An insight into the gut microbiota after Schistosoma japonicum eggs immunization in an experimental ulcerative colitis model.

Schistosome infection and schistosome-derived products have been implicated in the prevention and alleviation of inflammatory bowel disease by manipulating the host immune response, whereas the role of gut microbiota in this protective effect remains poorly understood. In this study, we found that the intraperitoneal immunization with Schistosoma japonicum eggs prior to dextran sulfate sodium (DSS) application significantly ameliorated the symptoms of DSS-induced acute colitis, which was characterized by higher body weight, lower disease activity index score and macroscopic inflammatory scores. We demonstrated that the immunomodulatory effects of S. japonicum eggs were accompanied by an influence on gut microbiota composition, abundance, and diversity, which increased the abundance of genus Turicibacter, family Erysipelotrichaceae, phylum Firmicutes, and decreased the abundance of genus Odoribacter, family Marinifilaceae, order Bacteroidales, class Bacteroidia, phylum Bacteroidota. In addition, Lactobacillus was identified as a biomarker that distinguishes healthy control mice from DSS-induced colitis mice. The present study revealed the importance of the gut microbiota in S. japonicum eggs exerting protective effects in an experimental ulcerative colitis (UC) model, providing an alternative strategy for the discovery of UC prevention and treatment drugs.

The clinical value of artificial intelligence in assisting junior radiologists in thyroid ultrasound: a multicenter prospective study from real clinical practice.

BACKGROUND: This study is to propose a clinically applicable 2-echelon (2e) diagnostic criteria for the analysis of thyroid nodules such that low-risk nodules are screened off while only suspicious or indeterminate ones are further examined by histopathology, and to explore whether artificial intelligence (AI) can provide precise assistance for clinical decision-making in the real-world prospective scenario. METHODS: In this prospective study, we enrolled 1036 patients with a total of 2296 thyroid nodules from three medical centers. The diagnostic performance of the AI system, radiologists with different levels of experience, and AI-assisted radiologists with different levels of experience in diagnosing thyroid nodules were evaluated against our proposed 2e diagnostic criteria, with the first being an arbitration committee consisting of 3 senior specialists and the second being cyto- or histopathology. RESULTS: According to the 2e diagnostic criteria, 1543 nodules were classified by the arbitration committee, and the benign and malignant nature of 753 nodules was determined by pathological examinations. Taking pathological results as the evaluation standard, the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of the AI systems were 0.826, 0.815, 0.821, and 0.821. For those cases where diagnosis by the Arbitration Committee were taken as the evaluation standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.946, 0.966, 0.964, and 0.956. Taking the global 2e diagnostic criteria as the gold standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.868, 0.934, 0.917, and 0.901, respectively. Under different criteria, AI was comparable to the diagnostic performance of senior radiologists and outperformed junior radiologists (all P < 0.05). Furthermore, AI assistance significantly improved the performance of junior radiologists in the diagnosis of thyroid nodules, and their diagnostic performance was comparable to that of senior radiologists when pathological results were taken as the gold standard (all p > 0.05). CONCLUSIONS: The proposed 2e diagnostic criteria are consistent with real-world clinical evaluations and affirm the applicability of the AI system. Under the 2e criteria, the diagnostic performance of the AI system is comparable to that of senior radiologists and significantly improves the diagnostic capabilities of junior radiologists. This has the potential to reduce unnecessary invasive diagnostic procedures in real-world clinical practice.

The impact of MIF deficiency on alterations of fecal microbiota in C57BL/6 mice induced by Trichinella spiralis infection.

