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The increasing demand for ready-to-eat fresh foods requires the use of non-thermal sterilization, hence, the application of antimicrobial peptides (AMPs) combined with ultrasound could serve as a novel food preservation method to prevent foodborne diseases. In this study, in silico tools were used to predict and screen potential AMPs from the antimicrobial amino acid sequence of myosin heavy chain of Larimichthys crocea. A novel AMP, designated as LCMHC, had strong antibacterial activity against Staphylococcus aureus when combined with low-intensity ultrasound treatment. The minimal inhibitory concentration (MIC) of LCMHC was 125 μg/mL when used alone but 31.25 μg/mL when combined with 0.3 W/cm2 ultrasound treatment. Structural analysis using circular dichroism (CD) revealed that peptide LCMHC has α-helical structure, which had slightly untwisting effect with increasing ultrasonic intensity. Transmission electron microscopy and permeability analysis of bacteria cell membrane showed that low-intensity ultrasound combined with peptide LCMHC could greatly improve the cell membrane permeability of S. aureus. Moreover, low intensity-ultrasound could assist the entry of more peptide LCMHC into bacterial cells to bind DNA. The findings here provide new insight into the potential application of peptide LCMHC combined with low-intensity ultrasound in the food industry. • A novel antimicrobial peptide, LCMHC, was identified from MHC sequence of L. crocea. • The MIC of LCMHC against S. aureus decreased 4-fold under ultrasound treatment. • Ultrasound improved the entry of LCMHC into S. aureus cells. • LCMHC had little untwisting effect at 2 h treatment with 0.3 W/cm2 ultrasound. [ABSTRACT FROM AUTHOR]

[Display omitted] • Development of a new self-assemble aromatic peptide (F-AP) platform functional as subunit vaccine adjuvant. • F-AP induces potent antibody titers in mice. • F-AP assists subunit vaccines escape from lysosome and induces dendritic cell differentiation. Compared with vaccines comprising inactivated or attenuated whole pathogens, the subunit vaccines based on protein antigens are safer and easier to manufacture. Yet subunit vaccines usually exhibit weak and nondurable immune responses, which is mainly due to their poor uptake by antigen-presenting cells. To address this issue, we develop a fluorinated aromatic peptide (F-AP), in which electronegativity of fluorine is to enhance its affinity with antigens and ability of transmembrane. In mice model, F-AP demonstrated over 4-fold and 501-fold higher antibody titers than AP and conventional aluminum adjuvant, respectively. Consistent with the antibody responses, F-AP greatly promoted the proliferation of T follicular helper cell and mature B cell. Intriguingly, conventional type 1 dendritic cells (cDC1) were also increased in lymph nodes with F-AP vaccination. And antigens localization experiments showed that F-AP help antigens escape from cell lysosomes, indicating that F-AP could potentially induce cellular immune responses through cDC1′s antigen cross-presentation function. Collectively, the data suggest that simple fluorine group modification on aromatic peptide, F-AP, could improve the immune response of subunit antigens. Thus, fluoridation strategy may provide a novel approach for nanomaterials enhancing the vaccination immune response of vaccines or immunotherapies. [ABSTRACT FROM AUTHOR]

The aim of the present study was to develop a transdermal drug delivery system for azasetron and evaluate the correlation between in vitro and in vivo release. The effects of different adhesives, permeation enhancers, and loadings of azasetron used in patches on the penetration of azasetron through rabbit skin were investigated using two-chamber diffusion cells in vitro. For in vivo studies, azasetron pharmacokinetic parameters in Bama miniature pigs were determined according to a noncompartment model method after topical application of transdermal patches and intravenous administration of azasetron injections. The best permeation profile was obtained with the formulation containing DURO-TAK 87-9301 as adhesive, 5% of isopropyl myristate as penetration enhancer, and 5% of azasetron. The optimal patch formulation exhibited sustained release profiles in vivo for 216 h. The in vivo absorption curve in Bama miniature pigs obtained by deconvolution approach using WinNonlin® program was correlated well with the in vitro permeation curve of the azasetron patch. These findings indicated that the developed patch for azasetron is promising for the treatment of delayed chemotherapy-induced nausea and vomiting, and the in vitro skin permeation experiments could be useful to predict the in vivo performance of transdermal azasetron patches. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:4540-4548, 2012 [ABSTRACT FROM AUTHOR]

• MoS 2 inherits the structure of the intermediate 1 T-MoS 2 with expanded interlayer distance. • The flower-like structure and few-layered MoS 2 promote the transport of sodium ions. • Increasing the storage site of Na+ leads to high specific capacity. • Faster kinetics of Na+ leads to significant C-rate performance. MoS 2 , high theoretical specific capacity (670 mAh g−1) and unique physical and chemical properties, is widely used as the anode of sodium-ion batteries (SIBs). However, the original MoS 2 , with its inferior inherent conductivity and serious volume variation during charge and discharge, often exhibits low actual capacity and poor rate performance. In this work, MoS 2 nanoflower was synthesized by sulfurization of molybdenum trioxide (MoS 2 -MT), which expanded interlayer distance without mixing with other materials. The expanded interlayer distance (about 0.68 nm) reduced the diffusion barrier of Na+. The larger specific surface area increased the contact area between the electrode material and the electrolyte, which provided more active sites for the insertion/extraction of Na+. As anode of SIBs, MoS 2 -MT achieved a high specific capacity of 535.3 mAh g−1 at 0.1 A g−1, and reserved 410 mAh g−1 at 1 A g−1 after 100 cycles with a capacity retention rate of 85.4%. At the same time, MoS 2 -MT also exhibited considerable rate performance that reserved 313.5 mAh g−1 at 5.0 A g−1. [ABSTRACT FROM AUTHOR]

