Search

Abstract: Photoelectrochemical water splitting has attracted increasing attention recently in the perspective of clean and sustainable energy economy. Herein, we reported the synthesis of NiO functionalized Mo doped BiVO4 (denoted as NiO/Mo:BiVO4) nanobelts and their enhanced photoelectrochemical activity for efficient water oxidation. The prepared NiO/Mo:BiVO4 p–n junction structure showed much higher water splitting activity than the pristine BiVO4 and Mo:BiVO4. Such obvious enhancement are due to the increased donor density by doping with Mo and fast separation of the photoexcited electron–hole pairs by the novel p–n junction composite structure. Under light irradiation, photoexcited holes in the conduction band (CB) of Mo:BiVO4 will conveniently transfer to the p-type NiO with the effect of the inner electric field. Meanwhile, the holes would oxidize the water into oxygen and the electrons transfer to the counter electrode (Pt electrode) to produce hydrogen. This novel p–n junction structure could open up new opportunities to develop high-performance photoanode for water splitting. [Copyright &y& Elsevier]

Food contamination from microbial deterioration requires the development of potent antimicrobial peptides (AMPs). The deployment of approved AMPs as dietary preservatives is limited due to barriers such as instability, toxicity, and high synthetic costs. This exploration utilizes the primary structural elements of the Trp-pocket backbone to engineer a series of β-hairpin AMPs (XWRWRPGXKXXR-NH 2 , X representing I, V, F, and/or L). Peptides WpLF, with Phe as X and Leu arranged at the 11th position, demonstrated exceptional selectivity index (SI = 123.08) and sterilization effects both in vitro and in vivo. WpLF consistently exhibited stable bacteriostasis, regardless of physiological salts, serum, and extreme pH. Mechanistic analysis indicated that the peptide penetrates microbial cell membranes, inducing membrane disruption, thereby impeding drug resistance evolution. Conclusively, AMPs engineered by the Trp-pocket skeleton hold substantial potential as innovative biological preservatives in food preservation, providing valuable insights for sustainable and safe peptide-based food preservatives. [Display omitted] • Trp-pocket backbone is successfully applied in β-hairpin antimicrobial peptides. • Optimal WpLF exhibits broad-spectrum bacteriostasis and superb biocompatibility. • WpLF targets microbial membrane integrity thus impeding drug resistance evolution. • WpLF proves stable efficacy in physiological barriers and peritonitis-sepsis model. • WpLF offers potential as a food preservative by suppressing bacterial proliferation. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are small molecular peptides widely existing in the innate immunity of organisms, serving as the first line of defense. Natural AMPs possess various biological activities and are difficult to develop drug resistance. However, they are easily broken down by digestive enzymes in the body. In recent years, increasing methods have been reported to enhance the stability of AMPs, including incorporation of unnatural amino acids, chemical modifications, strategic avoidance of enzyme cleavage sites, cyclization, and nano peptide design. This review summarizes the methods for improving the stability of AMPs against protease degradation, aiming to provide references for further research in this field.

Aims: The unstable antimicrobial activity of antimicrobial peptides (AMPs) under physiological conditions (especially the degradation instigated proteases) seems to be a persistent impediment for their successful implementation in clinical trials. Consequently, our objective was to devise AMP engineering frameworks that could sustain robust antibacterial efficacy within physiological environments., Methods: In this work, we harvested AMPs with stable antimicrobial activity under the physiological barriers through the combination of idealized amphiphiles and trypsin inhibitors., Results: We screened and identified the lead peptides IK3-A and IK3-S, which showed potent activity against Gram-negative bacteria, including multidrug-resistant (MDR) bacteria, and exhibited promising biocompatibility with mammalian cells. Remarkably, IK3-A and IK3-S maintained sustained antibacterial potency under physiological salts, serum, and protease conditions. Furthermore, both IK3-A and IK3-S kill Gram-negative bacteria by attacking the bacterial cell membrane and inducing oxidative damage (at high concentrations). Crucially, IK3-A and IK3-S have optimal safety and efficacy in mice., Conclusions: This is the first work to compare the effects of different trypsin inhibitors on the resistance of AMPs to protease hydrolysis on the same sequence platform. In conclusion, these findings provide guidance for the molecular design of AMPs with stable antibacterial activity under physiological conditions and facilitates the process of clinical translation of AMPs as antimicrobial biomaterials against MDR bacteria. Moreover, this may stimulate a more general interest in protease inhibitors as molecular scaffolds in the creation of highly stable peptide-based biomaterials., 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 © 2024 Elsevier Ltd. All rights reserved.)

