Comparative analysis of millet bran nanocelluloses with various morphologies: Revealing differences in the formation mechanism and structure characteristics.

To investigate the differences of nanocelluloses with various morphologies, ammonium persulphate (APS) oxidation, H3PO4 dissolution and regeneration, and ball milling combined with 1-butyl-3-methylimidazolium chloride ([BMIM]Cl) as a medium were applied to isolate cellulose nanocrystals (MCNCs), cellulose nanospheres (MCNSs) and cellulose fibrils (MCNFs) from millet bran. The structure, properties, and formation mechanism of three nanocelluloses were comparatively investigated by Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, atomic force microscope, scanning electronic microscope, and emulsifying ability evaluation. MCNCs had needle-like structures due to the removal of amorphous regions, MCNFs appeared fibrous structures due to swelling and mechanical force, and MCNSs displayed spherical structures through self-assembly. MCNCs and MCNFs were confirmed to exhibit cellulose I structures with crystallinities of 61.24 % and 50.09 %, respectively. MCNSs showed the highest crystallinity of 68.41 % with a cellulose II structure. MCNFs and MCNSs exhibited higher initial decomposition temperatures, while MCNCs showed the highest residual mass. MCNFs suspension showed the highest apparent viscosity, while MCNSs suspension demonstrated superior dispersion. MCNSs-emulsion displayed the smallest droplet size, and MCNFs-emulsion exhibited the highest viscosity. This study reveals the formation mechanisms and relationship between morphologies and properties of three millet bran nanocelluloses, providing a theoretical basis for their application.

Python data odyssey: Mining user feedback from google play store.

Context: The Google Play Store is widely recognized as one of the largest platforms for downloading applications, both free and paid. On a daily basis, millions of users avail themselves of this marketplace, sharing their thoughts through various means such as star ratings, user comments, suggestions, and feedback. These insights, in the form of comments and feedback, constitute a valuable resource for organizations, competitors, and emerging companies seeking to expand their market presence. These comments provide insights into app deficiencies, suggestions for new features, identified issues, and potential enhancements. Unlocking the potential of this repository of suggestions holds significant value. Objective: This study sought to gather and analyze user reviews from the Google Play store for leading game apps. The primary aim was to construct a dataset for subsequent analysis utilizing requirements engineering, machine learning, and competitive assessment. Methodology: The authors employed a Python-based web scraping method to extract a comprehensive set of over 429,000+ reviews from the Google Play pages of selected apps. The scraped data encompassed reviewer names (removed due to privacy), ratings, and the textual content of the reviews. Results: The outcome was a dataset comprising the extracted user reviews, ratings, and associated metadata. A total of 429,000+ reviews were acquired through the scraping process for popular apps like Subway Surfers, Candy Crush Saga, PUBG Mobile, among others. This dataset not only serves as a valuable educational resource for instructors, aiding in the training of students in data analysis, but also offers practitioners the opportunity for in-depth examination and insights (in the past data of top apps).

SDDSynergy: Learning Important Molecular Substructures for Explainable Anticancer Drug Synergy Prediction.

Drug combination therapies are well-established strategies for the treatment of cancer with low toxicity and fewer adverse effects. Computational drug synergy prediction approaches can accelerate the discovery of novel combination therapies, but the existing methods do not explicitly consider the key role of important substructures in producing synergistic effects. To this end, we propose a significant substructure-aware anticancer drug synergy prediction method, named SDDSynergy, to adaptively identify critical functional groups in drug synergy. SDDSynergy splits the task of predicting drug synergy into predicting the effect of individual substructures on cancer cell lines and highlights the impact of important substructures through a novel drug-cell line attention mechanism. And a substructure pair attention mechanism is incorporated to capture the information on internal substructure pairs interaction in drug combinations, which aids in predicting synergy. The substructures of different sizes and shapes are directly obtained from the molecular graph of the drugs by multilayer substructure information passing networks. Extensive experiments on three real-world data sets demonstrate that SDDSynergy outperforms other state-of-the-art methods. We also verify that many of the novel drug combinations predicted by SDDSynergy are supported by previous studies or clinical trials through an in-depth literature survey.

Newly identified peptide Nigrocin-OA27 inhibits UVB induced melanin production via the MITF/TYR pathway.

