Analysis of the sodium pump subunit ATP1A3 in glioma patients: Potential value in prognostic prediction and immunotherapy.

The ATP1A3 gene is associated with the development and progression of neurological diseases. However, the pathological function and therapeutic value of ATP1A3 in glioblastoma (GBM) remains unknown. In this study, we tried to explore the correlation between the ATP1A3 gene expression and immune features in GBM samples. We found that ATP1A3 gene expression levels showed significant negative correlation with immune checkpoints such as PD-L1, CTLA-4 and IDO1. Next, ATP1A3 gene expression levels showed significant negative correlation with the anti-cancer immune cell process, the immune score and stromal score. By grouping ATP1A3 expression levels, we found that that immunomodulator-related genes and tumor-associated immune cell effector gene expression levels were associated with lower ATP1A3 expression. In addition, immunotherapy prediction pathway activity and a majority of the anti-cancer immune cell process activity levels were also showed to be correlated with lower ATP1A3 gene expression. Further, nine prognostic factors were identified by prognostic analysis, and a GBM prognostic model (risk score) was established. We applied the model to the TCGA GBM training set sample and the GSE4412 validation set sample and found that patients in the high risk score subgroup had significantly shorter survival time, demonstrating the prognostic value and prognostic efficacy of the risk score. Furthermore, ATP1A3 overexpression has also been found to sensitize cancer cells to anti-PD-1 therapy. In conclusion, we showed that ATP1A3 is a highly promising treatment target in GBM and the risk score is an independent prognostic factor for cancer and can be used to help guide the prediction of survival time in patients with GBM.

Isolation of Human Milk Difucosyl Nona- and Decasaccharides by Ultrahigh-Temperature Preparative PGC-HPLC and Identification of Novel Difucosylated Heptaose and Octaose Backbones by Negative-Ion ESI-MSn.

Despite their many important physiological functions, past work on the diverse sequences of human milk oligosaccharides (HMOs) has been focused mainly on the highly abundant HMOs with a relatively low degree of polymerization (DP) due to the lack of efficient methods for separation/purification and high-sensitivity sequencing of large-sized HMOs with DP ≥ 10. Here we established an ultrahigh-temperature preparative HPLC based on a porous graphitized carbon column at up to 145 °C to overcome the anomeric α/ß splitting problem and developed further the negative-ion ESI-CID-MS/MS into multistage MSn using a combined product-ion scanning of singly charged molecular ion and doubly charged fragment ion of the branching Gal and adjacent GlcNAc residues. The separation and sequencing method allows efficient separation of a neutral fraction with DP ≥ 10 into 70 components, among which 17 isomeric difucosylated nona- and decasaccharides were further purified and sequenced. As a result, novel branched difucosyl heptaose and octaose backbones were unambiguously identified in addition to the conventional linear and branched octaose backbones. The novel structures of difucosylated DF-novo-heptaose, DF-novo-LNO I, and DF-novo-LNnO I were corroborated by NMR. The various fucose-containing Lewis epitopes identified on different backbones were confirmed by oligosaccharide microarray analysis.

Glycolysis, a driving force of rheumatoid arthritis.

Resident synoviocytes and synovial microvasculature, together with immune cells from circulation, contribute to pannus formation, the main pathological feature of rheumatoid arthritis (RA), leading to destruction of adjacent cartilage and bone. Seeds, fibroblast-like synoviocytes (FLSs), macrophages, dendritic cells (DCs), B cells, T cells and endothelial cells (ECs) seeds with high metabolic demands undergo metabolic reprogramming from oxidative phosphorylation to glycolysis in response to poor soil of RA synovium with hypoxia, nutrient deficiency and inflammatory stimuli. Glycolysis provides rapid energy supply and biosynthetic precursors to support pathogenic growth of these seeds. The metabolite lactate accumulated during this process in turn condition the soil microenvironment and affect seeds growth by modulating signalling pathways and directing lactylation modifications. This review explores in depth the survival mechanism of seeds with high metabolic demands in the poor soil of RA synovium, providing useful support for elucidating the etiology of RA. In addition, we discuss the role and major post-translational modifications of proteins and enzymes linked to glycolysis to inspire the discovery of novel anti-rheumatic targets.

