A Biomimetic Peptide Functions as Specific Extracellular Matrix for Quiescence of Stem Cells against Intervertebral Disc Degeneration.

Maintaining quiescence of stem cells is a potential way to decrease cell nutrition demand for restoring the organization. Herein, a biomimetic peptide to maintain quiescence of stem cells through C-X-C motif chemokine ligand 8 (CXCL8)-C-X-C motif chemokine receptor 1 (CXCR1) pathway against intervertebral disc degeneration (IVDD) is developed. First, it is confirmed that quiescence can be induced via inhibiting phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in nucleus pulposus stem cells (NPSCs). Meanwhile, it is well known that CXCR1, a chemokine receptor, can be targeted by CXCL8, resulting in cell proliferation via activating PI3K/Akt/mTOR pathway. Second, a biomimetic peptide (OAFF) that can bind to CXCR1 and form fibrous networks on NPSCs, mimicking extracellular matrix formation is developed. The multivalent effect and long-term binding to CXCR1 on NPSCs of OAFF fibers offer forcefully competitive inhibition with natural CXCL8, which induces NPSCs quiescence and ultimately overcomes obstacle in intradiscal injection therapy. In rat caudal disc puncture model, OAFF nanofibers still maintain at 5 weeks after operation and inhibit degeneration process of intervertebral disc in terms of histopathology and imageology. In situ fibrillogenesis of biomimetic peptide on NPSCs provides promising stem cells for intradiscal injection therapy against IVDD.

Research on the improvement path of grassroots social governance innovation performance in China--Qualitative comparative analysis based on 35 cases.

With the rapid development of China's economy and society, the innovation of grassroots social governance has become increasingly important. This paper constructs 35 grassroots social governance innovation samples. Using the TOE theoretical framework and a fuzzy set qualitative comparative analysis (fsQCA), this paper analyzes the joint effects and interactive relationships of multiple factors on grassroots social governance innovation performance from three dimensions: technology, organization, and environment. The research reveals that internal environmental openness is a necessary condition for achieving high innovation performance in grassroots social governance, and proposes four grouping models that affect the performance of grassroots social governance innovation. This paper explores the inner logic of grassroots social governance innovation from a histological perspective, and on this basis proposes an adaptive path to enhance the performance of grassroots social governance innovation.

A self-assembling peptide inhibits the growth and function of fungi via a wrapping strategy.

Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.

Resilience assessment and obstacle factor analysis of urban areas facing waterlogging disasters: a case study of Shanghai, China.

In recent years, accelerated global warming, rainstorms, typhoons, and other natural disasters have been frequently observed, bringing immeasurable direct and indirect economic losses to urban areas. Determining how to further enhance the resilience of urban areas has become an important topic in economic and social development. Therefore, based on waterlogging scenarios, this study uses a more accurate research method combining the subjective evaluation AHP (analytic hierarchy process) method and objective evaluation TOPSIS (Technique for Order of Preference by Similarity to Ideal Solution) method to evaluate the urban resilience of 16 districts of the Shanghai megacity as the research objects and divides the resilience grade results using the ArcGIS natural breakpoint method. The results show that (1) the overall resilience of all districts in Shanghai needs to be further improved. Among the 16 districts in Shanghai, Pudong New Area has the highest urban resilience level. There are more areas with moderate and above-moderate resilience levels, while some areas with low and moderate resilience levels are distributed mainly in the downtown area of Shanghai. (2) Through the analysis of obstacles to the development of urban resilience in the districts of Shanghai, such obstacles tend to be the same under the waterlogging disaster scenarios. Compared to ecological and social policy resilience indices, economic resilience indices and infrastructure resilience indices significantly impact the resilience of urban districts under waterlogging scenarios. The above conclusions can not only help improve the direction of urban resilience governance in various districts of Shanghai but also provide empirical theoretical experience for the resilient construction of urban areas in the future.

