Search

Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut–pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), the facilitation of short-chain fatty acids' (SCFAs) production, and the activation of glucagon-like peptide-1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we discuss research in other disease models that have used probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut–pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis. [ABSTRACT FROM AUTHOR]

Additive manufacturing, particularly the laser powder bed fusion (LPBF) technique, has ushered in a new era of intricate metallic component fabrication, leveraging the exceptional performance of the Ti6Al4V alloy. However, the intricate mechanical behavior of additively manufactured Ti6Al4V, particularly its anisotropic attributes stemming from non-equilibrium microstructures, presents a formidable challenge. In this study, we embark on a comprehensive exploration of the anisotropic mechanical properties exhibited by LPBFed Ti6Al4V alloy. The interplay between microstructure and tensile response is unraveled by integrating experimental investigations with crystal plasticity finite element (CPFE) simulations. The acquired empirical data with CPFE model predictions are harmonized through systematic tensile tests along distinct processing orientations. The results unveil the genesis of plastic anisotropy within the LPBFed Ti6Al4V alloy, ascribed to the emergence of columnar grains meticulously aligned along the building direction, despite the intricate material microstructure inherent to additive manufacturing. These findings collectively furnish a holistic comprehension of the intricate nexus between material attributes and the mechanical manifestations intrinsic to metal components realized through additive manufacturing modalities. [ABSTRACT FROM AUTHOR]

Previous studies examining the relationship between ingroup bias and resource scarcity have produced heterogeneous findings, possibly due to their focus on the allocation of positive resources (e.g. money). This study aims to investigate whether ingroup bias would be amplified or eliminated when perceived survival resources for counteracting negative stimuli are scarce. For this purpose, we exposed the participants and another confederate of the experimenters (ingroup/outgroup member) to a potential threat of unpleasant noise. Participants received some 'relieving resources' to counteract noise administration, the amount of which may or may not be enough for them and the confederate in different conditions (i.e. abundance vs. scarcity). First, a behavioural experiment demonstrated that intergroup discrimination manifested only in the scarcity condition; in contrast, the participants allocated similar amounts of resource to ingroup and outgroup members in the abundance condition, indicating a context‐dependent allocation strategy. This behavioural pattern was replicated in a follow‐up neuroimaging experiment, which further revealed that when contrasting scarcity with abundance, there was higher activation in the anterior cingulate cortex (ACC) as well as stronger functional connectivity of the ACC with the empathy network (including the temporoparietal junction and medial prefrontal cortex) for ingroup compared to outgroup members. We suggest that ACC activation reflects the mentalizing process toward ingroup over outgroup members in the scarcity condition. Finally, the ACC activation level significantly predicted the influence of resource scarcity on ingroup bias in hypothetical real‐life situations according to a follow‐up examination. [ABSTRACT FROM AUTHOR]

The effects of planting ryegrass combined with sludge addition and arbuscular mycorrhizal fungi (AMF) inoculation on organic carbon accumulation in reclaimed mine substrates (RMS) were investigated. A 6-year field experiment was carried out; in the 0–15-cm edaphic layer, a mixed matrix was constructed according to the ratio of fly ash to coal gangue to sludge=1∶6∶3 , with 0.5 kg/m2 of AMF inoculated and ryegrass sowed annually. The particle size, carbon fraction, enzyme activity, AMF-related protein and ryegrass rhizosphere effect of RMS aggregates were monitored regularly. The cumulative contribution of the above factors to organic carbon in RMS was quantitatively explored by path analysis. After reclamation, the texture of reclamation matrix in mining area was improved, the stability of aggregates augmented significantly with the proportion of large aggregates increased gradually. Organic carbon in RMS increased by 1.96 times to 38.12 g/kg ; the contents of total N and available P increased significantly year by year, mainly concentrated in aggregates. Path analysis showed that the underground biomass of ryegrass and 0.5–2-mm aggregates were the two factors with the strongest direct positive effect on organic carbon accumulation in RMS. In addition, available phosphatase and easily extractable glomalin affected the process through complex interaction with each other. A combination of ryegrass-AMF-sludge on a reclamation mining field could improve the quality of RMS through aggregates by promoting the process of soil formation, and ryegrass root growth conducive to organic carbon accumulation. [ABSTRACT FROM AUTHOR]

