The prognostic role of pre-treatment neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in esophageal squamous cell carcinoma treated with concurrent chemoradiotherapy.

PURPOSE: In this study, we retrospectively investigated the prognostic role of pre-treatment neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in esophageal squamous cell carcinoma patients (ESCC) treated with concurrent chemo-radiotherapy (CCRT). METHODS: We retrospectively analyzed the records of 338 patients with pathologically diagnosed esophageal squamous cell carcinoma that underwent concurrent chemo-radiotherapy from January 2013 to December 2017. Univariate and multivariate analyses were used to identify prognostic factors for progression free survival (PFS) and overall survival (OS). RESULTS: The result showed that the thresholds for NLR and PLR were 2.47 and 136.0 by receiver operating characteristic curve. High NLR and PLR were both associated with tumor length (P < 0.05). High NLR and PLR were significantly associated with poor PFS and OS. Multivariate analyses identified NLR, PLR and TNM stage were independent risk factors for PFS and OS. CONCLUSIONS: We show that the pre-treatment NLR and PLR may serve as prognostic indicators for esophageal squamous cell carcinoma treated with concurrent chemo-radiotherapy.

Preparation of a Polycarboxylate Superplasticizer with Different Monomer Regulations and Its Effect on Fluidity, Rheology, and Strength of Cement.

Polycarboxylate superplasticizers (PCEs) are indispensable functional ingredients in modern construction, and their usage is extensive. Herein, a polyether macromonomer (VPEG) with high reactivity was used to prepare VAPCEs with different interfacial adsorption properties (acid-ether ratio) at low temperatures and reacted in 30 min. The effects of various VAPCEs on the fluidity, rheology, and strength of cement were investigated with a w/c (water/cement) ratio of 0.35. Results showed that VAPCE-3 (acid-ether ratio is 3) exhibited the best dispersion, and the fluidity of cement slurry with VAPCE-3 (280 mm) is 278.38% higher than that of the control sample (74 mm). The reason is summarized as VAPCE-3 having good adsorption performance on the surface of cement particles and having a large steric hindrance between particles. The compressive strength of cement with VAPCE-3 was enhanced by 8.29% compared with pure cement in 3 days of curing age due to its densification on microstructure and lowest R orientation index of calcium hydroxide. With the amount of acrylic acid in VAPCE increasing, the flexural strength enhanced because a more cross-linking network was formed with Ca2+ in cement with the increase of COO- content in VAPCEs.

Expectations for employing Escherichia coli Nissle 1917 in food science and nutrition.

As a promising probiotic strain, Escherichia coli Nissle 1917 (EcN) has been demonstrated to confer beneficial effects on intestinal health, immune function, and pathogen prevention. Additionally, EcN has also been widely studied due to its clear genomic information, tractable gene regulation, and simple growth conditions. This review summarizes the various applications potential of EcN in food science and nutrition, including inflammation prevention, tumor-targeting therapy, antibacterial agents for food, and nutrient production with a focus on specific case studies. Moreover, we highlight the major challenges of employing EcN in food science and nutrition, including regulatory approval, stability during food processing, and consumer acceptance. Finally, we conclude with a discussion on perspectives related to employing EcN in food science and nutrition.

Predictors and prognosis of early neurological outcomes on patients with Vertebrobasilar artery occlusion undergoing endovascular treatment.

BACKGROUND: This research explored the factors influencing early neurological outcomes (ENO) in patients who had vertebrobasilar artery occlusion (VBAO) and received endovascular treatment (EVT), as well as examining the causal influence of ENO on the prognosis of VBAO patients. METHODS: A retrospective review was carried out on patients from 65 Chinese stroke centers, all within 24 hours of the estimated occlusion time. ENO includes early neurological improvement (ENI) and early neurological deterioration (END), defined as a decrease or an increase of at least 4 points in NIHSS score between baseline and 24 hours after EVT. Death within 24 hours after EVT also consider as END. END was further divided into explainable END and unexplainable END (unEND). Independent predictors of ENO and the association between ENO and outcomes in patients with VBAO were determined using center-adjusted analyses. The study developed a multivariate logistic regression model to examine the comparative risk of unEND versus explainable END on the clinical outcomes in VBAO patients. RESULTS: A total of 2257 patients were included. Glasgow Coma Scale (GCS) (OR 1.16, 95% CI 1.03-1.30) and successful reperfusion (OR 1.15, 95% CI 1.02-1.30) were associated with ENI. Baseline NIHSS (OR 0.60, 95% CI 0.53-0.68), successful reperfusion (OR 0.79, 95% CI 0.71-0.89) and puncture to reperfusion time (OR 1.17, 95% CI 1.03-1.33) were associated with END. When examining three-month prognostic indexes, both END and ENI were found to be linked to the three-month outcomes, but in opposite directions. A subgroup analysis of END suggested that unexplained END typically demonstrated a more favorable prognosis compared to explained END, although the prognosis remained generally unfavorable. CONCLUSIONS: ENO, whether they manifested as early improvement or deterioration, were linked to the prognosis of VBAO patients undergoing EVT. The outcomes after unEND were more favorable than those following explained END.