Melasma is a common skin disease induced by an increase in the content of melanin in the skin, which also causes serious physical and mental harm to patients. In this research, a novel peptide (Nigrocin-OA27) from Odorrana andersonii is shown to exert a whitening effect on C57 mice pigmentation model. The peptide also demonstrated non-toxic and antioxidant capacity, and can significantly reduce melanin content in B16 cells. Topical application effectively delivered Nigrocin-OA27 to skin's epidermal and dermal layers and exhibited significant preventive and whitening effects on the UVB-induced ear pigmentation model in C57 mice. The whitening mechanism of Nigrocin-OA27 may be related to reduced levels of the microphthalmia-associated transcription factor and the key enzyme for melanogenesis-tyrosinase (TYR). Nigrocin-OA27 also inhibited the catalytic activity by adhering to the active core of TYR, thereby reducing melanin formation and deposition. In conclusion, Nigrocin-OA27 may be a potentially effective external agent to treat melasma by inhibiting aberrant skin melanin synthesis.

Gut Distribution, Impact Factor, and Action Mechanism of Bacteriocin-Producing Beneficial Microbes as Promising Antimicrobial Agents in Gastrointestinal Infection.

Gastrointestinal (GI) infection by intestinal pathogens poses great threats to human health, and the therapeutic use of antibiotics has reached a bottleneck due to drug resistance. The developments of antimicrobial peptides produced by beneficial bacteria have drawn attention by virtue of effective, safe, and not prone to developing resistance. Though bacteriocin as antimicrobial agent in gut infection has been intensively investigated and reviewed, reviews on that of bacteriocin-producing beneficial microbes are very rare. It is important to explicitly state the prospect of bacteriocin-producing microbes in prevention of gastrointestinal infection towards their application in host. This review discusses the potential of gut as an appropriate resource for mining targeted bacteriocin-producing microbes. Then, host-related factors affecting the bacteriocin production and activity of bacteriocin-producing microbes in the gut are summarized. Accordingly, the multiple mechanisms (direct inhibition and indirect inhibition) behind the preventive effects of bacteriocin-producing microbes on gut infection are discussed. Finally, we propose several targeted strategies for the manipulation of bacteriocin-producing beneficial microbes to improve their performance in antimicrobial outcomes. We anticipate an upcoming emergence of developments and applications of bacteriocin-producing beneficial microbes as antimicrobial agent in gut infection induced by pathogenic bacteria.

Lanthanide Organic-Inorganic Hybrids for X-ray Scintillation and Imaging.

Two X-ray scintillators based on organic-inorganic hybrids were constructed by judiciously incorporating lanthanide cations and organic ligands within a single material. The obtained Eu-pba and Tb-pba not only feature excellent radiation, hydrolytic, and thermal stabilities but also exhibit a linear response to the X-ray dose rate with detection limits of 4.92 and 3.17 µGy s-1, respectively. We further present a flexible scintillator film fabricated by embedding Tb-pba in a polydimethylsiloxane (PDMS) polymer. Their incorporation enables X-ray imaging with a spatial resolution of approximately 10 lp mm-1. These results emphasize the potential of lanthanide organic-inorganic hybrids to achieve outstanding performance in X-ray scintillation and imaging.

Breaking boundaries in radiology: redefining AI diagnostics via raw data ahead of reconstruction.

