Bi-path color tunable plasmonic micro-nano hybrid structures for encrypted printing.

Colored information is crucial for humans to perceive the world. Plasmonic spectra modulation can serve as an effective means to create different colors. Although several solutions for plasmonic color-printing have been proposed, further information encryption has not received any attention. Herein, we exhibit a fine color modulation strategy to construct noble-metal-based micro-nano hybrid structures in the bi-path of photo-thermal deformation and liquid-phase-chemical reaction. Ag/Ta2O5 bi-layer films are ablated at the center of the machined lines of nanosecond pulsed laser, while silver nanoparticles are formed in other regions by thermal radiation of the infrared laser, which can be further dissolved and shape-modulated in KCl solution under different periods. The variation of size and spacing of nano-Ag particles results in a precise shift of plasmonic spectra in visible region. Colored information can be hidden by adjusting the scan number and the energy density during laser processing, and will emerge after the subsequent chemical dissolution reactions. The bi-path color adjustment strategy is easy to operate and can play a role in key information protection and color image switching.

Continuous tuning of pulse parameters in a soliton fiber laser by adjusting the effect of nonlinear polarization rotation: publisher's note.

This publisher's note contains a correction to Opt. Lett.49, 674 (2024)10.1364/OL.509981.

Continuous tuning of pulse parameters in a soliton fiber laser by adjusting the effect of nonlinear polarization rotation.

We demonstrate that through inserting a short length of highly birefringent small-core photonic crystal fiber (Hi-Bi SC-PCF) into a soliton fiber laser, the nonlinear polarization rotation effect in this laser can be manipulated, leading to continuous tuning of the output pulse parameters. In experiments, we observed that by adjusting the polarization state of light launched into the Hi-Bi SC-PCF and varying the cavity attenuation, the laser spectral width can be continuously tuned from ∼7.1 to ∼1.7 nm, corresponding to a pulse-width-tuning range from ∼350 fs to ∼1.56 ps. During the parameter tuning, the output pulses strictly follow the soliton area theory, giving an almost constant time-bandwidth-product of ∼0.31. This soliton fiber laser, being capable of continuous parameter tuning, could be applied as the seed source in ultrafast laser systems and may find some applications in nonlinear-optics and soliton-dynamics experiments.

GHz-rate 57-fs acousto-optic mode-locking fiber laser based on cascaded all-fiber pulse compression.

We demonstrate a compact ultrafast fiber laser system that can deliver 1.87 GHz pulse train at 1550 nm with a pulse energy of 52 pJ and an ultrashort pulse duration of 57 fs. While an acousto-optic mode-locking fiber laser was used as the seed light source at GHz rate, a stage of Er-doped fiber amplifier boosted the laser power to ∼320 mW, giving a pulse energy of ∼170 pJ. Then, a pulse compression setup was constructed, providing a high compression ratio of ∼10 with a total efficiency of ∼32%. In the cascaded compression configuration, multiple fiber samples with alternately normal and anomalous dispersion were fused together, providing efficient nonlinear spectral broadening while suppressing excessive pulse broadening over propagation. This GHz-rate ultrafast fiber laser, with compact configuration, broad optical spectrum, and high time-resolving ability could be used as the seed light source for constructing high-rate, high-power ultrafast laser systems and may find a few applications in optical measurements and microwave photonics.

Differential molecular responses of hemolymph and hepatopancreas of swimming crab, Portunus trituberculatus, infected with Ameson portunus (Microsporidia).

Ameson portunus (Microsporidia) has caused serious economic losses to the aquaculture industry of swimming crab, Portunus trituberculatus. The hemolymph and hepatopancreas are the main immune organs of P. trituberculatus, and the main sites of A. portunus infection. Elucidating the response characteristics of hemolymph and hepatopancreas to microsporidian infection facilitates the development of microsporidiosis prevention and control strategy. This study performed comparative transcriptomic analysis of hemolymph (PTX/PTXA) and hepatopancreas (PTG/PTGA) of P. trituberculatus uninfected and infected with A. portunus. The results showed that there were 223 and 1309 differentially expressed genes (DEGs) in PTX/PTXA and PTG/PTGA, respectively. The lysosome pathway was significantly enriched after the invasion of the hemolymph by A. portunus. Also, immune-related genes were all significantly up-regulated in the hemolymph and hepatopancreas, suggesting that the invasion by A. portunus may activate host immune responses. Unlike hemolymph, antioxidant and detoxification-related genes were also significantly up-regulated in the hepatopancreas. Moreover, metabolism-related genes were significantly down-regulated in the hepatopancreas, suggesting that energy synthesis, resistance to pathogens, and regulation of oxidative stress were suppressed in the hepatopancreas. Hemolymph and hepatopancreas have similarity and tissue specificity to microsporidian infection. The differential genes and pathways identified in this study can provide references for the prevention and control of microsporidiosis.

