Comparison of Ciprofol-Based and Propofol-Based Total Intravenous Anesthesia on Microvascular Decompression of Facial Nerve with Neurophysiological Monitoring: A Randomized Non-Inferiority Trial.

Purpose: Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few clinical studies on ciprofol. We sought to examine the safety and efficacy of ciprofol use for general anesthesia in neurosurgical individuals undergoing neurosurgical surgery with intraoperative neurophysiological monitoring (IONM). Patients and Methods: This single-center, non-inferiority, single-blind, randomized controlled trial was conducted from September 13, 2022 to September 22, 2023. 120 patients undergoing elective microvascular decompression surgery (MVD) with IONM were randomly assigned to receive either ciprofol or propofol. The primary outcome of this study was the amplitude of intraoperative compound muscle action potential decline, and the secondary outcome included the indexes related to neurophysiological monitoring and anesthesia outcomes. Results: The mean values of the primary outcome in the ciprofol group and the propofol group were 64.7±44.1 and 53.4±35.4, respectively. Furthermore, the 95% confidence interval of the difference was -25.78 to 3.12, with the upper limit of the difference being lower than the non-inferiority boundary of 6.6. Ciprofol could achieve non-inferior effectiveness in comparison with propofol in IONM of MVD. The result during anesthesia induction showed that the magnitude of the blood pressure drop and the incidence of injection pain in the ciprofol group were significantly lower than those in the propofol group (P<0.05). The sedative drug and norepinephrine consumption in the ciprofol group was significantly lower than that in the propofol group (P<0.05). Conclusion: Ciprofol is not inferior to propofol in the effectiveness and safety of IONM and the surgical outcome. Concurrently, ciprofol is more conducive to reducing injection pain and improving hemodynamic stability, which may be more suitable for IONM-related surgery, and has a broad application prospect.

Frailty is a Risk Factor for Postoperative Complications in Older Adults with Lumbar Degenerative Disease: A Prospective Cohort Study.

Objective: Frailty, representing the physiological reserve and tolerance of the body, serves as a crucial evaluation index of the overall status of the older adults. This study aimed to investigate the prevalence of preoperative frailty and its impact on postoperative outcomes among older adults with lumbar degenerative disease in China. Patients and Methods: In this prospective study, a total of 280 patients aged 60 and above, diagnosed with lumbar degenerative disease and scheduled for surgical intervention were enrolled. The prevalence of frailty pre-surgery was evaluated using the Tilburg Frailty Indicator (TFI) and the modified Frailty Index 11 (mFI-11). The primary outcome was postoperative complication within 30 days post-surgery. The secondary outcomes were the length of hospital stay, hospital costs, reoperation within 30 days post-surgery and unplanned readmission within 30 days post-discharge. Both univariable and multivariable logistic regression were employed to screen and identify the risk factors predisposing patients to postoperative complications. Results: A total of 272 older adults were included in the study ultimately. The frailty detection rates of TFI and mFI-11 were 15.8% (43/272) and 10.7% (29/272) respectively. Thirty-four patients (12.5%) encountered complications. Significantly elevated rates of complications, prolonged hospital stays, increased hospital costs, and heightened readmission rates were observed in the frail group compared to the non-frail group (P<0.05). Univariable analysis showed that the potential factors related to complications are TFI, mFI-11 and albumin. Multivariable logistic regression revealed that TFI was an independent risk factor for postoperative complications (OR=5.371, 95% CI: 2.338-12.341, P < 0.001). Conclusion: Frailty was an independent predictor of postoperative complications in older adults undergoing lumbar fusion surgery. Frailty assessment should be performed in such patients to improve preoperative risk stratification and optimize perioperative management strategies.

Multi-omics reveals the particle size effect of nanoplastics on the hepatopancreas and intestinal toxicity of crustacean model Neospoda palmata.