FK506-binding protein 9 (FKBP9) is involved in tumor malignancy by resistance to endoplasmic reticulum (ER) stress, and the up-regulation of FKBP9 is associated with patients' poor prognosis. The current knowledge of the molecular mechanisms is still limited. One previous study showed that FKBP9 could confer glioblastoma cell resistance to ER stress through ASK1-p38 signaling. However, the upstream regulatory mechanism of FKBP9 expression is still indistinct. In this study, we identified the FKBP9 binding proteins using co-immunoprecipitation followed by mass spectrometry. Results showed that FKBP9 interacted with the binding immunoglobulin protein (BiP). BiP bound directly to FKBP9 with high affinity. BiP prolonged the half-life of the FKBP9 protein and stabilized the FKBP9 protein. BiP and FKBP9 protein levels were positively correlated in patients with glioma, and patients with high expression of BiP and FKBP9 showed a worse prognosis. Further studies showed that FKBP9 knockout in genetically engineered mice inhibited intracranial glioblastoma formation and prolonged survival by decreasing cellular proliferation and ER stress-induced CHOP-related apoptosis. Moreover, normal cells may depend less on FKBP9, as shown by the absence of apoptosis upon FKBP9 knockdown in a non-transformed human cell line and overall normal development in homozygous knockout mice. These findings suggest an important role of BiP-regulated FKBP9-associated signaling in glioma progression and the BiP-FKBP9 axis may be a potential therapeutic target for glioma., (© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Emerging studies have focused on ways to treat cancers by modulating T cell activation. However, whether B cell receptor signaling in the tumor microenvironment (TME) can be harnessed for immunotherapy is unclear. Here, we report that an Asia-specific variant of human IgG1 containing a Gly396 to Arg396 substitution (hIgG1-G396R) conferred improved survival of patients with colorectal cancer (CRC). Mice with knockin of the murine functional homolog mIgG2c-G400R recapitulated the alleviated tumorigenesis and progression in murine colon carcinoma models. Immune profiling of the TME revealed broad mobilizations of IgG1+ plasma cells, CD8+ T cells, CD103+ DCs, and active tertiary lymphoid structure formation, suggesting an effective antitumor microenvironment in hIgG1-G396R CRC patients. Mechanistically, this variant potentiated tumor-associated antigen-specific (TAA-specific) plasma cell differentiation and thus antibody production. These elevated TAA-specific IgG2c antibodies in turn efficiently boosted the antibody-dependent tumor cell phagocytosis and TAA presentation to effector CD8+ T cells. Notably, adoptive transfer of TAA-specific class-switched memory B cells harboring this variant exhibited therapeutic efficacy in murine tumor models, indicating their clinical potential. All these results prompted a prospective investigation of hIgG1-G396R in patients with CRC as a biomarker for clinical prognosis and demonstrated that manipulating the functionality of IgG1+ memory B cells in tumors could improve immunotherapy outcomes.

Background: GINS4, an indispensable component of the GINS complex, is vital for a variety of cancer. However, no known empirical research has focused on exploring relationships between GINS4 and glioma. Thus, this study aims to understand and explain the role of GINS4 in glioma., Method: First, we used the data in the CGGA, TCGA, GEO, GEPIA, and HPA databases to explore the expression level of GINS4 in glioma, the correlation between GINS4 expression and the clinical features of glioma, its impact on the survival of glioma patients, and verified the analysis results through RT-qPCR, IHC, and meta-analysis. Subsequently, GSEA enrichment analysis is used to find the potential molecular mechanism of GINS4 to promote the malignant process of glioma and the anti-glioma drugs that may target GINS4 screened by CMap analysis. Moreover, we further explored the influence of the GINS4 expression on the immune microenvironment of glioma patients through the TIMER database., Results: Our results suggested that GINS4 was elevated in glioma, and the overexpression of GINS4 was connected with a vast number of clinical features. The next, GINS4 as an independent prognostic factor, which can result in an unfavorable prognosis of glioma. Once more, GINS4 may be participating in the oncogenesis of glioma through JAK-STAT signaling pathways, etc. 6-thioguanine, Doxazosin, and Emetine had potential value in the clinical application of drugs targeting GINS4. Finally, the expression exhibited a close relationship with some immune cells, especially Dendritic cells., Conclusion: GINS4 is an independent prognostic factor that led to a poor prognosis of glioma. The present study revealed the probable underlying molecular mechanisms of GINS4 in glioma and provided a potential target for improving the prognosis of glioma., (© 2021. The Author(s).)

