Squamous cell carcinoma of ear and temporal bone: A retrospective study on clinicopathological predictors.

BACKGROUND: Ear and temporal bone squamous cell carcinoma (ETBSCC) is a rare and aggressive malignant tumor with minimal clinicopathological studies. The object of this study was to retrospectively evaluate the predictive effect of clinicopathological variables on the 5-year overall survival (OS) rate of ETBSCC patients in a single tertiary medical center in Tianjin, China. METHODS: A cohort of 44 patients with diagnosed ETBSCC from December 2012 to August 2022 were retrospectively studied. Univariate and multivariate analysis were, respectively, performed for the assessment of clinicopathological predictors, including sex, age, history of chronic suppurative otitis media (CSOM), lesion side, diameter, the choice of surgical approach, parotidectomy, neck dissection, adjuvant therapies, T stage, lymph node metastasis, tumor grade, margin, perineural invasion (PNI), and Ki-67 index. RESULTS: Seventeen females and 27 males were included, with the mean age of 65 years old, ranging from 36 to 89 years. The 5-year OS rate was 43% (mean 51 months, 95% confidence interval [CI] = 39-64). Significant prediction of a worse prognosis for 5-year OS rate was observed under univariate analysis for advanced T stage, positive margin, identified PNI, and higher Ki-67 index, respectively. Advanced T stage was confirmed to be an independent prognostic factor strongly affecting 5-year OS rate among this cohort of patients using a multivariate cox proportional hazard model. CONCLUSION: We found that clinicopathological parameters, especially postoperative pathological parameters, play a critical role in predicting the prognosis of ETBSCC patients.

Naringin exerts antibacterial and anti-inflammatory effects on mice with Staphylococcus aureus-induced osteomyelitis.

Osteomyelitis is an invasive bone infection that can lead to severe pain and even disability, posing a challenge for orthopedic surgery. Naringin can reduce bone-related inflammatory conditions. This study aimed to elucidate the function and mechanism of naringin in a Staphylococcus aureus-induced mouse model of osteomyelitis. Femurs of S. aureus-infected mice were collected after naringin administration and subjected to microcomputed tomography to analyze cortical bone destruction and bone loss. Bacterial growth in femurs was also assessed. Proinflammatory cytokine levels in mouse femurs were measured using enzyme-linked immunosorbent assays. Pathological changes and bone resorption were analyzed using hematoxylin and eosin staining and tartrate-resistant acid phosphatase staining, respectively. Quantitative reverse transcription polymerase chain reaction and western blot analysis were used to quantify the messenger RNA and protein expression of osteogenic differentiation-associated genes in the femurs. The viability of human bone marrow-derived stem cells (hBMSCs) was determined using cell counting kit-8. Alizarin Red S staining and alkaline phosphatase staining were performed to assess the formation of mineralization nodules and bone formation in vitro. Notch signaling-related protein levels in femur tissues and hBMSCs were assessed using western blot analysis. Experimental results revealed that naringin alleviated S. aureus-induced cortical bone destruction and bone loss in mice by increasing the bone volume/total volume ratio. Naringin suppressed S. aureus-induced bacterial growth and inflammation in femurs. Moreover, it alleviated histopathological changes, inhibited bone resorption, and increased the expression of osteogenic markers in osteomyelitic mice. It increased the viability of hBMSCs and promoted their differentiation and bone mineralization in vitro. Furthermore, naringin activated Notch signaling by upregulating the protein levels of Notch1, Jagged1, and Hes1 in the femurs of model mice and S. aureus-stimulated hBMSCs. In conclusion, naringin reduces bacterial growth, inflammation, and bone resorption while upregulating the expression of osteogenic markers in S. aureus-infected mice and hBMSCs by activating Notch signaling.

Treg-derived TGF-ß1 dampens cGAS-STING signaling to downregulate the expression of class I MHC complex in multiple myeloma.