Trichinellosis caused by Trichinella spiralis (T. spiralis) is a major food-borne parasitic zoonosis worldwide. Prevention of trichinellosis is an effective strategy to improve patient quality of life. Macrophage migration inhibitory factor (MIF) is closely related to the occurrence and development of several parasitic diseases. Studying the impact of MIF deficiency (Mif-/- ) on the alterations in host fecal microbiota due to T. spiralis infection may contribute to proposing a novel dual therapeutic approach for trichinellosis. To reveal the diversity and differences in fecal microbial composition, feces were collected from T. spiralis-uninfected and T. spiralis-infected wild-type (WT) and MIF knockout (KO) C57BL/6 mice at 0, 7, 14, and 35 days post-infection (dpi), and the samples were sent for 16S rRNA amplicon sequencing on the Illumina NovaSeq platform. Flow cytometry was used to determine the expression levels of IFN-γ and IL-4 in the CD4+ /CD8+ T-cell sets of mouse spleens. The results showed that operational taxonomic unit (OTU) clustering, relative abundance of microbial composition, alpha diversity, and beta diversity exhibited significant changes among the eight groups. The LEfSe analysis selected several potential biomarkers at the genus or species level, including Akkermansia muciniphila, Lactobacillus murinus, Coprococcus catus, Firmicutes bacterium M10_2, Parabacteroides sp. CT06, and Bacteroides between the KTs and WTs groups. The predicted bacterial functions of the fecal microbiota were mainly involved in metabolism, such as the metabolism of carbohydrates, amino acids, energy, cofactors, vitamins, nucleotides, glycans, and lipids. Flow cytometry revealed an increased CD3+ CD8- /CD3+ CD8+ T-cell ratio and increased IFN-γ and IL-4 levels in CD3+ CD8- T-cell sets from WT and MIF KO mice at 7 dpi. The results indicated that both MIF KO and infection time have a significant influence on the CD3+ CD8- IFN-γ+ and CD3+ CD8- IL-4+ response in mice after T. spiralis. In conclusion, this research showed alterations of the fecal microbiota and immune response in both WT and MIF KO mice before and after T. spiralis infection. These results revealed a potential role of MIF in regulating the pathogenesis of trichinellosis related to the intestinal microbiota. Importantly, the selected potential biomarkers combined with MIF will also offer a novel therapeutic approach to treat trichinellosis in the future.

A key component Rxt3 in the Rpd3L histone deacetylase complex regulates development, stress tolerance, amylase production and kojic acid synthesis in Aspergillus oryzae.

Rpd3L is a highly conserved histone deacetylase complex in eukaryotic cells and participates in various cellular processes. However, the roles of the Rpd3L component in filamentous fungi remain to be delineated ultimately. In this study, we constructed two knockout mutants of Rpd3L's Rxt3 subunit and characterized their biological functions in A. oryzae. Phenotypic analysis showed that AoRxt3 played a positive role in hyphal growth and conidia formation. Deletion of Aorxt3 resulted in augmented tolerance to multiple stresses, including cell wall stress, cell membrane stress, endoplasmic reticulum stress, osmotic stress and oxidative stress. Noteworthily, we found that Aorxt3-deleting mutants showed a higher kojic acid production than the control strain. However, the loss of Aorxt3 led to a significant decrease in amylase synthesis. Our findings lay the foundation for further exploring the role of other Rpd3L subunits and provide a new strategy to improve kojic acid production in A. oryzae.

Transcriptional profile of Trichomonas vaginalis in response to metronidazole.

BACKGROUND: Trichomoniasis caused by Trichomonas vaginalis, combined with its complications, has long frequently damaged millions of human health. Metronidazole (MTZ) is the first choice for therapy. Therefore, a better understanding of its trichomonacidal process to ultimately reveal the global mechanism of action is indispensable. To take a step toward this goal, electron microscopy and RNA sequencing were performed to fully reveal the early changes in T. vaginalis at the cellular and transcriptome levels after treatment with MTZ in vitro. RESULTS: The results showed that the morphology and subcellular structures of T. vaginalis underwent prominent alterations, characterized by a rough surface with bubbly protrusions, broken holes and deformed nuclei with decreased nuclear membranes, chromatin and organelles. The RNA-seq data revealed a total of 10,937 differentially expressed genes (DEGs), consisting of 4,978 upregulated and 5,959 downregulated genes. Most DEGs for the known MTZ activators, such as pyruvate:ferredoxin oxidoreductase (PFOR) and iron-sulfur binding domain, were significantly downregulated. However, genes for other possible alternative MTZ activators such as thioredoxin reductase, nitroreductase family proteins and flavodoxin-like fold family proteins, were dramatically stimulated. GO and KEGG analyses revealed that genes for basic vital activities, proteostasis, replication and repair were stimulated under MTZ stress, but those for DNA synthesis, more complicated life activities such as the cell cycle, motility, signaling and even virulence were significantly inhibited in T. vaginalis. Meanwhile, increased single nucleotide polymorphism (SNP) and insertions - deletions (indels) were stimulated by MTZ. CONCLUSIONS: The current study reveals evident nuclear and cytomembrane damage and multiple variations in T. vaginalis at the transcriptional level. These data will offer a meaningful foundation for a deeper understanding of the MTZ trichomonacidal process and the transcriptional response of T. vaginalis to MTZ-induced stress or even cell death.

