Outer membrane vesicles generated by an exogenous bacteriophage lysin and protection against Acinetobacter baumannii infection.

BACKGROUND: The outer membrane vesicles (OMVs) produced by Gram-negative bacteria can modulate the immune system and have great potentials for bacterial vaccine development. RESULTS: A highly active Acinetobacter baumannii phage lysin, LysP53, can stimulate the production of OMVs after interacting with A. baumannii, Escherichia coli, and Salmonella. The OMVs prepared by the lysin (LOMVs) from A. baumannii showed better homogeneity, higher protein yield, lower endotoxin content, and lower cytotoxicity compared to the naturally produced OMVs (nOMVs). The LOMVs contain a significantly higher number of cytoplasmic and cytoplasmic membrane proteins but a smaller number of periplasmic and extracellular proteins compared to nOMVs. Intramuscular immunization with either LOMVs or nOMVs three times provided robust protection against A. baumannii infections in both pneumonia and bacteremia mouse models. Intranasal immunization offered good protection in the pneumonia model but weaker protection (20-40%) in the bacteremia model. However, with a single immunization, LOMVs demonstrated better protection than the nOMVs in the pneumonia mouse model. CONCLUSIONS: The novel lysin approach provides a superior choice compared to current methods for OMV production, especially for vaccine development.

Effects on growth performance and immunity of Monopterus albus after high temperature stress.

To investigate the impact of the effect of high temperature stimulation on Monopterus albus larvae after a certain period of time, five experimental groups were established at different temperatures. Then, the M. albus under high temperature stress was fed at 30°C for 70 days. After that, the growth index of the M. albus was counted and analyzed. In terms of growth index, high temperature stress had significant effects on FCR, FBW, WGR, and SGR of M. albus (p < 0.05). The SR increased after being stimulated by temperature (p < 0.1). The study revealed that liver cells of M. albus were harmed by elevated temperatures of 36°C and 38°C. In the experimental group, the activities of digestive enzymes changed in the same trend, reaching the highest point in the 32°C group and then decreasing, and the AMS activity in the 38°C group was significantly different from that in the 30°C group (p < 0.05). The activities of antioxidase in liver reached the highest at 34°C, which was significantly different from those at 30°C (p < 0.05). In addition, the expression levels of TLR1, C3, TNF-α, and other genes increased in the experimental group, reaching the highest point at 34°C, and the expression level of the IL-1ß gene reached the highest point at 32°C, which was significantly different from that at 30°C (p < 0.05). However, the expression level of the IRAK3 gene decreased in the experimental group and reached its lowest point at 34°C (p < 0.05). The expression level of the HSP90α gene increased with the highest temperature stimulus and reached its highest point at 38°C (p < 0.05). In the α diversity index of intestinal microorganisms in the experimental group, the observed species, Shannon, and Chao1 indexes in the 34°C group were the highest (p < 0.05), and ß diversity analysis revealed that the intestinal microbial community in the experimental group was separated after high temperature stimulation. At the phylum level, the three dominant flora are Proteus, Firmicutes, and Bacteroides. Bacteroides and Macrococcus abundance increased at the genus level, but Vibrio and Aeromonas abundance decreased. To sum up, appropriate high-temperature stress can enhance the immunity and adaptability of M. albus. These results show that the high temperature stimulation of 32°C-34°C is beneficial to the industrial culture of M. albus.

Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers.

Messenger RNA vaccines lack specificity for dendritic cells (DCs)-the most effective cells at antigen presentation. Here we report the design and performance of a DC-targeting virus-like particle pseudotyped with an engineered Sindbis-virus glycoprotein that recognizes a surface protein on DCs, and packaging mRNA encoding for the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or for the glycoproteins B and D of herpes simplex virus 1. Injection of the DC-targeting SARS-CoV-2 mRNA vaccine in the footpad of mice led to substantially higher and durable antigen-specific immunoglobulin-G titres and cellular immune responses than untargeted virus-like particles and lipid-nanoparticle formulations. The vaccines also protected the mice from infection with SARS-CoV-2 or with herpes simplex virus 1. Virus-like particles with preferential uptake by DCs may facilitate the development of potent prophylactic and therapeutic vaccines.

