Species-resolved, single-cell respiration rates reveal dominance of sulfate reduction in a deep continental subsurface ecosystem.

Rates of microbial processes are fundamental to understanding the significance of microbial impacts on environmental chemical cycling. However, it is often difficult to quantify rates or to link processes to specific taxa or individual cells, especially in environments where there are few cultured representatives with known physiology. Here, we describe the use of the redox-enzyme-sensitive molecular probe RedoxSensor™ Green to measure rates of anaerobic electron transfer physiology (i.e., sulfate reduction and methanogenesis) in individual cells and link those measurements to genomic sequencing of the same single cells. We used this method to investigate microbial activity in hot, anoxic, low-biomass (~103 cells mL-1) groundwater of the Death Valley Regional Flow System, California. Combining this method with electron donor amendment experiments and metatranscriptomics confirmed that the abundant spore formers including Candidatus Desulforudis audaxviator were actively reducing sulfate in this environment, most likely with acetate and hydrogen as electron donors. Using this approach, we measured environmental sulfate reduction rates at 0.14 to 26.9 fmol cell-1 h-1. Scaled to volume, this equates to a bulk environmental rate of ~103 pmol sulfate L-1 d-1, similar to potential rates determined with radiotracer methods. Despite methane in the system, there was no evidence for active microbial methanogenesis at the time of sampling. Overall, this method is a powerful tool for estimating species-resolved, single-cell rates of anaerobic metabolism in low-biomass environments while simultaneously linking genomes to phenomes at the single-cell level. We reveal active elemental cycling conducted by several species, with a large portion attributable to Ca. Desulforudis audaxviator.

MultiClassMetabo: A Superior Classification Model Constructed Using Metabolic Markers in Multiclass Metabolomics.

Multiclass metabolomics has become a popular technique for revealing the mechanisms underlying certain physiological processes, different tumor types, or different therapeutic responses. In multiclass metabolomics, it is highly important to uncover the underlying biological information on biosamples by identifying the metabolic markers with the most associations and classifying the different sample classes. The classification problem of multiclass metabolomics is more difficult than that of the binary problem. To date, various methods exist for constructing classification models and identifying metabolic markers consisting of well-established techniques and newly emerging machine learning algorithms. However, how to construct a superior classification model using these methods remains unclear for a given multiclass metabolomic data set. Herein, MultiClassMetabo has been developed for constructing a superior classification model using metabolic markers identified in multiclass metabolomics. MultiClassMetabo can enable online services, including (a) identifying metabolic markers by marker identification methods, (b) constructing classification models by classification methods, and (c) performing a comprehensive assessment from multiple perspectives to construct a superior classification model for multiclass metabolomics. In summary, MultiClassMetabo is distinguished for its capability to construct a superior classification model using the most appropriate method through a comprehensive assessment, which makes it an important complement to other available tools in multiclass metabolomics. MultiClassMetabo can be accessed at http://idrblab.cn/multiclassmetabo/.

Genomic and cytogenetic analyses reveal satellite repeat signature in allotetraploid okra (Abelmoschus esculentus).

BACKGROUND: Satellite repeats are one of the most rapidly evolving components in eukaryotic genomes and play vital roles in genome regulation, genome evolution, and speciation. As a consequence, the composition, abundance and chromosome distribution of satellite repeats often exhibit variability across various species, genome, and even individual chromosomes. However, we know little about the satellite repeat evolution in allopolyploid genomes. RESULTS: In this study, we investigated the satellite repeat signature in five okra (Abelmoschus esculentus) accessions using genomic and cytogenetic methods. In each of the five accessions, we identified eight satellite repeats, which exhibited a significant level of intraspecific conservation. Through fluorescence in situ hybridization (FISH) experiments, we observed that the satellite repeats generated multiple signals and exhibited variations in copy number across chromosomes. Intriguingly, we found that five satellite repeats were interspersed with centromeric retrotransposons, signifying their involvement in centromeric satellite repeat identity. We confirmed subgenome-biased amplification patterns of these satellite repeats through existing genome assemblies or dual-color FISH, indicating their distinct dynamic evolution in the allotetraploid okra subgenome. Moreover, we observed the presence of multiple chromosomes harboring the 35 S rDNA loci, alongside another chromosomal pair carrying the 5 S rDNA loci in okra using FISH assay. Remarkably, the intensity of 35 S rDNA hybridization signals varied among chromosomes, with the signals predominantly localized within regions of relatively weak DAPI staining, associated with GC-rich heterochromatin regions. Finally, we observed a similar localization pattern between 35 S rDNA and three satellite repeats with high GC content and confirmed their origin in the intergenic spacer region of the 35 S rDNA. CONCLUSIONS: Our findings uncover a unique satellite repeat signature in the allotetraploid okra, contributing to our understanding of the composition, abundance, and chromosomal distribution of satellite repeats in allopolyploid genomes, further enriching our understanding of their evolutionary dynamics in complex allopolyploid genomes.