Objective.In the realm of utilizing artificial intelligence (AI) for medical image analysis, the paradigm of 'signal-image-knowledge' has remained unchanged. However, the process of 'signal to image' inevitably introduces information distortion, ultimately leading to irrecoverable biases in the 'image to knowledge' process. Our goal is to skip reconstruction and build a diagnostic model directly from the raw data (signal).Approach. This study focuses on computed tomography (CT) and its raw data (sinogram) as the research subjects. We simulate the real-world process of 'human-signal-image' using the workflow 'CT-simulated data- reconstructed CT,' and we develop a novel AI predictive model directly targeting raw data (RCTM). This model comprises orientation, spatial, and global analysis modules, embodying the fusion of local to global information extraction from raw data. We selected 1994 patients with retrospective cases of solid lung nodules and modeled different types of data.Main results. We employed predefined radiomic features to assess the diagnostic feature differences caused by reconstruction. The results indicated that approximately 14% of the features had Spearman correlation coefficients below 0.8. These findings suggest that despite the increasing maturity of CT reconstruction algorithms, they still introduce perturbations to diagnostic features. Moreover, our proposed RCTM achieved an area under the curve (AUC) of 0.863 in the diagnosis task, showcasing a comprehensive superiority over models constructed from secondary reconstructed CTs (0.840, 0.822, and 0.825). Additionally, the performance of RCTM closely resembled that of models constructed from original CT scans (0.868, 0.878, and 0.866).Significance. The diagnostic and therapeutic approach directly based on CT raw data can enhance the precision of AI models and the concept of 'signal-to-image' can be extended to other types of imaging. AI diagnostic models tailored to raw data offer the potential to disrupt the traditional paradigm of 'signal-image-knowledge', opening up new avenues for more accurate medical diagnostics.

Theoretical Analysis of Microcavity Simultons Reinforced by χ

High-Q microcavities with quadratic and cubic nonlinearities add lots of versatility in controlling microcombs. Here, we study microcavity simulton and soliton dynamics reinforced by both χ^{(2)} and χ^{(3)} nonlinearities in a continuously pumped microcavity. Theoretical analysis based on the Lagrangian approach reveals the soliton peak power and gain-loss balance are impacted by the flat part of the intracavity pump, while the dark-pulse part of the pump leads to a nearly constant soliton group velocity change. We also derived a soliton conversion efficiency upper limit that is fully determined by the coupling condition and the quantum-limited soliton timing jitter in the χ^{(2,3)} system. Numerical simulations confirm the analytical results. Our theory is particularly useful for investigating AlN microcombs and sheds light on the interplay between χ^{(2)} and χ^{(3)} nonlinearities within microcavity simultons.

Nicotinamide mononucleotide pretreatment improves long-term isoflurane anesthesia-induced cognitive impairment in mice.

Postoperative cognitive dysfunction (POCD) is characterized by impaired cognitive function following general anesthesia and surgery. Oxidative stress is a significant pathophysiological manifestation underlying POCD. Previous studies have reported that the decline of nicotinamide adenine dinucleotide (NAD+) -dependent sirtuin 1 (SIRT1) contributes to the activation of oxidative stress. In this study, we investigated whether pretreatment of nicotinamide mononucleotide (NMN), an NAD+ intermediate, improves oxidative stress and cognitive function in POCD. The animal model of POCD was established in C57BL/6 J mice through 6 h isoflurane anesthesia-induced cognitive impairment. Mice were intraperitoneally injected with NMN for 7 days prior to anesthesia, after which oxidative stress and cognitive function were assessed. The level of oxidative stress was determined using flow cytometry analysis and assey kits. The fear condition test and the Y-maze test were utilized to evaluate contextual and spatial memory. Our results showed that cognitive impairment and increased oxidative stress were observed in POCD mice, as well as downregulation of NAD+ levels and related protein expressions of SIRT1 and nicotinamide phosphoribosyltransferase (NAMPT) in the hippocampus. And NMN supplementation could effectively prevent the decline of NAD+ and related proteins, and reduce oxidative stress and cognitive disorders after POCD. Mechanistically, the findings suggested that protection on cognitive function mediated by NMN pretreatment in POCD mice may be regulated by NAD+-SIRT1 signaling pathway. This study indicated that NMN preconditioning reduced oxidative stress damage and alleviated cognitive impairment in POCD mice.

PPARα agonist fenofibrate prevents postoperative cognitive dysfunction by enhancing fatty acid oxidation in mice.