Nano-plastics (NPs) have emerged as prevalent contaminants in aquatic ecosystems, gaining significant research interest. Nonetheless, limited research has addressed the toxicity mechanisms associated with PS-NPs (polystyrene nanoplastics) of varying particle sizes. In this investigation, genotoxicity, growth patterns, hepatopancreatic damage, and intestinal flora alterations in freshwater shrimp Neocaridina palmata (Shen 1948), subjected to 35 days PS-NPs exposure (two size PS-NPs: 75 nm and 200 nm were used for this experiment, and five concentrations were set: 0 mg/L, 0.5 mg/L, 2.5 mg/L, 5 mg/L, and 10 mg/L concentrations PS-NP concentrations were examined using RNA sequencing, histopathological analyses, enzyme activity assessments, and 16S rRNA sequencing. Noteworthy variations in differentially expressed genes (DEGs) were identified across groups exposed to different PS-NPs sizes. We observed that PS-NPs predominantly instigated cellular component-related processes and induced apoptosis and oxidative stress across tissues via the mitochondrial pathway. Although the 200 nm-PS-NPs are stronger than the 75 nm-PS-NPs in terms of fluorescence intensity, 75 nm-PS-NPs are more likely to promote apoptosis than 200 nm-PS-NPs. PS-NPs impeded standard energy provision in N. palmata, potentially contributing to decreased body length and weight. Moreover, PS-NPs inflicted damage on intestinal epithelial and hepatopancreatic tissues and significantly modified intestinal microbial community structures. Specifically, PS-NPs-induced intestinal damage was marked by a decline in some probiotics (notably Lactobacilli) and a surge in pathogenic bacteria. Moreover, supplementing N. palmata with Lactobacilli appeared ameliorate oxidative stress and strengthen energy metabolism. Our findings provided valuable insights into crustacean toxicity mechanisms when subjected to PS-NPs and the potential risks that different PS-NPs sizes posed to terrestrial ecosystems.

Micro/nano-plastics impacts in cardiovascular systems across species.

The widespread presence of microplastics and nanoplastics (MPs/NPs) in the environment has become a critical public health issue due to their potential to infiltrate and affect various biological systems. Our review is crucial as it consolidates current data and provides a comprehensive analysis of the cardiovascular impacts of MPs/NPs across species, highlighting significant implications for human health. By synthesizing findings from studies on aquatic and terrestrial organisms, including humans, this review offers insights into the ubiquity of MPs/NPs and their pathophysiological roles in cardiovascular systems. We demonstrated that exposure to MPs/NPs is linked to various cardiovascular ailments such as thrombogenesis, vascular damage, and cardiac impairments in model organisms, which likely extrapolate to humans. Our review critically evaluated methods for detecting MPs/NPs in biological tissues, assessing their toxicity, and understanding their behaviour within the vasculature. These findings emphasise the urgent need for targeted public health strategies and enhanced regulatory measures to mitigate the impacts of MP/NP pollution. Furthermore, the review underlined the necessity of advancing research methodologies to explore long-term effects and potential intergenerational consequences of MP/NP exposure. By mapping out the intricate links between environmental exposure and cardiovascular risks, our work served as a pivotal reference for future research and policymaking aimed at curbing the burgeoning threat of plastic pollution.

Intraoperative transcutaneous electroacupoint stimulation on early postoperative fatigue in patients with Parkinson's disease undergoing deep brain stimulation surgery.

Background: In this clinical trial, we evaluated the effects of transcutaneous electroacupoint stimulation (TEAS) on postoperative fatigue (POF) in Parkinson disease (PD) patients undergoing deep brain stimulation (DBS) surgery. Methods: A total 60 PD patients undergoing DBS surgery were enrolled. They were randomized to receive either electrical stimulation [alternative frequency 2/10 Hz, dense and disperse, intensity adjusted to the maximum tolerated by the participants (6-15 mAmp)] via surface electrodes (TEAS group) or surface electrodes only without electrical stimulation (Con group) at bilateral Zusanli and Sanyinjiao acupuncture points. All participants received their assigned intervention (TEAS or Con) during the 1st stage of surgery [(except during microelectrode recording (MER)] and the entire 2nd stage of surgery. Intraoperative anesthetic requirements were adjusted based on bispectral index (BIS) monitor. POF was assessed by Christensen fatigue scales (ChrFS), along with Quality of Recovery-15 (QoR-15) and mini-mental state examination (MMSE) postoperatively over a 7-day-period. We recorded the usage of rescue analgesics and anti-emetics. Results: Fifty-nine patients' datasets were included for final analyses. Fewer patients in TEAS experienced severe POF (defined as ChrFS ≥6) at T3 than those in the Con group (TEAS vs. Con: 7 vs. 22, p < 0.001). During the 1st stage of surgery, more patients in Con group required dexmedetomidine infusion (TEAS vs. Con: 2 vs. 6; P < 0.01). Total dosages of propofol and remifanil during the 2nd stage of surgery were TEAS vs. Con: 374.7 ± 61.2 vs 421.5 ± 81.9; p < 0.001 and 572.3 ± 82.0 vs. 662 ± 148.2; P < 0.001, respectively. Postoperative rescue analgesics (TEAS vs. Con: 2 vs. 6; P < 0.001) were used less in the TEAS group. TEAS patients reported better POF, MMSE and QoR15 scores than those in the Con group during most of the assessment period. Conclusions: Intraoperative TEAS decreased the severity of POF, reduced intraoperative anesthetic requirements and facilitated post-DBS recovery in this group of PD patients.