Prediction of the bioaccessibility and accumulation of cadmium in the soil-rice-human system based on optimized DGT and BCR coupled models.

Cadmium, as a typical heavy metal, has the potential to induce soil pollution and threaten human health through the soil-plant-human pathway. The conventional evaluation method based on the total content in soil cannot accurately represent the content migrated from the food chain to plants and the human body. Previous studies focused on the process of plant enrichment of heavy metals in soil, and very few studies directly predicted human exposure or risk through the labile state of Cd in soil. Hence, a relatively accurate and convenient prediction model of Cd release and translocation in the soil-rice-human system was developed. This model utilizes available Cd and soil parameters to predict the bioavailability of Cd in soil, as well as the in vitro bioaccessibility of Cd in cooked rice. The bioavailability of Cd was determined by the Diffusive Gradients in Thin-films technology and BCR sequential extraction procedure, offering in-situ quantification, which presents a significant advantage over traditional monitoring methods and aligns closely with the actual uptake of heavy metals by plants. The experimental results show that the prediction model based on the concentration of heavy metal forms measured by BCR sequential extraction procedure and diffusive gradients in thin-films technique can accurately predict the Cd uptake in rice grains, gastric and gastrointestinal phase (R2=0.712, 0.600 and 0.629). This model accurately predicts Cd bioavailability and bioaccessibility across the soil-rice-human pathway, informing actual human Cd intake, offering scientific support for developing more effective risk assessment methods.

CT-based and CTA-based posterior circulation ASPECTS in acute basilar artery occlusion: An Agreement Study.

BACKGROUND AND PURPOSE: The purpose of the present study was to evaluate the agreement on pc-ASPECTS (posterior circulation Acute Stroke Prognosis Early Computed Tomography Scores) based on non-contrast CT (NCCT) and CT angiography (CTA) source images in patients with acute basilar artery occlusion (BAO). METHODS: We prospectively enrolled consecutive patients with acute BAO from January 2022 to August 2022 at The First Affiliated Hospital of University of Science and Technology of China. The NCCT and CTA were scored independently by 15 raters during 2 different reading sessions at least 3 weeks apart. The pc-ASPECTS based on NCCT and CTA were analyzed on the full scale or were dichotomized (0-6 versus 7-10, 0-7 versus 8-10 and 0-8 versus 9-10). The level of agreement was measured using Fleiss κ Statistics. RESULTS: The median (IQR) CT-based pc-ASPECTS was 8 (6.75-9). The interrater agreement for CT-based pc-ASPECTS (κ=0.133 [0.132-0.133]) and CTA-based pc-ASPECTS (κ=0.204 [0.203-0.204]) was slight for all raters. Dichotomizations obtaining the highest concordance for the CT-based pc-ASPECTS (0-6 versus 7-10) and the CTA-based pc-ASPECTS (0-8 versus 9-10) failed to increase the interrater agreement to a substantial level (κ=0.350 [0.348-0.351] and 0.396 [0.395-0.398], respectively). Intrarater agreement for global CT-based pc-ASPECTS was less than substantial for the 14/15 raters and reached the level of substantial for the 3/15 raters with dichotomization. CONCLUSIONS: Agreement between clinicians assessing CT-based and CTA-based pc-ASPECTS cannot be sufficient to make reproducible clinical decisions and assessments. The dichotomization failed to improve interrater and intrarater agreement to the level of substantial.