Background: Due to high rates of incidence and disability, postoperative cognitive dysfunction (POCD) currently receives a lot of clinical attention. Disturbance of fatty acid oxidation is a potential pathophysiological manifestation underlying POCD. Peroxisome proliferator-activated receptor α (PPARα) is a significant transcription factor of fatty acid oxidation that facilitates the transfer of fatty acids into the mitochondria for oxidation. The potential role of PPARα intervention in POCD warrants consideration. Objective: The present study is aimed to investigate whether PPARα agonist fenofibrate (FF) could protect long-term isoflurane anesthesia-induced POCD model and to explore the potential underlying function of fatty acid oxidation in the process. Methods: We established the POCD model via 6 h long-term isoflurane anesthesia in vivo with C57BL/6J mice and in vitro with N2a cells. Cells and mice were pretreated with PPARα agonist FF before anesthesia, after which fatty acid oxidation and cognitive function were assessed. The level of fatty acid oxidation-related proteins was determined using western blotting. The contextual fear conditioning test was utilized to evaluate mice's learning and memory. Results: Our results showed that 6 h long-term isoflurane anesthesia induced contextual memory damage in mice, accompanied by decreases of fatty acid oxidation-related proteins (peroxisome proliferator-activated receptor γ coactivator 1α, carnitine palmitoyltransferase 1A, and PPARα) both in the hippocampus of POCD mice and in N2a cells. In the N2a cell model, pretreatment of PPARα agonist FF led to the upregulation of fatty acid oxidation-related proteins. In vivo results showed that preconditioned FF reached similar effects. More crucially, FF has been shown to reduce cognitive damage in mice after long-term isoflurane anesthesia. Additionally, our data showed that after blocking fatty acid oxidation by Etomoxir, FF failed to protect cognitive function from long-term isoflurane anesthesia. Conclusions: Pretreatment of PPARα agonist FF can protect against long-term isoflurane anesthesia-induced POCD by enhancing fatty acid oxidation.

Comparative chloroplast genome analyses provide insights into evolutionary history of Rhizophoraceae mangroves.

Background: The Rhizophoraceae family comprises crucial mangrove plants that inhabit intertidal environments. In China, eight Rhizophoraceae mangrove species exist. Although complete chloroplast (Cp) genomes of four Rhizophoraceae mangrove plants have been reported, the Cp genomes of the remaining four species remain unclear, impeding a comprehensive understanding of the evolutionary history of this family. Methods: Illumina high-throughput sequencing was employed to obtain the DNA sequences of Rhizophoraceae species. Cp genomes were assembled by NOVOPlasty and annotated using CpGAVAS software. Phylogenetic and divergence time analyses were conducted using MEGA and BEAST 2 software. Results: Four novel Cp genomes of Rhizophoraceae mangrove species (Bruguiera sexangula, Bruguiera gymnorrhiza, Bruguiera × rhynchopetala and Rhizophora apiculata) were successfully assembled. The four Cp genomes ranged in length from 163,310 to 164,560 bp, with gene numbers varying from 124 to 128. The average nucleotide diversity (Pi) value of the eight Rhizophoraceae Cp genomes was 0.00596. Phylogenetic trees constructed based on the complete Cp genomes supported the monophyletic origin of Rhizophoraceae. Divergence time estimation based on the Cp genomes of representative species from Malpighiales showed that the origin of Rhizophoraceae occurred at approximately 58.54-50.02 million years ago (Mya). The divergence time within the genus Rhizophora (∼4.51 Mya) was much earlier than the divergence time within the genus Bruguiera (∼1.41 Mya), suggesting recent speciation processes in these genera. Our data provides new insights into phylogenetic relationship and evolutionary history of Rhizophoraceae mangrove plants.

Characterization of LL37 Binding to Collagen through Peptide Modification with a Collagen-Binding Domain.

Collagen-based biomaterials loaded with antimicrobial peptides (AMPs) present a promising approach for promoting wound healing while providing protection against infections. In our previous work, we modified the AMP LL37 by incorporating a collagen-binding domain (cCBD) as an anchoring unit for collagen-based wound dressings. We demonstrated that cCBD-modified LL37 (cCBD-LL37) exhibited improved retention on collagen after washing with PBS. However, the binding mechanism of cCBD-LL37 to collagen remained to be elucidated. In this study, we found that cCBD-LL37 showed a slightly higher affinity for collagen compared to LL37. Our results indicated that cCBD inhibited cCBD-LL37 binding to collagen but did not fully eliminate the binding. This suggests that cCBD-LL37 binding to collagen may involve more than just one-site-specific binding through the collagen-binding domain, with non-specific interactions also playing a role. Electrostatic studies revealed that both LL37 and cCBD-LL37 interact with collagen via long-range electrostatic forces, initiating low-affinity binding that transitions to close-range or hydrophobic interactions. Circular dichroism analysis showed that cCBD-LL37 exhibited enhanced structural stability compared to LL37 under varying ionic strengths and pH conditions, implying potential improvements in antimicrobial activity. Moreover, we demonstrated that the release of LL37 and cCBD-LL37 into the surrounding medium was influenced by the electrostatic environment, but cCBD could enhance the retention of peptide on collagen scaffolds. Collectively, these results provide important insights into cCBD-modified AMP-binding mechanisms and suggest that the addition of cCBD may enhance peptide structural stability and retention under varying electrostatic conditions.