Multiple myeloma (MM) progression involves diminished tumor antigen presentation and an immunosuppressive microenvironment, characterized by diminished expression of major histocompatibility complexes (MHC) class I molecule and elevated programmed death ligand 1 (PDL1) in MM cells, along with an enriched population of regulatory T cells (Tregs). To investigate Treg's influence on MM cells, we established a co-culture system using Tregs from MM patients and the MM cell lines (MM.1S and SK-MM-1) in vitro and assessed the effects of intervening in the relevant pathways connecting Tregs and MM cells in vivo. In vitro, Tregs induced transforming growth factor beta-1 (TGF-ß1) production, downregulated MHC I members, and increased PDL1 expression in MM cells. Treg-derived TGF-ß1 suppressed the cGAS-STING pathway, contributing to the loss of MHC I molecule expression and PDL1 upregulation. Correspondingly, neutralizing TGF-ß1 or activating the cGAS-STING pathway restored MHC I and PDL1 expression, effectively countering the pro-tumorigenic effect of Tregs on MM cells in vivo. These data elucidated how Tregs influence tumor antigen presentation and immunosuppressive signal in MM cells, potentially providing therapeutic strategies, such as neutralizing TGF-ß1 or activating the cGAS-STING pathway, to address the immune escape and immunosuppressive dynamics in MM.

3-O-Methyl-D-Glucose Blunts Cold Ischemia Damage in Kidney via Inhibiting Ferroptosis.

BACKGROUND: The glucose derivative 3-O-methyl-D-glucose (OMG) is used as a cryoprotectant in freezing cells. However, its protective role and the related mechanism in static cold storage (CS) of organs are unknown. The present study aimed to investigate the effect of OMG on cod ischemia damage in cold preservation of donor kidney. METHODS: Pretreatment of OMG on kidney was performed in an isolated renal cold storage model in rats. LDH activity in renal efflux was used to evaluate the cellular damage. Indicators including iron levels, mitochondrial damage, MDA level, and cellular apoptosis were measured. Kidney quality was assessed via a kidney transplantation (KTx) model in rats. The grafted animals were followed up for 7 days. Ischemia reperfusion (I/R) injury and inflammatory response were assessed by biochemical and histological analyses. RESULTS: OMG pretreatment alleviated prolonged CS-induced renal damage as evidenced by reduced LDH activities and tubular apoptosis. Kidney with pCS has significantly increased iron, MDA, and TUNEL+ cells, implying the increased ferroptosis, which has been partly inhibited by OMG. OMG pretreatment has improved the renal function (p <0.05) and prolonged the 7-day survival of the grafting recipients after KTx, as compared to the control group. OMG has significantly decreased inflammation and tubular damage after KTx, as evidenced by CD3-positive cells and TUNEL-positive cells. CONCLUSION: Our study demonstrated that OMG protected kidney against the prolonged cold ischemia-caused injuries through inhibiting ferroptosis. Our results suggested that OMG might have potential clinical application in cold preservation of donor kidney.

Pain Prevalence and Management in a General Hospital Through Repeated Cross-Sectional Surveys in 2011 and 2021.

Background: There is great scope for improving the quality of pain management. Although pain prevalence has been investigated in several countries, few studies have comparatively assessed changes in pain prevalence and management over a span of multiple years. Aim: This work was aimed at determining the pain prevalence and evaluating the condition of pain management in a Chinese general hospital in 2021 and comparing them with corresponding data from 10 years ago. Methods: Repeated single-center cross-sectional studies were initiated on June 14th, 2011, and September 2nd, 2021, in the same tertiary grade A Chinese general hospital. The same structured questionnaire was used to collect inpatient data on pain intensity and classification and pain management outcomes. We performed statistical analyses to compare categorical variables to assess changes over time. Results: The sample sizes for the investigations in 2011 and 2021 were 2323 and 4454, respectively. In 2021, 24.34% of patients experienced pain; this percentage was significantly lower than that in 2011. Meanwhile, the prevalence of moderate and severe pain decreased from 14.73% in 2011 to 4.98% in 2021. The other six indicators of pain management outcomes also improved significantly. The percentages of patients using painkillers, opioid analgesics, and multiple analgesics increased from 44.61 to 51.38%, 24.01% to 44.61%, and 6.82% to 14.11%, respectively. Furthermore, the percentages of patients who received pain information and who actively reported pain increased from 27.56% to 96.5% and from 85.54% to 98.71%, respectively. The percentage of patients qualified to accurately use the Numerical Rating Scale increased from 10.5% to 79.98%. Conclusion: The quality and outcomes of pain management improved greatly after the establishment and implementation of the pain management system. Nonetheless, pain of different intensities is common after major surgeries, and it is recommended that hospitals popularize and implement perioperative multimodal analgesia strategies to reduce the incidence of postoperative pain.

Advanced Ag nanoparticles for the catalyzation of glyoxylic acid oxidation in through-holes electroless copper metallization.

