Cerebral 18F-FDG PET/CT Metabolism as Diagnostic Signature for Central Nervous System Toxicity After Immune Checkpoint Blockade Cancer Treatment.

Our aim was to investigate probable biomarkers specific to immune-related central nervous system toxicity (CNST) in cancer patients treated with immune checkpoint inhibitors (ICI) by analysis of 18F-FDG PET/CT images. Methods: Cancer patients receiving ICI treatment were enrolled in a multicenter observational study that analyzed regional metabolic changes before and during CNST onset from January 2020 to February 2022. In 1:1 propensity score-matched pairs, the regional SUVmean of each bilateral brain lobe of CNST patients (CNST+) was compared with that of patients who had central nervous system infections (CNSIs) and patients without CNST or CNSI (CNST-). In a validation cohort, patients were recruited from February 2022 to July 2023 and followed up for 24 wk after the start of ICI. Early changes in regional SUVmean at 5-6 wk after therapy initiation were evaluated for ability to predict later CNST onset. Results: Of 6,395 ICI-treated patients, 2,387 underwent prognostic 18F-FDG PET/CT and 125 of the scanned patients had CNST (median time from ICI treatment to onset, 9 wk; quartile range, 2-23 wk). Regional 18F-FDG PET/CT SUVmean changes were higher in CNST+ than in CNST- patients (117 patient pairs) but were lower than in CNSI patients (50 pairs). Differentiating analysis reached an area under the curve (AUC) of 0.83 (95% CI, 0.78-0.88) for CNST+ versus CNST- and of 0.80 (95% CI, 0.72-0.89) for CNST+ versus CNSI. Changes in SUVmean were also higher before CNST onset than for CNST- (60 pairs; AUC, 0.74; 95% CI, 0.66-0.83). In a validation cohort of 2,878 patients, preonset changes in SUVmean reached an AUC of 0.86 (95% CI, 0.79-0.94) in predicting later CNST incidence. Conclusion: Brain regional hypermetabolism could be detected during and before CNST clinical onset. CNST may be a distinct pathologic entity versus brain infections defined by 18F-FDG PET/CT brain scans. Regional SUV differences may be translated into early diagnostic tools based on moderate differentiating accuracy in our study.

The contributions of vaccination and natural infection to the production of neutralizing antibodies against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prototype strain and variants.

OBJECTIVES: To evaluate the neutralizing antibody (NAbs) levels against the SARS-CoV-2 Omicron variants BF.7, BQ.1, BQ.1.1, XBB.1, and XBB.1.5 after vaccination and natural infection. METHODS: The NAbs against the different viral strains of 490 SARS-CoV-2 infected and 187 uninfected individuals in Beijing COVID-19 outbreak during December 2022 to January 2023 were analyzed. RESULTS: In uninfected individuals, limited levels of NAbs were produced against both the prototype and variant strains after two doses vaccine, but significantly increased after three or four doses vaccine. The infected individuals had high NAbs levels against the BF.7, BQ.1, and BQ.1.1 variants and moderate NAbs levels against the XBB.1 and XBB.1.5 variants. The highest NAbs levels were observed after two inoculation doses. The third and fourth doses vaccine did not result in a significant increase the NAbs levels. After the last dose of vaccination, the NAbs levels peaked at 12 months for the prototype and BF.7 and between 6 to 12 months for the BQ.1, BQ.1.1, XBB.1, and XBB.1.5 variants. CONCLUSION: The immune response decreases as the virus mutates. If booster vaccination is considered necessary, it is suggested for at least 6 months after infection.

Loss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice.

Viral myocarditis, an inflammatory disease of the myocardium, is a significant cause of sudden death in children and young adults. The current coronavirus disease 19 pandemic emphasizes the need to understand the pathogenesis mechanisms and potential treatment strategies for viral myocarditis. Here, we found that TRIM29 was highly induced by cardiotropic viruses and promoted protein kinase RNA-like endoplasmic reticulum kinase (PERK)-mediated endoplasmic reticulum (ER) stress, apoptosis, and reactive oxygen species (ROS) responses that promote viral replication in cardiomyocytes in vitro. TRIM29 deficiency protected mice from viral myocarditis by promoting cardiac antiviral functions and reducing PERK-mediated inflammation and immunosuppressive monocytic myeloid-derived suppressor cells (mMDSC) in vivo. Mechanistically, TRIM29 interacted with PERK to promote SUMOylation of PERK to maintain its stability, thereby promoting PERK-mediated signaling pathways. Finally, we demonstrated that the PERK inhibitor GSK2656157 mitigated viral myocarditis by disrupting the TRIM29-PERK connection, thereby bolstering cardiac function, enhancing cardiac antiviral responses, and curbing inflammation and immunosuppressive mMDSC in vivo. Our findings offer insight into how cardiotropic viruses exploit TRIM29-regulated PERK signaling pathways to instigate viral myocarditis, suggesting that targeting the TRIM29-PERK axis could mitigate disease severity.