Non-linear relationship of serum albumin-to-globulin ratio and cognitive function in American older people: a cross-sectional national health and nutrition examination survey 2011-2014 (NHANES) study.

Background: Inflammation and liver function are associated with cognitive decline and dementia. Little is known about the serum albumin-to-globulin ratio on cognitive function. Objective: The objective of this study was to investigate the association between albumin-to-globulin ratio and cognitive function among the American older people. Methods: The public data available on the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 was used for this cross-sectional study. Participants aged ≥60 years completed the cognitive function assessments, including word learning and recall modules from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the animal fluency (AF) test, and the digit symbol substitution test (DSST). A composite cognition score was calculated to evaluate global cognition. The univariate and multivariate linear regression analysis, curve fitting, a threshold effect, along with a subgroup analysis and interaction tests were conducted. Results: Serum albumin-to-globulin ratio (per 0.1 unit) was positively associated DSST score (ß = 0.36, 95% CI: 0.21, 0.51), AF score (ß = 0.1, 95% CI: 0.04, 0.16) and global cognition score (ß = 0.05, 95% CI: 0.02, 0.07), after being fully adjusted, while albumin-to-globulin ratio was not related to CERAD score (ß = 0.05, 95% CI: -0.02, 0.12). A non-linear was observed in the dose-response relationship between albumin-to-globulin ratio and global cognition (P for non-linearity < 0.001). The subgroup analysis was overall stable, yet the interaction test was significant for age on global cognition (P for interaction = 0.036). Conclusion: The findings of this cross-sectional study suggested a positive and non-linear association between albumin-to-globulin ratio and cognitive function in the American older people. Maintaining albumin-to-globulin ratio with an appropriate range may be one of the therapeutic strategies to limit the progression of cognitive decline for the older people.

Design of a cryptococcus neoformans vaccine by subtractive proteomics combined with immunoinformatics.

The emergence of Cryptococcus neoformans has posed an undeniable burden to many regions worldwide, with its strains mainly entering the lungs through the respiratory tract and spreading throughout the body. Limitations of drug regimens, such as high costs and limited options, have directed our attention toward the promising field of vaccine development. In this study, the subtractive proteomics approach was employed to select target proteins from databases that can accurately cover serotypes A and D of the Cryptococcus neoformans. Further, two multi-epitope vaccines consisting of T and B cell epitopes were demonstrated that they have good structural stability and could bind with immune receptor to induce desired immune responses in silico. After further evaluation, these vaccines show the potential for large-scale production and applicability to the majority of the population of the world. In summary, these two vaccines have been theoretically proven to combat Cryptococcus neoformans infections, awaiting further experimental validation of their actual protective effects.

Opening and Constructing Stable Lithium-ion Channels within Polymer Electrolytes.

Lithium-ion batteries play an integral role in various aspects of daily life, yet there is a pressing need to enhance their safety and cycling stability. In this study, we have successfully developed a highly secure and flexible solid-state polymer electrolyte (SPE) through the in-situ polymerization of allyl acetoacetate (AAA) monomers. This SPE constructed an efficient Li+ transport channel inside and effectively improved the solid-solid interface contact of solid-state batteries to reduce interfacial impedance. Furthermore, it exhibited excellent thermal stability, an ionic conductivity of 3.82×10-4 S cm-1 at room temperature (RT), and a Li+ transport number (tLi+) of 0.66.  The numerous oxygen vacancies on layered inorganic SiO2 created an excellent environment for TFSI- immobilization. Free Li+ migrated rapidly at the C=O equivalence site with the poly(allyl acetoacetate) (PAAA) matrix. Consequently, when cycled at 0.5 C and RT, it displayed an initial discharge specific capacity of 140.6 mAh g-1 with a discharge specific capacity retention rate of 70% even after 500 cycles. Similarly, when cycled at a higher rate of 5 C, it demonstrated an initial discharge specific capacity of 132.3 mAh g-1 while maintaining excellent cycling stability.