• The first supramolecular nanofiber with superior bioactivity over the PDGF protein. • The nanofiber based on VRKKP provides multivalent binding sites for PDGFR. • The nanofiber efficiently promotes PDGFR oligomerization for the activity. • The nanofiber is promising for the ionizing radiation-induced injury repair. Platelet-derived growth factors (PDGFs) play crucial roles in regulating cell proliferation, apoptosis, and migration and have been recommended for injury repair in clinical practice. However, the low stability, poor biological barrier penetration ability, and high cost of protein drugs hinders their wide application. The development of small molecules or nanomaterials capable of simulating the bioactivity of PDGFs may overcome the shortcomings of PDGF proteins and expand their application. Herein, we report the first supramolecular nanofiber of the self-assembling peptide Nap-FFGVRKKP (Compound 1 ) with superior bioactivity over the PDGF protein. The peptide derivative Nap-FFG formed a β-sheet conformation, which mimicks the four-β-sheet peptide in PDGF, and the pentapeptide VRKKP from loop 3 in PDGF that is crucial for binding with the PDGF receptor. Therefore, the nanofibers possessed the multivalent loop 3 peptide on the surface that might assist oligomerization and activation of the PDGF receptor. The results indicated that our nanomaterials efficiently activated the PDGF signaling pathway and promoted NIH 3T3 cell proliferation and migration. Moreover, they significantly reduced the apoptosis rate caused by 10 Gy X-ray radiation from 33.60% to 5.83% and showed a good therapeutic effect on the ionizing radiation-induced injury repair by reducing the inflammatory response and enhancing skin regeneration. Our study offers a versatile strategy to construct nanomaterials with enhanced biological activity through multivalent interactions, and the development of PDGF mimics may overcome the limitation of PDGFs for their applications in injury repair, cell culture, cosmetics, and regenerative medicine. [ABSTRACT FROM AUTHOR]

Biodegradable and injectable hydrogels derived from natural polysaccharides have attracted extensive attention in biomedical applications due to their minimal invasiveness and ability to accommodate the irregular wound surfaces. In this work, we report the development of an in-situ-injectable, self-healing, antibacterial, hemostatic, and biocompatible hydrogel derived from the hybrid of N,O-carboxymethyl chitosan (N,O-CMC) and oxidized chondroitin sulfate (OCS), which did not require any chemical crosslinking. The N,O-CMC/OCS hydrogel could be readily produced under physiological conditions by varying the N,O-CMC-to-OCS ratio, relying on the Schiff base reaction between the –NH– functional groups of N,O-CMC and the -CHO functional groups of OCS. The results showed that the N,O-CMC2/OCS1 hydrogel had relatively long gelation time (133 s) and stable performances. The viability of NIH/3T3 cells and endothelial cells cultured with the N,O-CMC2/OCS1 hydrogel extract was roughly 85%, which demonstrated its low cell toxicity. Besides, the N,O-CMC2/OCS1 hydrogel revealed excellent antibacterial properties due to the inherent antibacterial ability of N,O-CMC. Importantly, the hydrogel tightly adhered to the biological tissue and demonstrated excellent in vivo hemostatic performance. Our work describing an injectable, self-healing, antibacterial, and hemostatic hydrogel derived from polysaccharides will likely hold good potential in serving as an enabling wound dressing material. • The injectable, self-healing hydrogel was fabricated based on N,O-CMC and OCS without any chemical crosslinking. • The hydrogel exhibited excellent antibacterial and hemostatic properties. • As a potential wound dressings, the hemostatic mechanism of N,O-CMC/OCS hydrogel was discussed. [ABSTRACT FROM AUTHOR]

An abstract of the article "Lentiviral Gene Transfer of RPE65 cDNA in Knock-Out Mouse Models of Leber Congenital Amaurosis," by Corinne Kostic and colleagues is presented.

Glycyrrhizin (GL) has immunoregulatory effects on various inflammatory diseases including hepatitis and nephritis. However, the mechanisms underlying the anti-inflammatory effect of GL on renal inflammation are not fully understood. Hepatorenal syndrome (HRS) is a functional acute renal impairment that occurs in severe liver disease, and we found that kidney injury also occurs in Con A-induced experimental hepatitis in mice. We previously found that GL can alleviate Con A-induced hepatitis by regulating the expression of IL-25 in the liver. We wanted to investigate whether GL can alleviate Con A-induced nephritis by regulating IL-25. IL-25 regulates inflammation by modulating type 2 immune responses, but the mechanism by which IL-25 affects kidney disease remains unclear. In this study, we found that the administration of GL enhanced the expression of IL-25 in renal tissues; the latter promoted the generation of type 2 macrophages (M2), which inhibited inflammation in the kidney caused by Con A challenge. IL-25 promoted the secretion of the inhibitory cytokine IL-10 by macrophages but inhibited the expression of the inflammatory cytokine IL-1β by macrophages. Moreover, IL-25 downregulated the Con A-mediated expression of Toll-like receptor (TLR) 4 on macrophages. By comparing the roles of TLR2 and TLR4, we found that TLR4 is required for the immunoregulatory effect of IL-25 on macrophages. Our data revealed that GL has anti-inflammatory effects on Con A-induced kidney injury and that the GL/IL-25/M2 axis participates in the anti-inflammatory process. This study suggested that GL is a potential therapeutic for protecting against acute kidney injury.