Immune dysregulation is not only a pathogenic mechanism in systemic lupus erythematosus (SLE) but also a potential cause of the link between SLE and cancer. The current understanding of SLE monocyte-associated biomarkers is limited, and the precise mechanism behind the link between SLE and cancer is uncertain. By using WGCNA and immune infiltration to analyze the GSE72326 dataset, we determined the most pertinent modules for monocytes and discovered eight candidate hub genes from them. The limma software was used to find genes that were differently expressed in SLE. The genes that overlapped between the two were chosen using a Venn diagram as the essential genes related to monocytes in SLE, and the essential genes were verified by several datasets. Correlation analysis and GSEA analysis were used to examine the probable immunological pathways connected to key genes. We examined the expression of hub genes in cancer and their interaction with monocytes using the GEPIA and TIMER databases to understand the significance of essential genes in tumorigenesis. In addition, we performed transcription factor identification. We discovered three biomarkers (IFI30, BLVRA, and RIN2) that are mostly involved in interferon-related signaling pathways and are associated with monocyte-mediated immune responses in SLE. The three important genes are also strongly expressed in a number of malignancies and have a relationship with monocytes. As a result, IFI30, BLVRA, and RIN2 may act as SLE-associated biomarkers of monocytes and as a bridge between SLE and tumors. We proposed that interferon-related signaling pathways might function as possible mediators of cancer risk in SLE. [ABSTRACT FROM AUTHOR]

"Social mindfulness" refers to being thoughtful of others and considering their needs before making decisions, and can be characterized by low-cost and subtle gestures. The present study compared the behavioral and neural responses triggered by observing others' socially mindful/unmindful choices and how these responses were modulated by the social status of the agency. At the behavioral level, observing socially mindful choices made observers feel better, rate the actors as more likable, and behave more cooperatively than did observing socially unmindful choices. Analysis of event-related potentials in the brain revealed that compared with socially unmindful choices, mindful choices elicited more negative feedback-related negativity (FRN). Notably, while this effect of social mindfulness was only significant when the actor's social status was medium and high, it was undetectable when the actor's social status was low. These results demonstrate that the social mindfulness of others can be rapidly detected and processed, as reflected by FRN, even though it does not seem to receive further, more elaborate evaluation. These findings indicated that low-cost cooperative behaviors such as social mindfulness can also be detected and appreciated by our brain, which may result in better mood and more cooperative behaviors in the perceivers. Besides, the perception of social mindfulness is sensitive to important social information, such as social status. [ABSTRACT FROM AUTHOR]

Oncolytic viruses represent a promising therapeutic modality, but they have yet to live up to their therapeutic potential. Safety and efficacy concerns impel us to identify least toxic oncolytic agents that would generate durable and multifaceted anti-tumor immune responses to disrupt the tumors. Here we describe a rational engineered oncolytic herpes virus (OVH) that is a selective killer for targeting tumors, has strong safety records, induces complete regression of tumors in multiple tumor models, and elicits potent antitumor immunity. By far, the potential of OVs in promoting the tumor antigen-specific humoral immune responses remains obscure. In this study, we found that effective treatment by OVH induced immunogenic cell death, which facilitates to elicit humoral immune responses. Depletion experiments revealed that B cells were required for maximal antitumor efficacy of oncolytic immunotherapy. Both serum transfer and antibody treatment experiments revealed that endogenous oncolysis-induced antigen-targeting therapeutic antibodies can lead to systemic tumor regression. Our data demonstrate that tumor-targeting immune modulatory properties confer oncolytic OVH virotherapy as potent immunotherapeutic cancer vaccines that can generate specific and efficacious antitumor humoral responses by eliciting endogenous tumor antigen-targeting therapeutic antibodies in situ, resulting in an efficacious and tumor-specific therapeutic effect. [ABSTRACT FROM AUTHOR]

Predictability has been suggested to modulate both the anticipation and perception of self-pain. Considering the overlapping neural circuits between self-pain and other-pain perceptions, the present study investigated how the predictability of forthcoming pain modulates the anticipation and perception of self-pain and other-pain. We used a balanced, within-participant experimental design in which a visual cue indicating the recipient, intensity and predictability of an upcoming painful electrical stimulation was presented before its delivery. Subjective ratings and electroencephalography activities to the anticipation and perception of self-pain and other-pain were recorded and compared between certain and uncertain conditions. Results showed that predictability affected the perception of self-pain and other-pain in a similar manner such that the differences in behavioral ratings and event-related potentials to high-intensity and low-intensity pain were significantly reduced when the intensity was uncertain. The strengths of predictability-induced modulation of self-pain and other-pain perceptions were positively correlated with each other. Furthermore, predictability also modulated the anticipation of both self-pain and other-pain such that pre-stimulus high-frequency α-oscillation power at sensorimotor electrodes contralateral to the stimulation side was maximally suppressed when anticipating certain high-intensity pain. These findings demonstrate that predictability-induced modulation on pain anticipation and perception was similarly applied to both self-pain and other-pain. [ABSTRACT FROM AUTHOR]