Discovery and development of novel 10,12-disubstituted aloperine derivatives against HCoV-OC43 by targeting allosteric site of host TMPRSS2.

By inducing steric activation of the 10CH bond with a 12-acyl group to form a key imine oxime intermediate, 20 novel (10S)-10,12-disubstituted aloperine derivatives were successfully synthesized and assessed for their antiviral efficacy against HCoV-OC43. Of them, compound 3i exhibited the moderate activities against HCoV-OC43, as well as against the SARS-CoV-2 variant EG.5.1 with the comparable EC50 values of 4.7 and 4.1 µM. A mechanism study revealed that it inhibited the protease activity of host TMPRSS2 by binding to an allosteric site, rather than the known catalytic center, different from that of camostat. Also, the combination of compound 3i and molnupiravir, as an RdRp inhibitor, showed an additive antiviral effect against HCoV-OC43. The results provide a new binding mode and lead compound for targeting TMPRSS2, with an advantage in combating broad-spectrum coronavirus.

Insights into the differential molecular response of non-germinated and germinated spores of Ameson portunus in vitro by comparative transcriptome analysis.

Ameson portunus, the recently discovered causative agent of "toothpaste disease" of pond-cultured swimming crabs in China has caused enormous economic losses in aquaculture. Understanding the process of spore germination is helpful to elucidate the molecular mechanism of its invasion of host cells. Here, we obtained mature and germinating spores by isolation and purification and in vitro stimulation, respectively. Then, non-germinated and germinated spores were subjected to the comparative transcriptomic analysis to disclose differential molecular responses of these two stages. The highest germination rate, i.e., 71.45 %, was achieved in 0.01 mol/L KOH germination solution. There were 9,609 significantly differentially expressed genes (DEGs), with 685 up-regulated and 8,924 down-regulated DEGs. The up-regulated genes were significantly enriched in ribosome pathway, and the down-regulated genes were significantly enriched in various metabolic pathways, including carbohydrate metabolism, amino acid metabolism and other metabolism. The results suggested that spores require various carbohydrates and amino acids as energy to support their life activities during germination and synthesize large amounts of ribosomal proteins to provide sites for DNA replication, transcription, translation and protein synthesis of the spores of A. portunus within the host cells. Functional genes related to spore germination, such as protein phosphatase CheZ and aquaporin, were also analyzed. The analysis of transcriptome data and identification of functional genes will help to understand the process of spore germination and invasion.

High Moisture-Barrier Performance of Double-Layer Graphene Enabled by Conformal and Clean Transfer.

Graphene films that can theoretically block almost all molecules have emerged as promising candidate materials for moisture barrier films in the applications of organic photonic devices and gas storage. However, the current barrier performance of graphene films does not reach the ideal value. Here, we reveal that the interlayer distance of the large-area stacked multilayer graphene is the key factor that suppresses water permeation. We show that by minimizing the gap between the two monolayers, the water vapor transmission rate of double-layer graphene can be as low as 5 × 10-3 g/(m2 d) over an A4-sized region. The high barrier performance was achieved by the absence of interfacial contamination and conformal contact between graphene layers during layer-by-layer transfer. Our work reveals the moisture permeation mechanism through graphene layers, and with this approach, we can tailor the interlayer coupling of manually stacked two-dimensional materials for new physics and applications.

A Conserved Intramolecular Ion-Pair Plays a Critical but Divergent Role in Regulation of Dimerization and Transport Function among the Monoamine Transporters.

