Cartilage-like protein hydrogels engineered via entanglement.

Load-bearing tissues, such as muscle and cartilage, exhibit high elasticity, high toughness and fast recovery, but have different stiffness (with cartilage being significantly stiffer than muscle)1-8. Muscle achieves its toughness through finely controlled forced domain unfolding-refolding in the muscle protein titin, whereas articular cartilage achieves its high stiffness and toughness through an entangled network comprising collagen and proteoglycans. Advancements in protein mechanics and engineering have made it possible to engineer titin-mimetic elastomeric proteins and soft protein biomaterials thereof to mimic the passive elasticity of muscle9-11. However, it is more challenging to engineer highly stiff and tough protein biomaterials to mimic stiff tissues such as cartilage, or develop stiff synthetic matrices for cartilage stem and progenitor cell differentiation12. Here we report the use of chain entanglements to significantly stiffen protein-based hydrogels without compromising their toughness. By introducing chain entanglements13 into the hydrogel network made of folded elastomeric proteins, we are able to engineer highly stiff and tough protein hydrogels, which seamlessly combine mutually incompatible mechanical properties, including high stiffness, high toughness, fast recovery and ultrahigh compressive strength, effectively converting soft protein biomaterials into stiff and tough materials exhibiting mechanical properties close to those of cartilage. Our study provides a general route towards engineering protein-based, stiff and tough biomaterials, which will find applications in biomedical engineering, such as osteochondral defect repair, and material sciences and engineering.

Heterozygous LRP1 deficiency causes developmental dysplasia of the hip by impairing triradiate chondrocytes differentiation due to inhibition of autophagy.

Developmental dysplasia of the hip (DDH) is one of the most common congenital skeletal malformations; however, its etiology remains unclear. Here, we conducted whole-exome sequencing in eight DDH families followed by targeted sequencing of 68 sporadic DDH patients. We identified likely pathogenic variants in the LRP1 (low-density lipoprotein receptor-related protein 1) gene in two families and seven unrelated patients. All patients harboring the LRP1 variants presented a typical DDH phenotype. The heterozygous Lrp1 knockout (KO) mouse (Lrp1+/-) showed phenotypes recapitulating the human DDH phenotypes, indicating Lrp1 loss of function causes DDH. Lrp1 knockin mice with a missense variant corresponding to a human variant identified in DDH (Lrp1R1783W) also presented DDH phenotypes, which were milder in heterozygotes and severer in homozygotes than those of the Lrp1 KO mouse. The timing of triradiate cartilage development was brought forward 1 or 2 wk earlier in the LRP-deficient mice, which leads to malformation of the acetabulum and femoral head. Furthermore, Lrp1 deficiency caused a significant decrease of chondrogenic ability in vitro. During the chondrogenic induction of mice bone marrow stem cells and ATDC5 (an inducible chondrogenic cell line), Lrp1 deficiency caused decreased autophagy levels with significant ß-catenin up-regulation and suppression of chondrocyte marker genes. The expression of chondrocyte markers was rescued by PNU-74654 (a ß-catenin antagonist) in an shRNA-Lrp1-expressed ATDC5 cell. Our study reveals a critical role of LRP1 in the etiology and pathogenesis of DDH, opening an avenue for its treatment.

Geometric Inhibition of Superflow in Single-Layer Graphene Suggests a Staggered-Flux Superconductivity in Bilayer and Trilayer Graphene.

In great contrast to the numerous discoveries of superconductivity in layer-stacked graphene systems, the absence of superconductivity in the simplest monolayer graphene remains quite puzzling. Here, through realistic computation of the electronic structure, we identify a systematic trend that superconductivity emerges only upon alteration of the low-energy electronic lattice from the underlying honeycomb atomic structure. We then demonstrate that this inhibition can result from geometric frustration of the bond lattice that disables the quantum phase coherence of the order parameter residing on it. In comparison, upon deviation from the honeycomb lattice, relief of geometric frustration allows robust superfluidity with nontrivial spatial structures. For the specific examples of bilayer and trilayer graphene under an external electric field, such a bond-centered order parameter would develop superfluidity with staggered flux that breaks the time-reversal symmetry. Our study also suggests the possible realization of the long-sought superconductivity in single-layer graphene via the application of unidirectional strain.