Binding-induced fibrillogenesis peptide inhibits RANKL-mediated osteoclast activation against osteoporosis.

Osteoporosis is primarily driven by an imbalance between bone resorption and formation, stemming from enhanced osteoclast activity during bone remodeling. At the crux of this mechanism lies the pivotal RANK-RANKL-OPG axis. In our study, we designed two binding-induced fibrillogenesis (BIF) peptides, namely BIFP and BIFY, targeting RANK and RANKL, respectively. These BIF peptides, with distinct hydrophilic and hydrophobic characteristics, assemble into nanoparticles (NPs) in aqueous solution. Through specific ligand-receptor interactions, these NPs efficiently target and bind to specific proteins, resulting in the formation of fibrous networks that effectively inhibit the RANK-RANKL associations. Experiments have confirmed the potent inhibitory effects of peptides on both osteoclast differentiation and function. Compared with the +RANKL controls, BIFP and BIFY demonstrated a more remarkable reduction in tartrate resistant acid phosphatase (TRAP)-positive cells, achieving an impressive decline of 82.8% and 70.7%, respectively. Remarkably, the administration of BIFP led to a substantial reduction in bone resorption pit area by 17.4%, compared to a significant increase of 92.4% in the +RANKL groups. In vivo experiments on an ovariectomized mouse model demonstrated that the BIFP treated group exhibited an impressive 2.6-fold elevation in bone mineral density and an astounding 4.0-fold enhancement in bone volume/total volume as against those of the PBS-treated group. Overall, BIF peptides demonstrate remarkable abilities to impede osteoclast differentiation, presenting promising prospects for the treatment of osteoporosis.

Biomimetic peptide nanoparticles participate in natural coagulation for hemostasis and wound healing.

Uncontrolled hemorrhage is a major problem both in surgical intervention and after trauma. Herein, we design an in situ constructable peptide network, mimicking and participating in the native coagulation process for enhanced hemostasis and wound healing. The network consists of two peptides including C6KL, mimicking platelets and C6KG, mimicking fibrin. The C6KL nanoparticles could bind to the collagen at the wound site and transform into C6KL nanofibers. The C6KG nanoparticles could bind to GPIIb/IIIa receptors on the surface of activated platelets and transform into C6KG nanofibers. The in situ formed peptide network could interwind platelets, fibrin and red blood cells, causing embolism at the wound site. In a lethal femoral artery, vein, and nerve cut model of rats, the amount of bleeding was reduced to 32.8% by C6KL and C6KG with chitosan/alginate. The biomimetic peptides show great clinical potential as trauma hemostatic agents.

An intelligent peptide recognizes and traps Mycobacterium tuberculosis to inhibit macrophage phagocytosis.

Tuberculosis is a major public health concern worldwide, and it is a serious threat to human health for a long period. Macrophage phagocytosis of Mycobacterium tuberculosis (M. tuberculosis) is a crucial process for granuloma formation, which shelters the bacteria and gives them an opportunity for re-activation and spread. Herein, we report an intelligent anti-microbial peptide that can recognize and trap the M. tuberculosis, inhibiting the macrophage phagocytosis process. The peptide (Bis-Pyrene-KLVFF-WHSGTPH, in abbreviation as BFH) first self-assembles into nanoparticles, and then forms nanofibers upon recognizing and binding M. tuberculosis. Subsequently, BFH traps M. tuberculosis by the in situ formed nanofibrous networks and the trapped M. tuberculosis are unable to invade host cells (macrophages). The intelligent anti-microbial peptide can significantly inhibit the phagocytosis of M. tuberculosis by macrophages, thereby providing a favorable theoretical basis for inhibiting the formation of tuberculosis granulomas.

Smart Peptide Defense Web In Situ Connects for Continuous Interception of IgE against Allergic Rhinitis.

