Sulfone-Functionalized Chichibabin's Hydrocarbons: Stable Diradicaloids with Symmetry Breaking Charge Transfer Contributing to NIR Emission beyond 900 nm.

While monoradical emitters have emerged as a new route toward efficient organic light-emitting diodes, the luminescence property of organic diradicaloids is still scarcely explored. Herein, by devising a novel radical-radical coupling-based synthetic approach, we report a new class of sulfone-functionalized Chichibabin's hydrocarbon derivatives, SD-1-3, featuring varied substituent patterns and moderate to high diradical characters of 0.44-0.70, as highly stable diradicaloids with rarely seen NIR emission beyond 900 nm. Via comprehensive experimental and theoretical investigations, we reveal that the optoelectronic and magnetic properties of these materials are significantly tuned by the variations of substitutions (H/CF3/OMe) on the molecular skeletons. More importantly, quantum chemical computations indicate that the embedding of sulfone groups has contributed to a breaking of their quasi-C2 symmetry of these diradicaloid molecules and results in an excited-state charge transfer character. Therefore, a remarkably deep NIR emissive wavelength of up to 998 nm, together with a large Stokes shift (∼386 nm), is achieved for the CF3-based SD-2 molecule in tetrahydrofuran. To the best of our knowledge, such a luminescent wavelength of SD-2 has represented the longest wavelengths among the currently reported organic fluorescent radicals. Overall, our work not only establishes a new synthetic approach toward stable Chichibabin's hydrocarbons but also paves the way for designing NIR emissive open-shell materials with both fundamental understanding and feasible control of their luminescent properties.

Association between metabolites in tryptophan-kynurenine pathway and inflammatory bowel disease: a two-sample Mendelian randomization.

Previous observational studies have suggested an association between tryptophan (TRP)-kynurenine (KYN) pathway and inflammatory bowel disease (IBD). However, whether there is a causal relationship among them remains unclear. Therefore, a two-sample Mendelian randomization (MR) study was conducted to explore the potential causal effects of crucial metabolites in TRP-KYN pathway on IBD and its subtypes. Using summary data from genome-wide association studies, a two-sample MR was employed to evaluate the genetic associations between TRP and KYN as exposures and IBD as an outcome. The inverse variance weighted method was used as the primary MR analysis, with MR-Egger, weighted mode, simple mode, and weighted median methods as complementary analyses. The odds ratios (OR) and 95% confidence intervals (CI) were determined for TRP-IBD (OR 0.739, 95% CI [0.697; 0.783]), TRP-UC (OR 0.875, 95% CI [0.814; 0.942]), TRP-CD (OR 0.685, 95% CI [0.613; 0.765]), KYN-IBD (OR 4.406, 95% CI [2.247; 8.641]), KYN-UC (OR 2.578, 95% CI [1.368; 4.858], and KYN-CD (OR 13.516, 95% CI [4.919; 37.134]). Collectively, the MR analysis demonstrated a significant protective association between TRP and IBD, whereas KYN was identified as a risk factor for IBD.

Magnetic Bistability in an Organic Radical-Based Charge Transfer Cocrystal.

We report herein an organic charge transfer cocrystal complex, consisting of a stable radical TPVr and an electron acceptor TCNQF4, as a rare sort of all-organic-based magnetic bistable materials with a thermally activated magnetic hysteresis loop over the temperature range from 170 to 260 K. Detailed X-ray crystallographic studies and theoretical calculations revealed that while a π-associated radical anion dimer was formed upon an integer charge transfer process from TPVr to the TCNQF4 molecules within the cocrystal lattice, the resulting TCNQF4·- π-dimers were found to exhibit varied intradimer π-stacking distances and singly occupied molecular orbital overlaps at different temperatures, thus yielding two different singlet states with distinct singlet-triplet gaps above and below the loop, which eventually contributed to the thermally excited molecular magnetic bistability.

Glutamine Regulates Gene Expression Profiles to Increase the Proliferation of Porcine Intestinal Epithelial Cells and the Expansion of Intestinal Stem Cells.