Emotional reactions to movies are typically similar between people. However, depressive symptoms decrease synchrony in brain responses. Less is known about the effect of depressive symptoms on intersubject synchrony in conscious stimulus-related processing. In this study, we presented amusing, sad and fearful movie clips to dysphoric individuals (those with elevated depressive symptoms) and control participants to dynamically rate the clips' valences (positive vs. negative). We analysed both the valence ratings' mean values and intersubject correlation (ISC). We used electrodermal activity (EDA) to complement the measurement in a separate session. There were no group differences in either the EDA or mean valence rating values for each movie type. As expected, the valence ratings' ISC was lower in the dysphoric than the control group, specifically for the sad movie clips. In addition, there was a negative relationship between the valence ratings' ISC and depressive symptoms for sad movie clips in the full sample. The results are discussed in the context of the negative attentional bias in depression. The findings extend previous brain activity results of ISC by showing that depressive symptoms also increase variance in conscious ratings of valence of stimuli in a mood-congruent manner., (© 2021. The Author(s).)

Previous studies have associated visual working memory (VWM) capacity with the use of internal attention. Retrocues, which direct internal attention to a particular object or feature dimension, can improve VWM performance (i.e., retrocue benefit, RCB). However, so far, no study has investigated the relationship between VWM capacity and the magnitudes of RCBs obtained from object-based and dimension-based retrocues. The present study explored individual differences in the magnitudes of object- and dimension-based RCBs and their relationships with VWM capacity. Participants completed a VWM capacity measurement, an object-based cue task, and a dimension-based cue task. We confirmed that both object- and dimension-based retrocues could improve VWM performance. We also found a significant positive correlation between the magnitudes of object- and dimension-based RCB indexes, suggesting a partly overlapping mechanism between the use of object- and dimension-based retrocues. However, our results provided no evidence for a correlation between VWM capacity and the magnitudes of the object- or dimension-based RCBs. Although inadequate attention control is usually assumed to be associated with VWM capacity, the results suggest that the internal attention mechanism for using retrocues in VWM retention is independent of VWM capacity.

Sustained attention encompasses a cascade of fundamental functions. The human ability to implement a sustained attention task is supported by brain networks that dynamically formed and dissolved through oscillatory synchronization. The decrement of vigilance induced by prolonged task engagement affects sustained attention. However, little is known about which stage or combinations are affected by vigilance decrement. Here, we applied an analysis framework composed of weighted phase lag index (wPLI) and tensor component analysis (TCA) to an EEG dataset collected during 80 min sustained attention task to examine the electrophysiological basis of such effect. We aimed to characterize the phase-coupling networks to untangle different phases involved in sustained attention and study how they are modulated by vigilance decrement. We computed the time-frequency domain wPLI from each block and subject and constructed a fourth-order tensor, containing the time, frequency, functional connectivity (FC), and blocks × subjects. This tensor was subjected to the TCA to identify the interacted and low-dimensional components representing the frequency-specific dynamic FC (fdFC). We extracted four types of neuromakers during a sustained attention task, namely the pre-stimulus alpha right-lateralized parieto-occipital FC, the post-stimulus theta fronto-parieto-occipital FC, delta fronto-parieto-occipital FC, and beta right/left sensorimotor FCs. All these fdFCs were impaired by vigilance decrement. These fdFCs, except for the beta left sensorimotor network, were restored by rewards, although the restoration by reward in the beta right sensorimotor network was transient. These findings provide implications for dissociable effects of vigilance decrement on sustained attention by utilizing the tensor-based framework.