Maribacter aquimaris sp. nov., isolated from seawater adjacent to Fildes Peninsula, Antarctica.

A novel Gram-stain-negative, aerobic, and rod-shaped bacterium with gliding motility, named strain ANRC-HE7T, was isolated from the seawater of Biological Bay adjacent to Fildes Peninsula, Antarctica. The optimal growth of this strain occurred at 28 °C, pH 7.5, and in the presence of 1.0% (w/v) NaCl. Strain ANRC-HE7T can produce amylase and harbors gene clusters involved in cellulose degradation. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain ANRC-HE7T formed a distinct lineage within the genus Maribacter and was closely related to Maribacter luteus RZ05T (98.4% sequence similarity), Maribacter polysiphoniae LMG 23671T (98.3%), and Maribacter arenosus CAU 1321T (97.3%). However, digital DNA-DNA hybridization and average nucleotide identity values between strain ANRC-HE7T and closely related strains were 17.4-49.1% and 70.9-92.7%, much lower than the cutoff values of 70% and 95%, respectively. On the other hand, strain ANRC-HE7T shared characteristics with most type strains within the genus. Its respiratory quinone was MK-6. The major fatty acids were iso-C15:0, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), and anteiso-C15:0. The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids, four unidentified phospholipids, and five unidentified glycolipids. The DNA G + C content of strain ANRC-HE7T was 40.1%. Based on the results of the biochemical, phylogenetic, and chemotaxonomic analyses, strain ANRC-HE7T is suggested to represent a novel species of the genus Maribacter, for which the name Maribacter aquimaris sp. nov. is proposed. The type strain is ANRC-HE7T (= MCCC 1K03787T = KCTC 72532T).

Mechanism underlying the effect of MnO2 nanosheets for A549 cell chemodynamic therapy.

MnO2 nanosheets (MnO2NSs) were synthesized by one-step method, and MnO2NSs were applied to A549 cell chemodynamic Therapy (CDT). The cytotoxicity, redox ability, and reactive oxygen species production of MnO2NSs have been investigated, and differences in cell metabolism during CDT were determined using liquid chromatography-mass spectrometry (LC-MS/MS). In addition, the metabolites of A549 lung cancer cells affected by MnO2NSs treatment are identified; metabolite differences were identified by PCA, PLS-DA, orthogonal PLS-DA, and other methods; and these differences were analyzed using non-targeted metabolomics. We found that A549 cells which were treated by MnO2NSs have 17 different metabolites and 9 metabolic pathways that varied markedly. Owing to their unique composition, structure, and physicochemical properties, MnO2NSs and their composites have become a favored type of nanomaterial used for CDT in cancer therapy. This work provides insights into the mechanism underlying the effects of MnO2NSs on the tumor microenvironment of A549 lung cancer cells, effectively making up for the deficiency of the study on cellular mechanism of CDT-induced apoptosis of cancer cells. It could aid the development of cancer CDT treatment strategies and help improve the use of nanomaterials in the clinical field.

Permeabilized whole cells containing co-expressed cyclomaltodextrinase and maltooligosyltrehalose synthase facilitate the synthesis of nonreducing maltoheptaose (N-G7) from ß-cyclodextrin.

BACKGROUND: Maltodextrin is an important bulk ingredient in food and other industries; however, drawbacks such as uneven polymerization and high reducibility limit its utilization. Nonreducing maltoheptaose (N-G7) is a good substitute for maltodextrin owing to its single degree of polymerization and its nonreducing properties. In this study, in vitro cell factory biotransformation of ß-cyclodextrin (ß-CD) to N-G7 is demonstrated using coexpressed cyclomaltodextrinase (CDase, EC 3.2.1.54) and maltooligosyltrehalose synthase (MTSase, EC 5.4.99.15). However, the cell membrane prevents ß-CD from entering the cell owing to its large diameter. RESULTS: The amylase-deficient permeabilized host ΔycjM-ΔmalS-ΔlpxM is utilized for the coexpression of recombinant CDase and MTSase. Deletion of lpxM effectively allows the entry of ß-cyclodextrin into the cell, despite its large diameter, without requiring any relevant cell membrane permeability-promoting reagent. This results in a 28.44% increase in the efficiency of ß-CD entry into the cell, thus enabling intracellular N-G7 synthesis without the extracellular secretion of recombinant CDase and MTSase. After reacting for 5.5 h, the highest purity of N-G7 (65.50%) is obtained. However, hydrolysis decreases the purity of N-G7 to 49.30%, thus resulting in a conversion rate of 40.16% for N-G7 when the reaction lasts 6 h. Precise control of reaction time is crucial for obtaining high-purity N-G7. CONCLUSION: Whole-cell catalysis avoids cell fragmentation and facilitates the creation of an eco-friendly, energy-efficient biotransformation system; thus, it is a promising approach for N-G7 synthesis. © 2023 Society of Chemical Industry.