The intestinal epithelium is known for its rapid self-renewal, and glutamine is crucial in providing carbon and nitrogen for biosynthesis. However, understanding how glutamine affects gene expression in the intestinal epithelium is limited, and identifying the essential genes and signals involved in regulating intestinal epithelial cell growth is particularly challenging. In this study, glutamine supplementation exhibited a robust acceleration of intestinal epithelial cell proliferation and stem cell expansion. RNA sequencing indicated diverse transcriptome changes between the control and glutamine supplementation groups, identifying 925 up-regulated and 1152 down-regulated genes. The up-regulated DEGs were enriched in the KEGG pathway of cell cycle and GO terms of DNA replication initiation, regulation of phosphatidylinositol 3-kinase activity, DNA replication, minichromosome maintenance protein (MCM) complex, and ATP binding, whereas the down-regulated DEGs were enriched in the KEGG pathway of p53 signaling pathway, TNF signaling pathway, and JAK-STAT signaling pathway and GO terms of inflammatory response and intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress. Furthermore, GSEA analysis revealed a significant up-regulation of the cell cycle, DNA replication initiation, ATP-dependent RNA helicase activity, and down-regulation of the TNF signaling pathway. The protein-protein association network of the intersecting genes highlighted the significance of DNA replication licensing factors (MCM3, MCM6, and MCM10) in promoting intestinal epithelial growth in response to glutamine. Based on these findings, we propose that glutamine may upregulate DNA replication licensing factors, leading to increased PI3K/Akt signaling and the suppression of TNF, JAK-STAT, and p53 pathways. Consequently, this mechanism results in the proliferation of porcine intestinal epithelial cells and the expansion of intestinal stem cells.

Single-cell and bulk transcriptomics reveals M2d macrophages as a potential therapeutic strategy for mucosal healing in ulcerative colitis.

Mucosal healing is essential for treating ulcerative colitis (UC), which results from imbalanced macrophage polarization and dysregulated inflammatory responses. However, the mechanisms of cellular communication and signal transduction that regulate mucosal healing among macrophage subtypes require further investigation. We use bulk and single-cell RNA sequencing analysis to reveal that macrophage subtypes vary in different UC states. At the same time, chemokine and angiogenesis signaling is strongly associated with M2 macrophage's infiltrated proportion. To get more insight into subtypes of macrophages in mucosal healing, we divided macrophages into M1, M2b, and M2d macrophages. Based on the differentially expressed genes (DEGs) between M2d and M1 macrophages, KEGG and GO analysis highlights M2d macrophages' ability to alleviate inflammation and promote epithelial healing. Trajectory analysis revealed opposite differentiation of macrophage subsets between UC and healthy groups, with M1 and M2d macrophages coexisting in the same differentiation branch under UC conditions. Along the pseudotime axis, CCL3 and VEGFA expression increased in UC, while IL10RA remained stable in UC but increased in healthy controls. CellChat identified CCL3-CCR1 has strong communication between M1 and M2d macrophages, while the IL10 signaling pathway is activated explicitly in M2d macrophages to mitigate inflammation and promote epithelial healing. We also speculate that high levels of VEGFA activate endothelial cells expressing VEGFR and worsen inflammation. To conclude, we suggested IL10 and VEGF signaling in M2d macrophages as potential therapeutic targets for mucosal healing. However, it is necessary to establish reliable methods for isolating and purifying M2d macrophages before these targets can be effectively utilized.

α-Cyano Triaryl[3]radialene: Unsymmetrical Stereo-configuration, Clustering-enhanced Excimer Emission, and Radical-involved Multimodal Information Switching.

[3]Radialene has a peculiar topology and cross-conjugation system, representing a unique molecular scaffold in organic materials. Herein, we report a special class of stereoisomeric α-cyano triaryl[3]radialenes (CTRs) that show concentration-caused quenching in solution but emit red-shifted and enhanced luminescence in the crystalline state. Clustering of multiple cyano groups and their through-space interactions with the [3]radialene ring significantly extend π-electron communication meanwhile rigidifying the propeller conformation multivalently, thus playing a key role behind the state-dependent luminescence. These radialenes with a substantial electron affinity undergo a reversible electron transfer transition to anionic radicals with good stability, showing switching of photoabsorption, photoluminescence and electron spin resonance (ESR) signal. We also established proof-of-concept applications of CTRs for multimodal information encryption and chemical sensing.