Can botulinum toxin injection alleviate the pain of bruxism? A Bayesian network analysis and a single-arm analysis.

Background/purpose: There is inconsistent evidence regarding whether the botulinum toxin A (BTA) injection can relieve pain caused by bruxism. This study aimed to estimate the efficiency of BTA injection in relieving pain caused by bruxism at different follow-up periods. Materials and methods: Five electronic databases were searched from 2005 to 2022 using search terms related to botulinum toxin and bruxism. Only controlled clinical trials were included. Two investigators reviewed each article and discussed any disagreements until a consensus was reached. Pain outcomes as evaluated by the visual analogue scale (VAS) were subjected to single-arm and Bayesian network meta-analyses. Pooling data were measured by a random-effects model. Results: Eleven studies with a total of 365 bruxism patients were included. According to the single-arm analyses of the pooled data, the reduction in bruxism-related pain after BTA injection measured 4.06 points (95% CI = 3.37 to 4.75) on the VAS, and the pain relief was significant in the first 6 months after treatment (P < 0.01). According to the Bayesian analysis, BTA also resulted in significantly greater pain relief than oral splinting (mean difference (MD), -1.5; 95% credible interval (CrI) = -2.7 to -0.19) or saline injection (MD, -3.3; 95% CrI = -6.2 to -0.32). Conclusion: BTA significantly relieves the pain of bruxism for 6 months after injection, and its therapeutic efficacy was higher than that of oral splinting. Nevertheless, further long-term follow-up randomized controlled trials comparing BTA with other management or drugs are warranted.

Design, Synthesis, and Pharmacological Evaluation of Spiro[carbazole-3,3'-pyrrolidine] Derivatives as cGAS Inhibitors for Treatment of Acute Lung Injury.

Overactivation of cyclic GMP-AMP synthase (cGAS) is implicated in the occurrence of many inflammatory and autoimmune diseases, and inhibition of cGAS with a specific inhibitor has been proposed as a potential therapeutic strategy. However, only a few low-potency cGAS inhibitors have been reported, and few are suitable for clinical investigation. As a continuation of our structural optimization on the reported cGAS inhibitor 6 (G140), we developed a series of spiro[carbazole-3,3'-pyrrolidine] derivatives bearing a unique 2-azaspiro[4.5]decane structural motif, among which compound 30d-S was identified with high cellular effects against cGAS. This compound showed improved plasma exposure, lower clearance, and an oral bioavailability of 35% in rats. Moreover, in the LPS-induced acute lung injury (ALI) mice model, oral administration of compound 30d-S at 30 mg/kg markedly reduced lung inflammation and alleviated histopathological changes. These results confirm that 30d-S is a new efficacious cGAS inhibitor and is worthy of further investigation.

Effects of combined drying techniques and cellulase hydrolysis on the nutritional value and sensory properties of shiitake mushrooms (Lentinus edodes).

Dried shiitake mushrooms offer rich nutritional value and unique sensory properties, prompting further investigation. The effects of different drying techniques (hot air drying (HAD), infrared hot air drying (IRHAD), pulsed vacuum drying (PVD), vacuum freeze drying (VFD), and natural drying (ND)) combined with enzymatic hydrolysis on the release of flavor compounds and nutrients from shiitake mushrooms were explored. The combination of HAD with cellulase hydrolysis yielded notably high levels of umami amino acids (5.4723 ± 0.1501 mg/g) and 5'-nucleotides (4.0536 ± 0.0062 mg/g), and superior volatile flavors. Combined with cellulase hydrolysis, IRHAD achieved the highest level of total sugars (6.57 ± 0.34 mg/mL), VFD resulted in the greatest soluble protein content (153.21 ± 0.23 µg/mL), PVD yielded the highest total phenolics content (93.20 ± 0.41 µg GAE/mL), and ND produced the maximum reducing sugar content (5.79 ± 0.13 mg/mL). This study addresses crucial gap in the post-drying processing of shiitake mushrooms, offering valuable insights for further product development of shiitake mushrooms.