The monoamine transporters, including the serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET), are the therapeutic targets for the treatment of many neuropsychiatric disorders. Despite significant progress in characterizing the structures and transport mechanisms of these transporters, the regulation of their transport functions through dimerization or oligomerization remains to be understood. In the present study, we identified a conserved intramolecular ion-pair at the third extracellular loop (EL3) connecting TM5 and TM6 that plays a critical but divergent role in the modulation of dimerization and transport functions among the monoamine transporters. The disruption of the ion-pair interactions by mutations induced a significant spontaneous cross-linking of a cysteine mutant of SERT and an increase in cell surface expression but with an impaired specific transport activity. On the other hand, similar mutations of the corresponding ion-pair residues in both DAT and NET resulted in an opposite effect on their oxidation-induced dimerization, cell surface expression, and transport function. Reversible biotinylation experiments indicated that the ion-pair mutations slowed down the internalization of SERT but stimulated the internalization of DAT. In addition, cysteine accessibility measurements for monitoring SERT conformational changes indicated that substitution of the ion-pair residues resulted in profound effects on the rate constants for cysteine modification in both the extracellular and cytoplasmatic substrate permeation pathways. Furthermore, molecular dynamics simulations showed that the ion-pair mutations increased the interfacial interactions in a SERT dimer but decreased it in a DAT dimer. Taken together, we propose that the transport function is modulated by the equilibrium between monomers and dimers on the cell surface, which is regulated by a potential compensatory mechanism but with different molecular solutions among the monoamine transporters. The present study provided new insights into the structural elements regulating the transport function of the monoamine transporters through their dimerization.

A novel mitochondria-related gene signature in esophageal carcinoma: prognostic, immune, and therapeutic features.

Esophageal carcinoma (ESCA) is a common and lethal malignant tumor worldwide. The mitochondrial biomarkers were useful in finding significant prognostic gene modules associated with ESCA owing to the role of mitochondria in tumorigenesis and progression. In the present work, we obtained the transcriptome expression profiles and corresponding clinical information of ESCA from The Cancer Genome Atlas (TCGA) database. Differential expressed genes (DEGs) were overlapped with 2030 mitochondria-related genes to get mitochondria-related DEGs. The univariate cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and multivariate cox regression were sequentially used to define the risk scoring model for mitochondria-related DEGs, and its prognostic value was verified in the external datasets GSE53624. Based on the risk score, ESCA patients were divided into high- and low-risk groups. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed to further investigate the difference between low- and high-risk groups at the gene pathway level. CIBERSORT was used to evaluate immune cell infiltration. The mutation difference between high- and low-risk groups was compared by using the R package "Maftools". Cellminer was used to assess the association between the risk scoring model and drug sensitivity. As the most important outcome of the study, a 6-gene risk scoring model (APOOL, HIGD1A, MAOB, BCAP31, SLC44A2, and CHPT1) was constructed from 306 mitochondria-related DEGs. Pathways including the "hippo signaling pathway" and "cell-cell junction" were enriched in the DEGs between high and low groups. According to CIBERSORT, samples with high-risk scores demonstrated a higher abundance of CD4+ T cells, NK cells, M0 and M2 macrophages, and a lower abundance of M1 macrophages. The immune cell marker genes were correlated with the risk score. In mutation analysis, the mutation rate of TP53 was significantly different between the high- and low-risk groups. Drugs with a strong correlation with the risk model were selected. In conclusion, we focused on the role of mitochondria-related genes in cancer development and proposed a prognostic signature for individualized integrative assessment.

Effects of enhanced recovery after surgery plus pulmonary rehabilitation on complications after video-assisted lung cancer surgery: a multicentre randomised controlled trial.

BACKGROUND: Lung cancer surgery is associated with a high incidence of postoperative pulmonary complications (PPCs). We evaluated whether enhanced recovery after surgery plus pulmonary rehabilitation was superior over enhanced recovery after surgery alone in reducing the incidence of postoperative PPCs and length of hospital stay. METHODS: In this pragmatic multicentre, randomised controlled, parallel-group clinical trial, eligible patients scheduled for video-assisted lung cancer surgery were randomly assigned (1:1) to either a newly developed programme that integrated preoperative and postoperative pulmonary rehabilitation components into a generic thoracic enhanced recovery after surgery pathway, or routine thoracic enhanced recovery after surgery. Primary outcome was the overall occurrence of PPCs within 2 weeks after surgery. Secondary outcomes were the occurrence of specific complications, time to removal of chest drain, and length of hospital stay (LOS). RESULTS: Of 428 patients scheduled for lung cancer surgery, 374 were randomised with 187 allocated to the experimental programme and 187 to control. Incidence of PPCs at 14 Days was 18.7% (35/187) in the experimental group and 33.2% (62/187) in the control group (intention-to-treat, unadjusted HR 0.524, 95% CI 0.347 to 0.792, p=0.002). Particularly, significant risk reduction was observed regarding pleural effusion, pneumonia and atelectasis. Time to removal of chest drain and LOS were not significantly reduced in the experimental group. CONCLUSIONS: Adding pulmonary rehabilitation to enhanced recovery after surgery appears to be effective in reducing the incidence of PPCs, but not LOS. Standard integration of pulmonary rehabilitation into thoracic enhanced recovery after surgery is a promising approach to PPC prophylaxis. TRIAL REGISTRATION NUMBER: ChiCTR1900024646.