Dual Charge Transfer Generated from Stable Mixed-Valence Radical Crystals for Boosting Solar-to-Thermal Conversion.

Realizing dual charge transfer (CT) based on stable organic radicals in one system is a long-sought goal, however, remains challenging. In this work, a stable mixed-valence radical crystal is designed via a surfactant-assisted method, namely TTF-(TTF+• )2 -RC (where TTF = tetrathiafulvalene), containing dual CT interactions. The solubilization of surfactants enables successful co-crystallization of mixed-valence TTF molecules with different polarity in aqueous solutions. Short intermolecular distances between adjacent TTF moieties within TTF-(TTF+• )2 -RC facilitate both inter-valence CT (IVCT) between neutral TTF and TTF+• , and inter-radical CT (IRCT) between two TTF+• in radical π-dimer, which are confirmed by single-crystal X-ray diffraction, solid-state absorption, electron spin resonance measurements, and DFT calculations. Moreover, TTF-(TTF+• )2 -RC reveals an open-shell singlet diradical ground state with the antiferromagnetic coupling of 2J = -657 cm-1 and an unprecedented temperature-dependent magnetic property, manifesting the main monoradical characters of IVCT at 113-203 K while the spin-spin interactions in radical dimers of IRCT are predominant at 263-353 K. Notably, dual CT characters endow TTF-(TTF+• )2 -RC with strong light absorption over the full solar spectrum and outstanding stability. As a result, TTF-(TTF+• )2 -RC exhibits significantly enhanced photothermal property, an increase of 46.6 °C within 180 s upon one-sun illumination.

Autophagy-mediated ferroptosis involved in nickel-induced nephrotoxicity in the mice.

Nickel, as a widely polluted metal, has been shown nephrotoxicity. Ferroptosis is a new type of cell death driven by iron-dependent lipid peroxidation. Our study found that nickel chloride (NiCl2) induced ferroptosis in mouse kidney and TCMK-1 cells. The iron content was significantly increased in the kidney and TCMK-1 cells after NiCl2 treatment. Lipid peroxidation and MDA content were significantly increased, and GSH content and T-SOD activity were significantly decreased after exposure to NiCl2. Moreover, NiCl2 increased COX-2 protein levels, decreased SLC7A11 and GPX4 protein levels, and elevated Ptgs2 mRNA levels. Next, the mechanism of Ni-induced ferroptosis was investigated. The results showed that NiCl2 induced autophagy in TCMK-1 cells, which promoted ferroptosis induced by NiCl2. Furthermore, the data of autophagy activation or inhibition experiment showed that autophagy facilitated ferroptosis through the degradation of the iron regulation protein NCOA4 and FTH1. Otherwise, iron chelator DFOM treatment inhibited ferroptosis induced by NiCl2. Finally, ferroptosis inhibitor Fer-1 treatment significantly alleviated cytotoxicity induced by NiCl2. To sum up, our above results showed that ferroptosis is involved in NiCl2-induced nephrotoxicity, and NiCl2 induces autophagy-dependent ferritin degradation, releases iron ions, leads to iron overload, and induces ferroptosis. This study supplies a new theoretical foundation for the study of nickel and renal toxicity.

Characteristics of pathology and transcriptome profiling reveal features of immune response of acutely infected and asymptomatic infected of carp edema virus in Koi.