Metabolomics and microbiome co-analysis reveals altered innate immune responses in Charybdis japonica following Aeromonas hydrophila infection.

A comprehensive bioinformatics analysis was conducted to elucidate the innate immune response of Charybdis japonica following exposure to Aeromonas hydrophila. This study integrated metabolomics, 16S rRNA sequencing, and enzymatic activity data to dissect the immune mechanisms activated in response to infection. Infection with A. hydrophila resulted in an increased abundance of beneficial intestinal genera such as Photobacterium spp., Rhodobacter spp., Polaribacter spp., Psychrilyobacter spp., and Mesoflavibacter spp. These probiotics appear to suppress A. hydrophila colonization by competitively dominating the intestinal microbiota. Key metabolic pathways affected included fatty acid biosynthesis, galactose metabolism, and nitrogen metabolism, highlighting their role in the crab's intestinal response. Enzymatic analysis revealed a decrease in activities of hexokinase, phosphofructokinase, and pyruvate kinase, which are essential for energy homeostasis and ATP production necessary for stress responses. Additionally, reductions were observed in the activities of acetyl-CoA carboxylase and fatty acid synthase. Gene expression analysis showed downregulation in Peroxiredoxin 1 (PRDX1), Peroxiredoxin 2 (PRDX2), glutathione-S-transferase (GST), catalase (CAT), and glutathione (GSH), with concurrent increases in malondialdehyde (MDA) levels, indicating severe oxidative stress. This study provides insights into the molecular strategies employed by marine crabs to counteract bacterial invasions in their natural habitat.

Gradual effects of gradient concentrations of perfluorooctane sulfonate on the antioxidant ability and gut microbiota of red claw crayfish (Cherax quadricarinatus).

Perfluorooctane sulfonate (PFOS) is a typical persistent organic pollutant that is characterized by environmental persistence, bioaccumulation, and toxicity. In this study, we investigated the gut microbial response of the red claw crayfish Cherax quadricarinatus after 28 days of exposure to 0 ng/L, 1 ng/L, 10 µg/L, or 10 mg/L of PFOS as a stressor. We measured oxidative stress-related enzyme activities and expression of molecules related to detoxification mechanisms to evaluate the toxic effects of PFOS. We found that PFOS disturbed microbial homeostasis in the gut of C. quadricarinatus, resulting in increased abundance of the pathogen Shewanella and decreased abundance of the beneficial bacterium Lactobacillus. The latter especially disturbed amino acid transport and carbohydrate transport. We also found that the activities of glutathione S-transferase and glutathione peroxidase were positively correlated with the expression levels of cytochrome P450 genes (GST1-1, GSTP, GSTK1, HPGDS, UGT5), which are products of PFOS-induced oxidative stress and play an antioxidant role in the body. The results of this study provided valuable ecotoxicological data to better understand the biological fate and effects of PFOS in C. quadricarinatus.

Amygdala-Targeted Relief of Neuropathic Pain: Efficacy of Repetitive Transcranial Magnetic Stimulation in NLRP3 Pathway Suppression.

This study investigates the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a nonpharmacological approach to treating neuropathic pain (NP), a major challenge in clinical research. Conducted on male Sprague-Dawley rats with NP induced through chronic constriction injury of the sciatic nerve, the research assessed pain behaviors and the impact of rTMS on molecular interactions within the amygdala. Through a comprehensive analysis involving Mechanical Withdrawal Threshold (MWT), Thermal Withdrawal Latency (TWL), RNA transcriptome sequencing, RT-qPCR, Western blotting, immunofluorescence staining, and Co-Immunoprecipitation (Co-IP), the study focused on the expression and interaction of integrin αvß3 and its receptor P2X7R. Findings reveal that rTMS significantly influences the expression of integrin αvß3 in NP models, suggesting an inhibition of the NP-associated NLRP3 inflammatory pathway through the disruption of integrin αvß3-P2X7R interactions. These outcomes highlight the potential of rTMS in alleviating NP by targeting molecular interactions within the amygdala, offering a promising therapeutic avenue for managing NP.

