tests and cervical vestibular evoked myogenic potential (cVEMP), can be useful for pediatric MD. Gd-MRI can be sensitive for detecting EH. Both systemic and postauricular administration of corticosteroids might be effective in alleviating vertigo and improving hearing. Prolongation of the follow-up period of pediatric MD is warranted.

Seco-cyclic phorbol derivatives and their anti-HIV-1 activities.

Phorbol esters are recognized for their dual role as anti-HIV-1 agents and as activators of protein kinase C (PKC). The efficacy of phorbol esters in binding with PKC is attributed to the presence of oxygen groups at positions C20, C3/C4, and C9 of phorbol. Concurrently, the lipids located at positions C12/C13 are essential for both the anti-HIV-1 activity and the formation of the PKC-ligand complex. The influence of the cyclopropane ring at positions C13 and C14 in phorbol derivatives on their anti-HIV-1 activity requires further exploration. This research entailed the hydrolysis of phorbol, producing seco-cyclic phorbol derivatives. The anti-HIV-1 efficacy of these derivatives was assessed, and the affinity constant (Kd) for PKC-δ protein of selected seco-cyclic phorbol derivatives was determined through isothermal titration calorimetry. The findings suggest that the chemical modification of cyclopropanols could affect both the anti-HIV-1 activity and the PKC binding affinity. Remarkably, compound S11, with an EC50 of 0.27 µmol·L-1 and a CC50 of 153.92 µmol·L-1, demonstrated a potent inhibitory effect on the intermediate products of HIV-1 reverse transcription (ssDNA and 2LTR), likely acting at the viral entry stage, yet showed no affinity for the PKC-δ protein. These results position compound S11 as a potential candidate for further preclinical investigation and for studies aimed at elucidating the pharmacological mechanism underlying its anti-HIV-1 activity.

Research progress on incomplete partition type 3 inner ear malformation.

PURPOSE: This review aims to provides a comprehensive overview of the latest research progress on IP-III inner ear malformation, focusing on its geneticbasis, imaging features, cochlear implantation, and outcome. METHODS: Review the literature on clinical and genetic mechanisms associated with IP-III. RESULTS: Mutations in the POU3F4 gene emerge as the principal pathogenic contributors to IP-III anomalies, primarily manifesting through inner ear potential irregularities leading to deafness. While cochlear implantation stands as the primary intervention for restoring hearing, the unique nature of the inner ear anomaly escalates the complexity of surgical procedures and postoperative results. Hence, meticulous preoperative assessment to ascertain surgical feasibility and postoperative verification of electrode placement are imperative. Additionally, gene therapy holds promise as a prospective treatment modality. CONCLUSIONS: IP-III denotes X-linked recessive hereditary deafness, with cochlear implantation currently serving as the predominant therapeutic approach. Clinicians are tasked with preoperative assement and individualized postoperative rehabilitation.

FUS unveiled in mitochondrial DNA repair and targeted ligase-1 expression rescues repair-defects in FUS-linked motor neuron disease.

This study establishes the physiological role of Fused in Sarcoma (FUS) in mitochondrial DNA (mtDNA) repair and highlights its implications to the pathogenesis of FUS-associated neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Endogenous FUS interacts with and recruits mtDNA Ligase IIIα (mtLig3) to DNA damage sites within mitochondria, a relationship essential for maintaining mtDNA repair and integrity in healthy cells. Using ALS patient-derived FUS mutant cell lines, a transgenic mouse model, and human autopsy samples, we discovered that compromised FUS functionality hinders mtLig3's repair role, resulting in increased mtDNA damage and mutations. These alterations cause various manifestations of mitochondrial dysfunction, particularly under stress conditions relevant to disease pathology. Importantly, rectifying FUS mutations in patient-derived induced pluripotent cells (iPSCs) preserves mtDNA integrity. Similarly, targeted introduction of human DNA Ligase 1 restores repair mechanisms and mitochondrial activity in FUS mutant cells, suggesting a potential therapeutic approach. Our findings unveil FUS's critical role in mitochondrial health and mtDNA repair, offering valuable insights into the mechanisms underlying mitochondrial dysfunction in FUS-associated motor neuron disease.

Enhancing Stability and Performance in Tin-Based Perovskite Field-Effect Transistors Through Hydrogen Bond Suppression of Organic Cation Migration.

Ion migration poses a substantial challenge in perovskite transistors, exerting detrimental effects on hysteresis and operational stability. This study focuses on elucidating the influence of ion migration on the performance of tin-based perovskite field-effect transistors (FETs). It is revealed that the high background carrier density in FASnI3 FETs arises not only from the oxidation of Sn2+ but also from the migration of FA+ ions. The formation of hydrogen bonding between FA+ and F- ions efficiently inhibits ion migration, leading to a reduction in background carrier density and an improvement in the operational stability of the transistors. The strategy of hydrogen bond is extended to fluorine-substituted additives to improve device performance. The incorporation of 4-fluorophenethylammonium iodide additives into FETs significantly minimizes the shift of turn-on voltage during cyclic measurements. Notably, an effective mobility of up to 30 cm2 V-1 s-1 with an Ion/off ratio of 107 is achieved. These findings hold promising potential for advancing tin-based perovskite technology in the field of electronics.