Allergic rhinitis (AR) is a chronic inflammatory reaction by immunoglobulin E (IgE) mediators after individual contact with allergens. It affects 10-40% of the world's population and reduces the quality of life. Long-term symptoms of rhinitis can cause inflammation to spread and trigger asthma, which can harm human health. Herein, we develop a Smart PeptIde defeNse (SPIN) web technique, which in situ constructs a peptide web, trapping IgE against AR. Two candidate SPINs, SPIN-1 and SPIN-2, are designed with different IgE-binding sequences. The SPIN-1 or SPIN-2 is able to bind to IgE and transform from nanoparticles into entangled nanofibers. In turn, the web of SPIN-1 or SPIN-2 acts as a long-term trap of IgE to prevent the IgE from binding to mast cells. SPIN-1 or SPIN-2 (10 mg/kg) is able to treat AR model Balb/c mice with high efficiency and reduced symptoms of rhinitis and inflammatory factors, even better than a first-line clinical drug, cetirizine (10 mg/kg). For example, the amount of IL-4 released in the AR group (185.5 ± 6.8 pg/mL) is significantly reduced after the treatment with SPIN-1 (70.4 ± 14.1 pg/mL), SPIN-2 (86.0 ± 9.3 pg/mL), or cetirizine (112.8 ± 19.3 pg/mL). More importantly, compared with the cetirizine group (1 day), the SPIN-1 or SPIN-2 group shows long-term therapeutic effects (1 week). The SPIN web technique shows the great potential for blocking IgE binding to mast cells in vivo, attenuating AR or other allergic reactions.

Association between serum phosphate and mortality in critically ill patients: a large retrospective cohort study.

OBJECTIVES: This research aims to explore the impact of serum phosphate on the mortality of critically ill patients. DESIGN: A retrospective large cohort study. SETTING: Our data were extracted from a publicly accessible database named 'Multiparameter Intelligent Monitoring in Intensive Care Database III'. PARTICIPANTS: 27 131 patients were included by clear definitions of selection and exclusion criteria. INTERVENTIONS: We used initial phosphate at admission as a design variable. Patients were divided into six groups with different serum phosphate levels and five groups at different intensive care unit (ICU) departments. PRIMARY AND SECONDARY OUTCOMES: 28-day and 90-day mortality were primary outcomes. All-cause mortality and length of stay ICU were secondary outcomes. RESULTS: Patients with very-high-normal serum phosphate, hypophosphataemia and hyperphosphataemia had worse outcomes. And the relationship between serum phosphate and the probability of 28-day or 90-day mortality had a linear relationship. After adjustment for potential confounders, hypophosphataemia and hyperphosphataemia were not significantly associated with 28-day or 90-day mortality. Nevertheless, at the medical ICU, hyperphosphataemia was associated with increased 28-day or 90-day mortality (HR=0.64, 95% CI 0.48 to 0.84, p=0.0017; HR=0.72, 95% CI 0.57 to 0.91, p=0.0067, respectively), using group 2 (≥2.5 mg/dL and <3.0 mg/dL) as the reference group. CONCLUSIONS: Patients with very-high-normal serum phosphate also had worse outcomes, it might be necessary to re-evaluate the definitions of the normal reference range for serum phosphate. Hypophosphataemia and hyperphosphataemia are not the independent risk factors of 28-day or 90-day ICU mortality, which leads us to consider whether phosphate monitoring is not a necessary measure in critically ill patients. But hyperphosphataemia was associated with increased 28-day or 90-day mortality at the medical ICU, which emphasises the potential importance of early diagnosis and treatment of hyperphosphataemia for the patients who were admitted to the medical ICU.

Alcohol-soluble electron-transport small molecule for fully solution-processed multilayer white electrophosphorescent devices.

A novel alcohol-soluble electron-transport material was designed and synthesized. This material not only possesses a high triplet energy and a low HOMO level but also exhibits excellent electron-transport properties and good film-forming ability. Efficient fully solution-processed multilayer white electrophosphorescent devices have been fabricated by using this alcohol-processable material as an orthogonal electron-transport layer.