Visible-light-mediated aerobic Ritter-type C-H amination of diarylmethanes using DDQ/tert-butyl nitrite.

A metal-free photocatalytic Ritter-type C-H amination of unactivated sp3 carbons using molecular oxygen as a terminal oxidant has been developed. By employing a co-catalytic system of 3-dichloro-4,5-dicyano-1,4-benzoquinone (DDQ) and tert-butyl nitrite (TBN), this novel strategy provides a low cost, sustainable and scalable way to synthesise a broad range of secondary amides in moderate to excellent yields under mild conditions.

Microwave ablation combined with cementoplasty under real-time temperature monitoring in the treatment of 82 patients with recurrent spinal metastases after radiotherapy.

BACKGROUND: The spine is the most frequently affected part of the skeletal system to metastatic tumors. External radiotherapy is considered the first-line standard of care for these patients with spine metastases. Recurrent spinal metastases after radiotherapy cannot be treated with further radiotherapy within a short period of time, making treatment difficult. We aimed to evaluate the effectiveness and safety of MWA combined with cementoplasty in the treatment of spinal metastases after radiotherapy under real-time temperature monitoring. METHODS: In this retrospective study, 82 patients with 115 spinal metastatic lesions were treated with MWA and cementoplasty under real-time temperature monitoring. Changes in visual analog scale (VAS) scores, daily morphine consumption, and Oswestry Disability Index (ODI) scores were noted. A paired Student's t-test was used to assess these parameters. Complications during the procedure were graded using the CTCAE version 5.0. RESULTS: Technical success was attained in all patients. The mean VAS score was 6.3 ± 2.0 (range, 4-10) before operation, and remarkable decline was noted in one month (1.7 ± 1.0 [P < .001]), three months (1.4 ± 0.8 [P < .001]), and six months (1.3 ± 0.8 [P < .001]) after the operation. Significant reductions in daily morphine consumption and ODI scores were also observed (P < .05). Cement leakage was found in 27.8% (32/115) of lesions, with no obvious associated symptoms. CONCLUSION: MWA combined with cementoplasty under real-time temperature monitoring is an effective and safe method for recurrent spinal metastases after radiotherapy.

Brassinosteroid Signaling Downstream Suppressor BIN2 Interacts with SLFRIGIDA-LIKE to Induce Early Flowering in Tomato.

Brassinosteroid (BR) signaling is very important in plant developmental processes. Its various components interact to form a signaling cascade. These components are widely studied in Arabidopsis; however, very little information is available on tomatoes. Brassinosteroid Insensitive 2 (BIN2), the downstream suppressor of BR signaling, plays a critical role in BR signal pathway, while FRIGIDA as a key suppressor of Flowering Locus C with overexpression could cause early flowering; however, how the BR signaling regulates FRIGIDA homologous protein to adjust flowering time is still unknown. This study identified 12 FRIGIDA-LIKE proteins with a conserved FRIGIDA domain in tomatoes. Yeast two-hybrid and BiFC confirmed that SlBIN2 interacts with 4 SlFRLs, which are sub-cellularly localized in the nucleus. Tissue-specific expression of SlFRLs was observed highly in young roots and flowers. Biological results revealed that SlFRLs interact with SlBIN2 to regulate early flowering. Further, the mRNA level of SlBIN2 also increased in SlFRL-overexpressed lines. The relative expression of SlCPD increased upon SlFRL silencing, while SlDWF and SlBIN2 were decreased, both of which are important for BR signaling. Our research firstly provides molecular evidence that BRs regulate tomato flowering through the interaction between SlFRLs and SlBIN2. This study will promote the understanding of the specific pathway essential for floral regulation.