Two hypotheses have been proposed to explain the formation manner for visual working memory (VWM) representations during the consolidation process: an all-or-none process hypothesis and a coarse-to-fine process hypothesis. However, neither the all-or-none process hypothesis nor the coarse-to-fine process hypothesis can stipulate clearly how VWM representations are formed during the consolidation process. In the current study, we propose a two-stage process hypothesis to reconcile these hypotheses. The two-stage process hypothesis suggests that the consolidation of coarse information is an all-or-none process in the early consolidation stage, while the consolidation of detailed information is a coarse-to-fine process in the late consolidation stage. By systematically manipulating the encoding time of memory stimuli, we asked participants to memorize one (Experiment 1) or two (Experiment 2) orientations in different encoding time intervals. We found that the memory rate increased linearly as the encoding time increased. More importantly, VWM precision remained constant when the encoding time was short, while the precision increased linearly as the encoding time increased when the encoding time was sufficient. These results supported the two-stage process hypothesis, which reconciles previous conflicting findings in the literature.

Background and Objective: It is challenging to conduct real-time identification of myocardial infarction (MI) due to artifact corruption and high dimensionality of multi-lead electrocardiogram (ECG). In the present study, we proposed an automated single-beat MI detection and localization system using dual-Q tunable Q-factor wavelet transformation (Dual-Q TQWT) denoising algorithm., Methods: After denoising and segmentation of ECG, a fourth-order wavelet tensor (leads × subbands × samples × beats) was constructed based on the discrete wavelet packet transform (DWPT), to represent the features considering the information of inter-beat, intra-beat, inter-frequency, and inter-lead. To reduce the tensor dimension and preserve the intrinsic information, the multilinear principal component analysis (MPCA) was employed. Afterward, 84 discriminate features were fed into a classifier of bootstrap-aggregated decision trees (Treebagger). A total of 78 healthy and 328 MI (6 types) records including 57557 beats were chosen from PTB diagnostic ECG database for evaluation., Results: The validation results demonstrated that our proposed MI detection and localization system embedded with Dual-Q TQWT and wavelet packet tensor decomposition outperformed commonly used discrete wavelet transform (DWT), empirical mode decomposition (EMD) denoising methods and vector-based PCA method. With the Treebagger classifier, we obtained an accuracy of 99.98% in beat level and an accuracy of 97.46% in record level training/testing for MI detection. We also achieved an accuracy of 99.87% in beat level and an accuracy of 90.39% in record level for MI localization., Conclusion: Altogether, the automated system brings potential improvement in automated detection and localization of MI in clinical practice., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interests exist., (Copyright © 2019. Published by Elsevier B.V.)

Viral infection triggers the formation of mitochondrial antiviral signaling protein (MAVS) aggregates, which potently promote immune signaling. Autophagy plays an important role in controlling MAVS-mediated antiviral signaling; however, the exact molecular mechanism underlying the targeted autophagic degradation of MAVS remains unclear. Here, we investigated the mechanism by which RNF34 regulates immunity and mitophagy by targeting MAVS. RNF34 binds to MAVS in the mitochondrial compartment after viral infection and negatively regulates RIG-I-like receptor (RLR)-mediated antiviral immunity. Moreover, RNF34 catalyzes the K27-/K29-linked ubiquitination of MAVS at Lys 297, 311, 348, and 362 Arg, which serves as a recognition signal for NDP52-dependent autophagic degradation. Specifically, RNF34 initiates the K63- to K27-linked ubiquitination transition on MAVS primarily at Lys 311, which facilitates the autophagic degradation of MAVS upon RIG-I stimulation. Notably, RNF34 is required for the clearance of damaged mitochondria upon viral infection. Thus, we elucidated the mechanism by which RNF34-mediated autophagic degradation of MAVS regulates the innate immune response, mitochondrial homeostasis, and infection., (© 2019 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Background: Acute liver failure (ALF) is a complicated clinical syndrome associated with high mortality, with liver transplantation as the only treatment option. Treatment of mesenchymal stem cells has shown a potential therapeutic option for acute liver failure. However, the lack of random clinical trials and large non-human primate studies makes it necessary to assess the efficacy and safety in the clinic., Methods: We treated the monkeys with peripheral delivery of human umbilical MSCs (hUC-MSCs) and investigated the role of hUC-MSCs in modulating the progress of acute liver failure., Results: The use of early peripheral infusion of human umbilical cord MSC infusion did not improve liver regeneration or modulate adaptive immunity. However, it significantly suppressed the hepatic aggregation and maturation of circulating monocytes and their IL-6 secretion, greatly improving liver histology, systemic homeostasis, and survival., Conclusions: Our study reveals the critical role of monocyte-derived IL-6 in initiating and accelerating acute liver failure and hUC-MSC treatment can disrupt the development of the inflammatory cascade by inhibiting monocyte activation. Early hUC-MSC treatment disrupts the development of the inflammatory cascade, indicating a potential clinical solution for acute liver failure.