While immunotherapy has shown efficacy in lung adenocarcinoma (LUAD) patients, many respond only partially or not at all. One limitation in improving outcomes is the lack of a complete understanding of immune checkpoint regulation. Here, we investigated a possible link between an environmental chemical receptor implicated in lung cancer and immune regulation, (the aryl hydrocarbon receptor/AhR), a known but counterintuitive mediator of immunosuppression (IFNγ), and regulation of two immune checkpoints (PD-L1 and IDO). AhR gene-edited LUAD cell lines, a syngeneic LUAD mouse model, bulk- and scRNA sequencing of LUADs and tumor-infiltrating leukocytes were used to map out a signaling pathway leading from IFNγ through the AhR to JAK/STAT, PD-L1, IDO, and tumor-mediated immunosuppression. The data demonstrate that: 1) IFNγ activation of the JAK/STAT pathway leading to PD-L1 and IDO1 upregulation is mediated by the AhR in murine and human LUAD cells, 2) AhR-driven IDO1 induction results in the production of Kynurenine (Kyn), an AhR ligand, which likely mediates an AhR→IDO1→Kyn→AhR amplification loop, 3) transplantation of AhR-knockout LUAD cells results in long-term tumor immunity in most recipients. 4) The 23% of AhR-knockout tumors that do grow do so at a much slower pace than controls and exhibit higher densities of CD8 + T cells expressing markers of immunocompetence, increased activity, and increased cell-cell communication. The data definitively link the AhR to IFNγ-induced JAK/STAT pathway and immune checkpoint-mediated immunosuppression and support the targeting of the AhR in the context of LUAD.

Neoadjuvant radiotherapy, a preoperative intervention regimen for reducing the stage of primary tumors and surgical margins, has gained increasing attention in the past decade. However, radiation-induced skin damage during neoadjuvant radiotherapy exacerbates surgical injury, remarkably increasing the risk of refractory wounds and compromising the therapeutic effects. Radiation impedes wound healing by increasing the production of reactive oxygen species and inducing cell apoptosis and senescence. Here, a self-assembling peptide (R-peptide) and hyaluronic-acid (HA)-based and cordycepin-loaded superstructure hydrogel is prepared for surgical incision healing after neoadjuvant radiotherapy. Results show that i) R-peptide coassembles with HA to form biomimetic fiber bundle microstructure, in which R-peptide drives the assembly of single fiber through π-π stacking and other forces and HA, as a single fiber adhesive, facilitates bunching through electrostatic interactions. ii) The biomimetic superstructure contributes to the adhesion and proliferation of cells in the surgical wound. iii) Aldehyde-modified HA provides dynamic covalent binding sites for cordycepin to achieve responsive release, inhibiting radiation-induced cellular senescence. iv) Arginine in the peptides provides antioxidant capacity and a substrate for the endogenous production of nitric oxide to promote wound healing and angiogenesis of surgical wounds after neoadjuvant radiotherapy., (© 2024 Wiley‐VCH GmbH.)

Mullite fiber felt is a promising material that may fulfill the demands of advanced flexible external thermal insulation blankets. However, research on the fabrication and performance of mullite fiber felt with high-temperature resistance and thermal stability is still lacking. In this work, mullite fibers were selected as raw materials for the fabrication of mullite fibrous porous materials with a three-dimensional net structure. Said materials' high-temperature resistance and thermal stability were investigated by assessing the effects of various heat treatment temperatures (1100 °C, 1300 °C, and 1500 °C) on the phase composition, microstructure, and performance of their products. When the heat treatment temperature was below 1300 °C, both the phase compositions and microstructures of products exhibited stability. The compressive rebound rate of the product before and after 1100 °C reached 92.9% and 84.5%, respectively. The backside temperature of the as-prepared products was 361.6 °C when tested at 1500 °C for 4000 s. The as-prepared mullite fibrous porous materials demonstrated excellent high-temperature resistance, thermal stability, thermal insulation performance, and compressive rebound capacity, thereby indicating the great potential of the as-prepared mullite fibrous porous materials in the form of mullite fiber felt within advanced flexible external thermal insulation blankets.