Vacancy-Enhanced Sb-N4 Sites for the Oxygen Reduction Reaction and Zn-Air Battery.

With the advantages of a Fenton-inactive characteristic and unique p electrons that can hybridize with O2 molecules, p-block metal-based single-atom catalysts (SACs) for the oxygen reduction reaction (ORR) have tremendous potential. Nevertheless, their undesirable intrinsic activity caused by the closed d10 electronic configuration remains a major challenge. Herein, an Sb-based SAC featuring carbon vacancy-enhanced Sb-N4 active centers, corroborated by the results of high-angle annular dark-field scanning transmission electron microscopy and X-ray absorption fine structure, has been developed for an incredibly effective ORR. The obtained SbSA-N-C demonstrates a positive half-wave potential of 0.905 V and excellent structural stability in alkaline environments. Density functional theory calculations reveal that the carbon vacancies weaken the adsorption between Sb atoms and the OH* intermediate, thus promoting the ORR performance. Practically, the SbSA-N-C-based Zn-air batteries achieve impressive outcomes, such as a high power density of 181 mW cm-2, showing great potential in real-world applications.

Transcriptome dynamics provides insights into divergences of the photosynthesis pathway between Saccharum officinarum and Saccharum spontaneum.

Saccharum spontaneum and Saccharum officinarum contributed to the genetic background of modern sugarcane cultivars. Saccharum spontaneum has shown a higher net photosynthetic rate and lower soluble sugar than S. officinarum. Here, we analyzed 198 RNA-sequencing samples to investigate the molecular mechanisms for the divergences of photosynthesis and sugar accumulation between the two Saccharum species. We constructed gene co-expression networks based on differentially expressed genes (DEGs) both for leaf developmental gradients and diurnal rhythm. Our results suggested that the divergence of sugar accumulation may be attributed to the enrichment of major carbohydrate metabolism and the oxidative pentose phosphate pathway. Compared with S. officinarum, S. spontaneum DEGs showed a high enrichment of photosynthesis and contained more complex regulation of photosynthesis-related genes. Noticeably, S. spontaneum lacked gene interactions with sulfur assimilation stimulated by photorespiration. In S. spontaneum, core genes related to clock and photorespiration displayed a sensitive regulation by the diurnal rhythm and phase-shift. Small subunit of Rubisco (RBCS) displayed higher expression in the source tissues of S. spontaneum. Additionally, it was more sensitive under a diurnal rhythm, and had more complex gene networks than that in S. officinarum. This indicates that the differential regulation of RBCS Rubisco contributed to photosynthesis capacity divergence in both Saccharum species.

4-Octyl itaconate alleviates experimental autoimmune prostatitis by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2/HO-1 pathway.