Computed Tomography‒Guided Microwave Ablation Combined with Osteoplasty for the Treatment of Bone Metastases: A Multicenter Clinical Study.

PURPOSE: To evaluate the efficacy and safety of combined microwave ablation (MWA) and osteoplasty as a palliative therapy for painful bone metastases. MATERIALS AND METHODS: As an extension of a previous limited single-center study, a retrospective review was conducted for 147 patients (77 male, 70 female) with painful bone metastases who underwent MWA combined with osteoplasty. In total, 102 (69.4%), 41 (27.9%), and 4 (2.7%) patients had spinal metastases, extraspinal metastases, and both, respectively. Treatment efficacy was determined by comparing visual analog scale (VAS) scores, daily morphine equivalent opioid consumption, and Oswestry disability index (ODI) scores before treatment and during the follow-up period (mean follow-up, 9.8 months; range 3-16). RESULTS: The mean VAS score significantly declined from 6.4 ± 2.3 before treatment to 3.2 ± 2.1, 1.9 ± 1.6, 1.8 ± 1.6, 1.8 ± 1.6, and 1.9 ± 1.6 at 24 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after treatment, respectively (P < .01). Furthermore, the mean daily morphine equivalent opioid consumption was significantly reduced from 81.5 ± 32.8 mg before treatment to 40.0 ± 20.6, 32.4 ± 10.2, 26.4 ± 10.0, 21.5 ± 8.3, and 19.3 ± 7.4 mg. The mean ODI score also declined after treatment (P < .0001). Major complications occurred in 4 of 147 patients, with 1 pathologic fracture, 1 nerve injury, and 2 mild skin infections. Minor cement leakages were observed at 69 sites (32.8%). CONCLUSIONS: MWA combined with osteoplasty is an effective and safe treatment for painful bone metastases.

Computed tomography-guided microwave ablation combined with percutaneous vertebroplasty for treatment of painful high thoracic vertebral metastases.

PURPOSE: To retrospectively evaluate the efficacy and safety of computed tomography (CT)-guided microwave ablation (MWA) combined with percutaneous vertebroplasty (PVP) as a treatment for painful high thoracic vertebral metastases (T1-T4). MATERIALS AND METHODS: In this retrospective study, 23 adult patients (33 high thoracic vertebral metastases) with moderate to severe pain were treated with CT-guided MWA and PVP. The procedural effectiveness was evaluated using a Visual Analog Scale (VAS), daily morphine consumption, and the Oswestry Disability Index (ODI) before and immediately after the procedure and during follow-up. RESULTS: Technical success was achieved in all patients. The mean pre-procedure VAS score and morphine doses were 6.7 ± 1.7 (5-10) and 105.2 ± 32.7 (30-150) mg, respectively. The mean VAS scores and daily morphine doses at 24 h and 1, 4, 12, and 24 weeks post-operatively were 3.2 ± 1.4 and 41.3 ± 9.6 mg; 1.8 ± 1.0 and 31.5 ± 12.2 mg; 1.4 ± 1.3 and 19.6 ± 12.4 mg; 1.1 ± 0.8 and 14.5 ± 9.6 mg; and 1.0 ± 0.7 and 13.9 ± 9.3 mg, respectively (all p < 0.001). ODI scores significantly decreased (p < 0.05). Minor cement leakage occurred in 10 patients (30.30%) with no symptoms. Follow-up imaging showed no local tumor progression. CONCLUSIONS: Preliminary results suggest MWA combined with PVP is an effective and safe treatment for painful high thoracic vertebral metastases (T1-T4) and can significantly relieve pain and improve the quality of life of patients. However, its efficacy should be confirmed by mid- and long-term studies.

Modification of Threonine-825 of SlBRI1 Enlarges Cell Size to Enhance Fruit Yield by Regulating the Cooperation of BR-GA Signaling in Tomato.