Microneedle drug delivery has recently emerged as a clinical method, and dissolving microneedles (DMNs) offer exclusive simplicity and efficiency, compared to the other kinds of microneedles. The tips of most currently available DMNs are cone/house-shaped to result in a lower penetration force. Penetration of the needle tips into the skin relies mainly on the back tape or external pressure, and their adhesion to the skin is relatively low. In addition, only the drug in the part of tips that are pierced into the dermis can be dissolved, resulting in drug waste. Inspired from the barbed structure of the honeybee stinger, we reported substrate-free DMNs with a barbed structure by a dual-molding process, which is suitable for mass production. Those DMNs showed 3-fold greater adhesion force between the needle tips and the skin, better dissolution and deeper penetration than house-shaped DMNs in vivo under the same conditions. For the in situ treatment of psoriasis in mice, the barbed DMNs required only the half dose of house-shaped DMNs to achieve similar efficacy., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The inherent immune and metabolic tumor microenvironment (TME) of most solid tumors adversely affect the antitumor efficacy of various treatments, which is an urgent issue to be solved in clinical cancer therapy. In this study, a mitochondrial localized in situ self-assembly system is constructed to remodel the TME by improving immunogenicity and disrupting the metabolic plasticity of cancer cells. The peptide-based drug delivery system can be pre-assembled into nanomicelles in vitro and form functional nanofibers on mitochondria through a cascade-responsive process involving reductive release, targeted enrichment, and in situ self-assembly. The organelle-specific in situ self-assemblyeffectively switches the role of mitophagy from pro-survival to pro-death, which finally induces intense endoplasmic reticulum stress and atypical type II immunogenic cell death. Disintegration of the mitochondrial ultrastructure also impedes the metabolic plasticity of tumor cells, which greatly promotes the immunosuppresive TME remodeling into an immunostimulatory TME. Ultimately, the mitochondrial localized in situ self-assembly system effectively suppresses tumor metastases, and converts cold tumors into hot tumors with enhanced sensitivity to radiotherapy and immune checkpoint blockade therapy. This study offers a universal strategy for spatiotemporally controlling supramolecular self-assembly on sub-organelles to determine cancer cell fate and enhance cancer therapy., (© 2024 Wiley‐VCH GmbH.)

Hepatic encephalopathy (HE) is often associated with endogenous serotonin (5-HT) disorders. However, the reason for elevated brain 5-HT levels due to liver failure remains unclear. This study aimed to investigate the mechanism by which liver failure increases brain 5-HT levels and the role in behavioral abnormalities in HE. Using bile duct ligation (BDL) rats as a HE model, we verified the elevated 5-HT levels in the cortex but not in the hippocampus and striatum, and found that this cortical 5-HT overload may be caused by BDL-mediated inhibition of UDP-glucuronosyltransferase 1A6 (UGT1A6) expression and activity in the cortex. The intraventricular injection of the UGT1A6 inhibitor diclofenac into rats demonstrated that the inhibition of brain UGT1A6 activity significantly increased cerebral 5-HT levels and induced HE-like behaviors. Co-immunofluorescence experiments demonstrated that UGT1A6 is primarily expressed in astrocytes. In vitro studies confirmed that NH 4 Cl activates the ROS-ERK pathway to downregulate UGT1A6 activity and expression in U251 cells, which can be reversed by the oxidative stress antagonist N-acetyl-l-cysteine and the ERK inhibitor U0126. Silencing Hepatocyte Nuclear Factor 4α (HNF4α) suppressed UGT1A6 expression whilst overexpressing HNF4α increased Ugt1a6 promotor activity. Meanwhile, both NH 4 Cl and the ERK activator TBHQ downregulated HNF4α and UGT1A6 expression. In the cortex of hyperammonemic rats, we also found activation of the ROS-ERK pathway, decreases in HNF4α and UGT1A6 expression, and increases in brain 5-HT content. These results prove that the ammonia-mediated ROS-ERK pathway activation inhibits HNF4α expression to downregulate UGT1A6 expression and activity, thereby increasing cerebral 5-HT content and inducing manic-like HE symptoms. This is the first study to reveal the mechanism of elevated cortical 5-HT concentration in a state of liver failure and elucidate its association with manic-like behaviors in HE., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device's soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention., (© 2024. The Author(s).)

Human action intent recognition has become increasingly dependent on computational accuracy, real-time responsiveness, and model lightness. Model selection, data filtering, and experimental design are three critical factors for the recognition of human intention in research. However, the performance of machine learning algorithms can vary depending on factors such as sensor location, the number of sensors used, channel selection, and dimensional combinations. Moreover, the collection of adequate and balanced data in such scenarios can be challenging. To address this issue, we present a comparative analysis of 12 commonly used machine learning algorithms for human action intention recognition. The synthetic minority oversampling technique is applied to fill in missing data. Traversing all possible combinations would require conducting 686 experiments, which is a daunting task in terms of both cost and efficiency. To tackle this challenge, we employ an orthogonal experiment design based on the Quasi-horizontal method. Our analysis indicates that lightGBM outperforms other algorithms in recognizing eight human daily activities. Furthermore, we conduct a polar difference and variance analysis based on a comprehensive balanced multi-metric orthogonal experiment for lightGBM using various sensor combinations and dimensions. The optimal combinations of different sensor numbers in terms of position, channel, and dimension are derived using this approach. Notably, our experimental design reduces the number of experiments required to only 49 times., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The acidosis anti-tumor therapy, based on the altered energy metabolism pathway of tumor cells, has been proposed as an attractive method for cancer selective treatment. However, the strategy of inducing tumor acidosis by using a single drug to simultaneously inhibit both lactate efflux and consumption has not been reported yet. Herein, an in situ enzyme-instructed self-assembly (EISA) system was rationally fabricated to induce tumor acidosis apoptosis for cancer selective therapy. Depending on the sequential effect of the in situ EISA system, the targeted drug was successively distributed on the membrane and intracellular, inhibiting MCT4 mediated lactate efflux and mitochondrial tricarboxylic acid (TCA) cycle mediated lactate consumption, respectively. Through the dual obstruction of lactate metabolism to trigger tumor acidosis, the in situ EISA nanomedicine showed selective growth and migration inhibition against cancer cells. In addition, the nanomedicine also displayed a radio-sensitization effect in vitro due to causing the mitochondrial dysfunction, and exhibited a prominent synergistic chemo-radiotherapy anti-tumor performance in vivo. Accordingly, this work demonstrated that the in situ EISA system could endow the LND with sequential-dual effects to induce tumor acidosis, which may provide an enlightening strategy for anticancer drug delivery and cancer selective therapy. STATEMENT OF SIGNIFICANCE: With the help of the sequential effect of in situ EISA , the serial attack of LND against different targets was effectively realized to induce tumor acidosis and combined chemo-radiotherapy, implying the importance of the relationship between structure and function, which could offer a distinctive inspiration for future drug delivery system design and anti-tumor application., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