ABSTRACT 'Snow lotus' is a famous Chinese Materia Medica derived from species of the genus Saussurea (Compositae). To differentiate three representative easily-confused snow lotus herbs, namely, Saussurea involucrata (Kar. et Kir.) Sch.-Bip, Saussurea laniceps Hand.-Mazz., and Saussurea medusa Maxim., macroscopic features of the three herbs were systemically observed, and microscopic features were compared by using ordinary light microscopy, polarized light microscopy and scanning electron microscopy (SEM). The results indicate that, as for macroscopic identification, capitula situation and arrangement, and as for microscopic identification, pollen grains, nonglandular hairs, glandular hairs, and cells of inner surface of the microdiodange can be used to authenticate the three snow lotus herbs. Comprehensive table comparing the characteristics were presented in this study. SEM has been found to provide a number of unique characteristics of pollen grains. Based on the observation of pollen grains, evolution sequence of the three species was speculated. The present method was proven to be efficient, convenient, simple, and reliable, which was successfully applied to the authentication of three snow lotus herbs. Microsc. Res. Tech.1 77:631-641, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

[Display omitted] • IWWTPs bacterial communities exhibited a clear species abundance distribution. • Deterministic processes dominate IWWTPs bacterial communities assembly. • Different IWWTPs harbor unique core bacterial community. • IWWTP bacterial community was strongly linked to activated sludge function. Microbial communities are responsible for biological treatment of many industrial wastewater, but our knowledge of their diversity, assembly patterns, and function is still poor. Here, we analyzed the bacterial communities of wastewater and activated sludge samples taken from 11 full-scale industrial wastewater treatment plants (IWWTPs) characterized by the same process design but different wastewater types and WWTP compartments. We found significantly different diversity and compositions of bacterial assemblages among distinct wastewater types and IWWTPs compartments. IWWTPs bacterial communities exhibited a clear species abundance distribution. The dispersal-driven process was weak in shaping IWWTP communities. Meanwhile, environmental and operating conditions were important factors in regulating the structure of the activated sludge community and pollutants removal, indicating that bacterial community was largely driven by deterministic mechanisms. The core microbial community in IWWTPs was different from that in municipal wastewater treatment plants (MWWTPs), and many taxa (e.g. the genus Citreitalea) rarely were detected before, indicating IWWTPs harbored unique core bacterial communities. Furthermore, we found that bacterial community compositions were strongly linked to activated sludge function. These findings are important to both microbial ecologists and environmental engineers, who may optimize the operation strategies jointly for maintaining biodiversity, which in turn may promote a more stable performance of the IWWTP. Overall, our study enhances the mechanistic understanding of the IWWTP microbial community diversity, assembly patterns, and function, and provides important implications for microbial ecology and wastewater treatment processes. [ABSTRACT FROM AUTHOR]

Infections caused by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) remain a serious global health issue, and the medical countermeasures available thus far are limited. Virus-neutralizing monoclonal antibodies (NAbs) are crucial tools for studying host-virus interactions and designing effective vaccines, and the discovery and development of these NAbs could be one approach to treat or prevent HSV infection. Here, we report the isolation of five HSV NAbs from mice immunized with both HSV-1 and HSV-2. Among these were two antibodies that potently cross-neutralized both HSV-1 and HSV-2 with the 50% virus-inhibitory concentrations (IC 50) below 200 ng/ml, one of which (4A3) exhibited high potency against HSV-2, with an IC 50 of 59.88 ng/ml. 4A3 neutralized HSV at the prebinding stage and prevented HSV infection and cell-to-cell spread. Significantly, administration of 4A3 completely prevented weight loss and improved survival of mice challenged with a lethal dose of HSV-2. Using structure-guided molecular modeling combined with alanine-scanning mutagenesis, we observed that 4A3 bound to a highly conserved continuous epitope (residues 216 to 220) within the receptor-binding domain of glycoprotein D (gD) that is essential for viral infection and the triggering of membrane fusion. Our results provide guidance for developing NAb drugs and vaccines against HSV. [ABSTRACT FROM AUTHOR]