Atypical BCR-ABL1 transcript in mixed phenotype acute leukemia with bone marrow necrosis.

Mixed phenotype acute leukemia (MPAL) is a type of acute leukemia in which encompasses mixed features of myeloid, T-lymphoid, and/or B-lymphoid differentiation. Philadelphia chromosome-positive (Ph+) MPAL is a rare subgroup with a poor prognosis and accounts for ＜1% of adult acute leukemia. Until now, there is still no consensus on how to best treat Ph+ MPAL. Here, we report a 62-year-old male with Ph+ (atypical e13a2 BCR-ABL1 fusion protein) MPAL. This patient presented with recurrent and intense bone pain due to bone marrow necrosis (BMN). Besides, he did not achieve a complete remission for the first two chemotherapies, until he received flumatinib combined with hyper-CVAD (B) (a dose-intensive regimen include methotrexate and cytarabine). To our knowledge, this is the first report to describe the coexistence of BMN and atypical e13a2 BCR-ABL1 transcripts in patients with MPAL. This finding will bring new understandings in the diagnosis and treatment of Ph+ MPAL.

The role of NLRP6 in the development and progression of neurological diseases.

The nervous system possesses the remarkable ability to undergo changes in order to store information; however, it is also susceptible to damage caused by invading pathogens or neurodegenerative processes. As a member of nucleotide-binding oligomerization domain-like receptor (NLR) family, the NLRP6 inflammasome serves as a cytoplasmic innate immune sensor responsible for detecting microbe-associated molecular patterns. Upon activation, NLRP6 can recruit the adapter protein apoptosis-associated speck-like protein (ASC) and the inflammatory factors caspase-1 or caspase-11. Consequently, inflammasomes are formed, facilitating the maturation and secretion of pro-inflammatory cytokines such as inflammatory factors-18 (IL-18) and inflammatory factors-1ß (IL-1ß). Precise regulation of NLRP6 is crucial for maintaining tissue homeostasis, as dysregulated inflammasome activation can contribute to the development of various diseases. Furthermore, NLRP6 may also play a role in the regulation of extraintestinal diseases. In cells of the brain, such as astrocytes and neurons, NLRP6 inflammasome are also present. Here, the assembly and subsequent activation of caspase-1 mediated by NLRP6 contribute to disease progression. This review aims to discuss the structure and function of NLRP6, explain clearly the mechanisms that induce and activate NLRP6, and explore its role within the central and peripheral nervous system.

Comparative efficacy of non-invasive brain stimulation for post-stroke cognitive impairment: a network meta-analysis.

BACKGROUND: Non-invasive brain stimulation (NIBS) is a burgeoning approach with the potential to significantly enhance cognition and functional abilities in individuals who have undergone a stroke. However, the current evidence lacks robust comparisons and rankings of various NIBS methods concerning the specific stimulation sites and parameters used. To address this knowledge gap, this systematic review and meta-analysis seek to offer conclusive evidence on the efficacy and safety of NIBS in treating post-stroke cognitive impairment. METHODS: A systematic review of randomized control trials (RCT) was performed using Bayesian network meta-analysis. We searched RCT in the following databases until June 2022: Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and EMBASE. We compared any active NIBS to control in terms of improving cognition function and activities of daily living (ADL) capacity following stroke. RESULTS: After reviewing 1577 retrieved citations, a total of 26 RCTs were included. High-frequency (HF)-repetitive transcranial magnetic stimulation (rTMS) (mean difference 2.25 [95% credible interval 0.77, 3.66]) was identified as a recommended approach for alleviating the global severity of cognition. Dual-rTMS (27.61 [25.66, 29.57]) emerged as a favorable technique for enhancing ADL function. In terms of stimulation targets, the dorsolateral prefrontal cortex exhibited a higher ranking in relation to the global severity of cognition. CONCLUSIONS: Among various NIBS techniques, HF-rTMS stands out as the most promising intervention for enhancing cognitive function. Meanwhile, Dual-rTMS is highly recommended for improving ADL capacity.