A Nanodrug Coated with Membrane from Brain Microvascular Endothelial Cells Protects against Experimental Cerebral Malaria.

Human malaria is a global life-threatening infectious disease. Cerebral malaria (CM) induced by Plasmodium falciparum parasites accounts for 90% of malaria deaths. Treating CM is challenging due to inadequate treatment options and the development of drug resistance. We describe a nanoparticle formulation of the antimalarial drug dihydroartemisinin that is coated in a biomimetic membrane derived from brain microvascular endothelial cells (BMECs) and test its therapeutic efficacy in a mouse model of experimental cerebral malaria (ECM). The membrane-coated nanoparticle drug has a prolonged drug-release profile and enhanced dual targeting killing efficacy toward parasites residing in red blood cells (iRBCs) and iRBCs obstructed in the BMECs (for both rodent and human). In a mice ECM model, the nanodrug protects the brain, liver, and spleen from infection-induced damage and improves the survival rate of mice. This so-called nanodrug offers new insight into engineering nanoparticle-based therapeutics for malaria and other parasitic pathogen infections.

Monomerization of abscisic acid receptors through CARKs-mediated phosphorylation.

Cytosolic ABA Receptor Kinases (CARKs) play a pivotal role in abscisic acid (ABA)-dependent pathway in response to dehydration, but their regulatory mechanism in ABA signaling remains unexplored. In this study, we showed that CARK4/5 of CARK family physically interacted with ABA receptors (RCARs/PYR1/PYLs), including RCAR3, RCAR11-RCAR14, while CARK2/7/11 only interacted with RCAR11-RCAR14, but not RCAR3. It indicates that the members in CARK family function redundantly and differentially in ABA signaling. RCAR12 can form heterodimer with RCAR3 in vitro and in vivo. Moreover, the members of CARK family can form homodimer or heterodimer in a kinase activity dependent manner. ITC (isothermal titration calorimetry) analysis demonstrated that the phosphorylation of RCAR12 by CARK1 enhanced the ABA binding affinity. The phosphor-mimic RCAR12T105D significantly displayed ABA-induced inhibition of the phosphatase ABI1 (ABA insensitive 1) activity, leading to upregulation of ABA-responsive genes RD29A and RD29B in cark157:RCAR12T105D transgenic plants, which exhibited ABA hypersensitive phenotype. The transcription factor ABI5 (ABA insensitive 5) activates the transcriptions of CARK1 and CARK3 by binding to ABA-response elements (ABREs) of their promoters. Collectively, our data imply that the dimeric CARKs phosphorylate homodimer or heterodimer ABA receptors, leading to monomerization for triggering ABA responses in Arabidopsis.

In Vitro Antioxidant Properties and Phenolic Profile of Acid Aqueous Ethanol Extracts from Torreya grandis Seed Coat.

Torreya grandis is an important economic forestry product in China, whose seeds are often consumed as edible nuts, or used as raw materials for oil processing. To date, as an important by-product of Torreya grandis, comprehensive studies regarding the Torreya grandis seed coat phenolic composition are lacking, which greatly limits its in-depth use. Therefore, in the present study, the Torreya grandis seed coat was extracted by acid aqueous ethanol (TE), and NMR and UHPLC-MS were used to identify the major phenolics. Together with the already known phenolics including protocatechuic acid, catechin, epigallocatechin gallate, and epicatechin gallate, the unreported new compound 2-hydroxy-2-(4-hydroxyphenylethyl) malonic acid was discovered. The results of the antioxidant properties showed that both TE and 2-hydroxy-2-(4-hydroxyphenylethyl) malonic acid exhibited strong ABTS, DPPH, and hydroxyl radical-scavenging activity, and significantly improved the O/W emulsion's oxidation stability. These results indicate that the TE and 2-hydroxy-2-(4-hydroxyphenylethyl) malonic acid could possibly be used in the future to manufacture functional foods or bioactive ingredients. Moreover, further studies are also needed to evaluate the biological activity of TE and 2-hydroxy-2-(4-hydroxyphenylethyl) malonic acid to increase the added value of Torreya grandis by-products.