A Rotating Cathode with Periodical Changes in Electrolyte Layer Thickness for High-Rate Li‒O2 Batteries.

Li-O2 batteries (LOBs) possess the highest theoretical gravimetric energy density among all types of secondary batteries, but they are still far from practical applications. The poor rate performance resulting from the slow mass transfer is one of the primary obstacles in LOBs. To solve this issue, a rotating cathode with periodic changes in the electrolyte layer thickness is designed, decoupling the maximum transfer rate of Li+ and O2. During rotation, the thinner electrolyte layer on the cathode facilitates the O2 transfer, and the thicker electrolyte layer enhances the Li+ transfer. As a result, the rotating cathode enables the LOBs to undergo 58 cycles at 2.5 mA cm-2 and discharge stably even at a high current density of 7.5 mA cm-2. Besides, it also makes the batteries exhibit a large discharge capacity of 6.8 mAh cm-2, and the capacity decay is much slower with increasing current density. Notably, this rotating electrode holds great promise for utilization in other electrochemical cells involving gas-liquid-solid triple-phase interfaces, suggesting a viable approach to enhance the mass transfer in such systems.

Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications.

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.

Progress of engineered bacteria for tumour therapy.

Finding novel therapeutic modalities, improving drug delivery efficiency and targeting, and reducing the immune escape of tumor cells are currently hot topics in the field of tumor therapy. Bacterial therapeutics have proven highly effective in preventing tumor spread and recurrence, used alone or in combination with traditional therapies. In recent years, a growing number of researchers have significantly improved the targeting and penetration of bacteria by using genetic engineering technology, which has received widespread attention in the field of tumor therapy. In this paper, we provide an overview and assessment of the advancements made in the field of tumor therapy using genetically engineered bacteria. We cover three major aspects: the development of engineered bacteria, their integration with other therapeutic techniques, and the current state of clinical trials. Lastly, we discuss the limitations and challenges that are currently being faced in the utilization of engineered bacteria for tumor therapy.

Direct synthesis of branched amines enabled by dual-catalyzed allylic C─H amination of alkenes with amines.

Direct conversion of hydrocarbons into amines represents an important and atom-economic goal in chemistry for decades. However, intermolecular cross-coupling of terminal alkenes with amines to form branched amines remains extremely challenging. Here, a visible-light and Co-dual catalyzed direct allylic C─H amination of alkenes with free amines to afford branched amines has been developed. Notably, challenging aliphatic amines with strong coordinating effect can be directly used as C─N coupling partner to couple with allylic C─H bond to form advanced amines with molecular complexity. Moreover, the reaction proceeds with exclusive regio- and chemoselectivity at more steric hinder position to deliver primary, secondary, and tertiary aliphatic amines with diverse substitution patterns that are difficult to access otherwise.

Homogeneous electrochemical ratiometric biosensor for MircoRNA detection based on UiO-66-NH2 signal probe and waste-free entropy-driven DNA machine.

The construction of efficient methods for highly sensitive and rapid detection of disease markers is essential for the early diagnosis of serious diseases. In this paper, taking advantage of the UiO-66-NH2 signal molecule in combination with a waste-free entropy-driven DNA machine, a novel homogeneous electrochemical ratiometric platform is developed to detect MircoRNA (miRNA). Metal-organic framework materials (UiO-66-NH2 MOF) and ferrocene were utilized as electrochemical signal tags and reference probes, respectively. The target-initiated waste-free three-dimensional (3D) entropy-driven DNA nanomachine is activated in the presence of miRNA, resulting in DNA-labeled-UiO-66-NH2 falling off from the electrode, leading to a decrease in the signal of UiO-66-NH2 at 0.83V. Our strategy can mitigate false positive responses induced by the DNA probes immobilized on electrodes in traditional distance-dependent signal adjustment ratiometric strategies. The proposed ratiometric platform demonstrates superior sensitivity (a detection limit of 9.8 fM), simplified operation, high selectivity, and high repeatability. The ratiometric biosensor is also applied to detect miRNA content in spiked serum samples.