Alternative signal pathways underly fertilization and egg activation in a fish with contrasting modes of spawning.

BACKGROUND: The processes of fertilization and egg activation are vital for early embryogenesis. However, while the mechanisms associated with key events during these processes differ among species and modes of spawning, the signal pathways underlying these processes are opaque for many fishes, including economically important species. RESULTS: We investigated phenotypic traits, ultrastructure and protein expression levels in the eggs of the topmouth culter (Culter alburnus), a protected and economically important freshwater fish that exhibits two spawning modes, producing semi-buoyant eggs and adhesive eggs. Unfertilized eggs of C. alburnus were examined, as well as eggs at fertilization and 30 min post fertilization. Our results showed that in semi-buoyant eggs, energy metabolism was activated at fertilization, followed by elevated protein expression of cytoskeleton and extracellular matrix (ECM)-receptor interactions that resulted in rapid egg swelling; a recognized adaptation for lotic habitats. In contrast, in adhesive eggs fertilization initiated the process of sperm-egg fusion and blocking of polyspermy, followed by enhanced protein expression of lipid metabolism and the formation of egg envelope adhesion and hardening, which are adaptive in lentic habitats. CONCLUSION: Our findings indicate that alternative signal pathways differ between modes of spawning and timing during the key processes of fertilization and egg activation, providing new insights into the molecular mechanisms involved in adaptive early embryonic development in teleost fishes.

Prevailing Charge Order in Overdoped La_{2-x}Sr_{x}CuO_{4} beyond the Superconducting Dome.

The extremely overdoped cuprates are generally considered to be Fermi liquid metals without exotic orders, whereas the underdoped cuprates harbor intertwined states. Contrary to this conventional wisdom, using Cu L_{3}-edge and O K-edge resonant x-ray scattering, we reveal a charge order (CO) correlation in overdoped La_{2-x}Sr_{x}CuO_{4} (0.35≤x≤0.6) beyond the superconducting dome. This CO has a periodicity of ∼6 lattice units with correlation lengths of ∼20 lattice units. It shows similar in-plane momentum and polarization dependence and dispersive excitations as the CO of underdoped cuprates, but its maximum intensity differs along the c direction and persists up to 300 K. This CO correlation cannot be explained by the Fermi surface instability and its origin remains to be understood. Our results suggest that CO is prevailing in the overdoped metallic regime and requires a reassessment of the picture of overdoped cuprates as weakly correlated Fermi liquids.

Tunable Van Hove Singularity without Structural Instability in Kagome Metal CsTi_{3}Bi_{5}.

In kagome metal CsV_{3}Sb_{5}, multiple intertwined orders are accompanied by both electronic and structural instabilities. These exotic orders have attracted much recent attention, but their origins remain elusive. The newly discovered CsTi_{3}Bi_{5} is a Ti-based kagome metal to parallel CsV_{3}Sb_{5}. Here, we report angle-resolved photoemission experiments and first-principles calculations on pristine and Cs-doped CsTi_{3}Bi_{5} samples. Our results reveal that the van Hove singularity (vHS) in CsTi_{3}Bi_{5} can be tuned in a large energy range without structural instability, different from that in CsV_{3}Sb_{5}. As such, CsTi_{3}Bi_{5} provides a complementary platform to disentangle and investigate the electronic instability with a tunable vHS in kagome metals.

Single-cell transcriptome analysis profiles the expression features of TMEM173 in BM cells of high-risk B-cell acute lymphoblastic leukemia.