Mitochondria-targeted fluorescent probe for simultaneously imaging viscosity and sulfite in inflammation models.

Many diseases in the human body are related to the overexpression of viscosity and sulfur dioxide. Therefore, it is essential to develop rapid and sensitive fluorescent probes to detect viscosity and sulfur dioxide. In the present work, we developed a dual-response fluorescent probe (ES) for efficient detection of viscosity and sulfur dioxide while targeting mitochondria well. The probe generates intramolecular charge transfer by pushing and pulling the electron-electron system, and the ICT effect is destroyed and the fluorescence quenched upon reaction with sulfite. The rotation of the molecule is inhibited in the high-viscosity system, producing a bright red light. In addition, the probe has good biocompatibility and can be used to detect sulfite in cells, zebrafish and mice, as well as upregulation of viscosity in LPS-induced inflammation models. We expect that the dual response fluorescent probe ES will be able to detect viscosity and sulfite efficiently, providing an effective means of detecting viscosity and sulfite-related diseases.

Microstrain-Stimulated Elastico-Mechanoluminescence with Dual-Mode Stress Sensing.

Elastico-mechanoluminescence technology has shown significant application prospects in stress sensing, artificial skin, remote interaction, and other research areas. Its progress mainly lies in realizing stress visualization and 2D or even 3D stress-sensing effects using a passive sensing mode. However, the widespread promotion of mechanoluminescence (ML) technology is hindered by issues such as high stress or strain thresholds and a single sensing mode based on luminous intensity. In this study, a highly efficient green-emitting ML with dual-mode stress-sensing characteristics driven by microscale strain is developed using LiTaO3:Tb3+. In addition to single-mode sensing based on the luminous intensity, the self-defined parameter (Q) is also introduced as a dual-mode factor for sensing the stress velocity. Impressively, the fabricated LiTaO3:Tb3+ film is capable of generating discernible ML signals even when supplied with strains as low as 500 µst. This is the current minimum strain value that can drive green-emitting ML. This study offers an ideal photonic platform for exploring the potential applications of rare-earth-doped elastico-ML materials in remote interaction devices, high-precision stress sensors, and single-molecule biological imaging.

Sebaceous hyperplasia of the eyelid: A comprehensive case report and literature review.

Introduction: Sebaceous gland hyperplasia of the eyelids, known as adenomatoid or pseudoadenomatous hyperplasia, is a rare benign condition. Optimal management strategies for this specific type of eyelid tumor require further investigation. Case presentation: The patient presented with a 21-year history of a progressively enlarged mass in the right lower eyelid. Previous treatments, including laser photocoagulation and surgical excision, have failed to prevent recurrence. The mass, characterized by a firm texture and low mobility, has raised concerns regarding malignancy. However, histopathological examination following surgical excision identified the mass as sebaceous gland hyperplasia. The patient's medical history was notable for benign gastrointestinal and intestinal polyps with no evidence of malignancy. Conclusions: A final diagnosis of eyelid sebaceous gland hyperplasia was established after surgical excision and comprehensive histopathological analyses. The patient's successful recovery without recurrence over a three-month follow-up period post-surgery highlights the efficacy of the surgical approach and the use of intraoperative frozen section pathological examination.

Targeted inhibition of transforming growth factor-ß type I receptor by AZ12601011 improves paraquat poisoning-induced multiple organ fibrosis.