Spinal sirtuin 2 attenuates bone cancer pain by deacetylating FoxO3a.

Bone cancer pain (BCP) is refractory to currently used analgesics. Recently, sirtuin 2 (SIRT2) was reported to play a vital role in neuropathic pain but its role in BCP remains unknown. It was hypothesized that spinal SIRT2 attenuates BCP by deacetylating FoxO3a and suppressing oxidative stress. The mouse model of BCP established by injecting tumor cells into the intramedullary space of the femur demonstrated that spinal SIRT2 and FoxO3a were downregulated in BCP development. Intrathecal administration of LV-SIRT2 reduced pain hypersensitivity (mechanical and thermal nociception) in BCP mice. Spinal SIRT2 overexpression upregulated FoxO3a and antioxidant genes (SOD2 and catalase) and inhibited FoxO3a acetylation, phosphorylation, and ubiquitination. Moreover, intrathecal administration of SIRT2 shRNA induced pain hypersensitivity in normal mice. Spinal SIRT2 knockdown downregulated FoxO3a and antioxidant genes and increased FoxO3a acetylation, phosphorylation, and ubiquitination. In summary, spinal SIRT2 increases FoxO3a expression in BCP mice and inhibits oxidative stress by deacetylating FoxO3a and further reducing FoxO3a phosphorylation, ubiquitination, and degradation, leading to BCP relief.

Effects of different concentrations and particle sizes of nanoplastics on gut microbiology, metabolism, and immunity in Chiromantes dehaani.

This study investigated the effects of nanoplastics (NPs) of varying particle sizes (75, 500, and 1000 nm) and concentrations (2.5 and 10 mg/L) on the gut health of Chiromantes dehaani. The experimental groups included a control (Cg0), and varying combinations of particle size and concentration. Our results showed that 75 nm NPs were more likely to enhance pathogenic bacterial growth than other sized NPs. Compared with CK, Low NPs concentrations (2.5 mg/L) raised total cholesterol (T-CHO) levels in the gut, while high concentrations significantly decreased both triglyceride (TG) and T-CHO levels (p < 0.05). The enzymatic activities of intestinal lipase and amylase were inhibited by NPs exposure, with greater inhibition at higher NPs concentrations. The 500 nm NPs exhibited a notably higher inhibitory effect than the 75 and 1000 nm NPs (P < 0.05). In terms of apoptosis, NPs exposure led to reduced mRNA expression of Bcl2 and increased expression of Caspase-3, Caspase-8, and Caspase-9, indicating an induction of apoptosis. This effect was more pronounced at higher NPs concentrations, with 75 nm NPs more likely to induce apoptosis in intestinal cells than 500 nm and 1000 nm NPs. Moreover, NPs triggered intestinal inflammatory responses, evidenced by the increased mRNA expression of TNF-ß, TNF-α, IL1ß, IL6, and IL8, and the decreased expression of IL10. High NPs concentrations were more likely to induce intestinal inflammation, with 500 nm NPs imparting the strongest effect. In summary, the study demonstrated that NPs, and particularly those at higher concentrations, disrupted the gut environment of C. dehaani by altering the microflora, reducing microbial diversity, inhibiting digestion and metabolism, inducing apoptosis, and triggering inflammation. Among the sizes of NPs tested, 500 nm NPs had the most significant adverse impact on digestion, metabolism, and inflammation, while 75 nm NPs most strongly induced apoptosis in C. dehaani's intestinal cells.

Exposure to polystyrene nanoplastics induces apoptosis, autophagy, histopathological damage, and intestinal microbiota dysbiosis of the Pacific whiteleg shrimp (Litopenaeus vannamei).