BACKGROUND: As an essential regulator of type I interferon (IFN) response, TMEM173 participates in immune regulation and cell death induction. In recent studies, activation of TMEM173 has been regarded as a promising strategy for cancer immunotherapy. However, transcriptomic features of TMEM173 in B-cell acute lymphoblastic leukemia (B-ALL) remain elusive. METHODS: Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were applied to determine the mRNA and protein levels of TMEM173 in peripheral blood mononuclear cells (PBMCs). TMEM173 mutation status was assessed by Sanger sequencing. Single-cell RNA sequencing (scRNA-seq) analysis was performed to explore the expression of TMEM173 in different types of bone marrow (BM) cells. RESULTS: The mRNA and protein levels of TMEM173 were increased in PBMCs from B-ALL patients. Besides, frameshift mutation was presented in TMEM173 sequences of 2 B-ALL patients. ScRNA-seq analysis identified the specific transcriptome profiles of TMEM173 in the BM of high-risk B-ALL patients. Specifically, expression levels of TMEM173 in granulocytes, progenitor cells, mast cells, and plasmacytoid dendritic cells (pDCs) were higher than that in B cells, T cells, natural killer (NK) cells, and dendritic cells (DCs). Subset analysis further revealed that TMEM173 and pyroptosis effector gasdermin D (GSDMD) restrained in precursor-B (pre-B) cells with proliferative features, which expressed nuclear factor kappa-B (NF-κB), CD19, and Bruton's tyrosine kinase (BTK) during the progression of B-ALL. In addition, TMEM173 was associated with the functional activation of NK cells and DCs in B-ALL. CONCLUSIONS: Our findings provide insights into the transcriptomic features of TMEM173 in the BM of high-risk B-ALL patients. Targeted activation of TMEM173 in specific cells might provide new therapeutic strategies for B-ALL patients.

The impact of GmTSA and GmALS on soybean salt tolerance: uncovering the molecular landscape of amino acid and secondary metabolism pathways.

KEY MESSAGE: GmTSA and GmALS were screened out for salt stress in soybean and explore the poteintial amino acid secondary metabolism pathways. Soybean (Glycine max L.) is an oil and protein crop of global importance, and salinity has significant effects on soybean growth. Here, a population of soybean chromosome segment substitution lines was screened to identify highly salt-tolerant lines. In total, 24 quantitative trait loci (QTLs) on seven chromosomes were associated with salt tolerance, and CSSL_R71 was selected for further analysis. Although numerous genes were differentially expressed in CSSL_R71 in response to salt statically no differently, transcript levels of classical salt-response genes, including those of the salt overly sensitive pathway. Rather, salt tolerance in CSSL_R71 was associated with changes in amino acid and lipid metabolism. In particular, changes in p-coumaric acid, shikimic acid, and pyrrole-2-carboxylic acid levels accompanied salt tolerance in CSSL_R71. Eleven differentially expressed genes (DEGs) related to amino acid and secondary metabolism were identified as candidate genes on the substituted chromosome fragment. Six of these showed differences in coding sequence between the parental genotypes. Crucially, overexpression of GmTSA (Glyma.03G158400, tryptophan synthase) significantly enhanced salt tolerance in soybean hairy roots, whereas overexpression of GmALS (Glyma.13G241000, acetolactate synthase) decreased salt tolerance. Two KASP markers were developed for GmALS and used to genotype salt-tolerant and salt-sensitive lines in the CSSL population. Non-synonymous mutations were directly associated with salt tolerance. Taken together, these data provide evidence that changes in amino acid and secondary metabolism have the potential to confer salt tolerance in soybean.

Usefulness of Therapeutic Drug Monitoring and Pharmacogenetics for a Patient Treated with Olanzapine, Buspirone, and Fluvoxamine: A Case Study.