In real life, it is not unusual that we face potential threats (i.e., physical stimuli and environments that may cause harm or danger) with other individuals together, yet it remains largely unknown how threat-induced anxious feelings influence prosocial behaviors such as resource sharing. In this study, we investigated this question by combining functional magnetic resonance imaging and a novel paradigm. Together with an anonymous partner, each participant faced the possibility of receiving a 10-s noise administration, which had a low or high probability to be a threat (i.e., the intensity of noise can induce a high level of unpleasantness). Each participant first reported her/his immediate feeling of anxiety about the current situation (being threatened by the unpleasant noise), then decided how to split a number of resources (which could relieve the noise) between her/him and the partner. Behavioral results revealed that the participants showed a selfish bias in the threat conditions than in the safe conditions, and that self-reported anxiety feeling significantly predicted this bias. Functional magnetic resonance imaging results revealed that: (1) the activation level of the anterior insula was correlated with self-reported anxiety and (2) the connectivity between the anterior insula and the temporoparietal junction was sensitive to the modulating effect of anxiety on the selfish bias. These findings indicate the neural correlates of the association between threat-induced anxiety and prosocial tendencies in social interactions., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Oncolytic viruses (OVs) are capable to inflame the tumor microenvironment (TME) and elicit infiltrating tumor-specific T cell responses. However, OV treatment negatively alters the cancer-immune set point in tumors to attenuate the antitumor immune response, which suggests the necessity of dissecting the immune landscape of the virus-treated tumors and developing novel strategies to maximize the potential of OVs. The aim of this study is to investigate the effect of the single-chain variable fragment (scFv)-armed OVs targeting PD-1 on the TME, and ultimately overcome localized immunosuppression to sensitize tumors to immunotherapies., Methods: A tumor-selective oncolytic herpes simplex virus vector was engineered to encode a humanized scFv against human PD-1 (hPD-1scFv) (YST-OVH). The antitumor efficacy of YST-OVH was explored in multiple therapeutic mouse models. The neurotoxicity and safety of YST-OVH were evaluated in nonhuman primates. The precise dynamics in the TME involved in YST-OVH treatment were dissected using cytometry by time-of-flight (CyTOF)., Results: The identified hPD-1scFv showed superior T-cell activating activity. Localized delivery of hPD-1scFv by YST-OVH promotes systemic antitumor immunity in humanized PD-1 mouse models of established cancer. Immune profiling of tumors using CyTOF revealed the enhanced antitumor effect of YST-OVH, which largely relied on CD8 + T cell activity by augmenting the tumor infiltration of effector CD8 + T cells and establishment of memory CD8 + T cells and reducing associated CD8 + T cell exhaustion. Furthermore, YST-OVH treatment modified the cancer-immune set point of tumors coupled to coexpression of CTLA-4 and TIM-3 on exhausted CD8 + T cells and high levels of CTLA-4 + Treg cells. A combination approach incorporating anti-CTLA-4 or anti-TIM-3 further improved efficacy by increasing tumor immunogenicity and activating antitumor adaptive immune responses. Moreover, this therapeutic strategy showed no neurotoxicity and was well tolerated in nonhuman primates. The benefit of intratumoral hPD-1scFv expression was also observed in humanized mice bearing human cancer cells., Conclusion: Localized delivery of PD-1 inhibitors by engineered YST-OVH was a highly effective and safe strategy for cancer immunotherapy. YST-OVH also synergized with CTLA-4 or TIM-3 blockade to enhance the immune response to cancer. These data provide a strong rationale for further clinical evaluation of this novel therapeutic approach., Competing Interests: Competing interests: XY, JH and JJ are employees of Beijing Wantai Biological Pharmacy, China. YL is an employee of Hangzhou Yangshengtang Biopharmaceutical, China. All other authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Oncolytic virotherapy can lead to systemic antitumor immunity, but the therapeutic potential of oncolytic viruses in humans is limited due to their insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). Here, we showed that locoregional oncolytic virotherapy upregulated the expression of PD-L1 in the TME, which was mediated by virus-induced type I and type II IFNs. To explore PD-1/PD-L1 signaling as a direct target in tumor tissue, we developed a novel immunotherapeutic herpes simplex virus (HSV), OVH-aMPD-1, that expressed a single-chain variable fragment (scFv) against PD-1 (aMPD-1 scFv). The virus was designed to locally deliver aMPD-1 scFv in the TME to achieve enhanced antitumor effects. This virus effectively modified the TME by releasing damage-associated molecular patterns, promoting antigen cross-presentation by dendritic cells, and enhancing the infiltration of activated T cells; these alterations resulted in antitumor T-cell activity that led to reduced tumor burdens in a liver cancer model. Compared with OVH, OVH-aMPD-1 promoted the infiltration of myeloid-derived suppressor cells (MDSC), resulting in significantly higher percentages of CD155 + granulocytic-MDSCs (G-MDSC) and monocytic-MDSCs (M-MDSC) in tumors. In combination with TIGIT blockade, this virus enhanced tumor-specific immune responses in mice with implanted subcutaneous tumors or invasive tumors. These findings highlighted that intratumoral immunomodulation with an OV expressing aMPD-1 scFv could be an effective stand-alone strategy to treat cancers or drive maximal efficacy of a combination therapy with other immune checkpoint inhibitors., (©2020 American Association for Cancer Research.)