Background: Preprocessed Event-related potential (ERP) data are usually organized in multi-way tensor, in which tensor decomposition serves as a powerful tool for data processing. Due to the limitation of computation burden for multi-way data and the low algorithm performance of stability and efficiency, multi-way ERP data are conventionally reorganized into low-order tensor or matrix before further analysis. However, the reorganization may hamper mode specification and spoil the interaction information among different modes., New Method: In this study, we applied a fifth-order tensor decomposition to a set of fifth-order ERP data collected by exerting proprioceptive stimulus on left and right hand. One of the latest nonnegative CANDECOMP/PARAFAC (NCP) decomposition methods implemented by alternating proximal gradient (APG) was employed. We also proposed an improved DIFFIT method to select the optimal component number for the fifth-order tensor decomposition., Results: By the fifth-order NCP model with a proper component number, the ERP data were fully decomposed into spatial, spectral, temporal, subject and condition factors in each component. The results showed more pairs of components with symmetric activation region in left and right hemisphere elicited by contralateral stimuli on hand., Comparison With Existing Method(s): In our experiment, more interesting components and coherent brain activities were extracted, compared with previous studies., Conclusions: The discovered activities elicited by proprioceptive stimulus are in line with those in relevant cognitive neuroscience studies. Our proposed method has proved to be appropriate and viable for processing high-order EEG data with well-preserved interaction information among all modes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Acute liver failure (ALF) is associated with high mortality, and a poor understanding of the underlying pathophysiology has resulted in a lack of effective treatments so far. Here, using an amatoxin-induced rhesus monkey model of ALF, we panoramically revealed the cellular and molecular events that lead to the development of ALF. The challenged monkeys with toxins underwent a typical course of ALF including severe hepatic injury, systemic inflammation and eventual death. Adaptive immune was not noticeably disturbed throughout the progress of ALF. A systematic examination of serum factors and cytokines revealed that IL-6 increase was the most rapid and drastic. Interestingly, we found that IL-6 was mainly produced by circulating monocytes. Furthermore, ablation of monocyte-derived IL-6 in mice decreased liver injury and systemic inflammation following chemical injection. Our findings reveal a critical role of circulating monocytes in initiating and accelerating ALF, indicating a potential therapeutic target in clinical treatment for ALF., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Triptolide (TP) has been used in the treatment of rheumatoid arthritis (RA), but its mechanism of action is not understood. T-cell activation and associated release of cytokines appear to be major factors in the pathogenesis of RA. The overexpression of T-cell receptor (TCR) variable gene (V gene) fragments can cause the activation and infiltration of autoreactive T cells. This study examines the effects of TP on rats with collagen-induced arthritis (CIA). The levels of interleukin-10 (IL-10) in the serum were examined with ELISA. Compared to the CIA group, the levels of IL-10 were greater in the TP treatment group. Real-time quantitative polymerase chain reaction confirmed that the expression of TCR V beta (BV) 15 and TCR BV19 was increased in the CIA group, whereas in the TP treatment group, the expression was decreased. In this study, TP was found to enhance IL-10 levels and decrease the expression levels of TCR BV15 and TCR BV19. These changes might help explain the effectiveness of TP in the treatment of RA., (Copyright © 2012 Wiley Periodicals, Inc.)