Molecular epidemiological surveillance of Africa and Asia imported malaria in Wuhan, Central China: comparison of diagnostic tools during 2011-2018.

BACKGROUND: Malaria remains a serious public health problem globally. As the elimination of indigenous malaria continues in China, imported malaria has gradually become a major health hazard. Well-timed and accurate diagnoses could support the timely implementation of therapeutic schedules, reveal the prevalence of imported malaria and avoid transmission of the disease. METHODS: Blood samples were collected in Wuhan, China, from August 2011 to December 2018. All patients accepted microscopy and rapid diagnosis test (RDT) examinations. Subsequently, each of the positive or suspected positive cases was tested for four human-infectious Plasmodium species by using 18S rRNA-based nested PCR and Taqman probe-based real-time PCR. The results of the microscopy and the two molecular diagnostic methods were analysed. Importation origins were traced by country, and the prevalence of Plasmodium species was analysed by year. RESULTS: A total of 296 blood samples, including 288 that were microscopy and RDT positive, 7 RDT and Plasmodium falciparum positive, and 1 suspected case, were collected and reanalysed. After application of the two molecular methods and sequencing, 291 cases including 245 P. falciparum, 15 Plasmodium vivax, 20 Plasmodium ovale, 6 Plasmodium malariae and 5 mixed infections (3 P. falciparum + P. ovale, 2 P. vivax + P. ovale) were confirmed. These patients had returned from Africa (95.53%) and Asia (4.47%). Although the prevalence displayed a small-scale fluctuation, the overall trend of the imported cases increased yearly. CONCLUSIONS: These results emphasize the necessity of combined utilization of the four tools for malaria diagnosis in clinic and in field surveys of potential risk regions worldwide including Wuhan.

General Strategy for in Situ Generation of a Coumarin-Cu2+ Complex for Fluorescent Water Sensing.

The detection of moisture in organic solvents is very important before their use in water-sensitive reactions. Herein, we report that coumarins D1 and D2 were able to generate the corresponding water-sensitive copper complexes D1-Cu and D2-Cu in common organic solvents, which can be used as efficient fluorescent turn-on sensors for water. Single-crystal diffraction analysis of the reaction product indicated that the sensing mechanism is based on the formation of a water-bridged 3D supramolecular hydrogen-bonding network. We demonstrated that a hydroxyl or amine group substituted at the 7-position of the coumarin framework played a key role in the water-sensing performance of D1-Cu and D2-Cu, by acting as a hydrogen bond acceptor in the supramolecular network. This provided a general strategy for designing such coumarin-based copper complexes for fluorescent water sensing. The water-sensing behavior of D1-Cu and D2-Cu were determined to be fast, pH tolerant, and sensitive. As low as 0.0525 wt % of water in methanol can be detected using D1-Cu as the sensor. Moreover, D1-Cu was successfully used for moisture sensing in real commercial products.

Solvent directed selective and sensitive fluorescence detection of target ions using a coumarin-pyridine probe.

The development of fluorescent probes to selectively and sensitively detect more than one target analyte under a given condition is a challenging task due to the lack of designing strategies. In this paper, we report the utilisation of the solvatochromic properties of a coumarin-pyridine based probe L1 to detect Mg2+ and PPi, respectively, by using different solvents such as acetonitrile, DMF and DMF-HEPES buffered solutions. When acetonitrile was used as the solvent, L1 was weakly fluorescent and showed a selective and sensitive fluorescence "turn on" response towards Mg2+ with a detection limit of 86 nM, while in DMF and DMF-HEPES buffered solutions, L1 was brightly fluorescent and was able to form a non-fluorescent L1-Fe3+ complex. The obtained L1-Fe3+ complex was further determined to be a selective and sensitive fluorescent "turn on" probe for PPi with a detection limit of 94 nM.

[Pathogen Identification in an Imported Case of Cutaneous Leishmaniasis].

In this study, immune and molecular biological methods were used to identify the pathogen in a blood sample from a patient with dermatosis. Venous blood was collected and tested with Leish rK39 dipsticks. The lesion sample was collected and fixed in 75% ethanol, and DNA was extracted. The internal transcribed spacer 1 of rDNA and N-acetylglucosamine-1-phosphate transferase of Leishmania were amplified with PCR using primers LITSR-L5.8S and NAGTL1s-NAGTL4, respectively. The amplified products were sequenced and analyzed by BLAST. Weakly positive results were obtained for the gold-labeled Leish rK39 dipstick serological test. PCR resulted in products of 404 bp and 1 405 bp with primers LITSR-L5.8S and NAGTL1-NAGTL4, respectively. Both were 99.7% homologous to the corresponding sequence of Leishmania major. The accession number of the two sequences were KU975160 and KX150476. The case of dermatosis is diagnosed as imported cutaneous leishmaniasis and the pathogen is L. major.