Constructing polynomial libraries for reservoir computing in nonlinear dynamical system forecasting.

Reservoir computing is an effective model for learning and predicting nonlinear and chaotic dynamical systems; however, there remains a challenge in achieving a more dependable evolution for such systems. Based on the foundation of Koopman operator theory, considering the effectiveness of the sparse identification of nonlinear dynamics algorithm to construct candidate nonlinear libraries in the application of nonlinear data, an alternative reservoir computing method is proposed, which creates the linear Hilbert space of the nonlinear system by including nonlinear terms in the optimization process of reservoir computing, allowing for the application of linear optimization. We introduce an implementation that incorporates a polynomial transformation of arbitrary order when fitting the readout matrix. Constructing polynomial libraries with reservoir-state vectors as elements enhances the nonlinear representation of reservoir states and more easily captures the complexity of nonlinear systems. The Lorenz-63 system, the Lorenz-96 system, and the Kuramoto-Sivashinsky equation are used to validate the effectiveness of constructing polynomial libraries for reservoir states in the field of state-evolution prediction of nonlinear and chaotic dynamical systems. This study not only promotes the theoretical study of reservoir computing, but also provides a theoretical and practical method for the prediction of nonlinear and chaotic dynamical system evolution.

[Clinical study on the treatment of postoperative recurrence of lumbar disc herniation with intervertebral fusion].

OBJECTIVE: To explore clinical effect of different intervertebral fusion devices (cage) in treating postoperative recurrent lumbar disc herniation (LDH). METHODS: One hundred and forty-two LDH patients with recurrence after simple intervertebral disc nucleus pulpoideectomy from January 2019 to January 2021 were retrospectively analyzed. All patients were treated with combined underchannel fixation and interbody fusion and divided into a single anatomical group,two-anatomical group and a single banana group according to types and numbers of implanted cage. There were 51 patients in a single anatomical group,included 29 males and 22 females,aged from 39 to 65 years old with an average of (53.74±5.68) years old;body mass index (BMI) ranged from 18.62 to 28.13 kg·m-2 with an average of (22.08±2.15) kg·m-2;the interval between operation and recurrence ranged from 0.5 to 4.0 years with an average of (2.7±0.8) years;5 patients with L3,4,35 patients with L4,5 and 11 patients with L5S1;a single anatomical cage was implanted. There were 46 patients in two-anatomical group,included 25 males and 21 females,aged from 37 to 66 years old with an average of (54.52±6.02) years old;BMI ranged from 18.25 to 28.44 kg·m-2 with an average of (21.74±1.83) kg·m-2;the interval between operation and recurrence ranged from 0.5 to 5.0 years with an average of (2.7±0.9) years;4 patients with L3,4,32 patients with L4,5 and 10 patients with L5S1;two-anatomical cages were implanted. There were 45 patients in a single banana group,included 22 males and 23 females,aged from 38 to 65 years old with an average of (54.49±6.45) years old;BMI ranged from 18.85 to 28.20 kg·m-2 with an average of (21.63±1.59) kg·m-2;the interval between operation and recurrence ranged from 0.5 to 5.0 years with an average of (2.6±1.0) years;3 patients with L3,4,36 patients with L4,5 and 16 patients with L5S1;a single banana cage was implanted. Operation time,intraoperative blood loss,incision length,postoperative incision drainage volume,hospital stay and complications among 3 groups were observed and compared. The height of intervertebral space before and after operation,curvature of lordosis and the postoperative intervertebral fusion were compared. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate degree of lumbar pain and lumbar function before operation,1 and 6 months after operation,respectively. RESULTS: All patients among 3 groups were followed up at least 6 months,and no cases were fell out. There were no significant difference in operation time,intraoperative blood loss,incision length,postoperative incision drainage volume and hospital stay among 3 groups (P>0.05). At 6 months after operation,the height of intervertebral space in two-anatomical group and a single group were [(11.08±1.78) mm,(10.95±1.62) mm],curvature of lordosis were [(12.05±1.86) °,(11.63±1.57) °],which were higher than those in a single dissection group (10.14±1.54) mm,(10.92±1.45) °,and the difference were statistically significant (P<0.05). The interbody fusion rate between two-anatomical and a banana group (95.65%,95.56%) were higher than that in a single anatomical group (78.43%) at 6 months after operation (P<0.05). VAS and ODI of lumbar among 3 groups were decreased at 1 and 6 months after operation (P<0.05). There was no significant difference in complications among 3 groups (P>0.05). CONCLUSION: The three fusion devices could achieve significant results in treating postoperative recurrence of LDH,but the implantation of two-anatomical cage and a single banana cage are more helpful to maintain the height of intervertebral space and lordosis curvature of patients with postoperative recurrence of LDH,and obtain good intervertebral fusion results.