LHPP (Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase) is a protein histidine phosphatase that modulates a hidden posttranslational modification called histidine phosphorylation. LHPP also acts as a tumor suppressor, which plays a pivotal role in various cellular processes. However, whether LHPP participates in the regulation of invertebrate's immunity is still unknown. Here we characterized a LHPP homolog in P. vannamei (designated Pv LHPP), with a 807 bp length of open reading frame (ORF) encoding a putative protein of 268 amino acids. Sequence analysis revealed that Pv LHPP contains a typical hydrolase 6 and hydrolase-like domain, which was conserved from invertebrate to vertebrate. Pv LHPP was ubiquitously expressed in tissues and induced in hemocyte and hepatopancreas by Vibrio parahaemolyticus, Streptococcus iniae and white spot syndrome virus (WSSV) challenge, indicating that Pv LHPP participated in the immune responses. Moreover, silencing of Pv LHPP followed by V. parahaemolyticus inhibited hemocyte apoptosis. This study enriches our current insight on shrimp immunity, and provides novel perspective to understand immune-regulatory role of Pv LHPP., Competing Interests: The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (© 2023 The Author(s).)

Hierarchical self-assembly based on peptides in nature is a multi-component interaction process, providing a broad platform for various bionanotechnological applications. However, the study of controlling the hierarchical structure transformation via the cooperation rules of different sequences is still rarely reported. Herein, we report a novel strategy of achieving higher hierarchical structures through cooperative self-assembly of hydrophobic tripeptides with reverse sequences. We unexpectedly found that Nap-FVY and its reverse sequence Nap-YVF self-assembled into nanospheres, respectively, while their mixture formed nanofibers, obviously exhibiting a low-to-high hierarchical structure transformation. Further, this phenomenon was demonstrated by the other two collocations. The cooperation of Nap-VYF and Nap-FYV afforded the transformation from nanofibers to twisted nanoribbons, and the cooperation of Nap-VFY and Nap-YFV realized the transformation from nanoribbons to nanotubes. The reason may be that the cooperative systems in the anti-parallel β-sheet conformation created more hydrogen bond interactions and in-register π-π stacking, promoting a more compact molecular arrangement. This work provides a handy approach for controlled hierarchical assembly and the development of various functional bionanomaterials.

During growth and aging, the role of the hippocampus in memory depends on its interactions with related brain regions. Particularly, two subregions, anterior hippocampus (aHipp) and posterior hippocampus (pHipp), play different and critical roles in memory processing. However, age-related changes of hippocampus subregions on structure and function are still unclear. Here, we investigated age-related structural and functional characteristics of 106 participants (7-85 years old) in resting state based on fractional anisotropy (FA) and functional connectivity (FC) in aHipp and pHipp in the lifespan. The correlation between FA and FC was also explored to identify the coupling. Furthermore, the Wechsler Abbreviated Scale of Intelligence (WASI) was used to explore the relationship between cognitive ability and hippocampal changes. Results showed that there was functional separation and integration in aHipp and pHipp, and the number of functional connections in pHipp was more than that in aHipp across the lifespan. The age-related FC changes showed four different trends (U-shaped/inverted U-shaped/linear upward/linear downward). And around the age of 40 was a critical period for transformation. Then, FA analyses indicated that all effects of age on the hippocampal structures were nonlinear, and the white matter integrity of pHipp was higher than that of aHipp. In the functional-structural coupling, we found that the age-related FA of the right aHipp (aHipp.R) was negatively related to the FC. Finally, through the WASI, we found that the age-related FA of the left aHipp (aHipp.L) was positively correlated with verbal IQ (VERB) and vocabulary comprehension (VOCAB.T), the FA of aHipp.R was only positively correlated with VERB, and the FA of the left pHipp (pHipp.L) was only positively correlated with VOCAB.T. These FC and FA results supported that age-related normal memory changes were closely related to the hippocampus subregions. We also provided empirical evidence that memory ability was altered with the hippocampus, and its efficiency tended to decline after age 40., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 Jianling Tan et al.)