Advanced Ag nanoparticles (Ag NPs) were prepared by wet chemical oxidation-reduction method, using mainly the tannic acid as reducing agent and carboxymethylcellulose sodium as stabilizer. The prepared Ag NPs uniformly disperse and are stable for more than one month without agglomeration. The studies of transmission electron microscopy (TEM) and ultraviolet-visible (UV-vis) absorption spectroscopy indicate that the Ag NPs are in homogeneous sphere with only 4.4 nm average size and narrow particle size distribution. Electrochemical measurements reveal that the Ag NPs behave excellent catalytic activity for electroless copper plating using glyoxylic acid as reducing agent. In situ fourier transform infrared (in situ FTIR) spectroscopic analysis combined with density functional theory (DFT) calculation illustrate that the molecular oxidation of glyoxylic acid catalyzed by Ag NPs is as the following routes: glyoxylic acid molecule first is adsorbed on Ag atoms with carboxyl oxygen terminal, then hydrolyzed to diol anionic intermediate, and last oxidized to oxalic acid. Time-resolved in situ FTIR spectroscopy further reveals the real-time reactions of electroless copper plating as follows: glyoxylic acid is continuously oxidized to oxalic acid and releases electrons at the active catalyzing spots of Ag NPs, and Cu(II) coordination ions are in situ reduced by the electrons. Based on the excellent catalytic activity, the advanced Ag NPs can replace the expensive Pd colloids catalyst and successfully apply in through-holes metallization of printed circuit board (PCB) by electroless copper plating.

Electronic Beam Steering Metamaterial Antenna with Dual-Tuned Mode of Liquid Crystal Material.

In this study, a dual-tuned mode of liquid crystal (LC) material was proposed and adopted on reconfigurable metamaterial antennas to expand the fixed-frequency beam-steering range. The novel dual-tuned mode of the LC is composed of double LC layers combined with composite right/left-handed (CRLH) transmission line theory. Through a multi-separated metal layer, the double LC layers can be loaded with controllable bias voltage independently. Therefore, the LC material exhibits four extreme states, among which the permittivity of LC can be varied linearly. On the strength of the dual-tuned mode of LC, a CRLH unit cell is elaborately designed on three-layer substrates with balanced dispersion values under arbitrary LC state. Then five CRLH unit cells are cascaded to form an electronically controlled beam-steering CRLH metamaterial antenna on a downlink Ku satellite communication band with dual-tuned characteristics. The simulated results demonstrate that the metamaterial antenna features' continuous electronic beam-steering capacity from broadside to -35° at 14.4 GHz. Furthermore, the beam-steering properties are implemented in a broad frequency band from 13.8 GHz to 17 GHz, with good impedance matching. The proposed dual-tuned mode can make the regulation of LC material more flexible and enlarge the beam-steering range simultaneously.

Mechanism of Cations Suppressing Proton Diffusion Kinetics for Electrocatalysis.

Proton transfer is crucial for electrocatalysis. Accumulating cations at electrochemical interfaces can alter the proton transfer rate and then tune electrocatalytic performance. However, the mechanism for regulating proton transfer remains ambiguous. Here, we quantify the cation effect on proton diffusion in solution by hydrogen evolution on microelectrodes, revealing the rate can be suppressed by more than 10 times. Different from the prevalent opinions that proton transport is slowed down by modified electric field, we found water structure imposes a more evident effect on kinetics. FTIR test and path integral molecular dynamics simulation indicate that proton prefers to wander within the hydration shell of cations rather than to hop rapidly along water wires. Low connectivity of water networks disrupted by cations corrupts the fast-moving path in bulk water. This study highlights the promising way for regulating proton kinetics via a modified water structure.

Type 1 diabetes mellitus induced by PD-1 inhibitors in China: a report of two cases.

The immune-related adverse events associated with immunotherapy may affect endocrine glands and other tissues. Two Chinese patients with malignancies were treated with programmed cell death-1 (PD-1) inhibitors (nivolumab and pembrolizumab) and followed up with biochemical tests over 1 year. After PD-1 treatment for 6 to 10 months, the patients developed symptoms of diabetes, ketoacidosis, and insulin secretion failure. Type 1 diabetes mellitus was confirmed by the characteristic fluctuation of blood glucose that was controlled with multiple daily insulin injections. Neither patient's insulin depletion status was reversed in subsequent years. To decrease the life-threatening complications of diabetic hyperosmolar syndrome and ketoacidosis caused by type 1 diabetes mellitus, it is necessary to monitor the blood glucose and hemoglobin A1c levels. Islet ß-cell autoantibodies and human leukocyte antigen genes can provide additional information in select cases.

TXNIP knockout improves cardiac function after myocardial infarction by promoting angiogenesis and reducing cardiomyocyte apoptosis.