Population genetic patterns across the native and invasive range of a widely distributed seagrass: Phylogeographic structure, invasive history and conservation implications.

Aim: The seagrass Zostera japonica is a dramatically declined endemic species in the Northwestern Pacific from the (sub)tropical to temperate areas, however, it is also an introduced species along the Pacific coast of North America from British Columbia to northern California. Understanding the population's genetic patterns can inform the conservation and management of this species. Location: North Pacific. Methods: We used sequences of the nuclear rDNA internal transcribed spacer (ITS) and chloroplast trnK intron maturase (matK), and 24 microsatellite loci to survey 34 native and nonnative populations (>1000 individuals) of Z. japonica throughout the entire biogeographic range. We analysed the phylogeographic relationship, population genetic structure and genetic diversity of all populations and inferred possible origins and invasion pathways of the nonnative ones. Results: All markers revealed a surprising and significant deep divergence between northern and southern populations of Z. japonica in the native region separated by a well-established biogeographical boundary. A secondary contact zone was found along the coasts of South Korea and Japan. Nonnative populations were found to originate from the central Pacific coast of Japan with multiple introductions from at least two different source populations, and secondary spread was likely aided by waterfowl. Main Conclusions: The divergence of the two distinct clades was likely due to the combined effects of historical isolation, adaptation to distinct environments and a contemporary physical barrier created by the Yangtze River, and the warm northward Kuroshio Current led to secondary contact after glacial separation. Existing exchanges among the nonnative populations indicate the potential for persistence and further expansion. This study not only helps to understand the underlying evolutionary potential of a widespread seagrass species following global climate change but also provides valuable insights for conservation and restoration.

Energy Transfer and Exciton Relaxation in B880-B800-RC Complex through Two-Dimensional Electronic Spectroscopy.

The light-harvesting (LH) and reaction center (RC) core complex of purple bacterium Roseiflexus castenholzii, B880-B800-RC, are different from those of the typical photosynthetic unit, (B850-B800)x-B880-RC. To investigate the excitation flowing dynamics in this unique complex, two-dimensional electronic spectroscopy is employed. The obtained time constants for the exciton relaxation in B880, exciton relaxation in B800, B800 → B880 energy transfer (EET), and B880 → closed RC EET are 43 fs, 177 fs, 1.9 ps, and 205 ps, respectively. These time constants result in an overall EET efficiency similar to that of the typical photosynthetic unit. Analysis of the oscillatory signals reveals that while several vibronic coherences are involved in the exciton relaxation process, only one prominent vibronic coherence, with a frequency of 27 cm-1 and coupled to the B880 electronic transition, may contribute to the B800 → B880 EET process.