BACKGROUND: Chronic prostatitis demonstrates a prevalence rate of nearly 5%-10% among young and middle-aged individuals, significantly affecting their daily lives. Researchers have obtained significant outcomes investigating the anti-inflammatory properties of itaconic acid (IA) and its derivative, 4-Octyl itaconate (4-OI), against diverse chronic inflammatory disorders, such as osteoarthritis and airway inflammation. Nevertheless, whether IA can also exert anti-inflammatory effects in chronic prostatitis requires extensive research and validation. METHODS: Human prostate tissues obtained through transurethral prostate resection (TURP) from individuals were divided into three groups based on different levels of inflammation using hematoxylin and eosin staining (H&E). Subsequently, immunohistochemistry (IHC) was employed to detect the expression of immune-responsive gene 1 (IRG-1) in these different groups. The animal experiment of this study induced experimental autoimmune prostatitis (EAP) in nonobese diabetic mice through intradermal prostate antigen injection and complete Freund's adjuvant. Then, the experimental group received intraperitoneal injections of different doses of 4-OI, while the control group received injections of saline. Western blot (WB), H&E staining, and TUNEL staining helped analyze the prostate tissues, while enzyme-linked immunosorbent assay (ELISA) helped evaluate serum inflammatory factors. Reactive oxygen species, superoxide dismutase (SOD), and malondialdehyde (MDA) were assessed for oxidative stress across experimental groups. RESULTS: IHC analysis of human prostate tissue depicts that IRG-1 expression enhances as prostate inflammation worsens, highlighting the critical role of IA in human prostatitis. The application of 4-OI increased Nrf2/HO-1 expression while inhibited NLRP3 expression following the WB results, and its application resulted in a decrease in cell pyroptosis in prostate tissue, demonstrated by the results of TUNEL staining. Administering a Nrf2 inhibitor ML385 1 h before intraperitoneal injection of 50 mg/kg 4-OI reversed the previous conclusion, further confirming the above conclusion from another perspective. Meanwhile, the ELISA results of serum inflammatory factors (IL-1ß, IL-6, and TNF-α), as well as the measurements of oxidative stress markers MDA and SOD, further confirmed the specific anti-inflammatory effects of 4-OI in EAP. CONCLUSIONS: The present study indicates that 4-OI can alleviates EAP by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2/HO-1 pathway, which may facilitate a novel approach toward prostatitis treatment.

Sodium butyrate alleviates experimental autoimmune prostatitis by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway.

BACKGROUND: Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) leads to severe discomfort in males and loss of sperm quality. Current therapeutic options have failed to achieve satisfactory results. Sodium butyrate (NaB) plays a beneficial role in reducing inflammation, increasing antioxidant capacities, and improving organ dysfunction; additionally NaB has good safety prospects and great potential for clinical application. The purpose of the current research was to study the effect of NaB on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP) mice. METHODS: The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. Then, EAP mice received daily intraperitoneal injections of NaB (100, 200, or 400 mg/kg/day) for 16 days, from Days 26 to 42. We then explored anti-inflammatory potential mechanisms of NaB by studying the effects of Nrf2 inhibitor ML385 and HO-1 inhibitor zinc protoporphyrin on prostate inflammation and pelvic pain using this model. On Day 42, hematoxylin-eosin staining and dihydroethidium staining were used to evaluate the histological changes and oxidative stress levels of prostate tissues. Chronic pelvic pain was assessed by applying Von Frey filaments to the lower abdomen. The levels of inflammation-related cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor were detected by enzyme-linked immunosorbent assay. The regulation of Nrf2/HO-1 signaling pathway and the expression of NLRP3 inflammasome-related protein in EAP mice were detected by western blot analysis assay. RESULTS: Compared with the EAP group, chronic pain development, histological manifestations, and cytokine levels showed that NaB reduced the severity of EAP. NaB treatment could inhibit NLRP3 inflammasome activation. Mechanism studies showed that NaB intervention could alleviate oxidative stress in EAP mice through Nrf2/HO-1 signal pathway. Nrf2/HO-1 pathway inhibitors can inhibit NaB -mediated oxidative stress. The inhibitory effect of NaB on the activation of NLRP3 inflammasome and anti-inflammatory effect can also be blocked by Nrf2/HO-1 pathway. CONCLUSIONS: NaB treatment can alleviates prostatic inflammation and pelvic pain associated with EAP by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway. NaB has the potential as an effective agent in the treatment of EAP.

The high electron mobility for spin-down channel of two-dimensional spin-polarized half-metallic ferromagnetic EuSi2N4 monolayer.