Brassinosteroids (BRs) are growth-promoting phytohormones that can efficiently function by exogenous application at micromolar concentrations or by endogenous fine-tuning of BR-related gene expression, thus, precisely controlling BR signal strength is a key factor in exploring the agricultural potential of BRs. BRASSINOSTEROID INSENSITIVE1 (BRI1), a BR receptor, is the rate-limiting enzyme in BR signal transduction, and the phosphorylation of each phosphorylation site of SlBRI1 has a distinct effect on BR signal strength and botanic characteristics. We recently demonstrated that modifying the phosphorylation sites of tomato SlBRI1 could improve the agronomic traits of tomato to different extents; however, the associated agronomic potential of SlBRI1 phosphorylation sites in tomato has not been fully exploited. In this research, the biological functions of the phosphorylation site threonine-825 (Thr-825) of SlBRI1 in tomato were investigated. Phenotypic analysis showed that, compared with a tomato line harboring SlBRI1, transgenic tomato lines expressing SlBRI1 with a nonphosphorylated Thr-825 (T825A) exhibited a larger plant size due to a larger cell size and higher yield, including a greater plant height, thicker stems, longer internodal lengths, greater plant expansion, a heavier fruit weight, and larger fruits. Molecular analyses further indicated that the autophosphorylation level of SlBRI1, BR signaling, and gibberellic acid (GA) signaling were elevated when SlBRI1 was dephosphorylated at Thr-825. Taken together, the results demonstrated that dephosphorylation of Thr-825 can enhance the functions of SlBRI1 in BR signaling, which subsequently activates and cooperates with GA signaling to stimulate cell elongation and then leads to larger plants and higher yields per plant. These results also highlight the agricultural potential of SlBRI1 phosphorylation sites for breeding high-yielding tomato varieties through precise control of BR signaling.

Oxygen Vacancy-Driven Reversible Free Radical Catalysis for Environment-Adaptive Cancer Chemodynamic Therapy.

Amplifying free radical production by chemical dynamic catalysis to cause oxidative damage to cancer cells has received extensive interest for cancer-specific therapy. The major challenge is inevitable negative modulation on the tumor microenvironment (TME) by these species, hindering durable effectiveness. Here we show for the first time an oxygen vacancy-rich Bi-based regulator that allows environment-adaptive free radical catalysis. Specifically, the regulator catalyzes production of highly toxic O2.- and . OH in cancer cells via logic enzymatic reactions yet scavenges accumulation of free radicals and immunosuppressive mediators in TME-associated noncancerous cells. Atomic-level mechanistic studies reveal that such dual-modal regulating behavior is dominated by oxygen vacancies that well fit for free radical catalytic kinetics, along with distinguished cellular fates of this regulator. With this smart regulator, a "two birds with one shot" cancer dynamic therapy can be expected.

Lactobacillus rhamnosus FLRH93 protects against intestinal damage in mice induced by 5-fluorouracil.

5-Fluorouracil (5-FU) is widely used as a chemotherapeutic drug for the treatment of cancer but it has toxic side effects. It can induce severe intestinal damage and even lead to death. The purpose of this study was to investigate whether milk fermented with Lactobacillus rhamnosus FLRH93 could alleviate intestinal damage induced by 5-FU. The results of injury intervention in a mouse model showed that milk fermented with Lb. rhamnosus FLRH93 significantly ameliorated intestinal injury caused by 5-FU. The results of hematoxylin and eosin staining showed that mice fed Lb. rhamnosus FLRH93 preserved the villus/crypt ratio and reduced the loss of goblet cells in ileum sections of 5-FU-treated animal. Further, administration of fermented milk upregulated expression of Bcl-2 in the intestinal tract and downregulated the expression of NLRP3, thus reducing the production of inflammatory factors interleukin 1-ß and tumor necrosis factor-α. The survival rate of mice treated with fermented milk was twice that of mice not fed fermented milk after continuous oral administration of 5-FU. In conclusion, Lb. rhamnosus FLRH93 has positive effects on body injury and could be used to prevent intestinal damage caused by cancer chemotherapy.

Regulation of proinflammatory monocyte activation by the kynurenine-AhR axis underlies immunometabolic control of depressive behavior in mice.