E3 ubiquitin ligase CHIP interacts with transferrin receptor 1 for degradation and promotes cell proliferation through inhibiting ferroptosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the major form of liver malignancy with high incidence and mortality. Identifying novel biomarkers and understanding regulatory mechanisms underlying the development and progression of HCC are critical for improving diagnosis, treatment and patient outcomes. Carboxyl terminus of Hsc-70-interacting protein (CHIP) is a well-described U-box-type E3 ubiquitin ligase which promotes the ubiquitination and degradation of numerous tumor-associated proteins. Recent studies have shown that CHIP can play as a tumor-suppressor gene or an oncogene in different kinds of malignancies. To date, the function and mechanism of CHIP in hepatocellular carcinoma remains largely unknown. Based on TCGA data, we found that compared with high CHIP expression, the overall survival of HCC patients with low expression of CHIP was better. In addition, CHIP overexpression markedly enhanced HCC cell proliferation and colony formation. Conversely, knockdown of CHIP restrained the proliferation and colony formation of HCC cells. Meanwhile, knockdown of CHIP decreased mitochondrial cristae or ruptured outer mitochondrial membrane, promoted the accumulation of Fe2+ and ferroptosis of HCC cells. Further research for the first time confirmed that CHIP interacts and degrades transferrin receptor 1 (TfR1) by ubiquitin-proteasome pathway, which leads to the inhibition of ferroptosis and promotes the proliferation of HCC cells. The analysis of proteomics data from CPTAC revealed a negative correlation between CHIP and TfR1 protein expression levels in HCC. These findings indicate that CHIP acts as a negative modulator of ferroptosis and functions as an oncogene in HCC.

Construction of a gene model related to the prognosis of patients with gastric cancer receiving immunotherapy and exploration of COX7A1 gene function.

BACKGROUND: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. METHODS: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. RESULTS: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). CONCLUSIONS: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.

Males armed with big weapons win fights at limited cost in ant-mimicking jumping spiders.

A core assumption of sexual selection theory is that sexually selected weapons, specialized morphological structures used directly in male contests, can improve an individual's reproductive success but only if the bearer can overcome associated costs, the negative effects on the bearer's fitness components. However, recent studies have shown that producing and wielding exaggerated weapons may not necessarily be costly. Rather, some traits can be selected for supporting, or compensating for, the expense of producing and wielding such exaggerated weapons. In the ant-mimicking jumping spider Myrmarachne gisti, exaggerated chelicerae are borne only by adult males and not females, showing sexual dimorphism and steep positive allometry with body size. Here, we determine the potential benefits of bearing exaggerated chelicerae during male contests and explore the potential for costs in terms of prey-capture efficiency and compensation between chelicera size and neighboring trait size. While males with longer chelicerae won most of their male-male contests, we found no significant differences in prey-capture efficiency between males and females regardless of whether prey was winged or flightless. Males' elongated chelicerae thus do not impede their efficiency at capturing prey. Furthermore, we found that the sizes of all neighboring traits are positively correlated with chelicera size, suggesting that these traits may be under correlational selection. Taken together, our findings suggest that M. gisti males armed with the exaggerated chelicerae that function as weapons win more fights at limited cost for performance in prey capture and compensate for neighboring structures.

PI3K/AKT mediated De novo fatty acid synthesis regulates RIG-1/MDA-5-dependent type I IFN responses in BVDV-infected CD8+T cells.