Paraquat (PQ) causes fatal poisoning that leads to systemic multiple organ fibrosis, and transforming growth factor (TGF)-ß1 plays a critical role in this process. In this study, we aimed to investigate the effects of AZ12601011 (a small molecular inhibitor of TGFßRI) on PQ-induced multiple organ fibrosis. We established a mouse model of PQ in vivo and used PQ-treated lung epithelial cell (A549) and renal tubular epithelial cells (TECs) in vitro. Haematoxylin-eosin and Masson staining revealed that AZ12601011 ameliorated pulmonary, hepatic, and renal fibrosis, consistent with the decrease in the levels of fibrotic indicators, alpha-smooth muscle actin (α-SMA) and collagen-1, in the lungs and kidneys of PQ-treated mice. In vitro data showed that AZ12601011 suppressed the induction of α-SMA and collagen-1 in PQ-treated A549 cells and TECs. In addition, AZ12601011 inhibited the release of inflammatory factors, interleukin (IL)-1ß, IL-6, and tumour necrosis factor-α. Mechanistically, TGF-ß and TGFßRI levels were significantly upregulated in the lungs and kidneys of PQ-treated mice. Cellular thermal shift assay and western blotting revealed that AZ12601011 directly bound with TGFßRI and blocked the activation of Smad3 downstream. In conclusion, our findings revealed that AZ12601011 attenuated PQ-induced multiple organ fibrosis by blocking the TGF-ß/Smad3 signalling pathway, suggesting its potential for PQ poisoning treatment.

Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera.

In response to the urgent need for potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapeutics, this study introduces an innovative nucleoside tailoring strategy leveraging ribonuclease targeting chimeras. By seamlessly integrating ribonuclease L recruiters into nucleosides, we address RNA recognition challenges and effectively inhibit severe acute respiratory syndrome coronavirus 2 replication in human cells. Notably, nucleosides tailored at the ribose 2'-position outperform those modified at the nucleobase. Our in vivo validation using hamster models further bolsters the promise of this nucleoside tailoring approach, positioning it as a valuable asset in the development of innovative antiviral drugs.

Induced Anionic Functional Group Orientation-Assisted Stable Electrode-Electrolyte Interphases for Highly Reversible Zinc Anodes.

Dendrite growth and other side-reaction problems of zinc anodes in aqueous zinc-ion batteries heavily affect their cycling lifespan and Coulombic efficiency, which can be effectively alleviated by the application of polymer-based functional protection layer on the anode. However, the utilization rate of functional groups is difficult to improve without destroying the polymer chain. Here, a simple and well-established strategy is proposed by controlling the orientation of functional groups (─SO3H) to assist the optimization of zinc anodes. Depending on the electrostatic effect, the surface-enriched ─SO3H groups increase the ionic conductivity and homogenize the Zn2+ flux while inhibiting anionic permeation. This approach avoids the destruction of the polymer backbone by over-sulfonation and amplifies the effect of functional groups. Therefore, the modified sulfonated polyether ether ketone (H-SPEEK) coating-optimized zinc anode is capable of longtime stable zinc plating/stripping, and moreover an enhanced cycling steadiness under high current densities is also detected in a series of Zn batteries with different cathode materials, which achieved by the inclusion of H-SPEEK coating without causing any harmful effects on the electrolyte and cathode. This work provides an easy and efficient approach to further optimize the plating/stripping of cations on metal electrodes, and sheds lights on the scale-up of high-performance aqueous zinc-ion battery technology.

Structural network topologies are associated with deep brain stimulation outcomes in Meige syndrome.

Deep brain stimulation (DBS) is an effective therapy for Meige syndrome (MS). However, the DBS efficacy varies across MS patients and the factors contributing to the variable responses remain enigmatic. We aim to explain the difference in DBS efficacy from a network perspective. We collected preoperative T1-weighted MRI images of 76 MS patients who received DBS in our center. According to the symptomatic improvement rates, all MS patients were divided into two groups: the high improvement group (HIG) and the low improvement group (LIG). We constructed group-level structural covariance networks in each group and compared the graph-based topological properties and interregional connections between groups. Subsequent functional annotation and correlation analyses were also conducted. The results indicated that HIG showed a higher clustering coefficient, longer characteristic path length, lower small-world index, and lower global efficiency compared with LIG. Different nodal betweennesses and degrees between groups were mainly identified in the precuneus, sensorimotor cortex, and subcortical nuclei, among which the gray matter volume of the left precentral gyrus and left thalamus were positively correlated with the symptomatic improvement rates. Moreover, HIG had enhanced interregional connections within the somatomotor network and between the somatomotor network and default-mode network relative to LIG. We concluded that the high and low DBS responders have notable differences in large-scale network architectures. Our study sheds light on the structural network underpinnings of varying DBS responses in MS patients.

