To evaluate the effects on biochemicals, antioxidants, immune responses and disease resistance of the snakehead fish, following exposure to deltamethrin at 0.061, 0.121, 0.242, 0.485 and 0.970 μg/L. ...After 28 d, the biochemical, the levels of antioxidant enzymes and immune enzymes in liver, spleen, kidney and intestine were negatively related to the concentrations of deltamethrin exposure. Likewise, the survival rates of the fish after 7 d challenge with Aeromonas veronii were negatively related. The levels of IL-1β, IL-8, TNF-α, Hsp70 and malondialdehyde in liver, spleen, kidney and intestine were positively connected to the concentrations of deltamethrin exposure. Results demonstrated that environmentally relevant concentrations (0.121, 0.242, 0.485 and 0.970 μg/L) inhibited the biochemicals, antioxidants and immune responses and disease resistance of snakehead fish.
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•Deltamethrin exposure reduce the hepatopancreas function in C. argus.•Deltamethrin exposure caused tremendous oxidative damage of C. argus.•Deltamethrin exposure significantly suppressed the immune responses of C. argus.•Deltamethrin exposure caused a decrease in resistance to pathogen infection.
Recording electrophysiological information such as brain neural signals is of great importance in health monitoring and disease diagnosis. However, foreign body response and performance loss over ...time are major challenges stemming from the chemomechanical mismatch between sensors and tissues. Herein, microgels are utilized as large crosslinking centers in hydrogel networks to modulate the tradeoff between modulus and fatigue resistance/stretchability for producing hydrogels that closely match chemomechanical properties of neural tissues. The hydrogels exhibit notably different characteristics compared to nanoparticles reinforced hydrogels. The hydrogels exhibit relatively low modulus, good stretchability, and outstanding fatigue resistance. It is demonstrated that the hydrogels are well suited for fashioning into wearable and implantable sensors that can obtain physiological pressure signals, record the local field potentials in rat brains, and transmit signals through the injured peripheral nerves of rats. The hydrogels exhibit good chemomechanical match to tissues, negligible foreign body response, and minimal signal attenuation over an extended time, and as such is successfully demonstrated for use as long‐term implantable sensory devices. This work facilitates a deeper understanding of biohybrid interfaces, while also advancing the technical design concepts for implantable neural probes that efficiently obtain physiological information.
A strategy is proposed using microgels as large crosslinking centers in hydrogel networks to modulate the tradeoff between modulus and fatigue resistance/stretchability. The prepared hydrogels can be used to obtain physiological signals, record the local field potentials in brains, and transmit signals through injured peripheral nerves. The appropriate performances lead to negligible foreign body response and signal attenuation with time.
The (pro)renin receptor (PRR) is a multifunctional integral membrane protein that serves as a component of the vacuolar H
-ATPase (V-ATPase) and also activates (pro)renin. We recently showed that ...full-length PRR, found as part of a V-ATPase sub-complex, is abundant in extracellular vesicles shed by osteoclasts. Here, we tested whether these extracellular vesicles stimulate (pro)renin. Extracellular vesicles isolated from the conditioned media of RAW 264.7 osteoclast-like cells or primary osteoclasts were characterized and counted by nanoparticle tracking. Immunoblotting confirmed that full-length PRR was present. Extracellular vesicles from osteoclasts dose-dependently stimulated (pro)renin activity, while extracellular vesicles from 4T1 cancer cells, in which we did not detect PRR, did not activate (pro)renin. To confirm that the ability of extracellular vesicles from osteoclasts to stimulate (pro)renin activity was due to the PRR, the "handle region peptide" from the PRR, a competitive inhibitor of PRR activity, was tested. It dose-dependently blocked the ability of extracellular vesicles to stimulate the enzymatic activity of (pro)renin. In summary, the PRR, an abundant component of extracellular vesicles shed by osteoclasts, stimulates (pro)renin activity. This represents a novel mechanism by which extracellular vesicles can function in intercellular regulation, with direct implications for bone biology.
Ginsenoside Rh2 (G-Rh2), a rare ginsenoside isolated from red ginseng, has considerable anti-cancer activity and induces apoptosis in a variety of cancer cells, but its activity in esophageal cancer ...cells is unclear. In this study, we examined the cytotoxic activity of (20S) G-Rh2 in highly differentiated esophageal squamous ECA109 cells and poorly differentiated esophageal squamous TE-13 cells. (20S) G-Rh2 exerted intense cytotoxicity in ECA109 and TE-13 cells with an IC50 of 2.9 and 3.7 μg/mL, respectively. After treatment with G-Rh2, Bcl-2, and Bcl-xL, the two main anti-apoptosis Bcl-2 family proteins upregulated, and Bax and Bak, the two key pro-apoptosis proteins translocated to mitochondria in both cell lines. At the same time, cytochrome c and Smac released from mitochondria, followed by caspase-9 activation, indicating that a mitochondria-mediated intrinsic apoptosis pathway was activated in both cell lines upon treatment with (20S) G-Rh2. It is noteworthy that (20S) G-Rh2 upregulated the transcription and protein expression of two death receptors, Fas and DR5, and subsequently activated Caspase-8 in the TE-13 cells but not in the ECA109 cells. Taken together, we demonstrated the potent anti-esophageal cancer cell activity of (20S) G-Rh2 and showed its working mechanism in two differentiated esophageal cancer cells, which can provide important evidence for developing an effective strategy for anti-esophageal cancer treatment.