Synthesis of chiral sulfilimines by organocatalytic enantioselective sulfur alkylation of sulfenamides.

Sulfilimines are versatile synthetic intermediates and important moieties in bioactive molecules. However, their applications in drug discovery are underexplored, and efficient asymmetric synthetic methods are highly desirable. Here, we report a transition metal-free pentanidium-catalyzed sulfur alkylation of sulfenamides with exclusive chemoselectivity over nitrogen and high enantioselectivity. The reaction conditions were mild, and a wide range of enantioenriched aryl and alkyl sulfilimines were obtained. The synthetic utility and practicability of this robust protocol were further demonstrated through gram-scale reactions and late-stage functionalization of drugs.

A real-world evaluation of the diagnostic accuracy of radiologists using positive predictive values verified from deep learning and natural language processing chest algorithms deployed retrospectively.

Objectives: This diagnostic study assessed the accuracy of radiologists retrospectively, using the deep learning and natural language processing chest algorithms implemented in Clinical Review version 3.2 for: pneumothorax, rib fractures in digital chest X-ray radiographs (CXR); aortic aneurysm, pulmonary nodules, emphysema, and pulmonary embolism in CT images. Methods: The study design was double-blind (artificial intelligence [AI] algorithms and humans), retrospective, non-interventional, and at a single NHS Trust. Adult patients (≥18 years old) scheduled for CXR and CT were invited to enroll as participants through an opt-out process. Reports and images were de-identified, processed retrospectively, and AI-flagged discrepant findings were assigned to two lead radiologists, each blinded to patient identifiers and original radiologist. The radiologist's findings for each clinical condition were tallied as a verified discrepancy (true positive) or not (false positive). Results: The missed findings were: 0.02% rib fractures, 0.51% aortic aneurysm, 0.32% pulmonary nodules, 0.92% emphysema, and 0.28% pulmonary embolism. The positive predictive values (PPVs) were: pneumothorax (0%), rib fractures (5.6%), aortic dilatation (43.2%), pulmonary emphysema (46.0%), pulmonary embolus (11.5%), and pulmonary nodules (9.2%). The PPV for pneumothorax was nil owing to lack of available studies that were analysed for outpatient activity. Conclusions: The number of missed findings was far less than generally predicted. The chest algorithms deployed retrospectively were a useful quality tool and AI augmented the radiologists' workflow. Advances in knowledge: The diagnostic accuracy of our radiologists generated missed findings of 0.02% for rib fractures CXR, 0.51% for aortic dilatation, 0.32% for pulmonary nodule, 0.92% for pulmonary emphysema, and 0.28% for pulmonary embolism for CT studies, all retrospectively evaluated with AI used as a quality tool to flag potential missed findings. It is important to account for prevalence of these chest conditions in clinical context and use appropriate clinical thresholds for decision-making, not relying solely on AI.

Crosstalk between CD8+ T cells and mesenchymal stromal cells in intestine homeostasis and immunity.

The intestine represents the most complex cellular network in the whole body. It is constantly faced with multiple types of immunostimulatory agents encompassing from food antigen, gut microbiome, metabolic waste products, and dead cell debris. Within the intestine, most T cells are found in three primary compartments: the organized gut-associated lymphoid tissue, the lamina propria, and the epithelium. The well-orchestrated epithelial-immune-microbial interaction is critically important for the precise immune response. The main role of intestinal mesenchymal stromal cells is to support a structural framework within the gut wall. However, recent evidence from stromal cell studies indicates that they also possess significant immunomodulatory functions, such as maintaining intestinal tolerance via the expression of PDL1/2 and MHC-II molecules, and promoting the development of CD103+ dendritic cells, and IgA+ plasma cells, thereby enhancing intestinal homeostasis. In this review, we will summarize the current understanding of CD8+ T cells and stromal cells alongside the intestinal tract and discuss the reciprocal interactions between T subsets and mesenchymal stromal cell populations. We will focus on how the tissue residency, migration, and function of CD8+ T cells could be potentially regulated by mesenchymal stromal cell populations and explore the molecular mediators, such as TGF-ß, IL-33, and MHC-II molecules that might influence these processes. Finally, we discuss the potential pathophysiological impact of such interaction in intestine hemostasis as well as diseases of inflammation, infection, and malignancies.