Background: Numerous microorganisms are found in aquaculture ponds, including several pathogenic bacteria. Infection of cultured animals by these pathogens results in diseases and metabolic dysregulation. However, changes in the metabolic profiles that occur at different infection stages in the same ponds and how these metabolic changes can be modulated by exogenous metabolites in Penaeus vannamei remain unknown., Results: Here, we collected gastrointestinal tract (GIT) samples from healthy, diseased, and moribund P. vannamei in the same aquaculture pond for histological, metabolic, and transcriptome profiling. We found that diseased and moribund shrimp with empty GITs and atrophied hepatopancreas were mainly infected with Vibrio parahaemolyticus and Vibrio harveyi. Although significant dysregulation of crucial metabolites and their enzymes were observed in diseased and moribund shrimps, diseased shrimp expressed high levels of taurine and taurine metabolism-related enzymes, while moribund shrimp expressed high levels of hypoxanthine and related metabolism enzymes. Moreover, a strong negative correlation was observed between taurine levels and the relative abundance of V. parahaemolyticus and V. harveyi. Besides, exogenous taurine enhanced shrimp survival against V. parahaemolyticus challenge by increasing the expression of key taurine metabolism enzymes, mainly, cysteine dioxygenase (CDO) and cysteine sulfinic acid decarboxylase (CSD)., Conclusions: Our study revealed that taurine metabolism could be modulated by exogenous supplementation to improve crustacean immune response against pathogenic microbes. Video Abstract., (© 2022. The Author(s).)

Monitoring sleep conditions is of importance for sleep quality evaluation and sleep disease diagnosis. Accurate respiration detection provides key information about sleep conditions. Here, we propose a perforated temperature sensor that can be worn below the nasal cavity to monitor breath. The sensing system consists of two perforated temperature sensors, signal conditioning circuits, a transmission module, and a supporting analysis algorithm. The perforated structure effectively enhances the sensitivity of the system and shortens the response time. The sensor's response time is 0.07 s in air and sensitivity is 1.4‱°C -1 . The device can achieve a monitoring respiratory temperature range between normal room temperature and 40 °C. The simple and standard micromachining process ensures low cost and high reproducibility. We achieved the monitoring of different breathing patterns, such as normal breathing, panting, and apnea, which can be applied to sleep breath monitoring and exercise information recording.

What Is Already Known About This Topic?: Rehabilitation is an essential part of achieving health for all, whereas the estimates of rehabilitation needs, especially for elderly individuals in China, are not clear., What Is Added by This Report?: Compared with 1990, the prevalence and years of life lived with disability for health conditions in need of rehabilitation in China increased by 71.3% and 77.0% in 2019, respectively, at a rate much higher than the global average., What Are the Implications for Public Health Practices?: This study mainly presents scientific data and a systematic analysis of the current state and challenges of rehabilitation needs for elderly individuals (aged 60 and above) in China based on the World Health Organization Rehabilitation Need Estimator., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2022.)

As it is closely associated with tumor proliferation, metastasis, and the immunosuppressive microenvironment, the dysfunctional Hippo pathway has become an extremely attractive target for treating multiple cancers. However, to date, the corresponding chemotherapeutic nanomedicines have not been developed. Herein, a supramolecular self-delivery nanomedicine with in situ transforming capacity was tailor-constructed for Hippo-pathway restoration, and its inhibitory effect against tumor growth and metastasis was investigated in a highly aggressive triple-negative breast cancer (TNBC) model. Stimulated by overexpressed glutathione (GSH) and esterase in cancer cells, the self-assembled nanomedicine transformed from inactive nanospheres to active nanofibers conjugating tyrosvaline and spatiotemporally synchronously released the covalently linked flufenamic acid in situ , together activating the maladjusted Hippo pathway by simultaneously acting on different targets upstream and downstream. The transcriptional expression of Yes-associated protein (YAP) and related growth-promoted genes were significantly reduced, finally significantly repressing the proliferation and metastasis of cancer cells. Additionally, the Hippo-pathway restoration showed an excellent radiosensitization effect, making the targeted therapy combined with radiotherapy display a prominent synergistic in vivo anticancer effect against TNBC. This work reports a specifically designed smart nanomedicine to restore the function of the Hippo pathway and sensitize radiotherapy, providing an attractive paradigm for targeted drug delivery and cancer combination therapy.

H + intercalation, as a critical battery chemistry, enables electrodes' high rate performance due to the fast diffusion kinetics of H + . In this work, more water molecules are introduced into δ-MnO 2 by the protonation of δ-MnO 2 with abundant oxygen vacancies. Benefiting from the structure with a close arrangement of water molecules in interlayers, the Grotthuss transport of proton is achieved in the energy storage of the δ-MnO 2 cathode. As a result, the δ-MnO 2 cathode exhibits an ultrahigh rate performance with a capacity of 368.1 mAh g -1 at 0.5 A g -1 and 83.4 mAh g -1 at 50 A g -1 , which has a capacity retention of 73% after 1100 cycles at 10 A g -1 . The study of the storage mechanism reveals that the Grotthuss intercalation of proton predominates the storage process, which empowers the cathode with high rate performance.