Bovine viral diarrhea virus (BVDV) has caused massive economic losses in the cattle business worldwide. Fatty acid synthase (FASN), a key enzyme of the fatty acid synthesis (FAS) pathway, has been shown to support virus replication. To investigate the role of fatty acids (FAs) in BVDV infection, we infected CD8+T lymphocytes obtained from healthy cattle with BVDV in vitro. During early cytopathic (CP) and noncytopathic (NCP) BVDV infection in CD8+ T cells, there is an increase in de novo lipid biosynthesis, resulting in elevated levels of free fatty acids (FFAs) and triglycerides (TG). BVDV infection promotes de novo lipid biosynthesis in a dose-dependent manner. Treatment with the FASN inhibitor C75 significantly reduces the phosphorylation of PI3K and AKT in BVDV-infected CD8+ T cells, while inhibition of PI3K with LY294002 decreases FASN expression. Both CP and NCP BVDV strains promote de novo fatty acid synthesis by activating the PI3K/AKT pathway. Further investigation shows that pharmacological inhibitors targeting FASN and PI3K concurrently reduce FFAs, TG levels, and ATP production, effectively inhibiting BVDV replication. Conversely, the in vitro supplementation of oleic acid (OA) to replace fatty acids successfully restored BVDV replication, underscoring the impact of abnormal de novo fatty acid metabolism on BVDV replication. Intriguingly, during BVDV infection of CD8+T cells, the use of FASN inhibitors prompted the production of IFN-α and IFN-ß, as well as the expression of interferon-stimulated genes (ISGs). Moreover, FASN inhibitors induce TBK-1 phosphorylation through the activation of RIG-1 and MDA-5, subsequently activating IRF-3 and ultimately enhancing the IFN-1 response. In conclusion, our study demonstrates that BVDV infection activates the PI3K/AKT pathway to boost de novo fatty acid synthesis, and inhibition of FASN suppresses BVDV replication by activating the RIG-1/MDA-5-dependent IFN response.

Multifunctional MXene/PEDOT:PSS-Based Phase Change Organohydrogels for Electromagnetic Interference Shielding and Medium-Low Temperature Infrared Stealth.

Electromagnetic interference (EMI) shielding and infrared stealth technologies are essential for military and civilian applications. However, it remains a significant challenge to integrate various functions efficiently into a material efficiently. Herein, a minimalist strategy to fabricate multifunctional phase change organohydrogels (PCOHs) was proposed, which were fabricated from polyacrylamide (PAM) organohydrogels, MXene/PEDOT:PSS hybrid fillers, and sodium sulfate decahydrate (Na2SO4·10H2O, SSD) via one-step photoinitiation strategies. PCOHs with a high enthalpy value (130.7 J/g) and encapsulation rate (98%) could adjust the temperature by triggering a phase change of SSD, which can hide infrared radiation to achieve medium-low temperature infrared stealth. In addition, the PCOH-based sensor has good strain sensing ability due to the incorporation of MXene/PEDOT:PSS and can precisely monitor human movement. Remarkably, benefiting from the electron conduction of the three-dimensional conductive network and the ion conduction of the hydrogel, the EMI shielding efficiency (k) of PCOHs can reach 99.99% even the filler content as low as 1.8 wt %. Additionally, EMI shielding, infrared stealth, and sensing-integrated PCOHs can be adhered to arbitrary targets due to their excellent flexibility and adaptability. This work offers a promising pathway for fabricating multifunctional phase change materials, which show great application prospects in military and civilian fields.

Far-Infrared Therapy Based on Graphene Ameliorates High-Fat Diet-Induced Anxiety-Like Behavior in Obese Mice via Alleviating Intestinal Barrier Damage and Neuroinflammation.

The consumption of a high-fat diet (HFD) has been implicated in the etiology of obesity and various neuropsychiatric disturbances, including anxiety and depression. Compelling evidence suggests that far-infrared ray (FIR) possesses beneficial effects on emotional disorders. However, the efficacy of FIR therapy in addressing HFD-induced anxiety and the underlying mechanisms remain to be elucidated. Here, we postulate that FIR emitted from a graphene-based therapeutic device may mitigate HFD-induced anxiety behaviors. The graphene-FIR modify the gut microbiota in HFD-mice, particularly by an enriched abundance of beneficial bacteria Clostridiaceae and Erysipelotrichaceae, coupled with a diminution of harmful bacteria Lachnospiraceae, Anaerovoracaceae, Holdemania and Marvinbryantia. Graphene-FIR also improved intestinal barrier function, as evidenced by the augmented expression of the tight junction protein occludin and G protein-coupled receptor 43 (GPR43). In serum level, we observed the decreased free fatty acids (FFA), lipopolysaccharides (LPS), diamine oxidase (DAO) and D-lactate, and increased the glucagon-like peptide-2 (GLP-2) levels in graphene-FIR mice. Simultaneously, inflammatory cytokines IL-6, IL-1ß, and TNF-α manifested a decrease subsequent to graphene-FIR treatment in both peripheral and central system. Notably, graphene-FIR inhibited over expression of astrocytes and microglia. We further noticed that the elevated the BDNF and decreased TLR4 and NF-κB expression in graphene-FIR group. Overall, our study reveals that graphene-FIR rescued HFD-induced anxiety via improving the intestine permeability and the integrity of blood-brain barrier, and reduced inflammatory response by down regulating TLR4/NF-κB inflammatory pathway.