Elevated kynurenine (Kyn) production from tryptophan (Trp) metabolism is a biomarker of immune dysregulation in depression, but its mechanistic contributions to the behavioral symptoms are poorly defined. In this study, Kyn was shown to be a metabolic regulator of proinflammatory monocytes that orchestrated peripheral immune activation and neuroinflammation in depressive mice. Kyn-induced depressive behavior was paralleled by brain infiltration of proinflammatory monocytes and astrocytic activation. Kyn enhanced chemokine (C-C motif) ligand-2-mediated chemotaxis of monocytes and their proinflammatory capability on cocultured astrocytes in vitro, which involved the activation of aryl hydrocarbon receptor (AhR) signaling. Kyn augmented, whereas pharmacological AhR blockade rescued, systemic inflammation-induced monocyte trafficking, neuroimmune disturbance, and depressive-like behavior in mice. The behavior-exacerbating effects of the Kyn-AhR axis were dampened with prior depletion of functional monocytes in the periphery. The findings in our study extend understanding of an immunologic effect of Kyn that links Trp metabolism and inflammatory signaling in depression pathology, with potential therapeutic implications for depressive disorders.-Zang, X., Zheng, X., Hou, Y., Hu, M., Wang, H., Bao, X., Zhou, F., Wang, G., Hao, H. Regulation of proinflammatory monocyte activation by the kynurenine-AhR axis underlies immunometabolic control of depressive behavior in mice.

Kynurenic acid/GPR35 axis restricts NLRP3 inflammasome activation and exacerbates colitis in mice with social stress.

Psychological stress is well known to increase colitis susceptibility and promote relapse. Metabolic changes are commonly observed under psychological stress, but little is known how this relates to the progression of colitis. Here we show that kynurenic acid (KA) is an endogenous driver of social stress-exacerbated colitis via regulating the magnitude of NLRP3 inflammasome. Chronic social defeat stress (CSDS) in mice induced colonic accumulation of KA, and mice receiving KA during CSDS had defects in colonic NLRP3 inflammasome activation. Mechanistically, KA activated GPR35 signaling to induce autophagy-dependent degradation of NLRP3 in macrophages, thereby suppressing IL-1ß production. Socially defeated mice with KA treatment displayed enhanced vulnerability to subsequent dextran sulphate sodium (DSS)-induced colonic injury and inflammatory disturbance, and this effect was reversed by autophagic inhibition that blocked the NLRP3-suppressive effect of KA. Thus, our research describes a mechanism by which KA/GPR35 signaling represses adaptive NLRP3 inflammasome activation to increase colitis susceptibility and suggests a potential metabolic target for the intervention of stress-related colonic disorder.

Marinomonas flavescens sp. nov., isolated from seawater adjacent to Fildes Peninsula, Antarctica.

A Gram-negative bacterium, namely strain ANRC-JHZ47T, was isolated from a seawater sample collected at Biological Bay, Fildes Peninsula, Antarctica. Cells of strain ANRC-JHZ47T were rod-shaped and motile by a single polar flagellum. Strain ANRC-JHZ47T was aerobic, oxidase-negative, and catalase-positive. The strain grew at 4-37 °C (optimum, 25 °C), pH at 3.5-10.0 (optimum, pH 5.5) and in NaCl at 1-7.0 % (w/v; optimum, 2-3 %). Strain ANRC-JHZ47T used Q-8 as the predominant respiratory quinone. Its predominant fatty acids were C16 : 0 (21.9 %), C12 : 0 (12.6 %), C19 : 0cyclo ω8c (12.4 %), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c; 13.1 %), C10 : 0 3-OH (11.3 %) and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c; 6.0 %). Its major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, one unidentified aminolipid and five unknown polar lipids. The DNA G+C content was 42.6 mol%. Strain ANRC-JHZ47T showed the highest 16S rRNA gene sequence similarity to Marinomonas arenicola KMM 3893T (97.9 %), followed by Marinomonas primoryensis KMM 3633T (97.6 %), Marinomonas profundimaris D104T (97.2 %) and Marinomonas pollencensis IVIA-Po-185T (97.0 %). Furthermore, the average nucleotide identity values between strain ANRC-JHZ47T and M. arenicola KMM 3893T, M. primoryensis KMM 3633T and M. profundimaris D104T were 79.8, 74.0, and 74.1 %, respectively. The in silico DNA-DNA hybridization values between them were 22.5±2.5, 20.4±2.3 and 19.9±2.3 %, respectively. Based on the results of phenotypic and phylogenetic analyses, strain ANRC-JHZ47T is considered to represent a novel species of the genus Marinomonas, for which the name Marinomonas flavescens sp. nov. is proposed. The type strain is ANRC-JHZ47T (=MCCC 1K03604T=KCTC 72113T).