Establishment and application of a rapid diagnostic method for BVDV and IBRV using recombinase polymerase amplification-lateral flow device.

Bovine Viral Diarrhea Virus (BVDV) and Infectious Bovine Rhinotracheitis Virus (IBRV) are the two most prevalent infectious diseases in cattle. They both can cause persistent infection and immunosuppression, resulting in significant economic losses in the livestock industry. Therefore, rapid detection of early BVDV and IBRV infections is crucial. In this study, a method for the rapid detection of BVDV and IBRV was established by using recombinase polymerase amplification (RPA) combined with lateral flow device (LFD). By optimizing the temperature and time conditions of the RPA reaction, the sensitivity, specificity, and clinical performance were evaluated. The results indicated that the RPA reaction could be completed at 40°C within 25 min. The LOD for BVDV and IBRV by RPA-LFD were 5.1 × 101 copies/µL and 6.65 × 101 copies/µL, respectively, with no cross-reactivity observed with other viruses such as CSFV, BRSV, BPIV3, BRV, and BCoV. Testing of 32 clinical samples showed consistent results between RPA-LFD and qPCR. The RPA-LFD method established in this study can be used for the rapid clinical detection of BVDV and IBRV, which providing a rapid and convenient molecular biology approach for on-site rapid detection and epidemiological investigations. Simultaneously, it offers technical support for the prevention and control of these viruses.

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus.

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation.

Xiaochaihu granules (XCHG) are extensively used to treat fever. Nevertheless, the underlying mechanism remains elusive. This study aimed to explore the potential of XCHG in mitigating yeast-induced fever and the underlying metabolic pathways. The chemical composition of XCHG was ascertained using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), followed by integrated network analysis to predict potential targets. We then conducted experimental validation using pharmacological assays and metabolomics analysis in a yeast-induced mouse fever model. The study identified 133 compounds in XCHG, resulting in the development of a comprehensive network of herb-compound-biological functional modules. Subsequently, molecular dynamic (MD) simulations confirmed the stability of the complexes, including γ-aminobutyric acid B receptor 2 (GABBR2)-saikosaponin C, prostaglandin endoperoxide synthases (PTGS2)-lobetyolin, and NF-κB inhibitor IκBα (NFKBIA)-glycyrrhizic acid. Animal experiments demonstrated that XCHG reduced yeast-induced elevation in NFKBIA's downstream regulators [interleukin (IL)-1ß and IL-8], inhibited PTGS2 activity, and consequently decreased prostaglandin E2 (PGE2) levels. XCHG also downregulated the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), corticotropin releasing hormone (CRH), and adrenocorticotrophin (ACTH). These corroborated the network analysis results indicating XCHG's effectiveness against fever in targeting NFKBIA, PTGS2, and GABBR2. The hypothalamus metabolomics analysis identified 14 distinct metabolites as potential antipyretic biomarkers of XCHG. In conclusion, our findings suggest that XCHG alleviates yeast-induced fever by regulating inflammation/immune responses, neuromodulation, and metabolism modules, providing a scientific basis for the anti-inflammatory and antipyretic properties of XCHG.

Ultrasound elastography predicts anticoagulation in lower extremity deep vein thrombosis.

OBJECTIVE: To investigate predictors of anticoagulation efficacy in deep venous thrombosis (DVT) by ultrasound elastography (UE). METHODS: The basic clinical, laboratory and ultrasound treatment data of fifty-eight patients with DVT were collected and analyzed. Then the results of ultrasound after 3-month anticoagulation treatment were compared among different groups. Multiple logistic regression analysis was used to identify independent risk factors that affected anticoagulation efficacy. The predictive efficacy of each independent risk factor was accessed by drawing operating characteristic (ROC) curves. RESULTS: According to the regression analysis, the elastic modulus (OR = 0.631, P = 0.001) and strain rate ratio (OR = 0.332, P = 0.006) were identified as independent risk factors for the effectiveness of anticoagulation therapy in patients with DVT. According to the ROC curves, elastic modulus and strain rate ratio could predict effective anticoagulation therapy for DVT, and the optimal threshold values were 22.10 kPa and 1.80 respectively. The corresponding AUC values were 0.879 and 0.854, with a sensitivity of 71.4% and 59.5%, a specificity of 93.7%, and a Youden index of 65.1% and 62.7%, respectively. CONCLUSIONS: The elastic modulus (≤22.10 kPa) or strain rate ratio (≤1.80) of the thrombus were independent predictors for the effectiveness of anticoagulation therapy.

col1a2+ fibroblasts/muscle progenitors finetune xanthophore countershading by differentially expressing csf1a/1b in embryonic zebrafish.