Light-Quality-Adapted Carotenoid Photoprotection in the Photosystem of Roseiflexus castenholzii.

The photosystem of filamentous anoxygenic phototroph Roseiflexus (Rfl.) castenholzii comprises a light-harvesting (LH) complex encircling a reaction center (RC), which intensely absorbs blue-green light by carotenoid (Car) and near-infrared light by bacteriochlorophyll (BChl). To explore the influence of light quality (color) on the photosynthetic activity, we compared the pigment compositions and triplet excitation dynamics of the LH-RCs from Rfl. castenholzii was adapted to blue-green light (bg-LH-RC) and to near-infrared light (nir-LH-RC). Both LH-RCs bind γ-carotene derivatives; however, compared to that of nir-LH-RC (12%), bg-LH-RC contains substantially higher keto-γ-carotene content (43%) and shows considerably faster BChl-to-Car triplet excitation transfer (10.9 ns vs 15.0 ns). For bg-LH-RC, but not nir-LH-RC, selective photoexcitation of Car and the 800 nm-absorbing BChl led to Car-to-Car triplet transfer and BChl-Car singlet fission reactions, respectively. The unique excitation dynamics of bg-LH-RC enhances its photoprotection, which is crucial for the survival of aquatic anoxygenic phototrophs from photooxidative stress.

Sevelamer reverses liver fibrosis by deactivation of hepatic stellate cells.

Liver fibrosis is a chronic liver disease characterized by a progressive wound healing response caused by chronic liver injury. Currently, there are no approved clinical treatments for liver fibrosis. Sevelamer is used clinically to treat hyperphosphatemia and has shown potential therapeutic effects on liver diseases. However, there have been few studies evaluating the therapeutic effects of sevelamer on liver fibrosis, and the specific mechanisms are still unclear. In this study, we investigated the antifibrotic effects of sevelamer-induced low inorganic phosphate (Pi) stress in vitro and in vivo and analyzed the detailed mechanisms. We found that low Pi stress could inhibit the proliferation of activated hepatic stellate cells (HSCs) by promoting apoptosis, effectively suppressing the migration and epithelial-mesenchymal transition (EMT) of hepatic stellate cells. Additionally, low Pi stress significantly increased the antioxidant stress response. It is worth noting that low Pi stress indirectly inhibited the activation and migration of HSCs by suppressing transforming growth factor ß (TGF-ß) expression in macrophages. In a rat model of liver fibrosis, oral administration of sevelamer significantly decreased blood phosphorus levels, improved liver function, reduced liver inflammation, and increased the antioxidant stress response in the liver. Our study revealed that the key mechanism by which sevelamer inhibited liver fibrosis involved binding to gastrointestinal phosphate, resulting in a decrease in blood phosphorus levels, the downregulation of TGF-ß expression in macrophages, and the inhibition of HSC migration and fibrosis-related protein expression. Therefore, our results suggest that sevelamer-induced low Pi stress can attenuate hepatic stellate cell activation and inhibit the progression of liver fibrosis, making it a potential option for the treatment of liver fibrosis and other refractory chronic liver diseases.