Anti-angiogenic effect of exo-LncRNA TUG1 in myocardial infarction and modulation by remote ischemic conditioning.

The successful use of exosomes in therapy after myocardial infarction depends on an improved understanding of their role in cardiac signaling and regulation. Here, we report that exosomes circulating after myocardial infarction (MI) carry LncRNA TUG1 which downregulates angiogenesis by disablement of the HIF-1α/VEGF-α axis and that this effect can be counterbalanced by remote ischemic conditioning (RIC). Rats with MI induced through left coronary artery ligation without (MI model) and with reperfusion (ischemia/reperfusion I/R model) were randomized to RIC, or MI (I/R) or sham-operated (SO) control. Data from one cohort study and one randomized-controlled trial of humans with MI were also utilized, the former involving patients who had not received percutaneous coronary intervention (PCI) and the latter patients with PCI. Exosome concentrations did not differ between intervention groups (RIC vs. control) in rats (MI and I/R model) as well as humans (with and without PCI). However, MI and I/R exosomes attenuated HIF-1α, VEGF-α, and endothelial function. LncRNA TUG1 was increased in MI and I/R exosomes, but decreased in SO and RIC exosomes. HIF-1α expression was downregulated with MI and I/R exosomes but increased with RIC exosomes. Exosome inhibition suppressed HIF-1α upregulation through RIC exosomes. VEGF-α was identified as HIF-1α-regulated target gene. Knockdown of HIF-1α decreased VEGF-α, endothelial cell capability, and tube formation. Overexpression of HIF-1α exerted opposite effects. Transfection and co-transfection of 293 T cells with exosome-inhibitor GW4869 and HIF-1α inhibitor si-HIF-1α confirmed the exosomal-LncRNA TUG1/HIF-1α/VEGF-α pathway. LncRNA TUG1 is a potential therapeutic target after MI with or without reperfusion through PCI.

Constructing a novel mitochondrial-related gene signature for evaluating the tumor immune microenvironment and predicting survival in stomach adenocarcinoma.

BACKGROUND: The incidence and mortality of gastric cancer ranks fifth and fourth worldwide among all malignancies, respectively. Accumulating evidences have revealed the close relationship between mitochondrial dysfunction and the initiation and progression of stomach cancer. However, rare prognostic models for mitochondrial-related gene risk have been built up in stomach cancer. METHODS: In current study, the expression and prognostic value of mitochondrial-related genes in stomach adenocarcinoma (STAD) patients were systematically analyzed to establish a mitochondrial-related risk model based on available TCGA and GEO databases. The tumor microenvironment (TME), immune cell infiltration, tumor mutation burden, and drug sensitivity of gastric adenocarcinoma patients were also investigated using R language, GraphPad Prism 8 and online databases. RESULTS: We established a mitochondrial-related risk prognostic model including NOX4, ALDH3A2, FKBP10 and MAOA and validated its predictive power. This risk model indicated that the immune cell infiltration in high-risk group was significantly different from that in the low-risk group. Besides, the risk score was closely related to TME signature genes and immune checkpoint molecules, suggesting that the immunosuppressive tumor microenvironment might lead to poor prognosis in high-risk groups. Moreover, TIDE analysis demonstrated that combined analysis of risk score and immune score, or stromal score, or microsatellite status could more effectively predict the benefit of immunotherapy in STAD patients with different stratifications. Finally, rapamycin, PD-0325901 and dasatinib were found to be more effective for patients in the high-risk group, whereas AZD7762, CEP-701 and methotrexate were predicted to be more effective for patients in the low-risk group. CONCLUSIONS: Our results suggest that the mitochondrial-related risk model could be a reliable prognostic biomarker for personalized treatment of STAD patients.