The two-dimensional (2D) monolayer material MoSi2N4 was successfully synthesized in 2020[Hong et al., Science 369, 670, (2020)], exhibiting a plethora of new phenomena and unusual properties, with good stability at room temperature. However, MA2Z4 family monolayer materials involve primarily transition metal substitutions for M atoms. In order to address the research gap on lanthanide and actinide MA2Z4 materials, this work conducts electronic structure calculations on novel 2D MSi2N4 (M = La, Eu) monolayer materials by employing first-principles methods and CASTEP. High carrier mobility is discovered in the indirect bandgap semiconductor 2D LaSi2N4 monolayer (~5400 cm2 V-1 s-1) and in the spin (spin-down channel) carrier mobility of the half-metallic ferromagnetic EuSi2N4 monolayer (~2800 cm2 V-1 s-1). EuSi2N4 monolayer supplements research on spin carrier mobility in half-metallic ferromagnetic monolayer materials at room temperature and possesses a magnetic moment of 5 µB, which should not be underestimated. Furthermore, due to the unique electronic band structure of EuSi2N4 monolayer (with the spin-up channel exhibiting metallic properties and the spin-down channel exhibiting semiconductor properties), it demonstrates a 100% spin polarization rate, presenting significant potential applications in fields such as magnetic storage, magnetic sensing, and spintronics.

Heterostructured Co-Doped-Cu2O/Cu Synergistically Promotes Water Dissociation for Improved Electrochemical Nitrate Reduction to Ammonia.

Electrochemical nitrate reduction reaction (NO3RR) has recently emerged as a promising approach for sustainable ammonia synthesis and wastewater treatment, while the activity and selectivity for ammonia production have remained low. Herein, rational design and controllable synthesis of heterostructured Co-doped Cu2O/Cu nanoparticles embedded in carbon framework (Co-Cu2O/Cu@C) is reported for NO3RR. The Co-Cu2O/Cu@C exhibits a high ammonia yield rate of 37.86 mg h-1 mg-1 cat. with 98.1% Faraday efficiency, which is higher than those obtained for most of the Cu-based catalysts under similar conditions. Density functional theory calculations indicated that the strong electronic interactions at Cu/Co-Cu2O interface facilitate the N species deoxygenation process and doping of Co promotes water dissociation to generate *H for the N species hydrogenation process, leading to enhanced NO3RR performance. This work provides a new design strategy toward high-performance catalysts toward NO3RR for ammonia generation.

A facile Immunoregulatory Constructional Design by Proanthocyanidin Optimizing Directional Chitosan Microchannel.

Improving the interconnected structure and bioregulatory function of natural chitosan is beneficial for optimizing its performance in bone regeneration. Here, a facile immunoregulatory constructional design is proposed for developing instructive chitosan by directional freezing and alkaline salting out. The molecular dynamics simulation confirmed the assembly kinetics and structural features of various polyphenols and chitosan molecules. Along with the in vitro anti-inflammatory, antioxidative, promoting bone mesenchymal stem cell (BMSC) adhesion and proliferation performance, proanthocyanidin optimizing chitosan (ChiO) scaffold presented an optimal immunoregulatory structure with the directional microchannel. Transcriptome analysis in vitro further revealed the cytoskeleton- and immune-regulation effect of ChiO are the key mechanism of action on BMSC. The rabbit cranial defect model (Φ = 10 mm) after 12 weeks of implantation confirmed the significantly enhanced bone reconstitution. This facile immunoregulatory directional microchannel design provides effective guidance for developing inducible chitosan scaffolds.

Benzoquinone-Lubricated Intercalation in Manganese Oxide for High-Capacity and High-Rate Aqueous Aluminum-Ion Battery.

Aqueous aluminum-ion batteries are attractive post-lithium battery technologies for large-scale energy storage in virtue of abundant and low-cost Al metal anode offering ultrahigh capacity via a three-electron redox reaction. However, state-of-the-art cathode materials are of low practical capacity, poor rate capability, and inadequate cycle life, substantially impeding their practical use. Here layered manganese oxide that is pre-intercalated with benzoquinone-coordinated aluminum ions (BQ-AlxMnO2) as a high-performance cathode material of rechargeable aqueous aluminum-ion batteries is reported. The coordination of benzoquinone with aluminum ions not only extends interlayer spacing of layered MnO2 framework but reduces the effective charge of trivalent aluminum ions to diminish their electrostatic interactions, substantially boosting intercalation/deintercalation kinetics of guest aluminum ions and improving structural reversibility and stability. When coupled with Zn50Al50 alloy anode in 2 m Al(OTf)3 aqueous electrolyte, the BQ-AlxMnO2 exhibits superior rate capability and cycling stability. At 1 A g-1, the specific capacity of BQ-AlxMnO2 reaches ≈300 mAh g-1 and retains ≈90% of the initial value for more than 800 cycles, along with the Coulombic efficiency of as high as ≈99%, outperforming the AlxMnO2 without BQ co-incorporation.