BACKGROUND: A patient, with a mental disorder caused by an intracranial infection, treated with olanzapine, fluvoxamine, and buspirone. The plasma exposure of olanzapine was too high at standard doses, with evidence indicating that it was caused by drug-drug interactions. METHODS: Using pharmacogenomics and therapeutic drug monitoring to guide drug dose adjustment for a patient in clinical practice. RESULTS: The patient underwent pharmacogenetic testing in addition to therapeutic drug monitoring as part of a pharmacist-led comprehensive evaluation of medication therapy management in a clinical setting, resulting in improved clinical efficacy that allowed discharge from a psychiatric hospital. CONCLUSIONS: This case study demonstrates that therapeutic drug monitoring combined with pharmacogenetic-guided dose adjustment can aid in the management of patients receiving complex pharmacological treatments.

Online education isn't the best choice: evidence-based medical education in the post-epidemic era-a cross-sectional study.

BACKGROUND: The COVID-19 pandemic led many educational institutions to shift to online courses, making blended education a significant trend in teaching. We examined the effectiveness of blended learning in an evidence-based medicine course. METHODS: We compared the examination scores of a blended learning group, an online only group, and a traditional offline group and conducted a questionnaire survey on students' preferences for different learning modes and the reasons for their preferences. A total of 2100 undergraduate students in clinical medicine were included in this cross-sectional study. Examination results were collected, and questionnaires were administered to the study participants. We compared the mean scores and exam pass rates of the three teaching groups using ANOVA and c2test for multiple comparisons. RESULTS: The blended group's exam scores and pass rate were significantly higher than those of the offline and online groups. Furthermore, 71.6% preferred the blended teaching mode. In the survey on " learning effectiveness", the majority of the students believed that blended education could better enhance the initiative of learning, the interest of the course, the pertinence of the learning content, the comprehension of evidence-based medical thinking, and the basic skills of evidence-based practice. Subsequently, in a questionnaire administered to a blended group of students, their foremost reason for liking online instruction was 'flexible in time and space' (99%), followed by 'can be viewed repeatedly, facilitating a better understanding of knowledge points' (98%). Their foremost reason for liking offline teaching was 'helps to create a good learning atmosphere' (97%), followed by 'teachers can control students' learning status in real time' (89%). CONCLUSIONS: This study explored the effectiveness of learning in evidence-based medicine courses by comparing the learning outcomes and personal perceptions of three different teaching modes. This is the first cross-sectional study in which three different teaching models are compared and discussed in an evidence-based medicine course. We also elaborate on the specific instructional protocols for each model. This study shows that using a blended education approach in evidence-based medicine courses can improve students' learning motivation, autonomy, and satisfaction. It also enhances instructional efficiency, thereby improving students' understanding of the course content.

The sensing mechanism of fluorescent probe for PhSH and the process of ESIPT.

The detection mechanism of fluorescent probe FQ-DNP (DNP: 2,4-dinitropheno) for PhSH and the detailed ESIPT process of its product 2-(6-(diethylamino) quinolin-2-yl)-3-Hydroxy-4H-chromen-4-one (FQ-OH) have been revealed by density functional theory (DFT) and time-dependent density functional theory (TD-DFT). For FQ-OH, the decreased bond length of H6-N7 and RDG analysis illustrate that the strength of hydrogen bond H6-N7 has been enlarged after photoexcitation, creating a good condition for ESIPT. To illustrate the ESIPT process in detail, the potential energy curves are performed and the transition state reaction energy is calculated. In the S0 state, the FQ-OH could happen proton transfer (PT) to form keto, but the keto form is more unstable than enol form. After photoexcitation, in the S1 state, FQ-OH could happen PT to produce stable keto form. Excited dynamic simulation shows that PT happens at 71.5 fs. The calculated absorption and emission spectra are in agreement with the experimental data, and the calculated Stokes shift is 160 nm. Frontier molecular orbitals (FMOs) and hole-electron analysis show that twisted intramolecular charge transfer (TICT) is responsible for the fluorescent quenching of FQ-DNP.