Knee osteoarthritis: Current status and research progress in treatment (Review).

Knee osteoarthritis (KOA) is a common chronic articular disease worldwide. It is also the most common form of OA and is characterized by high morbidity and disability rates. With the gradual increase in life expectancy and ageing population, KOA not only affects the quality of life of patients, but also poses a burden on global public health. OA is a disease of unknown etiology and complex pathogenesis. It commonly affects joints subjected to greater loads and higher levels of activity. The knee joint, which is the most complex joint of the human body and bears the greatest load among all joints, is therefore most susceptible to development of OA. KOA lesions may involve articular cartilage, synovium, joint capsule and periarticular muscles, causing irreversible articular damage. Factors such as mechanical overload, inflammation, metabolism, hormonal changes and ageing serve key roles in the acceleration of KOA progression. The clinical diagnosis of KOA is primarily based on combined analysis of symptoms, signs, imaging and laboratory examination results. At present, there is no cure for KOA and the currently available therapies primarily focus on symptomatic treatment and delay of disease progression. Knee replacement surgery is typically performed in patients with advanced disease. The current study presents a review of epidemiological characteristics, risk factors, histopathological manifestations, pathogenesis, diagnosis, treatment modalities and progress in KOA research.

miR-186-5p targets TGFßR2 to inhibit RAW264.7 cell migration and proliferation during mouse skin wound healing.

BACKGROUND: Active peptides play a vital role in the development of new drugs and the identification and discovery of drug targets. As the first reported native peptide homodimer with pro-regenerative potency, OA-GP11d could potentially be used as a novel molecular probe to help elucidate the molecular mechanism of skin wound repair and provide new drug targets. METHODS: Bioinformatics analysis and luciferase assay were adopted to determine microRNAs (miRNAs) and its target. The prohealing potency of the miRNA was determined by MTS and a Transwell experiment against mouse macrophages. Enzyme-linked immunosorbent assay, realtime polymerase chain reaction, and western blotting were performed to explore the molecular mechanisms. RESULTS: In this study, OA-GP11d was shown to induce Mus musculus microRNA-186-5p (mmu-miR-186-5p) down-regulation. Results showed that miR-186-5p had a negative effect on macrophage migration and proliferation as well as a targeted and negative effect on TGF-ß type II receptor (TGFßR2) expression and an inhibitory effect on activation of the downstream SMAD family member 2 (Smad2) and protein-p38 kinase signaling pathways. Importantly, delivery of a miR-186-5p mimic delayed skin wound healing in mice. CONCLUSION: miR-186-5p regulated macrophage migration and proliferation to delay wound healing through the TGFßR2/Smad2/p38 molecular axes, thus providing a promising new pro-repair drug target.

A new peptide, VD11, promotes structural and functional recovery after spinal cord injury.

The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury. It is therefore a priority to develop new drugs that can promote structural and functional recovery after spinal cord injury. Previous studies have shown that peptides can promote substantial repair and regeneration of injured tissue. While amphibians have a pronounced ability to regenerate the spinal cord, few studies have investigated the effect of amphibian spinal cord-derived peptides on spinal cord injury. Here we report for the first time the successful identification and isolation of a new polypeptide, VD11 (amino acid sequence: VDELWPPWLPC), from the spinal cord of an endemic Chinese amphibian (Odorrana schmackeri). In vitro experiments showed that VD11 promoted the secretion of nerve growth factor and brain-derived neurotrophic factor in BV2 cells stimulated with lipopolysaccharide, as well as the proliferation and synaptic elongation of PC12 cells subjected to hypoxia. In vivo experiments showed that intravertebral injection of VD11 markedly promoted recovery of motor function in rats with spinal cord injury, alleviated pathological damage, and promoted axonal regeneration. Furthermore, RNA sequencing and western blotting showed that VD11 may affect spinal cord injury through activation of the AMPK and AKT signaling pathways. In summary, we discovered a novel amphibian-derived peptide that promotes structural and functional recovery after spinal cord injury.