In Situ Engineering Multifunctional Active Sites of Ruthenium-Nickel Alloys for pH-Universal Ampere-Level Current-Density Hydrogen Evolution.

Developing robust non-platinum electrocatalysts with multifunctional active sites for pH-universal hydrogen evolution reaction (HER) is crucial for scalable hydrogen production through electrochemical water splitting. Here ultra-small ruthenium-nickel alloy nanoparticles steadily anchored on reduced graphene oxide papers (Ru-Ni/rGOPs) as versatile electrocatalytic materials for acidic and alkaline HER are reported. These Ru-Ni alloy nanoparticles serve as pH self-adaptive electroactive species by making use of in situ surface reconstruction, where surface Ni atoms are hydroxylated to produce bifunctional active sites of Ru-Ni(OH)2 for alkaline HER, and selectively etched to form monometallic Ru active sites for acidic HER, respectively. Owing to the presence of Ru-Ni(OH)2 multi-site surface, which not only accelerates water dissociation to generate reactive hydrogen intermediates but also facilitates their recombination into hydrogen molecules, the self-supported Ru90Ni10/rGOP hybrid electrode only takes overpotential of as low as ≈106 mV to deliver current density of 1000 mA cm-2, and maintains exceptional stability for over 1000 h in 1 m KOH. While in 0.5 m H2SO4, the Ru90Ni10/rGOP hybrid electrode exhibits acidic HER catalytic behavior comparable to commercially available Pt/C catalyst due to the formation of monometallic Ru shell. These electrochemical behaviors outperform some of the best Ru-based catalysts and make it attractive alternative to Pt-based catalysts toward highly efficient HER.

WZ-3146 acts as a novel small molecule inhibitor of KIF4A to inhibit glioma progression by inducing apoptosis.

BACKGROUND: Glioma is considered the most common primary malignant tumor of the central nervous system. Although traditional treatments have not achieved satisfactory outcomes, recently, targeted therapies for glioma have shown promising efficacy. However, due to the single-target nature of targeted therapy, traditional targeted therapies are ineffective; thus, novel therapeutic targets are urgently needed. METHODS: The gene expression data for glioma patients were derived from the GEO (GSE4290, GSE50161), TCGA and CGGA databases. Next, the upregulated genes obtained from the above databases were cross-analyzed, finally, 10 overlapping genes (BIRC5, FOXM1, EZH2, CDK1, KIF11, KIF4A, NDC80, PBK, RRM2, and TOP2A) were ultimately screened and only KIF4A expression has the strongest correlation with clinical characteristics in glioma patients. Futher, the TCGA and CGGA database were utilized to explore the correlation of KIF4A expression with glioma prognosis. Then, qRT-PCR and Western blot was used to detect the KIF4A mRNA and protein expression level in glioma cells, respectively. And WZ-3146, the small molecule inhibitor targeting KIF4A, were screened by Cmap analysis. Subsequently, the effect of KIF4A knockdown or WZ-3146 treatment on glioma was measured by the MTT, EdU, Colony formation assay and Transwell assay. Ultimately, GSEA enrichment analysis was performed to find that the apoptotic pathway could be regulated by KIF4A in glioma, in addition, the effect of WZ-3146 on glioma apoptosis was detected by flow cytometry and Western blot. RESULTS: In the present study, we confirmed that KIF4A is abnormally overexpressed in glioma. In addition, KIF4A overexpression is a key indicator of glioma prognosis; moreover, suppressing KIF4A expression can inhibit glioma progression. We also discovered that WZ-3146, a small molecule inhibitor of KIF4A, can induce apoptosis in glioma cells and exhibit antiglioma effects. CONCLUSION: In conclusion, these observations demonstrated that targeting KIF4A can inhibit glioma progression. With further research, WZ-3146, a small molecule inhibitor of KIF4A, could be combined with other molecular targeted drugs to cooperatively inhibit glioma progression.