Koi sleepy disease (KSD) is a high mortality and infection viral disease caused by carp edema virus (CEV), which was a serious threat to aquaculture of common carp and export trade of Koi worldwide. Asymptomatic infection is an important cause of the difficulty in preventing KSD and its worldwide spread, because asymptomatic infection can be activated under appropriate condition. However, the understanding of the molecular correlates of these infections is still unknown. The purpose of this study was to compare the pathology change, enzyme activity, immunoglobulin activity, host and viral gene expression differences in acutely infected and cohabiting asymptomatic Koi infected with CEV. Healthy Koi were used as a control. The gross pathology, histopathology and ultrastructural pathology showed the difference and characteristics damage to the tissues of Koi under different infection conditions. Periodic Acid-Schiff stain (PAS), enzyme activity and immunoglobulin activity revealed changes in the immune response of gill tissue between acutely infected, asymptomatic infected and healthy Koi. A total of 111 and 2484 upregulated genes and 257 and 4940 downregulated genes were founded in healthy Koi vs asymptomatic infected Koi and healthy Koi vs acutely infected Koi, respectively. Additionally, 878 upregulated genes and 1089 downregulated genes were identified in asymptomatic vs. acutely infected Koi. Immune gene categories and their corresponding genes in different comparison groups were revealed. A total of 3, 59 and 28 immune-related genes were identified in the group of healthy Koi vs asymptomatic infected Koi, healthy Koi vs acutely infected Koi and asymptomatic infected Koi vs acutely infected Koi, respectively. Nineteen immune-related genes have the same expression manner both in healthy Koi vs acutely infected Koi and asymptomatic Koi vs acutely infected Koi, while 9 immune-related genes were differentially expressed only in asymptomatic Koi vs acutely infected Koi, which may play a role in viral reactivation. In addition, 8 differentially expressed genes (DEGs) were validated by quantitative reverse transcription PCR (RT-qPCR), and the results were consistent with the RNA-Seq results. In conclusion, the data obtained in this study provide new evidence for further elucidating CEV-host interactions and the CEV infection mechanism and will facilitate the implementation of integrated strategies for controlling CEV infection and spread.

Change of serum lipoproteins and its potential use in stratifying patients with sepsis among neonates.

BACKGROUND: Changes of serum lipoprotein concentration during bacteremia or sepsis are observed and lipoproteins concentration facilitate the evaluation severity of sepsis in adults, but its clinical usage is still unclear. Here, we analyzed the lipoprotein concentration in neonates with sepsis and discussed its use in stratifying patients. METHODS: This is a retrospective study involved 88 culture-proven septic patients. Clinical and microbiology data of involved patients were collected via inquiring databases of our institute. Patients were grouped according to blood culture results or procalcitonin level; the difference between groups were analyzed. RESULTS: Compared with uninfected group, there is no change of triglyceride (TG) concentrations and significant decrease of Total cholesterol (TC) concentration in septic patients. There is no significant difference between Gram-positive and Gram-negative-related septic patients in terms of serum TG and TC concentration. Other than group with procalcitonin level of 0.5-2 ng/ml, both serum TG and TC concentration were decreased while serum procalcitonin level increasing. CONCLUSIONS: Our results indicated that serum lipoprotein concentration may be recommended to help diagnosis of bacteria and to evaluate the severity of sepsis.

Photoelectromagnetic Responsive Adaptive Porous Frameworks through Dynamic Covalent Chemistry of Tetraarylethylene-backboned Aryldicyanomethyl Radicals.

Dynamic materials undergoing adaptive solid-state transitions are attractive for soft mechanics and information technology. Here, we report a novel porous framework system based on macrocyclic trimers assembled from open-shell tetraarylethylene building blocks with aryldicyanomethyl radicals as coupling linkers. Under mechanical, thermal, or chemical stimuli, the framework showed adaptability by activating conformational dynamics and radical-based transformations, thus displaying macroscopic responsiveness in terms of light absorption, luminescence, and magnetism. We studied the dynamic processes by variable-temperature nuclear magnetic resonance (VT-NMR), variable-temperature electron spin resonance (VT-ESR), and superconducting quantum interference device (SQUID) measurement and further established a proof-of-concept application for multi-modal information encryption. The strategy may open avenues for rational design of solid-state photoelectromagnetic dynamic materials by merging dynamic covalent coupling chemistry and functional aggregation principles.