Efficient Anchoring of Erianthus arundinaceus Chromatin Introgressed into Sugarcane by Specific Molecular Markers

Erianthus arundinaceus is a valuable gene reservoir for sugarcane improvement. However, insufficient molecular markers for high-accuracy identification and tracking of the introgression status of E. arundinaceus chromatin impede sugarcane breeding. Fortunately, suppression subtractive hybridization (SSH) technology provides an excellent opportunity for the development of high-throughput E. arundinaceus-specific molecular markers at a reasonable cost. In this study, we constructed a SSH library of E. arundinaceus. In total, 288 clones of E. arundinaceus-specific repetitive sequences were screened out and their distribution patterns on chromosomes were characterized by fluorescence in situ hybridization (FISH). A subtelomeric repetitive sequence Ea086 and a diffusive repetitive sequence Ea009, plus 45S rDNA-bearing E. arundinaceus chromosome repetitive sequence EaITS were developed as E. arundinaceus-specific molecular markers, namely, Ea086-128, Ea009-257, and EaITS-278, covering all the E. arundinaceus chromosomes for high-accuracy identification of putative progeny. Both Ea086-128 and Ea009-257 were successfully applied to identify the authenticity of F1, BC1, BC2, BC3, and BC4 progeny between sugarcane and E. arundinaceus. In addition, EaITS-278 was a 45S rDNA-bearing E. arundinaceus chromosome-specific molecular marker for rapid tracking of the inherited status of this chromosome in a sugarcane background. Three BC3 progeny had apparently lost the 45S rDNA-bearing E. arundinaceus chromosome. We reported herein a highly effective and reliable SSH-based technology for discovery of high-throughput E. arundinaceus-specific sequences bearing high potential as molecular markers. Given its reliability and savings in time and efforts, the method is also suitable for development of species-specific molecular markers for other important wild relatives to accelerate introgression of wild relatives into sugarcane.

Derivation and validation of a lipid-covered prognostic model for mature T-cell lymphomas.

BACKGROUND: Mature T-cell lymphomas (MTCLs), a group of diseases with high aggressiveness and vulnerable prognosis, lack for the accurate prognostic stratification systems at present. Novel prognostic markers and models are urgently demanded. Aberrant lipid metabolism is closely related to the tumor progression but its prognostic significance in MTCLs remains unexplored. This study aims to investigate the relationship between dysregulated lipid metabolism and survival prognosis of MTCLs and establish a novel and well-performed prognostic scoring system for MTCL patients. METHODS: A total of 173 treatment-naive patients were enrolled in this study. Univariate and multivariate Cox regression analysis were performed to assess the prognostic significance of serum lipid profiles and screen out independent prognostic factors, which constituted a novel prognostic model for MTCLs. The performance of the novel model was assessed in the training and validation cohort, respectively, by examining its calibration, discrimination and clinical utility. RESULTS: Among the 173 included patients, 115 patients (01/2006-12/2016) constituted the training cohort and 58 patients (01/2017-06/2020) formed the validation cohort. Univariate analysis revealed declined total cholesterol (TC, P = 0.000), high-density lipoprotein cholesterol (HDL-C, P = 0.000) and increased triglycerides (TG, P = 0.000) correlated to inferior survival outcomes. Multivariate analysis revealed extranodal involved sites ≥ 2 (hazard ratio [HR]: 2.439; P = 0.036), ß2-MG ≥ 3 mg/L (HR: 4.165; P = 0.003) and TC < 3.58 mmol/L (HR: 3.338; P = 0.000) were independent predictors. Subsequently, a novel prognostic model, EnBC score, was constructed with these three factors. Harrell's C-index of the model in the training and validation cohort was 0.840 (95% CI 0.810-0.870) and 0.882 (95% CI 0.822-0.942), respectively, with well-fitted calibration curves. The model divided patients into four risk groups with distinct OS [median OS: not available (NA) vs. NA vs. 14.0 vs. 4.0 months, P < 0.0001] and PFS (median PFS: 84.0 vs. 19.0 vs. 8.0 vs. 1.5 months, P < 0.0001). Time-dependent receiver operating characteristic curve and decision curve analysis  further revealed that EnBC score provided higher diagnostic capacity and clinical benefit, compared with International Prognostic Index (IPI). CONCLUSION: Firstly, abnormal serum lipid metabolism was demonstrated significantly related to the survival of MTCL patients. Furthermore, a lipid-covered prognostic scoring system was established and performed well in stratifying patients with MTCLs.

Estimating the fraction of unreported infections in epidemics with a known epicenter: An application to COVID-19.