A novel approach to evaluation of tumor response for advanced pulmonary adenocarcinoma using the intertumoral heterogeneity response score.

Treatment response and prognosis estimation in advanced pulmonary adenocarcinoma are challenged by the significant heterogeneity of the disease. The current Response Evaluation Criteria in Solid Tumors (RECIST) criteria, despite providing a basis for solid tumor response evaluation, do not fully encompass this heterogeneity. To better represent these nuances, we introduce the intertumoral heterogeneity response score (THRscore), a measure built upon and expanding the RECIST criteria. This retrospective study included patients with 3-10 measurable advanced lung adenocarcinoma lesions who underwent first-line chemotherapy or targeted therapy. The THRscore, derived from the coefficient of variation in size for each measurable tumor before and 4-6 weeks posttreatment, unveiled a correlation with patient outcomes. Specifically, a high THRscore was associated with shorter progression-free survival, lower tumor response rate, and a higher tumor mutation burden. These associations were further validated in an external cohort, confirming THRscore's effectiveness in stratifying patients based on progression risk and treatment response, and enhancing the utility of RECIST in capturing complex tumor behaviors in lung adenocarcinoma. These findings affirm the promise of THRscore as an enhanced tool for tumor response assessment in advanced lung adenocarcinoma, extending the RECIST criteria's utility.

Changes in Phytohormones and Transcriptomic Reprogramming in Strawberry Leaves under Different Light Qualities.

Strawberry plants require light for growth, but the frequent occurrence of low-light weather in winter can lead to a decrease in the photosynthetic rate (Pn) of strawberry plants. Light-emitting diode (LED) systems could be used to increase Pn. However, the changes in the phytohormones and transcriptomic reprogramming in strawberry leaves under different light qualities are still unclear. In this study, we treated strawberry plants with sunlight, sunlight covered with a 50% sunshade net, no light, blue light (460 nm), red light (660 nm), and a 50% red/50% blue LED light combination for 3 days and 7 days. Our results revealed that the light quality has an effect on the contents of Chl a and Chl b, the minimal fluorescence (F0), and the Pn of strawberry plants. The light quality also affected the contents of abscisic acid (ABA), auxin (IAA), trans-zeatin-riboside (tZ), jasmonic acid (JA), and salicylic acid (SA). RNA sequencing (RNA-seq) revealed that differentially expressed genes (DEGs) are significantly enriched in photosynthesis antenna proteins, photosynthesis, carbon fixation in photosynthetic organisms, porphyrin and chlorophyll metabolisms, carotenoid biosynthesis, tryptophan metabolism, phenylalanine metabolism, zeatin biosynthesis, and linolenic acid metabolism. We then selected the key DEGs based on the results of a weighted gene co-expression network analysis (WGCNA) and drew nine metabolic heatmaps and protein-protein interaction networks to map light regulation.

Synthesis and Biological Evaluation of New Dihydrofuro[3,2-b]piperidine Derivatives as Potent α-Glucosidase Inhibitors.

Inhibition of glycoside hydrolases has widespread application in the treatment of diabetes. Based on our previous findings, a series of dihydrofuro[3,2-b]piperidine derivatives was designed and synthesized from D- and L-arabinose. Compounds 32 (IC50 = 0.07 µM) and 28 (IC50 = 0.5 µM) showed significantly stronger inhibitory potency against α-glucosidase than positive control acarbose. The study of the structure-activity relationship of these compounds provides a new clue for the development of new α-glucosidase inhibitors.

Injectable Double Crosslinked Hydrogel-Polypropylene Composite Mesh for Repairing Full-Thickness Abdominal Wall Defects.

Abdominal wall defects are common clinical diseases, and mesh repair is the standard treatment method. The most commonly used polypropylene (PP) mesh in clinical practice has the advantages of good mechanical properties, stable performance, and effective tissue integration effect. However, direct contact between abdominal viscera and PP mesh can lead to severe abdominal adhesions. To prevent this, the development of a hydrogel-PP composite mesh with anti-adhesive properties may be an effective measure. Herein, biofunctional hydrogel loaded with rosmarinic acid is developed by modifying chitosan and Pluronic F127, which possesses suitable physical and chemical properties and commendable in vitro biocompatibility. In the repair of full-thickness abdominal wall defects in rats, hydrogels are injected onto the surface of PP mesh and applied to intraperitoneal repair. The results indicate that the use of hydrogel-PP composite mesh can alleviate abdominal adhesions resulting from traditional PP mesh implantation by decreasing local inflammatory response, reducing oxidative stress, and regulating the fibrinolytic system. Combined with the tissue integration ability of PP mesh, hydrogel-PP composite mesh has great potential for repairing full-thickness abdominal wall defects.