Kynurenine pathway metabolites modulated the comorbidity of IBD and depressive symptoms through the immune response.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is defined as chronic inflammation in the gastrointestinal tract. Notably, more than 20% of people with IBD experience depressive symptoms. Understanding the immunological mechanism of chronic intestinal inflammation on cognitive behavior has become a key research focus. Previous studies have shown that a dysregulated immune response contributes to chronic inflammation and depressive symptoms. The tolerant phenotype exhibited by immune cells regulates the course of chronic inflammation in distinct ways. In addition, neuroglia, such as microglia and astrocytes specific to the brain, are also influenced by deregulated inflammation to mediate the development of depressive symptoms. The kynurenine pathway (KP), a significant tryptophan metabolic pathway, transforms tryptophan into a series of KP metabolites that modulate chronic inflammation and depressive symptoms. In particular, indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in the KP, is activated by chronic inflammation and leads to the production of kynurenine. In addition, disruption of the brain-gut axis induced by IBD allows kynurenine to cross the blood-brain barrier (BBB) and form a series of neuroactive kynurenine metabolites in glial cells. Among them, quinolinic acid continuously accumulates in the brain, indicating depression. Thus, KP metabolites are critical for driving the comorbidity of IBD and depressive symptoms. In this review, the pathological mechanism of KP metabolite-mediated chronic intestinal inflammation and depressive symptoms by regulating the immune response is summarized according to the latest reports.

Nickel induces hepatotoxicity by mitochondrial biogenesis, mitochondrial dynamics, and mitophagy dysfunction.

Nickel (Ni) is an important and widely hazardous chemical industrial waste. Excessive Ni exposure could cause multi-organs toxicity in human and animals. Liver is the major target organ of Ni accumulation and toxicity, however, the precise mechanism is still unclear. In this study, nickel chloride (NiCl2 )-treatment induced hepatic histopathological changes in the mice, and, transmission electron microscopy results showed mitochondrial swollen and deformed of hepatocyte. Next, the mitochondrial damages including mitochondrial biogenesis, mitochondrial dynamics, and mitophagy were measured after NiCl2 administration. The results showed that NiCl2 suppressed mitochondrial biogenesis by decreasing PGC-1α, TFAM, and NRF1 protein and mRNA expression levels. Meanwhile, the proteins involved in mitochondrial fusion were reduced by NiCl2 , such as Mfn1 and Mfn2, however, mitochondrial fission proteins Drip1 and Fis1 were significantly increased. The up-regulation of mitochondrial p62 and LC3II expression indicated that NiCl2 increased mitophagy in the liver. Moreover, the receptor-mediated mitophagy and ubiquitin (Ub)-dependent mitophagy were detected. NiCl2 promoted PINK1 accumulation and Parkin recruitment on mitochondria. And, the receptor proteins of mitophagy Bnip3 and FUNDC1 were increased in the NiCl2 -treated mice liver. Overall, these results show that NiCl2 could induce mitochondria damage in the liver of mice, and, dysfunction of mitochondrial biogenesis, mitochondrial dynamics and mitophagy involved in the molecular mechanism of NiCl2 -induced hepatotoxicity.

A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway.

Multiple myeloma (MM), the second most common haematological malignancy, is currently incurable because patients often develop multiple drug resistance and experience subsequent relapse of the disease. This study aims to identify a potential therapeutic agent that can counter bortezomib (BTZ) resistance in MM. DCZ0358, a novel alkaloid compound, is found to exert potent cytotoxic effects against BTZ-resistant MM cells in vivo and in vitro. The anti-myeloma activity of DCZ0358 is associated with inhibition of cell proliferation, promotion of cell apoptosis via caspase-mediated apoptotic pathways, and induction of G0/G1 phase arrest via downregulation of cyclin D1, CDK4, and CDK6. Further investigation of the molecular mechanism shows that DCZ0358 suppresses the JAK2/STAT3 signaling pathway. In conclusion, DCZ0358 can successfully counter BTZ resistance in MM cells. This study provides evidence that warrants future preclinical assessments of DCZ0358 as a therapeutic agent against BTZ resistance in MM.

Evaluation of microbiological epidemiology and clinical characteristics of maternal bloodstream infection: a 10 years retrospective study.