Radiotherapy is one of the conventional tumor treatments, while its abscopal therapeutic efficacy is severely hampered by the immunosuppressive tumor microenvironment. To address this challenge, we herein report on the morphology-adaptable peptide-based therapeutics for efficiently reversing the immunosuppression in the combinatorial radio-immunotherapy through simultaneous checkpoint blocking and induction of immunogenic cell death. The peptide-based therapeutics were created via co-assembling a pentapeptide containing a 4-amino proline residue with its derivatives containing IDO-1 inhibitor NLG919. The resulting therapeutics underwent pH-adaptable morphological transformation between nanofibrils and nanoparticles and released NLG919 upon GSH cleavage. In vivo studies confirmed that the pH-adaptable morphologies of the therapeutics facilitated their tumor accumulation and retention at tumor sites compared to morphology-persistent counterparts, thus resulting in efficient delivery of IDO-1 inhibitors. Simultaneously treating the tumor-bearing mice with the therapeutics and external γ-ray radiation boosted the tumor immunogenicity via inducing ICD cascade of the tumor cells and reverse the immunosuppressive tumor microenvironment due to the inhibition of IDO-1 for depletion of tryptophan. Our findings strongly demonstrate that the morphology-adaptable peptide-based therapeutics exhibit the capability to reverse the immunosuppressive tumor microenvironment during irradiation, thus providing a new strategy for the combinatorial radio-immunotherapy., (Copyright © 2021. Published by Elsevier B.V.)

Metal oxides are widely employed in heterogeneous catalysis, but it remains challenging to determine their exact structure and understand the reaction mechanisms at the molecular level due to their structural complexity, in particular for binary oxides. This paper describes the observation of the strong electronic interaction between In 2 O 3 and monoclinic ZrO 2 (m-ZrO 2 ) by quasi-in-situ XPS experiments combined with theoretical studies, which leads to support-dependent methanol selectivity. In 2 O 3 /m-ZrO 2 exhibits methanol selectivity up to 84.6% with a CO 2 conversion of 12.1%. Moreover, at a wide range of temperatures, the methanol yield of In 2 O 3 /m-ZrO 2 is much higher than that of In 2 O 3 /t-ZrO 2 (t-: tetragonal), which is due to the high dispersion of the In-O-In structure over m-ZrO 2 as determined by in situ Raman spectra. The electron transfer from m-ZrO 2 to In 2 O 3 is confirmed by XPS and DFT calculations and improves the electron density of In 2 O 3 , which promotes H 2 dissociation and hydrogenation of formate intermediates to methanol. The concept of the electronic interaction between an oxide and a support provides guidelines to develop hydrogenation catalysts.

Zika virus (ZIKV) is a flavivirus linked to multiple birth defects including microcephaly, known as congenital ZIKV syndrome. The identification of host factors involved in ZIKV replication may guide efficacious therapeutic interventions. In genome-wide transcriptional studies, we found that ZIKV infection triggers aryl hydrocarbon receptor (AHR) activation. Specifically, ZIKV infection induces kynurenine (Kyn) production, which activates AHR, limiting the production of type I interferons (IFN-I) involved in antiviral immunity. Moreover, ZIKV-triggered AHR activation suppresses intrinsic immunity driven by the promyelocytic leukemia (PML) protein, which limits ZIKV replication. AHR inhibition suppressed the replication of multiple ZIKV strains in vitro and also suppressed replication of the related flavivirus dengue. Finally, AHR inhibition with a nanoparticle-delivered AHR antagonist or an inhibitor developed for human use limited ZIKV replication and ameliorated newborn microcephaly in a murine model. In summary, we identified AHR as a host factor for ZIKV replication and PML protein as a driver of anti-ZIKV intrinsic immunity.

The aim of the present study was to evaluate the expression levels of the aryl hydrocarbon receptor (AHR) and its target gene CYP1B1 and to correlate their expression with Wnt5a/b-β-catenin, the CD44 + /CD24 (-/low) cancer stem cell (CSC) subset and factors associated with poor prognosis in inflammatory breast cancer (IBC) and non-IBC patients. The methods of analysis used were quantitative real-time PCR, western blotting, immunohistochemistry and flow cytometry. Compared to non-IBC tissues, IBC tissues exhibited the overexpression of AHR and its target gene/protein CYP1B1. AHR and CYP1B1 mRNA levels were associated with the poor clinical prognosis markers tumour grade, lymphovascular invasion, cell proliferation and lymph node metastasis. Furthermore, AHR expression correlated with the expression of Wnt5a/b and β-catenin signalling molecules, and Wnt5a mRNA expression was downregulated in the SUM149 human IBC cell line and the MDA-MB-231 non-IBC cell line upon inhibition of AHR. AHR gene knockout (CRISPR-Cas9) inhibits CYP1B1 and Wnt5a expression in the IBC cell line. The CD44 + /CD24 (-/low) subset was significantly correlated with the expression of AHR, CYP1B1, Wnt5a/b and β-catenin in IBC tissues. The overexpression of AHR and its target CYP1B1 correlated with the expression of Wnt5a/b and β-catenin, CSCs, and poor clinical prognostic factors of IBC. Thus, targeting AHR and/or its downstream target molecules CYP1B1 and Wnt5a/b may represent a therapeutic approach for IBC.