Quercetin ameliorates celiac-related intestinal inflammation caused by wheat gluten through modulating oxidative stress, Th1/Th2/Treg balance, and intestinal microflora structure.

Celiac disease is a chronic inflammatory autoimmune disease of the small bowel, and about 1% of the world's population is afflicted with celiac disease. To date, the most efficient treatment option is that the patient is required to strictly follow a gluten-free diet for their entire life, but it's difficult to adhere to and can lead to new nutritional imbalances, making it urgent to find novel nutritional interventions. Our aim was to explore the effects of nutritional intervention with quercetin on the celiac toxic effects of wheat gluten. This study systematically assessed the regulatory roles of quercetin on intestinal oxidative damage, immune response, inflammatory damage, and intestinal microflora dysbiosis in celiac disease by utilizing the established celiac in vitro and in vivo models induced by gluten. We discovered that quercetin could play a crucial role in intervening in celiac pathogenesis, not only owing to its antioxidant properties, but also because it modulates immune cell function and the intestinal microflora structure, particularly the regulation of Th1/Th2/Treg immune cell subpopulations and their functions, inhibition of the abundance of celiac disease marker flora such as Clostridium_celatum and Bacteroides_acidifaciens, and upregulation of the abundance of beneficial flora such as Butyricoccus_pullicaecorum and Bifidobacterium_longum, which ultimately worked together to ameliorate the celiac-related intestinal inflammation triggered by gluten. This study might provide new insights into the regulation of gut immunity and intestinal microflora homeostasis, as well as the potential application of quercetin in celiac disease.

Prognostic value of 18F-FDG lesion dissemination features in patients with peripheral T-cell lymphoma (PTCL).

PURPOSE: To explore the prognostic value of the distance between the two lesions that were farthest apart (Dmax) on baseline 18F-FDG PET/CT in peripheral T lymphoma (PTCL) and establish a new prognostic model for predicting the survival outcomes of patients with PTCL. METHODS: In this study, a retrospective analysis of 95 patients with PTCL who underwent baseline 18F-FDG PET/CT was performed to assess the predictive value of Dmax. The total metabolic tumour volume (TMTV), total lesion glycolysis (TLG), standardized uptake value (SUV), and Dmax were calculated with LIFEx software. Progression-free survival (PFS) and overall survival (OS) were used as endpoints. The prognostic model was developed based on the results of the multivariate analysis. The time-dependent area under the ROC curve (tdAUC), calibration curves, Harrell C-index, and decision curve analysis (DCA) were used to assess the model. RESULTS: Patients were followed up for a median of 17.0 months. Multivariate analysis showed that bone marrow biopsy (BMB) and Dmax were independent predictors of PFS (HR: 1.889, P = 0.039; HR: 1.965, P = 0.047) and OS (HR: 1.923, P = 0.031; HR: 1.982, P = 0.034). The model consisting of Dmax, TMTV, and BMB had substantial prognostic value for survival outcomes of PTCL and could successfully identify four groups of patients with significantly different prognoses (χ2 = 13.731, P = 0.003 for PFS; χ2 = 11.841, P = 0.008 for OS). The tdAUC, C-index, calibration curves, and DCA supported that the model was superior to the prognostic index for T-cell lymphoma (PIT) and International Prognostic Index (IPI) scores. CONCLUSION: BMB and Dmax were independent predictors of PTCL in our study. Moreover, a prognostic model based on the Dmax, TMTV, and BMB could be useful for predicting the survival outcomes of patients with PTCL.

Regulation of CD8+ T memory and exhaustion by the mTOR signals.