Near-infrared mechanoluminescence sensor: A new method for on-site infrastructure detection.

Near-infrared mechanoluminescence is a phenomenon that produces high penetrating near-infrared light under external stimulation. Near-infrared light coincides with the biological window, lower optical loss, and the fact that the mechanoluminescence material is a medium that converts mechanical energy into light energy. The near-infrared mechanoluminescence material has potential application prospects in the fields of biological imaging, medical diagnosis, and monitoring of building materials. In this article, we report on a perovskite-type Sr3Sn2O7:Nd3+ near-infrared mechanoluminescence material, and its peaks locate in the first near-infrared window (800-1000 nm) and the second near-infrared window (1080, 1350 nm), respectively. Under the condition of pre-sintering with Li2CO3 as flux, the best sintering conditions are obtained, and the luminescence of material is in perfect agreement with the applied mechanical stress. In addition, a near-infrared mechanoluminescence sensor is proposed to solve the problem of building damage and timely maintenance.

Lotus (Nelumbo nucifera): a multidisciplinary review of its cultural, ecological, and nutraceutical significance.

This comprehensive review systematically examines the multifarious aspects of Nelumbo nucifera, elucidating its ecological, nutritional, medicinal, and biomimetic significance. Renowned both culturally and scientifically, Nelumbo nucifera manifests remarkable adaptability, characterized by its extensive distribution across varied climatic regions, underpinned by its robust rhizome system and prolific reproductive strategies. Ecologically, this species plays a crucial role in aquatic ecosystems, primarily through biofiltration, thereby enhancing habitat biodiversity. The rhizomes and seeds of Nelumbo nucifera are nutritionally significant, being rich sources of dietary fiber, essential vitamins, and minerals, and have found extensive culinary applications. From a medicinal perspective, diverse constituents of Nelumbo nucifera exhibit therapeutic potential, including anti-inflammatory, antioxidant, and anti-cancer properties. Recent advancements in preservation technology and culinary innovation have further underscored its role in the food industry, highlighting its nutritional versatility. In biomimetics, the unique "lotus effect" is leveraged for the development of self-cleaning materials. Additionally, the transformation of Nelumbo nucifera into biochar is being explored for its potential in sustainable environmental practices. This review emphasizes the critical need for targeted conservation strategies to protect Nelumbo nucifera against the threats posed by climate change and habitat loss, advocating for its sustainable utilization as a species of significant value.

The Main Mechanisms of Mesenchymal Stem Cell-Based Treatments against COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a clinical manifestation of hypoxic respiratory failure and acute respiratory distress syndrome. However, COVID-19 still lacks of effective clinical treatments so far. As a promising potential treatment against COVID-19, stem cell therapy raised recently and had attracted much attention. Here we review the mechanisms of mesenchymal stem cell-based treatments against COVID-19, and provide potential cues for the effective control of COVID-19 in the future. METHODS: Literature is obtained from databases PubMed and Web of Science. Key words were chosen for COVID- 19, acute respiratory syndrome coronavirus 2, mesenchymal stem cells, stem cell therapy, and therapeutic mechanism. Then we summarize and critically analyze the relevant articles retrieved. RESULTS: Mesenchymal stem cell therapy is a potential effective treatment against COVID-19. Its therapeutic efficacy is mainly reflected in reducing severe pulmonary inflammation, reducing lung injury, improving pulmonary function, protecting and repairing lung tissue of the patients. Possible therapeutic mechanisms might include immunoregulation, anti-inflammatory effect, tissue regeneration, anti-apoptosis effect, antiviral, and antibacterial effect, MSC - EVs, and so on. CONCLUSION: Mesenchymal stem cells can effectively treat COVID-19 through immunoregulation, anti-inflammatory, tissue regeneration, anti-apoptosis, anti-virus and antibacterial, MSC - EVs, and other ways. Systematically elucidating the mechanisms of mesenchymal stem cell-based treatments for COVID-19 will provide novel insights into the follow-up research and development of new therapeutic strategies in next step.