Animals evolve diverse pigment patterns to adapt to the natural environment. Countershading, characterized by a dark-colored dorsum and a light-colored ventrum, is one of the most prevalent pigment patterns observed in vertebrates. In this study, we reveal a mechanism regulating xanthophore countershading in zebrafish embryos. We found that csf1a and csf1b mutants altered xanthophore countershading differently: csf1a mutants lack ventral xanthophores, while csf1b mutants have reduced dorsal xanthophores. Further study revealed that csf1a is expressed throughout the trunk, whereas csf1b is expressed dorsally. Ectopic expression of csf1a or csf1b in neurons attracted xanthophores into the spinal cord. Blocking csf1 signaling by csf1ra mutants disrupts spinal cord distribution and normal xanthophores countershading. Single-cell RNA sequencing identified two col1a2+ populations: csf1ahighcsf1bhigh muscle progenitors and csf1ahighcsf1blow fibroblast progenitors. Ablation of col1a2+ fibroblast and muscle progenitors abolished xanthophore patterns. Our study suggests that fibroblast and muscle progenitors differentially express csf1a and csf1b to modulate xanthophore patterning, providing insights into the mechanism of countershading.

Dynamic transcriptome profiling revealed a key gene ZmJMJ20 and pathways associated with cadmium stress in maize.

Cadmium (Cd) pollution in soil poses a global concern due to its serious impacts on human health and ecological security. In plants, tremendous efforts have been made to identify some key genes and pathways in Cd stress responses. However, studies on the roles of epigenetic factors in response to Cd stress were still limited. In the study, we first gain insight into the gene expression dynamics for maize seedlings under 0 h, 12 h, and 72 h Cd stress. As a result, six distinct groups of genes were identified by hierarchical clustering and principal component analysis. The key pathways associated with 12 h Cd stress were protein modifications including protein ubiquitination, signal transduction by protein phosphorylation, and histone modification. Whereas, under 72 h stress, main pathways were involved in biological processes including phenylalanine metabolism, response to oxygen-containing compounds and metal ions. Then to be noted, one of the most highly expressed genes at 12 h under Cd treatment is annotated as histone demethylases (ZmJMJ20). The evolutionary tree analysis and domain analysis showed that ZmJMJ20 belonged to the JmjC-only subfamily of the Jumonji-C (JmjC) family, and ZmJMJ20 was conserved in rice and Arabidopsis. After 72 h of Cd treatment, the zmjmj20 mutant created by EMS treatment manifested less severe chlorosis/leaf yellowing symptoms compared with wild-type plants, and there was no significant difference in Fv/Fm and φPSII value before and after Cd treatment. Moreover, the expression levels of several photosynthesis-related down-regulated genes in EMS mutant plants were dramatically increased compared with those in wild-type plants at 12 h under Cd treatment. Our results suggested that ZmJMJ20 plays an important role in the Cd tolerance response pathway and will facilitate the development of cultivars with improved Cd stress tolerance.

Discovery of Urea Derivatives of Celastrol as Selective Peroxiredoxin 1 Inhibitors against Colorectal Cancer Cells.

Peroxiredoxin (PRDX1) is a tumor-overexpressed antioxidant enzyme for eliminating excessive reactive oxygen species (ROS) to protect tumor cells from oxidative damage. Herein, a series of celastrol urea derivatives were developed based on its cocrystal structure with PRDX1, with the aim of pursuing a PRDX1-specific inhibitor. Among them, derivative 15 displayed potent anti-PRDX1 activity (IC50 = 0.35 µM) and antiproliferative potency against colon cancer cells. It covalently bound to Cys-173 of PRDX1 (KD = 0.37 µM), which was secured by the cocrystal structure of PRDX1 with an analogue of 15 while exhibiting weak inhibitory effects on PRDX2-PRDX6 (IC50 > 50 µM), indicating excellent PRDX1 selectivity. Treatment with 15 dose-dependently decreased the mitochondria membrane potential of SW620 cells, probably due to ROS induced by PRDX1 inhibition, leading to cell apoptosis. In colorectal cancer cell xenograft model, it displayed potent antitumor efficacy with superior safety to celastrol. Collectively, 15 represents a promising PRDX1 selective inhibitor for the development of anticolorectal cancer agents.