Objective: Although the incidence of bloodstream infection (BSI) during pregnancy is relatively low, it can lead to unfavorable outcomes. The aim of our study was to analyze the clinical and microbiological characteristics of maternal bacteremia and to assess maternal and fetal outcomes. Methods: Our study was a retrospective study conducted in a tertiary women and children's hospital in Guangzhou, China, from 2013 to 2022. Data were extracted from medical records and the laboratory information system. The participants were divided into groups, and the difference between the groups was analyzed. Results: The incidence of maternal BSI during the 10 years study period was 10.2 cases/10,000 maternities, with a peak found from 2014 to 2016. Escherichia coli (48%) was the predominant causative pathogen, followed by Streptococcus agalactiae (13%). Gestational diabetes mellitus (GDM) (15%) was the most common underlying condition among maternal BSI episodes. Urinary tract (13%) and genital tract (28%) were the predominant source of BSI. About 14% of neonates were infected, and BSI was the most common type of infection. E. coli was the predominant pathogen in mother-neonate pairs with concurrent BSI. Premature rupture of membranes (PROM, OR:4.68) and preterm birth (OR:3.98) were the risk factors predicting neonatal infection. More than 85% of the E. coli were resistant to ampicillin (AMP) and 50% of the E. coli were extended-spectrum ß-lactamase (ESBL)-producing bacteria. Conclusion: Maternal BSI is a rare event, but continuous monitoring on the aspects of pathogen composition, antimicrobial resistance characteristics, and risk factors for adverse outcomes remains necessary to further reduce poor outcomes and mitigate bacterial resistance.

Protective effect of cinnamaldehyde on channel catfish infected by drug-resistant Aeromonas hydrophila.

The protective effect of cinnamaldehyde on channel catfish infected by drug-resistant Aeromonas hydrophila CW strain was explored by observing the clinical signs and histopathology, measuring the cumulative mortality, serum biochemical and non-specific immune indicators, and intestinal microbiota in this study. The cumulative survival rate of the cinnamaldehyde within 14 days was significantly higher than that of the challenge group, which was 70% and 20%, respectively. Compared with the challenge group, the activities of lysozyme, superoxide dismutase, and glutathione peroxidase in the treatment group were increased, while there was no significant difference in catalase activity. Compared with the challenge group, the histopathology results showed that the injury of liver, spleen, and kidney was significantly alleviated after cinnamaldehyde treatment. The results of intestinal microbiota showed that the proportion of Proteobacteria in the challenge group was significantly increased, and the proportion of Aeromonas sp. reached 30% based on the analysis of species classification level. The composition of dominant species in the treatment group was similar to the control group. In conclusion, cinnamaldehyde increased the cumulative survival rate of channel catfish infected by A. hydrophila. It could protect channel catfish through improving the non-specific immune function of channel catfish, alleviating the pathological lesions of liver, spleen, kidney, and intestine, and maintaining the relative balance of the intestinal microbiota. Therefore, cinnamaldehyde could be a candidate drug for the treatment of A. hydrophila infection.

DCZ0014, a novel compound in the therapy of diffuse large B-cell lymphoma via the B cell receptor signaling pathway.

Diffuse large B cell lymphoma (DLBCL) is a clinical and genetically heterogeneous lymphoid malignancy. Although R-CHOP (rituximab plus cyclophosphamide, vincristine, doxorubicin, and prednisone) treatment can improve the survival rate of patients with DLBCL, more than 30% of patients exhibit treatment failure, relapse, or refractory disease. Therefore, novel drugs or targeted therapies are needed to improve the survival of patients with DLBCL. The compound DCZ0014 is a novel chemical similar to berberine. In this study, we found that DCZ0014 significantly inhibited the proliferation and activity of DLBCL cells, and induced cell apoptosis. Following treatment with DCZ0014, DLBCL cells accumulated in G0/G1-phase of the cell cycle and showed decreased mitochondrial membrane potential. Additionally, DCZ0014 inhibited DNA synthesis, enhanced DNA damage in DLBCL cells, as well as inhibited Lyn/Syk in B cell receptor signaling pathway. Further experiments demonstrated that DCZ0014 did not significantly affect peripheral blood mononuclear cells. Tumor xenograft model showed that DCZ0014 not only inhibited tumor growth but also extended the survival time of mice. Thus, DCZ0014 showed potential for clinical application in the treatment of patients with DLBCL.

Resveratrol induces AMPK and mTOR signaling inhibition-mediated autophagy and apoptosis in multiple myeloma cells.