We develop an analytically tractable method to estimate the fraction of unreported infections in epidemics with a known epicenter and estimate the number of unreported COVID-19 infections in the U.S. during the first half of March 2020. Our method utilizes the covariation in initial reported infections across U.S. regions and the number of travelers to these regions from the epicenter, along with the results of an early randomized testing study in Iceland. Using our estimates of the number of unreported infections, which are substantially larger than the number of reported infections, we also provide estimates for the infection fatality rate using data on reported COVID-19 fatalities from U.S. counties.

Dihydromyricetin attenuates Escherichia coli lipopolysaccharide-induced ileum injury in chickens by inhibiting NLRP3 inflammasome and TLR4/NF-κB signalling pathway.

Lipopolysaccharide (LPS) as a major component of Escherichia coli cell wall can cause inflammation and cell death. Dihydromyricetin (ampelopsin, DHM) is a natural flavonoid compound with anti-inflammatory, anti-oxidant and anti-bacterial effects. The preventive effects of DHM against ileum injury remain unclear. Here, we explored the protective role of DHM against LPS-induced ileum injury in chickens. In this study, DHM significantly attenuated LPS-induced alteration in diamine oxidase, malondialdehyde, reduced glutathione, glutathione peroxidase and superoxide dismutase levels in chicken plasma and ileum. Histology evaluation showed that the structure of blood vessels in ileum was seriously fragmented and presence of necrotic tissue in the lumen in the LPS group. Scanning electron microscopic observation revealed that the surface of the villi was rough and uneven, the structure was chaotic, and the normal finger shape was lost in the LPS group. In contrast, 0.05% and 0.1% DHM treatment partially alleviated the abnormal morphology. Additionally, DHM maintained the barrier function by restoring the protein expression of occludin, claudin-1 and zonula occludens protein-1. DHM inhibited apoptosis through the reduction of the expression of bax and caspase-3 and restored the expression of bcl-2. Importantly, DHM could reduce ileum NLR family pyrin domain-containing 3 (NLRP3), caspase-1, interleukin (IL)-1ß and IL-18 expression to protect tissues from pyroptosis and inhibited toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signalling pathway. In summary, DHM attenuated the ileum mucosal damage, oxidative stress and apoptosis, maintained barrier function, inhibited NLRP3 inflammasome and TLR4/NF-κB signalling pathway activation triggered by Escherichia coli LPS.

Focus on exosomes-From pathogenic mechanisms to the potential clinical application value in lymphoma.

Exosomes are highly specialized and functional bilayer membranous particles. They have been considered as vehicles for transporting and delivering a large number of proteins, lipids, and nucleic acids (gene, noncoding RNA, DNA) from parental to recipient cells. In hematological malignancies, exosomes are involved in the tumorigenesis, including producing growth factors, hindering antitumor immunoreaction, promote inflammation, angiogenesis, and hypercoagulation. With the deepening of understanding, exosomes have ignited great interests and ever-increasing efforts into the therapeutic application among scientists, such as biomarkers, therapeutic target, drug delivery system, and vaccines. Here, we discuss the most recent studies on the functions and the emerging therapeutic applications of exosomes in lymphoma.

The Leptin Resistance.

Leptin is an adipocyte-derived hormone, which contributes to the homeostatic regulation of energy balance and metabolism through humoral and neural pathways. Leptin acts on the neurons in certain brain areas such as the hypothalamus, hippocampus, and brain stem to regulate food intake, thermogenesis, energy expenditure, and homeostasis of glucose/lipid metabolism. The pathologically increased circulating leptin is a biomarker of leptin resistance, which is common in obese individuals. Leptin resistance is defined by a reduced sensitivity or a failure in response of the brain to leptin, showing a decrease in the ability of leptin to suppress appetite or enhance energy expenditure, which causes an increased food intake and finally leads to overweight, obesity, cardiovascular diseases, and other metabolic disorders. Leptin resistance is a challenge for clinical treatment or drug discovery of obesity. Until recently, emerging evidence has been showing novel mechanisms of the leptin resistance. Here, we summarized the advances and controversy of leptin resistance and associated diseases, for better understanding the physiology and pathophysiology of leptin as well as the new strategies for treating obesity and metabolic disorders.