Broadband nonlinear modulation of incoherent light using a transparent optoelectronic neuron array.

Nonlinear optical processing of ambient natural light is highly desired for computational imaging and sensing. Strong optical nonlinear response under weak broadband incoherent light is essential for this purpose. By merging 2D transparent phototransistors (TPTs) with liquid crystal (LC) modulators, we create an optoelectronic neuron array that allows self-amplitude modulation of spatially incoherent light, achieving a large nonlinear contrast over a broad spectrum at orders-of-magnitude lower intensity than achievable in most optical nonlinear materials. We fabricated a 10,000-pixel array of optoelectronic neurons, and experimentally demonstrated an intelligent imaging system that instantly attenuates intense glares while retaining the weaker-intensity objects captured by a cellphone camera. This intelligent glare-reduction is important for various imaging applications, including autonomous driving, machine vision, and security cameras. The rapid nonlinear processing of incoherent broadband light might also find applications in optical computing, where nonlinear activation functions for ambient light conditions are highly sought.

Platinum Surface Water Orientation Dictates Hydrogen Evolution Reaction Kinetics in Alkaline Media.

The fundamental understanding of sluggish hydrogen evolution reaction (HER) kinetics on a platinum (Pt) surface in alkaline media is a topic of considerable debate. Herein, we combine cyclic voltammetry (CV) and electrical transport spectroscopy (ETS) approaches to probe the Pt surface at different pH values and develop molecular-level insights into the pH-dependent HER kinetics in alkaline media. The change in HER Tafel slope from ∼110 mV/decade in pH 7-10 to ∼53 mV/decade in pH 11-13 suggests considerably enhanced kinetics at higher pH. The ETS studies reveal a similar pH-dependent switch in the ETS conductance signal at around pH 10, suggesting a notable change of surface adsorbates. Fixed-potential calculations and chemical bonding analysis suggest that this switch is attributed to a change in interfacial water orientation, shifting from primarily an O-down configuration below pH 10 to a H-down configuration above pH 10. This reorientation weakens the O-H bond in the interfacial water molecules and modifies the reaction pathway, leading to considerably accelerated HER kinetics at higher pH. Our integrated studies provide an unprecedented molecular-level understanding of the nontrivial pH-dependent HER kinetics in alkaline media.

Overlapping cytoplasms segmentation via constrained multi-shape evolution for cervical cancer screening.

Segmenting overlapping cytoplasms in cervical smear images is a clinically essential task for quantitatively measuring cell-level features to screen cervical cancer This task, however, remains rather challenging, mainly due to the deficiency of intensity (or color) information in the overlapping region Although shape prior-based models that compensate intensity deficiency by introducing prior shape information about cytoplasm are firmly established, they often yield visually implausible results, as they model shape priors only by limited shape hypotheses about cytoplasm, exploit cytoplasm-level shape priors alone, and impose no shape constraint on the resulting shape of the cytoplasm In this paper, we present an effective shape prior-based approach, called constrained multi-shape evolution, that segments all overlapping cytoplasms in the clump simultaneously by jointly evolving each cytoplasm's shape guided by the modeled shape priors We model local shape priors (cytoplasm-level) by an infinitely large shape hypothesis set which contains all possible shapes of the cytoplasm In the shape evolution, we compensate intensity deficiency for the segmentation by introducing not only the modeled local shape priors but also global shape priors (clump-level) modeled by considering mutual shape constraints of cytoplasms in the clump We also constrain the resulting shape in each evolution to be in the built shape hypothesis set for further reducing implausible segmentation results We evaluated the proposed method in two typical cervical smear datasets, and the extensive experimental results confirm its effectiveness.

A Novel Bifunctional Alginate Lyase and Antioxidant Activity of the Enzymatic Hydrolysates.