Nanoplastics (NPs) are widely distributed environmental pollutants that can disrupt intestinal immunity of crustaceans. In this study, the effects of NPs on gut immune enzyme activities, cell morphology, apoptosis, and microbiota diversity of Litopenaeus vannamei were investigated. L. vannamei was exposed to five concentrations of NPs (0, 0.1, 1, 5, and 10 mg/L) for 28 days. The results showed that higher concentrations of NPs damaged the intestinal villi, promoted formation of autophagosomes, increased intestinal non-specific immunoenzyme activities, and significantly increased apoptosis at 10 mg/L. In response to exposure to NPs, the expression levels of ATG3, ATG4, ATG12, Caspase-3, p53, and TNF initially increased and then decreased. In addition, the concentration of NPs was negatively correlated to the expression levels of the genes of interest and intestinal enzyme activities, suggesting that exposure to NPs inhibited apoptosis and immune function. The five dominant phyla of the gut microbiota (Proteobacteria, Firmicutes, Bacteroidetes, Acidobacteria, and Actinomycetes) were similar among groups exposed to different concentrations of NPs, but the abundances tended to differ. Notably, exposure to NPs increased the abundance of pathogenic bacteria. These results confirm that exposure to NPs negatively impacted intestinal immune function of L. vannamei. These findings provide useful references for efficient breeding of L. vannamei.

Detection and prediction of pathogenic microorganisms in aquaculture (Zhejiang Province, China).

The detection and prediction of pathogenic microorganisms play a crucial role in the sustainable development of the aquaculture industry. Currently, researchers mainly focus on the prediction of water quality parameters such as dissolved oxygen for early warning. To provide early warning directly from the pathogenic source, this study proposes an innovative approach for the detection and prediction of pathogenic microorganisms based on yellow croaker aquaculture. Specifically, a method based on quantitative polymerase chain reaction (qPCR) is designed to detect the Cryptocaryon irritans (Cri) pathogenic microorganisms. Furthermore, we design a predictive combination model for small samples and high noise data to achieve early warning. After performing wavelet analysis to denoise the data, two data augmentation strategies are used to expand the dataset and then combined with the BP neural network (BPNN) to build the fusion prediction model. To ensure the stability of the detection method, we conduct repeatability and sensitivity tests on the designed qPCR detection technique. To verify the validity of the model, we compare the combined BPNN to long short-term memory (LSTM). The experimental results show that the qPCR method provides accurate quantitative measurement of Cri pathogenic microorganisms, and the combined model achieves a good level. The prediction model demonstrates higher accuracy in predicting Cri pathogenic microorganisms compared to the LSTM method, with evaluation indicators including mean absolute error (MAE), recall rate, and accuracy rate. Especially, the accuracy of early warning is increased by 54.02%.

Puerarin inhibits NHE1 activity by interfering with the p38 pathway and attenuates mitochondrial damage induced by myocardial calcium overload in heart failure rats.

Previous studies have shown that puerarin plays a key role in protecting humans and animals from cardiovascular diseases. The exact mechanism of the therapeutic effect of puerarin on various cardiovascular diseases (protective effect on cardiomyocytes) is still unclear. In the present study, we identify the role of puerarin in an animal model of experimental heart failure (HF) and explore its underlying mechanisms. The HF rat model is induced by intraperitoneal injection of adriamycin (ADR), and puerarin is administered intragastrically at low, medium, and high concentrations. We demonstrate that puerarin significantly improves myocardial fibrosis and inflammatory infiltration and, as a result, improves cardiac function in ADR-induced HF rats. Mechanistically, we find for the first time that puerarin inhibits overactivated Na +/H + exchange isoform 1 (NHE1) in HF, which may improve HF by decreasing Na + and Ca 2+ ion concentrations and attenuating mitochondrial damage caused by calcium overload; on the other hand, puerarin inhibits the activation of the p38 pathway in HF, reduces the expressions of TGF-ß and proinflammatory cytokines, and suppresses myocardial fibrosis. In conclusion, our results suggest that Puerarin is an effective drug against HF and may play a protective role in the myocardium by inhibiting the activation of p38 and its downstream NHE1.

Comparative analysis of whole-transcriptome RNA expression of lung tissue of Chinese soft-shell turtle infected by Trionyx sinensis Hemorrhagic Syndrome Virus.