Purpose: The standard treatment for mid or low locally advanced rectal cancer is neoadjuvant therapy followed by surgical resection. Laparoscopic surgery has recently been applied for the treatment of rectal cancer. However, few studies have reported the outcomes of laparoscopic surgery for elderly patients with rectal cancer after neoadjuvant therapy. This study aimed to investigate the short- and long-term outcomes of laparoscopic surgery for elderly patients with rectal cancer after neoadjuvant therapy., Methods: Patients received a total dose of 50.4 Gy over 5.5 weeks (45 Gy in 25 fractions to the pelvid and 5.4 Gy boost in 3 fractions to the primary tumor). Laparoscopic surgery for rectal cancer after neoadjuvant therapy was performed at our hospital on 89 elderly patients aged 75 years or older (the elderly group) from January 2008 to January 2016. Outcomes of the 89 patients were compared to those of 269 patients younger than 75 years enrolled during the same time period (the nonelderly group)., Results: Compared with the nonelderly group, the Charlson comorbidity index (CCI) and American Society of Anesthesiologists (ASA) scores were higher in the elderly group. For short-term outcomes, there were no statistically significant differences. Differences between the two groups in the 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were not statistically significant., Conclusion: Although the CCI was higher in elderly patients than in the nonelderly patients, laparoscopic surgery after neoadjuvant therapy was safe and effective in elderly patients with rectal cancer. Therefore, in the absence of any contraindications, laparoscopic surgery after neoadjuvant therapy is an appropriate treatment approach for elderly patients with rectal cancer.

A novel vaccine adjuvant based on a supramolecular hydrogel of a D-tetra-peptide is reported. Antigens can be easily incorporated into the hydrogel by a vortex or by gently shaking before injection. The vaccines can stimulate strong CD8+ T-cell responses, which significantly inhibits tumor growth. This novel adjuvant is expected to enable a wide range of sub-unit vaccines and help the production of antibodies., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The endogenous ligand-activated aryl hydrocarbon receptor (AHR) plays an important role in numerous biologic processes. As the known number of AHR-mediated processes grows, so too does the importance of determining what endogenous AHR ligands are produced, how their production is regulated, and what biologic consequences ensue. Consequently, our studies were designed primarily to determine whether ER - /PR - /Her2 - breast cancer cells have the potential to produce endogenous AHR ligands and, if so, how production of these ligands is controlled. We postulated that: 1) malignant cells produce tryptophan-derived AHR ligand(s) through the kynurenine pathway; 2) these metabolites have the potential to drive AHR-dependent breast cancer migration; 3) the AHR controls expression of a rate-limiting kynurenine pathway enzyme(s) in a closed amplification loop; and 4) environmental AHR ligands mimic the effects of endogenous ligands. Data presented in this work indicate that primary human breast cancers, and their metastases, express high levels of AHR and tryptophan-2,3-dioxygenase (TDO); representative ER - /PR - /Her2 - cell lines express TDO and produce sufficient intracellular kynurenine and xanthurenic acid concentrations to chronically activate the AHR. TDO overexpression, or excess kynurenine or xanthurenic acid, accelerates migration in an AHR-dependent fashion. Environmental AHR ligands 2,3,7,8-tetrachlorodibenzo[p]dioxin and benzo[a]pyrene mimic this effect. AHR knockdown or inhibition significantly reduces TDO2 expression. These studies identify, for the first time, a positive amplification loop in which AHR-dependent TDO2 expression contributes to endogenous AHR ligand production. The net biologic effect of AHR activation by endogenous ligands, which can be mimicked by environmental ligands, is an increase in tumor cell migration, a measure of tumor aggressiveness., (Copyright © 2016 by The Author(s).)

HNF-4alpha (hepatocyte nuclear factor-4alpha) is a key regulator of liver-specific gene expression. To understand the mechanisms governing the regulation of HNF-4alpha function during the APR (acute-phase response), the effects of transcription co-activators, including p300, PGC-1alpha (peroxisome-proliferator-activated receptor-gamma co-activator-1alpha) and SRC (steroid receptor co-activator)-1alpha were investigated in an injury cell model. We have shown previously that the HNF-4alpha-sensitive APR genes ApoB (apolipoprotein B), TTR (transthyretin) and alpha1-AT (alpha1-antitrypsin) were regulated at the DNA binding and transcriptional levels after cytokine stimulation. We now show that co-activators have a differential impact on the transactivation of HNF-4alpha-sensitive genes via HNF-4alpha-binding sites in ApoB, TTR or alpha1-AT promoters. PGC-1alpha strongly enhances the transactivation of ApoB and alpha1-AT and, to a lesser extent, of TTR, whereas SRC-1alpha and p300 only have a weak or no effect on these three genes. More importantly, it was found that PGC-1alpha has a novel role in the modulation of the binding ability of HNF-4alpha in response to cytokine treatment. Using in vitro and in vivo approaches, electrophoretic mobility-shift and chromatin immunoprecipitation assays, we demonstrate that the reduced HNF-4alpha-DNA binding ability induced by cytokines is eliminated by overexpression of PGC-1alpha. Cytokine treatment does not significantly alter the protein levels of HNF-4alpha and PGC-1alpha, but it does reduce the recruitment of PGC-1alpha to HNF-4alpha-binding sites and thereby decreases transcriptional activity. These results establish the importance of PGC-1alpha for HNF-4alpha function and describe a new HNF-4alpha-dependent regulatory mechanism that is involved in the response to injury.