Enhancement of the sensing performance and stability of a MOF based-molecularly imprinted polymer by utilizing dual-ligands and triethanolamine catalysis.

In this work, a terbium MOF-based molecularly imprinted polymer (Tb-MOF@SiO2@MIP) was prepared using two ligands as organic linkers and triethanolamine (TEA) as a catalyst to improve the sensing performance and stability of the fluorescence sensors. The obtained Tb-MOF@SiO2@MIP was then characterized using a transmission electron microscope (TEM), energy dispersive spectroscopy (EDS) Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and thermogravimetric analysis (TGA). The results revealed that Tb-MOF@SiO2@MIP was successfully synthesized with a thin imprinted layer of 76 nm. The synthesized Tb-MOF@SiO2@MIP maintained 96% of its original fluorescence intensity after 44 days in aqueous environments because of appropriate coordination models between the imidazole ligands as a nitrogen donor and Tb (Ⅲ). Furthermore, TGA analysis results indicated that an increase in the thermal stability of Tb-MOF@SiO2@MIP was attributed to the thermal barrier from a MIP layer. The Tb-MOF@SiO2@MIP sensor responded well to the addition of imidacloprid (IDP) in the range of 2.07-150 ng mL-1 with a low detection limit of 0.67 ng mL-1. In vegetable samples, the sensor can quickly detect IDP levels with the average recovery ranging from 85.10 to 99.85% and RSD values ranging from 0.59 to 5.82%. The UV-vis absorption spectrum and density functional theory analysis results revealed that the inner filter effect and dynamic quenching process both contributed to the sensing process of Tb-MOF@SiO2@MIP.

LL37 and collagen-binding domain-mediated LL37 binding with type I collagen: Quantification via QCM-D.

Antimicrobial peptide (AMP)-loaded biomaterials may represent a viable alternative for stimulating wound healing while protecting against infections. Previously, to develop an efficient delivery system for the cathelicidin antimicrobial peptide, LL37, our lab modified LL37 with a collagen-binding domain derived from collagenase (cCBD) as an anchoring unit to collagen-based wound dressings. However, a direct quantification of unmodified LL37 and cCBD-LL37 binding with collagen has not been performed. In this study, we used quartz crystal microbalance with dissipation monitoring (QCM-D), immunohistochemistry (IHC), and atomic force microscopy (AFM) to establish and characterize an adsorbed layer of type I collagen on the QCM-D sensor and quantify peptide-collagen binding. A collagen deposition protocol was successfully established by measuring concentration-dependent deposition of collagen in QCM-D, and collagen self-assembly was observed by IHC and AFM. Hydrophobicity is known to affect the behavior of collagen adsorption. Therefore, we compared the deposition of collagen on hydrophilic SiO2-coated sensors vs. hydrophobic polystyrene (PS)-coated sensors via QCM-D, and found that the hydrophobic surface yielded more collagen adsorption, which suggested that hydrophobic surfaces are preferable for collagen layer establishment. There was no significant difference between LL37 and cCBD-LL37 binding with collagen, but the cCBD-LL37 showed better retention on the collagen after washing with PBS, indicating that there is an advantage to using cCBD as an anchoring unit to collagen. Collectively, these results provide important information on cCBD-mediated AMP-binding mechanisms and establish an effective method for quantifying peptide-collagen binding.

New antimicrobial peptide-antibiotic combination strategy for Pseudomonas aeruginosa inactivation.