Exciting-frequency-adaptive amplitude/phase hybrid holographic inscription in plasmonic polymers.

Plasmonic holography is generally regarded as an effective technology for 3D display that meets the requirements of the human visual system. However, low readout stability and large cross talk in the frequency field during a plasmonic photo-dissolution reaction set a huge obstacle for application of color holography. Herein, we propose a new, to the best of our knowledge, route toward producing exciting frequency sensitive holographic-inscription based on plasmonic nano-Ag adaptive growth. Donor-molecule-doped plasmonic polymers on polyethylene terephthalate substrates exhibit wide spectral response range, accurate optical frequency sensing, and bending durability. The resonant plasmonic particles act as optical antennas and transfer energy to surrounding organic matrices for nanocluster production and non-resonant particle growth. The surface relief hologram is also highly dependent on the excitation frequency, so we successfully obtain a controllable cross-periodic structure with amplitude/phase mixed information, as well as color holographic display. This work provides a bright way to high-density storage, information steganography, and virtual/augmented reality.

Semi-spontaneous temporal evolution of relief/fluorescence hybrid gratings for holographic encryption.

Holographic systems can reconstruct the entire wavefront of light which are developed as an excellent platform of information encryption. Although holography has utilized multiple modulation dimensions, little attention is given to its combination with fluorescence emitting. Herein, we propose a semi-spontaneous time-dependent encryption strategy of hybrid holographic fringes with surface relief and fluorescent emission mediated by a plasmonic polymer doped with fluorescent dyes. It is found that the two kinds of optical characteristic regions exhibit unique temporal evolution from the overlapped mode to the staggered one. The mode switching is closely related to the strong quenching effect of gold ions and nanoparticles which are dominant at the early and later recording stages, respectively. Thus, the real and deceptive information are recorded at different holographic writing periods. High-secret information of texts or images is constructed by the array of different sets of holographic fringes and is identified by comparing the dual-channel results of confocal laser scanning microscopes. This work puts a bright way to dynamic holographic encryption.

Micro-algal astaxanthin improves lambda-cyhalothrin-induced necroptosis and inflammatory responses via the ROS-mediated NF-κB signaling in lymphocytes of carp (Cyprinus carpio L.).

Lambda-cyhalothrin (LCY) is a widely used toxic pesticide that causes harmful effects on the immune organs of fish and aquatic species. Micro-algal astaxanthin (MAA), a heme pigment found in haematococcus pluvialis, has been shown to benefit antioxidants and immunity in aquaculture. To investigate how MAA protects carp lymphocytes from LCY-induced immunotoxicity, a model of fish lymphocytes treated with LCY and/or MAA was established. Lymphocytes from carp (Cyprinus carpio L.) were given LCY (80 µM) and/or MAA (50 µM) as a treatment for a period of 24 h. Firstly, LCY exposure resulted in excessive ROS and malondialdehyde production and reduces antioxidant enzymes (SOD and CAT), indicating a reduced capacity of the antioxidant system. Secondly, the results of flow cytometry and AO/EB labeling proved that lymphocytes treated with LCY have a larger ratio of necroptosis. In addition, LCY upregulated the levels of necroptosis-related regulatory factors (RIP1, RIP3 and MLKL) via the ROS-mediated NF-κB signaling pathway in lymphocytes. Thirdly, LCY treatment caused increased secretion of inflammatory genes (IL-6, INF-γ, IL-4, IL-1ß and TNF-α), leading to immune dysfunction in lymphocytes. Surprisingly, LCY-induced immunotoxicity was inhibited by MAA treatment, indicating that it effectively attenuated the LCY-induced changes described above. Overall, we concluded that MAA treatment could ameliorate LCY-induced necroptosis and immune dysfunction by inhibiting the ROS-mediated NF-κB signaling in lymphocytes. It provides insights into the protection of farmed fish from agrobiological threats in fish under LCY and the value of MAA applications in aquaculture.

Thioredoxin reductase 3 suppression promotes colitis and carcinogenesis via activating pyroptosis and necrosis.