Engineering Flat Bands in Twisted-Bilayer Graphene away from the Magic Angle with Chiral Optical Cavities.

Twisted bilayer graphene (TBG) is a recently discovered two-dimensional superlattice structure which exhibits strongly correlated quantum many-body physics, including strange metallic behavior and unconventional superconductivity. Most of TBG exotic properties are connected to the emergence of a pair of isolated and topological flat electronic bands at the so-called magic angle, θ≈1.05°, which are nevertheless very fragile. In this work, we show that, by employing chiral optical cavities, the topological flat bands can be stabilized away from the magic angle in an interval of approximately 0.8°<θ<1.3°. As highlighted by a simplified theoretical model, time reversal symmetry breaking (TRSB), induced by the chiral nature of the cavity, plays a fundamental role in flattening the isolated bands and gapping out the rest of the spectrum. Additionally, TRSB suppresses the Berry curvature and induces a topological phase transition, with a gap closing at the Γ point, towards a band structure with two isolated flat bands with Chern number equal to 0. The efficiency of the cavity is discussed as a function of the twisting angle, the light-matter coupling and the optical cavity characteristic frequency. Our results demonstrate the possibility of engineering flat bands in TBG using optical devices, extending the onset of strongly correlated topological electronic phases in moiré superlattices to a wider range in the twisting angle.

Augmented type 2 inflammatory response in allergic rhinitis patients experiencing systemic reactions to house dust mite subcutaneous immunotherapy.

BACKGROUND: Subcutaneous immunotherapy (SCIT) can induce systemic reactions (SRs) in certain patients, but the underlying mechanisms remain to be fully elucidated. METHODS: AR patients who were undergoing standardized HDM SCIT (Alutard, ALK) between 2018 and 2022 were screened. Those who experienced two consecutive SRs were included in the study group. A control group was established, matched 1:1 by gender, age, and disease duration with the study group, who did not experience SRs during SCIT. Clinical and immunological parameters were recorded and analyzed both before SCIT and after 1 year of treatment. RESULTS: A total of 161 patients were included, with 79 (49.07%) in the study group. The study group had a higher proportion of AR combined asthma (26.8% vs. 51.8%, p < 0.001) and higher levels of sIgE to HDM and HDM components (all p < .001). Serum IL-4 and IL-13 levels in the study group were higher than those in the control group (p < .05). The study group received a lower maintenance dosage of HDM extracts injections than control group due to SRs (50000SQ vs. 100000SQ, p < .05). After 1 year of SCIT, the VAS score, the lung function parameters of asthmatic patients over 14 years old significantly improved in both groups (all p < .05). After a 7-day exposure to 20 µg/mL HDM extracts, the percentages of Th1, Th17, Tfh10, and Th17.1 in PBMCs decreased, while the Tfh13 cells significantly increased in the study group (p < .05). CONCLUSION: The type 2 inflammatory response is augmented in HDM-induced AR patients who experienced SRs during SCIT. Despite this, SCIT remains effective in these patients when administered with low-dosage allergen extracts.

Prognostic and clinicopathological value of osteopontin expression in non-small cell lung cancer: a meta-analysis and systematic review.