CD8+ T cells are the key executioners of the adaptive immune arm, which mediates antitumor and antiviral immunity. Naïve CD8+ T cells develop in the thymus and are quickly activated in the periphery after encountering a cognate antigen, which induces these cells to proliferate and differentiate into effector cells that fight the initial infection. Simultaneously, a fraction of these cells become long-lived memory CD8+ T cells that combat future infections. Notably, the generation and maintenance of memory cells is profoundly affected by various in vivo conditions, such as the mode of primary activation (e.g., acute vs. chronic immunization) or fluctuations in host metabolic, inflammatory, or aging factors. Therefore, many T cells may be lost or become exhausted and no longer functional. Complicated intracellular signaling pathways, transcription factors, epigenetic modifications, and metabolic processes are involved in this process. Therefore, understanding the cellular and molecular basis for the generation and fate of memory and exhausted CD8+ cells is central for harnessing cellular immunity. In this review, we focus on mammalian target of rapamycin (mTOR), particularly signaling mediated by mTOR complex (mTORC) 2 in memory and exhausted CD8+ T cells at the molecular level.

Cardiac exposure in left-sided breast cancer patients undergoing deep inspiratory breath hold radiation therapy.

Background: Left-sided breast cancer (BC) patients undergoing post-operative radiation therapy (PRT) may have higher risk of late cardiovascular toxicity, which may be reduced by hearth-sparing RT techniques. This study evaluated dosimetric parameters of the deep inspiration breath hold (DIBH) compared to free breathing (FB) RT. We analysed factors impacting on doses to the heart and cardiac substructures and sought anatomic factors allowing patient selection for DIBH. Methods: The study group included 67 left-sided BC patients who underwent RT after breast-conserving surgery or mastectomy. Patients treated with DIBH were trained to hold their breath. Computed tomography (CT) scans were performed in both FB and DIBH patients. Plans were generated using 3-dimensional (3D) conformal RT. The dosimetric variables were obtained from dose-volume histograms, and the anatomical variables were derived from the CT scans. The variables in the two groups were compared by t-test, the U test, and the chi-squared test. Correlation analysis was performed using Pearson's correlation coefficient. Receiver operating characteristic curves were used to analyze the efficacy of the predictors. Results: Compared to the FB, DIBH allowed for a mean dose reduction to the heart, left anterior descending coronary artery (LAD), left ventricle (LV), and right ventricle (RV) by 30.0%, 38.7%, 39.3%, and 34.7%, respectively. DIBH markedly increased the heart height (HH), heart chest wall distance (HCWD), the mean distance between the ipsilateral lung and breast (DBIB), and decreased the heart-chest wall length (HCWL) (P<0.05). The different value of HH, DBIB, HCWL, and HCWD between DIBH and FB were 1.31, 1.95, -0.67, and 0.22 cm, respectively (all P<0.05). ΔHH was an independent predictor of the mean dose to the heart, LAD, LV, and RV, with the area under the curve values of 0.818, 0.725, 0.821, and 0.820, respectively. Conclusions: DIBH significantly reduced the dose to the entire heart and its substructures in left-sided BC patients undergoing post-operative RT. ΔHH predicts the mean dose to the heart and its substructures. These results may inform patient selection for DIBH.

The Nutritional Intervention of Resveratrol Can Effectively Alleviate the Intestinal Inflammation Associated With Celiac Disease Induced by Wheat Gluten.

Background and Aims: Wheat gluten is a critical trigger for celiac disease, often causing inflammatory lesions and oxidative stress damage in the intestines of patients. In daily life, it is difficult for celiac disease patients to strictly avoid the dietary intake of gluten, which makes complementary preventive therapy particularly urgent. As such, we investigated the alleviating effects of resveratrol in vivo and in vitro models of celiac disease. Methods: We established in vivo and in vitro models of gluten protein-induced celiac disease. The intervention effect of resveratrol was defined well based on relevant indicators of inflammation, immunity and oxidative stress, and its possible involvement in signaling pathways and genes were also identified. Results: Resveratrol was effective in reducing intestinal oxidative stress and inflammatory damage induced by wheat gluten in both cell and mouse models for celiac disease. We identified correlations between the genes (Fgf15, Nr0b2, Aire and Ubd) and signaling pathways (PPAR, AMPK and FoxO) in which resveratrol performed critical roles. Conclusions: Resveratrol contributed to regulate development of autoimmunity through up-regulation of Aire and Ubd genes and promote nutrient absorption in intestine through down-regulation of Fgf15 and Nr0b2 genes, as well as played a role in regulating complex response system of oxidative stress, inflammatory response and immune response in intestine by activating PPAR, AMPK and FoxO signaling pathways, thus effectively alleviating the intestinal symptoms of celiac disease.