BACKGROUND: Txnrd3 as selenoprotein plays key roles in antioxidant process and sperm maturation. Inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, are becoming significantly increasing disease worldwide in recent years which are proved relative to diet, especially selenium intake. METHODS: In the present study, 8-week-old C57BL/6N male Txnrd3-/-, Txnrd3-/ + , Txnrd3 + / + mice, weight 25-30 g, were randomly chosen and each group with 30 mice. Feed 3.5% DSS drinking water and normal water continuously for 7 days. Mouse colon cancer cells (CT26) were cultured in vitro to establish Txnrd3 overexpressed/knocked-down model by cell transfection technology. Morphology and ultrastructure, calcium levels, ROS level, cell death were observed and detected in vivo and vitro. RESULTS: In Txnrd3-/-mice, ulcerative colitis was more severe, the morphological and ultrastructural lesions were also more prominent compared with wild-type mice, accompanied by the significantly increased expression of NLRP3, Caspase1, RIPK3, and MLKL. Overexpression of Txnrd3 could lead to increased oxidative stress through intracellular calcium outflow-induced oxidative stress increase followed by necrosis and pyroptosis pathway activation and further inhibit the growth and proliferation of colon cancer cells. CONCLUSION: Txnrd3 overexpression leads to intracellular calcium outflow and increased ROS, which eventually leads to necrosis and focal death of colon cancer cells, while causing Txnrd3-/- mice depth of the crypt deeper, weakened intestinal secretion and immune function and aggravate the occurrence of ulcerative colitis. The present study lays a foundation for the prevention and treatment of ulcerative colitis and colon carcinoma in clinic treatment.

Role of Txnrd3 in NiCl2-induced kidney cell apoptosis in mice: Potential therapeutic effect of melatonin.

Nickel (Ni) exposure is a significant risk factor for kidney dysfunction and oxidative stress injury in humans. Thioredoxin reductase 3 (Txnrd3), an important enzyme in animals, plays a role in maintaining cellular homeostasis and regulating oxidative stress. However, its protective effect against kidney injury has been determined. Melatonin (Mel) has antioxidant and anti-apoptotic effects and therefore may be a preventive and therapeutic agent for kidney injury. Our study aimed to investigate the roles of Mel and Txnrd3 in the treatment of nickel-induced renal injury. We divided 80 wild-type mice and 80 Txnrd3 -/- mice (C57BL/6 N) into a control group treated with saline, Ni group treated with 10 mg/kg NiCl2, Mel group treated with 2 mg/kg Mel, and Ni + Mel group given NiCl2 and Mel for 21 days. Histopathological and ultrastructural observation of the kidney showed that nuclei were wrinkled and mitochondrial cristae were broken in the Ni group, and these changes were significantly attenuated by Mel treatment. Mitochondrial and nuclear damage improved significantly in the Ni + Mel and Txnrd3-/- Ni + Mel groups. Furthermore, NiCl2 exposure decreased T-AOC, SOD, and GSH activities in the kidney. The decreases in antioxidant enzyme activity were attenuated by Mel, and these improvements were abolished by Txnrd3 knockout. NiCl2-induced increases in the mRNA and protein levels of apoptosis factors (Bax, Cyt-c, caspase-3, and caspase-9) were attenuated by Mel treatment, and Txnrd3 knockout abolished the repressive effect of Mel on apoptosis genes. Overall, we concluded that Mel improves oxidative stress and apoptosis induced by NiCl2 by regulating Txnrd3 expression in the kidney. Our results provide evidence for the role of Mel in NiCl2-induced kidney injury and identify Txnrd3 as a potential therapeutic target for renal injury.

Imbalance of Microbacterial Diversity Is Associated with Functional Prognosis of Stroke.