Compared with men, female accounts for a larger proportion of patients with depression. Behavioral genetics researches find gender differences in genetic underpinnings of depression. We found that ...gender differences exist in heritability and the gene associated with depression after reviewing relevant research. Both genes and gene-environment interactions contribute to the risk of depression in a gender-specific manner. We detailed the relationships between serotonin transporter gene-linked promoter region (5-HTTLPR) and depression. However, the results of these studies are very different. We explored the reasons for the contradictory conclusions and provided some suggestions for future research on the gender differences in genetic underpinnings of depression.
Osteoclasts are cells of the hematopoietic lineage that are specialized to resorb bone. In osteoclasts, the actin cytoskeleton engages in at least two unusual activities that are required for ...resorption. First, microfilaments form a dynamic and structurally elaborate actin ring. Second, microfilaments bind vacuolar H⁺-ATPase (V-ATPase) and are involved in forming the V-ATPase-rich ruffled plasma membrane. The current review examines these two specialized functions with emphasis on the identification of new therapeutic opportunities. The actin ring is composed of substructures called podosomes that are interwoven to form a cohesive superstructure. Studies examining the regulation of the formation of actin rings and its constituent proteins are reviewed. Areas where there are gaps in the knowledge are highlighted. Microfilaments directly interact with the V-ATPase through an actin binding site in the B2-subunit of V-ATPase. This binding interaction is required for ruffled membrane formation. Recent studies show that an inhibitor of the interaction blocks bone resorption in pre-clinical animal models, including a model of post-menopausal osteoporosis. Because the unusual actin-based resorption complex is unique to osteoclasts and essential for bone resorption, it is likely that deeper understanding of its underlying mechanisms will lead to new approaches to treat bone disease.
Accumulation of immunosuppressive protein programmed death-ligand 1 (PD-L1) has been documented in several cancers and contributes to the evasion of the host immune system. However, cancer ...cell-intrinsic signaling-dependent control of PD-L1 expression remains to be elucidated. Herein, we aimed to identify the let-7 family of microRNAs as candidates that up-regulate tumor cell PD-L1 expression and mediates immune evasion of head and neck squamous cell carcinoma (HNSCC).
The expression of let-7 family and PD-L1 was quantified in HNSCC tissues and adjacent normal tissues. PD-L1 degradation was evaluated in HNSCC cells in response to elevated expressions of let-7a or let-7b. The regulation of let-7 family on PD-L1 degradation through a mechanism involving T-cell factor-4 (TCF-4) control of β-catenin/STT3 pathway was evaluated. Immune recognition of HNSCC in vivo was examined in subcutaneous tumor-bearing C3H mice in the presence of let-7a/b and/or CTLA-4 antibody.
The let-7 family were significantly down-regulated in the context of HNSCC, sharing a negative correlation with PD-L1 expression. Glycosylated PD-L1 was detected in HNSCC cells, which was reduced by let-7a/b over-expression. TCF-4, the target of let-7a/b, activated the β-catenin/STT3 pathway and promoted PD-L1 degradation. In vivo analysis demonstrated that let-7a/b over-expression potentiated anticancer immunotherapy by CTLA-4 blockade.
Taken together, our findings highlight targeting let-7 family as a potential strategy to enhance immune checkpoint therapy for HNSCC.
Flexible and wearable biosensors have received tremendous attention over the past decade owing to their great potential applications in the field of health and medicine. Wearable biosensors serve as ...an ideal platform for real-time and continuous health monitoring, which exhibit unique properties such as self-powered, lightweight, low cost, high flexibility, detection convenience, and great conformability. This review introduces the recent research progress in wearable biosensors. First of all, the biological fluids often detected by wearable biosensors are proposed. Then, the existing micro-nanofabrication technologies and basic characteristics of wearable biosensors are summarized. Then, their application manners and information processing are also highlighted in the paper. Massive cutting-edge research examples are introduced such as wearable physiological pressure sensors, wearable sweat sensors, and wearable self-powered biosensors. As a significant content, the detection mechanism of these sensors was detailed with examples to help readers understand this area. Finally, the current challenges and future perspectives are proposed to push this research area forward and expand practical applications in the future.
We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian ...Nosocomial Infection Surveillance Program hospitals during 2015-2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015-2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.
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