Polyvinyl alcohol/chitosan quaternary ammonium salt composite hydrogel with directional macroporous structure for photothermal synergistic antibacterial and wound healing promotion.

After skin tissue trauma, wound infections caused by bacteria posed a great threat to skin repair. However, resistance to antibiotics, the current treatment of choice for bacterial infections, greatly affected the efficiency of anti-infection and wound healing. Therefore, there has been a critical need for the development of novel antimicrobial materials and advanced therapeutic methods to aid in skin repair. In this paper, rGO-PDA@ZIF-8 nanofillers were prepared by coating graphene oxide (GO) with dopamine (DA), followed by in situ growth of zeolite imidazolate framework-8 (ZIF-8). Using polyvinyl alcohol (PVA) and chitosan quaternary ammonium salt (CS) as matrix materials, along with polyethylene glycol (PEG) as a pore-forming agent, and rGO-PDA@ZIF-8 as an antimicrobial nano-filler, we successfully prepared rGO-PDA@ZIF-8/PVA/CS composite hydrogels with a directional macroporous structure using bidirectional freezing method and phase separation technique. This hydrogel exhibited excellent mechanical properties, good solubility and water retention capabilities. In addition, the hydrogel demonstrated excellent biocompatibility. Most notably, it not only exhibited excellent bactericidal effect against E. coli and S. aureus (99.1 % and 99.0 %, respectively) under the synergistic effect of intrinsic antibacterial activity and photothermal antibacterial, but also exhibited the ability to promote wound healing, making it a promising candidate for wound healing applications.

Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration.

Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We found that OPTN C-terminus truncation (OPTN∆C) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a striking decrease of axonal mitochondria. Surprisingly, we discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C-terminus dependent manner. Encouragingly, overexpressing OPTN/TRAK1/KIF5B reverses not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes striking ON regeneration. Therefore, in addition to generating new animal models for NTG and ALS, our results establish OPTN as a novel facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.

Unraveling the nuclear isotope tapestry: Applications, challenges, and future horizons in a dynamic landscape.

Nuclear isotopes, distinct atoms characterized by varying neutron counts, have profoundly influenced a myriad of sectors, spanning from medical diagnostics and therapeutic interventions to energy production and defense strategies. Their multifaceted applications have been celebrated for catalyzing revolutionary breakthroughs, yet these advancements simultaneously introduce intricate challenges that warrant thorough investigation. These challenges encompass safety protocols, potential environmental detriments, and the complex geopolitical landscape surrounding nuclear proliferation and disarmament. This comprehensive review embarks on a deep exploration of nuclear isotopes, elucidating their nuanced classifications, wide-ranging applications, intricate governing policies, and the multifaceted impacts of their unintended emissions or leaks. Furthermore, the study meticulously examines the cutting-edge remediation techniques currently employed to counteract nuclear contamination while projecting future innovations in this domain. By weaving together historical context, current applications, and forward-looking perspectives, this review offers a panoramic view of the nuclear isotope landscape. In conclusion, the significance of nuclear isotopes cannot be understated. As we stand at the crossroads of technological advancement and ethical responsibility, this review underscores the paramount importance of harnessing nuclear isotopes' potential in a manner that prioritizes safety, sustainability, and the greater good of humanity.