Trionyx sinensis Hemorrhagic Syndrome Virus (TSHSV), the first aquatic arterivirus identified in China, causes severe mortality to T. sinensis. In this study, we sought to determine the functions of T. sinensis mRNAs and non-coding RNAs (ncRNAs) that were differentially expressed (DE) over different periods of TSHSV infection of T. sinensis lung. We used RT-qPCR to validate the sequencing results of select RNAs, confirming their reliable and referable nature. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict multiple biological functions and signaling pathways in various comparison groups (1-day versus mock, 3-day versus 1-day, and 5-day versus 3-day). Multiple types of differentially expressed RNA, including mRNA, lncRNA, circRNA, and miRNA, were associated with cardiac dysfunction, coagulation abnormalities, and arachidonic acid metabolism at day 1. Pre-inflammatory cytokines and inflammatory factors such as PLA2G4A, cPLA2, γ-GGT1, TNFRSF14, TCP11L2, PTER CYP2J2 and LTC4S, were noticeably regulated at the same time. On day 3, multiple GO terms and KEGG pathways were implicated, including those related to virus defense, apoptosis, pyroptosis, and inflammatory response. Notably, key genes such as RSAD2, TRIM39, STAT4, CASP1, CASP14, MYD88, CXCL3, CARD11, ZBP1, and ROBO4 exhibited significant regulation. The lncRNAs and circRNAs that targeted the genes involved in viral recognition (TLR5), apoptosis (CARD11), pyroptosis (ZBP1), inflammatory processes (NEK7, RASGRP4, and SELE) and angiogenesis (ROBO4) exhibited significant regulation. Significantly regulated miRNAs were primarily linked to genes involved in apoptosis (Let-7f-3p, miR-1260a, miR-455-3p), and inflammation (miR-146a, miR-125a, miR-17a, miR-301b, and miR-30a-3p). The findings could advance our understanding of the host immunological response to TSHSV and offer new ideas for developing effective strategies to prevent infection of T. sinensis.

Bifidobacteria in disease: from head to toe.

Bifidobacteria as a strictly anaerobic gram-positive bacteria, is widely distributed in the intestine, vagina and oral cavity, and is one of the first gut flora to colonize the early stages of life. Intestinal flora is closely related to health, and dysbiosis of intestinal flora, especially Bifidobacteria, has been found in a variety of diseases. Numerous studies have shown that in addition to maintaining intestinal homeostasis, Bifidobacteria may be involved in diseases covering all parts of the body, including the nervous system, respiratory system, genitourinary system and so on. This review collects evidence for the variation of Bifidobacteria in typical diseases among various systems, provides mild and effective therapeutic options for those diseases that are difficult to cure, and moves Bifidobacteria from basic research to further clinical applications.

Electrolyte Modulation Strategies for Low-Temperature Zn Batteries.

Aqueous rechargeable Zn metal batteries (ARZBs) are extensively studied recently because of their low-cost, high-safety, long lifespan, and other unique merits. However, the terrible ion conductivity and insufficient interfacial redox dynamics at low temperatures restrict their extended applications under harsh environments such as polar inspections, deep sea exploration, and daily use in cold regions. Electrolyte modulation is considered to be an effective way to achieve low-temperature operation for ARZBs. In this review, first, the fundamentals of the liquid-solid transition of water at low temperatures are revealed, and an in-depth understanding of the critical factors for inferior performance at low temperatures is given. Furthermore, the electrolyte modulation strategies are categorized into anion/concentration regulation, organic co-solvent/additive introduction, anti-freezing hydrogels construction, and eutectic mixture design strategies, and emphasize the recent progress of these strategies in low-temperature Zn batteries. Finally, promising design principles for better electrolytes are recommended and future research directions about high-performance ARZBs at low temperatures are provided.

Nerve Growth Factor/Tyrosine Kinase A Receptor Pathway Enhances Analgesia in an Experimental Mouse Model of Bone Cancer Pain by Increasing Membrane Levels of δ-Opioid Receptors.