Resveratrol, a natural compound extracted from the skins of grapes, berries, or other fruits, has been shown to have anti-tumor effects against multiple myeloma (MM) via promoting apoptosis and inhibiting cell viability. In addition to apoptosis, autophagy also plays a significant role in anti-tumor effects. However, whether autophagy is involved in anti-MM activity of resveratrol remains unclear. In this study, human MM cell lines U266, RPMI-8226, and NCI-H929 were treated with resveratrol. Cell Counting Kit-8 assay and colony formation assay were used to measure cell viability. Western blot analysis was used to detect apoptosis- and autophagy-associated proteins. 3-Methyladenine (3-MA) was applied to inhibit autophagy. Results showed that resveratrol inhibited cell viability and colony formation via promoting apoptosis and autophagy in MM cell lines U266, RPMI-8226, and NCI-H929. Resveratrol promoted apoptosis-related proteins, Caspase-3 activating poly-ADP-ribose polymerase and Caspase-3 cleavage, and decreased the protein level of Survivin in a dose-dependent manner. Additionally, resveratrol upregulated the levels of LC3 and Beclin1 in a dose-dependent way, indicating that autophagy might be implicated in anti-MM effect of resveratrol. Furthermore, 3-MA relieved the cytotoxicity of resveratrol by blocking the autophagic flux. Resveratrol increased the phosphorylation of adenosine monophosphate (AMP)-activated protein kinase and decreased the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream substrates p70S6K and 4EBP1 in a dose-dependent manner, leading to autophagy. Therefore, our results suggest that resveratrol exerts anti-MM effects through apoptosis and autophagy, which can be used as a new therapeutic strategy for MM in clinic.

Preliminary Evaluation of Recombinant EPC1 and TPx for Serological Diagnosis of Animal Cystic Echinococcosis.

Animal cystic echinococcosis (CE) is one of the most important helminthic diseases and affects many mammalian intermediate hosts. Practical and effective diagnosis is crucial for animal CE control. Two different recombinant antigens derived from Echinococcus granulosus, Echinococcus protoscolex calcium binding protein 1 (rEg-EPC1) and thioredoxin peroxidase (rEg-TPx), were evaluated in this study to detect the specific immunoglobulin G (IgG) in sheep and goat with CE by the indirect enzyme-linked immunosorbent assays. The diagnostic effect of the above-listed proteins was determined to their sensitivity and specificity and compared with hydatid cyst fluid, two previously reported immunogenic recombinant proteins (dihydrofolate reductase and P29), and two commercial kits available in China. Of these, the best diagnostic results were obtained in the anti-TPx IgG ELISA, with 92.6% sensitivity, 98.8% specificity, and no cross-reactivity with anti-Eg95 IgG. Recombinant E. granulosus thioredoxin peroxidase shows good potential for serological diagnosis of animal cystic echinococcosis.

Study the antibacterial mechanism of cinnamaldehyde against drug-resistant Aeromonas hydrophila in vitro.

Aeromonas hydrophila, a highly infectious pathogen, causes several infections in aquatic animals and huge economic losses. Antibiotics are often used to treat A. hydrophila infections. However, overuse and irrational usage of antibiotics has led to severe antibiotic residues and emergence of resistance. There is therefore an urgent need for a new sustainable drug to control bacterial infection. Cinnamaldehyde, a plant-derived ingredient, has been found to have good antibacterial activity against A. hydrophila in vitro, but its mechanism of action remains unknown. In this study, we investigated the mechanism of cinnamaldehyde against A. hydrophila by evaluating the effects of cinnamaldehyde on A. hydrophila cell growth, cell morphology, electrical conductivity, lactate dehydrogenase (LDH), protein metabolism and DNA. The minimal inhibitory concentration and minimum bactericidal concentration of cinnamaldehyde were 256 and 512 µg/mL, respectively. Microscopy results showed disrupted cell wall and membrane, loss of cytoplasm, interior cavitation and unusual binary fission in the cinnamaldehyde-treated group. Electrical conductivity, LDH activity content and DNA extravasation in cinnamaldehyde-treated A. hydrophila increased by 7.14%, 16.75% and 20.29 µg/mL, respectively. Furthermore, nucleic acid fluorescence intensity and density decreased over time in the cinnamaldehyde-treated group. Taken together, these findings suggest that cinnamaldehyde can inhibit the growth of A. hydrophila by disrupting cell membranes and affecting protein metabolism.