Objectives: There is mounting evidence to suggest that the pathophysiology of stroke is greatly influenced by the microbiota of the gut and its metabolites, in particular short-chain fatty acids (SCFAs). The primary purpose of the study was to evaluate whether the levels of SCFAs and the gut microbiota are altered in poststroke patients and to examine the relationship between these alterations and the physical condition, intestinal health, pain, or nutritional status of patients. Methods: Twenty stroke patients and twenty healthy controls were enrolled in the current study, and their demographics were matched. Gas chromatography was used to determine the fecal SCFAs, and 16S rRNA gene sequencing was used to evaluate their fecal microbiota. Microbial diversity and richness were examined using the diversity indices alpha and beta, and taxonomic analysis was utilized to determine group differences. The relationships between the gut microbiome and fecal SCFAs, discriminant bacteria, and poststroke clinical outcomes were analyzed. Results: Less community richness (ACE and Chao) was observed in the poststroke patients (P < 0.05), but the differences between the poststroke group and the healthy control group in terms of species diversity (Shannon and Simpson) were not statistically significant. The makeup of the poststroke gut microbiota was distinct from that of the control group, as evidenced by beta diversity. Then, the relative abundances of the taxa in the poststroke and control groups were compared in order to identify the specific microbiota changes. At the level of phylum, the poststroke subjects showed a significant increase in the relative abundances of Akkermansiaceae, Fusobacteriota, Desulfobacterota, Ruminococcaceae, and Oscillospirales and a particularly noticeable decrease in the relative abundance of Acidobacteriota compared to the control subjects (P < 0.05). In regard to SCFA concentrations, lower levels of fecal acetic acid (P = 0.001) and propionic acid (P = 0.049) were found in poststroke subjects. Agathobacter was highly correlated with acetic acid level (r = 0.473, P = 0.002), whereas Fusobacteria (r = -0.371, P = 0.018), Flavonifractor (r = -0.334, P = 0.034), Desulfovibrio (r = -0.362, P = 0.018), and Akkermansia (r = -0.321, P = 0.043) were negatively related to acetic acid levels. Additionally, the findings of the correlation analysis revealed that Akkermansia (r = -0.356, P = 0.024), Desulfovibrio (r = -0.316, P = 0.047), and Alloprevotella (r = -0.366, P = 0.020) were significantly negatively correlated with high-density lipoprotein cholesterol. In addition, the Neurogenic Bowel Dysfunction score (r = 0.495, P = 0.026), Barthel index (r = -0.531, P = 0.015), Fugl-Meyer Assessment score (r = -0.565, P = 0.009), Visual Analogue Scale score (r = 0.605, P = 0.005), and Brief Pain Inventory score (r = 0.507, P = 0.023) were significantly associated with alterations of distinctive gut microbiota. Conclusions: Stroke generates extensive and substantial alterations in the gut microbiota and SCFAs, according to our findings. The differences of intestinal flora and lower fecal SCFA levels are closely related to the physical function, intestinal function, pain, or nutritional status of poststroke patients. Treatment strategies aimed at modulating the gut microbiota and SCFAs may have the potential to enhance the clinical results of patients.

Curcumin alleviates ketamine-induced oxidative stress and apoptosis via Nrf2 signaling pathway in rats' cerebral cortex and hippocampus.

AIMS: To investigate curcumin's protective effect on nerve damage caused by ketamine anesthesia via the Nrf2 signaling pathway. Rats and PC12 cells were used in this experiment to investigate the mechanism of nerve injury caused by ketamine anesthesia. Furthermore, our findings suggest that curcumin may affect oxidative stress and apoptosis by targeting the Nrf2 pathway, thereby alleviating the nerve injury caused by ketamine. METHODS: The rat cerebral cortex and hippocampus were stained with Nissl and immunohistochemistry to determine the number of neurons and the expression of Caspase-3, Bcl-2, and Bax. CCK-8 assay was used to determine the optimal concentration of ketamine, curcumin, and H2 O2 in PC12 cells. Flow cytometry was used to detect changes in reactive oxygen species and the rate of apoptosis in each group. To determine whether Nrf2 entered the nucleus, immunofluorescence was used. Both tissues and cells were subjected to RT-PCR and Western blotting detection at the same time. The levels of oxidative stress were determined using a malondialdehyde (MDA) and superoxide dismutase (SOD) assay kit. RESULTS: Ketamine reduced the number of neurons in the cortex and hippocampus of rats. The proteins Bax and Caspase-3 were upregulated, while Bcl-2 was down-regulated in the cortex and hippocampus. The viability of PC12 cells has decreased. MDA content increased while SOD activity decreased in cortex, hippocampus, and PC12 cells. Ketamine had an effect on the expression of some genes in the Nrf2 signaling pathway as well as apoptosis. Curcumin pretreatment may be able to prevent ketamine-induced damage. CONCLUSIONS: The oxidative stress and apoptosis caused by ketamine during growth of the cerebral cortex, hippocampus, and PC12 cells may be decreased by curcumin's activation of the Nrf2 signaling pathway. Our research provides a potential strategy for the secure administration of anesthetics in medical settings.