BACKGROUND: Although Osteopontin (OPN) has been reported to be associated with many different human cancers, the data on non-small cell lung cancer (NSCLC) are not definitive. This study aimed to explore the prognostic effect of OPN expression and clinicopathological characteristics in patients with NSCLC. METHODS: This study followed all aspects of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) report. PubMed, Embase and the Cochrane Library were searched to identify the relative studies. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to estimate the prognostic value of the OPN in patients with NSCLC. The odds ratio (OR) was calculated to represent the relationship between OPN expression and clinicopathological parameters. RESULTS: A total of fifteen studies with 2173 participants were finally included. The results revealed that high expression of OPN was significantly associated with poorer overall survival (OS) (HR = 1.89; 95%CI = 1.68-2.11; p < 0.001). Moreover, a significant correlation was observed between increased OPN expression and poorly differentiated (well and moderately differentiated vs. poorly differentiated; pooled OR = 0.38; 95% CI = 0.23-0.64; p < 0.001), lymph node metastasis (absence vs. presence; pooled OR = 0.49; 95%CI = 0.32-0.74; p < 0.001), and distant metastasis (absence vs. presence; pooled OR = 0.18; 95%CI = 0.11-0.29; p < 0.001). CONCLUSION: This meta-analysis implies that OPN might be a valuable biomarker for a poor prognosis and poor clinicopathological outcomes for patients with NSCLC.

Our findings suggest that osteopontin is an important biomarker for poor prognosis and poor clinicopathological outcome in Non-small cell lung cancer (NSCLC) patients.Increased expression of osteopontin in NSCLC patients is associated not only with poorer survival but also with tumor differentiation, lymph node metastasis, and distant metastasis.This may be due to that osteopontin promotes multiple pathological processes including cancer cell proliferation, invasion, tumor progression, and metastasis in NSCLC.

Evaluation of the immunoprotective effect of the recombinant Eimeria intestinalis rhoptry protein 25 and rhoptry protein 30 on New Zealand rabbits.

BACKGROUND: Rabbit coccidiosis is a parasitism caused by either one or multiple co-infections of Eimeria species. Among them, Eimeria intestinalis is the primary pathogen responsible for diarrhea, growth retardation, and potential mortality in rabbits. Concerns regarding drug resistance and drug residues have led to the development of recombinant subunit vaccines targeting Eimeria species as a promising preventive measure. The aim of this study was to assess the immunoprotective efficacy of recombinant subunit vaccines comprising EiROP25 and EiROP30 (rhoptry proteins (ROPs)) against E. intestinalis infection in rabbits. METHODS: Cloning, prokaryotic expression, and protein purification were performed to obtain EiROP25 and EiROP30. Five groups of fifty 35-day-old Eimeria-free rabbits were created (unchallenged control group, challenged control group, vector protein control group, rEiROP25 group, and rEiROP30 group), with 10 rabbits in each group. Rabbits in the rEiROP25 and rEiROP30 groups were immunized with the recombinant proteins (100 µg per rabbit) for primary and booster immunization (100 µg per rabbit) at a two-week intervals, and challenged with 7 × 104 oocysts per rabbit after an additional two-week interval. Two weeks after the challenge, the rabbits were euthanized for analysis. Weekly collections of rabbit sera were made to measure changes in specific IgG and cytokine level. Clinical symptoms and pathological changes after challenge were observed and recorded. At the conclusion of the animal experiment, lesion scores, the relative weight increase ratio, the oocyst reduction rate, and the anticoccidial index were computed. RESULTS: Rabbits immunized with rEiROP25 and rEiROP30 exhibited relative weight gain ratios of 56.57% and 72.36%, respectively. Oocysts decreased by 78.14% and 84.06% for the rEiROP25 and rEiROP30 groups, respectively. The anticoccidial indexes were 140 and 155. Furthermore, there was a noticeable drop in intestinal lesions. After the primary immunization with rEiROP25 and rEiROP30, a week later, there was a notable rise in specific IgG levels, which remained elevated for two weeks following challenge (P < 0.05). Interleukin (IL)-2 levels increased markedly in the rEiROP25 group, whereas IL-2, interferon gamma (IFN-γ), and IL-4 levels increased substantially in the rEiROP30 group (P < 0.05). CONCLUSION: Immunization of rabbits indicated that both rEiROP25 and rEiROP30 are capable of inducing an increase in specific antibody levels. rEiROP25 triggered a Th1-type immune protection response, while rEiROP30 elicited a Th1/Th2 mixed response. EiROP25 and EiROP30 can generate a moderate level of immune protection, with better efficacy observed for EiROP30. This study provides valuable insights for the promotion of recombinant subunit vaccines targeting rabbit E. intestinalis infection.