Novel antimicrobials or new treatment strategies are urgently needed to treat Pseudomonas aeruginosa (P. aeruginosa) related infections and especially to address the problem of antibiotic resistance. We propose a novel strategy that combines the human antimicrobial peptide (AMP) LL37 with different antibiotics to find synergistic AMP-antibiotic combinations against P. aeruginosa strains in vitro. Our results showed that LL37 exhibited synergistic inhibitory and bactericidal effects against P. aeruginosa strains PAO1 and PA103 when combined with the antibiotics vancomycin, azithromycin, polymyxin B, and colistin. In addition, LL37 caused strong outer membrane permeabilization, as demonstrated through measurement of an increased uptake of the fluorescent probe N-phenyl-1-naphthylamine. The membrane permeabilization effects appear to explain why it was easier to rescue the effectiveness of the antibiotic toward the bacteria because the outer membrane of P. aeruginosa exhibits barrier function for antibiotics. Furthermore, the change in the zeta potential was measured for P. aeruginosa strains with the addition of LL37. Zeta potentials for P. aeruginosa strains PAO1 and PA103 were -40.9 and -10.9 mV, respectively. With the addition of LL37, negative zeta potentials were gradually neutralized. We found that positively charged LL37 can interact with and neutralize the negatively charged bacterial outer membrane through electrostatic interactions, and the process of neutralization is believed to have contributed to the increase in outer membrane permeability. Finally, to further illustrate the relationship between outer membrane permeabilization and the uptake of antibiotics, we used LL37 to make the outer membrane of P. aeruginosa strains more permeable, and minimum inhibitory concentrations (MICs) for several antibiotics (colistin, gentamicin, polymyxin B, vancomycin, and azithromycin) were measured. The MICs decreased were twofold to fourfold, in general. For example, the MICs of azithromycin and vancomycin decreased more than fourfold when against P. aeruginosa strain PAO1, which were the greatest decrease of any of the antibiotics tested in this experiment. As for PA103, the MIC of polymyxin B2 decreased fourfold, which was the strongest decrease seen for any of the antibiotics tested in this experiment. The increased uptake of antibiotics not only demonstrates the barrier role of the outer membrane but also validates the mechanism of synergistic effects that we have proposed. These results indicate the great potential of an LL37-antibiotic combination strategy and provide possible explanations for the mechanisms behind this synergy.

OL-FS13 alleviates experimental cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion (I/R) is the main cause of neurological injury after stroke. However, existing treatments for I/R injury are relatively poor, and relevant drugs need to be further explored. Amphibians have received increasing attention as a resource bank of bioactive peptides. However, reports on neuroprotective peptides from amphibians remain extremely rare. Here, we identified a new neuroprotective peptide (OL-FS13, amino acid sequence: FSLLLTWWRRRVC) from the odorous frog species Odorrana livida using a constructed cDNA library. OL-FS13 significantly improving infarct volume, behavioral and histological abnormalities in rats, and also showed neuroprotective activities in PC12 cell (by oxygen glucose deprivation/reoxygenation, OGD/R). Mechanistically, OL-FS13 increased the level of antioxidative enzymes to resist oxidative stress and alleviated endoplasmic reticulum (ER) stress induced by I/R and OGD/R. The use of ML385 (Nrf2 inhibitor) indicated that OL-FS13 relieved nerve damage caused by oxidative and ER stress by increasing the nuclear displacement of Nrf2. Collectively, this research provides a novel drug candidate for the clinical cerebral I/R curation.

Synthesis of palm sheath derived-porous carbon for selective CO2 adsorption.

Biomass-derived porous carbons are regarded as the most preferential adsorbents for CO2 capture due to their well-developed textural properties, tunable porosity and low cost. Herein, novel porous carbons were facilely prepared by activation of palm sheath for the highly selective separation of CO2 from gas mixtures. The textural features of carbon materials were characterized by the analysis of surface morphology and N2 isotherms for textural characterization. The as-prepared carbon adsorbents possess an excellent CO2 adsorption capacity of 3.48 mmol g-1 (298 K) and 5.28 mmol g-1 (273 K) at 1 bar, and outstanding IAST selectivities of CO2/N2, CO2/CH4, and CH4/N2 up to 32.7, 7.1 and 4.6 at 298 K and 1 bar, respectively. Also, the adsorption evaluation criteria of the vacuum swing adsorption (VSA) process, the breakthrough experiments, and the cyclic experiments have comprehensively demonstrated the palm sheath derived porous carbons as efficient adsorbents for practical applications.