Alginate lyase Aly448, a potential new member of the polysaccharide lyase (PL) 7 family, which was cloned and identified from the macroalgae-associated bacterial metagenomic library, showed bifunctionality. The molecular docking results revealed that Aly448 has two completely different binding sites for alginate (polyMG), poly-α-l-guluronic acid (polyG), and poly-ß-d-mannuronic acid (polyM) substrates, respectively, which might be the molecular basis for the enzyme's bifunctionality. Truncational results confirmed that predicted key residues affected the bifunctionality of Aly448, but did not wholly explain. Besides, Aly448 presented excellent biochemical characteristics, such as higher thermal stability and pH tolerance. Degradation of polyMG, polyM, and polyG substrates by Aly448 produced tetrasaccharide (DP4), disaccharide (DP2), and galactose (DP1), which exhibited excellent antioxidant activity. These findings provide novel insights into the substrate recognition mechanism of bifunctional alginate lyases and pave a new path for the exploitation of natural antioxidant agents.

Deacetylase Sirtuin 1 mitigates type I IFN- and type II IFN-induced signaling and antiviral immunity.

Type I and type II IFNs are important immune modulators in both innate and adaptive immunity. They transmit signaling by activating JAK-STAT pathways. Sirtuin 1 (SIRT1), a class III NAD+-dependent deacetylase, has multiple functions in a variety of physiological processes. Here, we characterized the novel functions of SIRT1 in the regulation of type I and type II IFN-induced signaling. Overexpression of SIRT1 inhibited type I and type II IFN-induced interferon-stimulated response element activation. In contrast, knockout of SIRT1 promoted type I and type II IFN-induced expression of ISGs and inhibited viral replication. Treatment with SIRT1 inhibitor EX527 had similar positive effects. SIRT1 physically associated with STAT1 or STAT3, and this interaction was enhanced by IFN stimulation or viral infection. By deacetylating STAT1 at K673 and STAT3 at K679/K685/K707/K709, SIRT1 downregulated the phosphorylation of STAT1 (Y701) and STAT3 (Y705). Sirt1+/- primary peritoneal macrophages and Sirt1+/- mice exhibited enhanced IFN-induced signaling and antiviral activity. Thus, SIRT1 is a novel negative regulator of type I and type II IFN-induced signaling through its deacetylase activity.IMPORTANCESIRT1 has been reported in the precise regulation of antiviral (RNA and DNA) immunity. However, its functions in type I and type II IFN-induced signaling are still unclear. In this study, we deciphered the important functions of SIRT1 in both type I and type II IFN-induced JAK-STAT signaling and explored the potential acting mechanisms. It is helpful for understanding the regulatory roles of SIRT1 at different levels of IFN signaling. It also consolidates the notion that SIRT1 is an important target for intervention in viral infection, inflammatory diseases, or even interferon-related therapies.

Quorum sensing effect of chiral d-glutamine on the modulation of the intestinal microbiota of mice by Lactiplantibacillus plantarum A3.

BACKGROUND: Amino acids (AAs) are the building blocks of proteins, but they also serve as biological compounds in biochemical processes, and d-AA isomers are increasingly being recognized as important signaling molecules. As the main organic substrate used by cells in the intestinal tract, the role of the chiral specificity of glutamine is still largely ignored. RESULTS: In a previous study, we found that d-glutamine affected the quorum sensing of Lactiplantibacillus plantarum A3, promoted the release of signaling molecule AI-2 and up-regulated the expression of the LuxS gene. The results showed that when d-glutamine and L. plantarum A3 were simultaneously applied to a mouse model, the diversity and abundance of intestinal flora in both male and female mice were increased. Interestingly, the simultaneous effect of d-glutamine and L. plantarum A3 on the bacterial diversity and abundance of male mice was significantly higher than that of female mice. In addition, the combination of d-glutamine and L. plantarum A3 can improve the host microecology by enhancing the population of Firmicutes such as Lactobacillus and Lachnospiraceae, reducing the population of Fusobacterium and Bacteroides and affecting metabolic pathways such as AA metabolism and transporter transport. CONCLUSION: d-Glutamine, as a signaling molecule, can better stimulate the endogenous d-glutamine synthesis in mice and be utilized by L. plantarum A3. Furthermore, sex differences in the changes of intestinal microflora are also found in this research. This research sheds some light on the adoption of d-AAs combined with lactic acid bacteria in intestinal tract health treatment. © 2024 Society of Chemical Industry.