Intra- and Interimage Reliability of Inter-Rectus Distance Measurements Determined via Ultrasound Imaging by the Same or Different Testers in Women in the Early Postpartum Period.

OBJECTIVES: No consensus regarding the optimal position and location for the measurement of the inter-rectus distance (IRD) via ultrasound (US) has been reached. By investigating the intra- and interimage reliability of IRD measurements taken in different positions and at different locations within and between testers, this study provides a theoretical basis for the current situation. METHODS: The IRD was measured via US in 46 women at 42-60 days after delivery at the superior margin of the umbilicus and 3 cm above, 5 cm above and 3 cm below the umbilicus while the women were in the supine, crunch and standing positions. In the interimage test, every participant was tested 2 times by Physician X and 1 time by Physician Y; in the intraimage test, the images collected by Physician X during the first test were saved in the machines, and two measurements were performed by Physician X and one measurement was performed by Physician Y. Paired t tests and intraclass correlation coefficients (ICCs) were calculated. RESULTS: Only the first IRD measurements by tester X and tester Y at 3 cm below the umbilicus in the crunch position were significantly different (9.56 ± 6.00 versus 11.00 ± 5.55) (P < .05). All the ICCs were greater than .75, and the intratester ICCs were greater than or equal to the corresponding intertester ICCs. The ICCs at 3 cm below the umbilicus were the smallest in the supine and crunch positions and the largest in the standing position due to the increased frequency of IRD values of 0. The ICCs for the crunch position were greatest according to the intraimage test but smallest according to the interimage test. The interimage ICCs between the two testers in the supine position at the superior margin, 3 cm above, 5 cm above, and 3 cm below the umbilicus were .972, .974, .975, and .956, respectively. CONCLUSIONS: Ultrasound imaging (USI) is a reliable method for measuring the IRD in women in the early postpartum period. The dynamic measurement of the IRD at or above the umbilicus in the supine position by different testers in real time showed the highest reliability.

Sufu negatively regulates both initiations of centrosome duplication and DNA replication.

Centrosome duplication and DNA replication are two pivotal events that higher eukaryotic cells use to initiate proliferation. While DNA replication is initiated through origin licensing, centrosome duplication starts with cartwheel assembly and is partly controlled by CP110. However, the upstream coordinator for both events has been, until now, a mystery. Here, we report that suppressor of fused protein (Sufu), a negative regulator of the Hedgehog (Hh) pathway playing a significant role in restricting the trafficking and function of glioma-related (Gli) proteins, acts as an upstream switch by facilitating CP110 phosphorylation by CDK2, promoting intranuclear Cdt1 degradation and excluding prereplication complex (pre-RC) components from chromosomes, independent of its canonical function in the Hh pathway. We found that Sufu localizes to both the centrosome and the nucleus and that knockout of Sufu induces abnormalities including centrosome amplification, increased nuclear size, multipolar spindle formation, and polyploidy. Serum stimulation promotes the elimination of Sufu from the centrosome by vesicle release at the ciliary tip and from the nucleus via protein degradation, which allows centrosome duplication and DNA replication to proceed. Collectively, this work reveals a mechanism through which Sufu negatively regulates the G1-S transition.

Phantom study of a self-shielded X-ray bone age assessment instrument against scattered radiation in children.

Hand-wrist radiography is the most common and accurate method for evaluating children's bone age. To reduce the scattered radiation of radiosensitive organs in bone age assessment, we designed a small X-ray instrument with radioprotection function by adding metal enclosure for X-ray shielding. We used a phantom operator to compare the scattered radiation doses received by sensitive organs under three different protection scenarios (proposed instrument, radiation personal protective equipment, no protection). The proposed instrument showed greater reduction in the mean dose of a single exposure compared with radiation personal protective equipment especially on the left side which was proximal to the X-ray machine (≥80.0% in eye and thyroid, ≥99.9% in breast and gonad). The proposed instrument provides a new pathway towards more convenient and efficient radioprotection.