BACKGROUND: The role of nerve growth factor (NGF)/tyrosine kinase A receptor (TrKA) signaling, which is activated in a variety of pain states, in regulating membrane-associated δ-opioid receptor (mDOR) expression is poorly understood. The hypothesis was that elevated NGF in bone cancer tumors could upregulate mDOR expression in spinal cord neurons and that mDOR agonism might alleviate bone cancer pain. METHODS: Bone cancer pain (BCP) was induced by inoculating Lewis lung carcinoma cells into the femoral marrow cavity of adult C57BL/6J mice of both sexes. Nociceptive behaviors were evaluated by the von Frey and Hargreaves tests. Protein expression in the spinal dorsal horn of animals was measured by biochemical analyses, and excitatory synaptic transmission was recorded in miniature excitatory synaptic currents. RESULTS: The authors found that mDOR expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.18 ± 0.01 g vs. mean ± SD: 0.13 ± 0.01 g, n = 4, P < 0.001) and that administration of the DOR agonist deltorphin 2 (Del2) increased nociceptive thresholds (Del2 vs. vehicle, median [25th, 75th percentiles]: 1.00 [0.60, 1.40] g vs. median [25th, 75th percentiles]: 0.40 [0.16, 0.45] g, n = 10, P = 0.001) and reduced miniature excitatory synaptic current frequency in lamina II outer neurons (Del2 vs. baseline, mean ± SD: 2.21 ± 0.81 Hz vs. mean ± SD: 2.43 ± 0.90 Hz, n = 12, P < 0.001). Additionally, NGF expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.36 ± 0.03 vs. mean ± SD: 0.16 ± 0.02, n = 4, P < 0.001), and elevated NGF was associated with enhanced mDOR expression via TrKA signaling. CONCLUSIONS: Activation of mDOR produces analgesia that is dependent on the upregulation of the NGF/TrKA pathway by increasing mDOR levels under conditions of BCP in mice.

Nano-plastics and gastric health: Decoding the cytotoxic mechanisms of polystyrene nano-plastics size.

Gastrointestinal diseases exert a profound impact on global health, leading to millions of healthcare interventions and a significant number of fatalities annually. This, coupled with escalating healthcare expenditures, underscores the need for identifying and addressing potential exacerbating factors. One emerging concern is the pervasive presence of microplastics and nano-plastics in the environment, largely attributed to the indiscriminate usage of disposable plastic items. These nano-plastics, having infiltrated our food chain, pose a potential threat to gastrointestinal health. To understand this better, we co-cultured human gastric fibroblasts (HGF) with polystyrene nano-plastics (PS-NPs) of diverse sizes (80, 500, 650 nm) and meticulously investigated their cellular responses over a 24-hour period. Our findings revealed PS particles were ingested by the cells, with a notable increase in ingestion as the particle size decreased. The cellular death induced by these PS particles, encompassing both apoptosis and necrosis, showcased a clear dependence on both the particle size and its concentration. Notably, the larger PS particles manifested more potent cytotoxic effects. Further analysis indicated a concerning reduction in cellular membrane potential, alongside a marked increase in ROS levels upon PS particles exposure. This suggests a significant disruption of mitochondrial function and heightened oxidative stress. The larger PS particles were especially detrimental in causing mitochondrial dysfunction. In-depth exploration into the PS particles impact on genes linked with the permeability transition pore (PTP) elucidated that these PS particles instigated an internal calcium rush. This surge led to a compromise in the mitochondrial membrane potential, which in tandem with raised ROS levels, further catalyzed DNA damage and initiated cell death pathways. In essence, this study unveils the intricate mechanisms underpinning cell death caused by PS particles in gastric epithelial cells and highlighting the implications of PS particles on gastrointestinal health. The revelations from this research bear significant potential to shape future healthcare strategies and inform pertinent environmental policies.

Isolation and characterization of a novel temperate bacteriophage infecting Aeromonas hydrophila isolated from a Macrobrachium rosenbergii larvae pond.

Aeromonas hydrophila is an opportunistic pathogen that frequently leads to significant mortality in various commercially cultured aquatic species. Bacteriophages offer an alternative strategy for pathogens elimination. In this study, we isolated, identified, and characterized a novel temperate A. hydrophila phage, designated as P05B. The bacteriophage P05B is a myovirus based on its morphological features, and possesses the capability to lyse A. hydrophila strains isolated from shrimp. The optimal multiplicity of infection (MOI), adsorption rate, latent period, and burst size for phage P05B were determined to be 0.001, 91.7 %, 20 min, and 483 PFU/cell, respectively. Phage P05B displayed stability across a range of temperatures (28-50 °C) and pH values (4.0-10.0). Sequence analysis unveiled that the genome of phage P05B comprises 32,302 base pairs with an average G + C content of 59.4 %. A total of 40 open reading frames (ORF) were encoded within the phage P05B genome. The comparative genomic analyses clearly implied that P05B might represent a novel species of the genus Bielevirus under Peduoviridae family. A phylogenetic tree was reconstructed, demonstrating that P05B shares a close evolutionary relationship with other Aeromonas and Aeromonas phages. In conclusion, this study increased our knowledge about a new temperate phage of A. hydrophila with strong lytic ability.