Background: Myocardial infarction (MI) is a common cause of death. Thioredoxin-interacting protein (TXNIP) expression increases after MI, and it exerts a negative regulatory effect on cardiac function after MI. Our study aimed to investigate the specific regulatory mechanism of TXNIP on angiogenesis and cardiomyocyte apoptosis after MI. Methods: The TXNIP gene knock-in (TXNIP-KI) and knock-out (TXNIP-KO) mice were generated, respectively. Eight-week-old male TXNIP-KO, TXNIP-KI, and wild type (WT) mice were subjected to MI by permanent ligation of the left anterior descending artery. Cardiomyocyte apoptosis was detected by TUNEL assay on the 4th post-surgery day. The expressions of TXNIP, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), phosphorylated protein kinase B (p-AKT), p-AMP-activated protein kinase (p-AMPK), cleaved caspase-3, and caspase-3 were detected by Western blot. Quantitative real-time PCR was performed to detect the expression of TXNIP, HIF-1α, VEGF, prolyl hydroxylase (PHD) 1, and factor inhibiting HIF (FIH). In addition, the superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in each group were also measured. On day 7 after MI, the hearts of sacrificed animals were analyzed by immunohistochemistry to assess CD31 expression and determine the density of angiogenesis. One month after treatment, the cardiac functional and structural changes were determined by echocardiography and the level of myocardial fibrosis was observed by Masson staining. Results: Compared with WT mice, TXNIP-KO mice had a significantly improved cardiac functional recovery after MI, and the proportion of myocardial fibrosis area was dramatically reduced, cardiomyocyte apoptosis was decreased, and angiogenesis was significantly increased; TXNIP-KI mice reversed in these changes. The expression of HIF-1α, p-AKT, and p-AMPK increased after MI in TXNIP-KO mice, and the mRNA expression of PHD 1 and FIH decreased. TXNIP-KI mice reversed in these changes. Conclusions: After MI, TXNIP down-regulated the level of HIF-1α and VEGF, reduced the number of angiogenesis, increased cardiomyocyte apoptosis, and ultimately led to a poor prognosis of ischemic myocardium. TXNIP was a protein with negative effects after MI and was expected to be a target for the prevention and treatment of MI.

Screening gene signatures for clinical response subtypes of lung transplantation.

Lung is the most important organ in the human respiratory system, whose normal functions are quite essential for human beings. Under certain pathological conditions, the normal lung functions could no longer be maintained in patients, and lung transplantation is generally applied to ease patients' breathing and prolong their lives. However, several risk factors exist during and after lung transplantation, including bleeding, infection, and transplant rejections. In particular, transplant rejections are difficult to predict or prevent, leading to the most dangerous complications and severe status in patients undergoing lung transplantation. Given that most common monitoring and validation methods for lung transplantation rejections may take quite a long time and have low reproducibility, new technologies and methods are required to improve the efficacy and accuracy of rejection monitoring after lung transplantation. Recently, one previous study set up the gene expression profiles of patients who underwent lung transplantation. However, it did not provide a tool to predict lung transplantation responses. Here, a further deep investigation was conducted on such profiling data. A computational framework, incorporating several machine learning algorithms, such as feature selection methods and classification algorithms, was built to establish an effective prediction model distinguishing patient into different clinical subgroups, corresponding to different rejection responses after lung transplantation. Furthermore, the framework also screened essential genes with functional enrichments and create quantitative rules for the distinction of patients with different rejection responses to lung transplantation. The outcome of this contribution could provide guidelines for clinical treatment of each rejection subtype and contribute to the revealing of complicated rejection mechanisms of lung transplantation.

Identifying luminal and basal mammary cell specific genes and their expression patterns during pregnancy.

Mammary gland is present in all mammals and usually functions in producing milk to feed the young offspring. Mammogenesis refers to the growth and development of mammary gland, which begins at puberty and ends after lactation. Pregnancy is regulated by various cytokines, which further contributes to mammary gland development. Epithelial cells, including basal and luminal cells, are one of the major components of mammary gland cells. The development of basal and luminal cells has been observed to significantly differ at different stages. However, the underlying mechanisms for differences between basal and luminal cells have not been fully studied. To explore the mechanisms underlying the differentiation of mammary progenitors or their offspring into luminal and myoepithelial cells, the single-cell sequencing data on mammary epithelia cells of virgin and pregnant mouse was deeply investigated in this work. We evaluated features by using Monte Carlo feature selection and plotted the incremental feature selection curve with support vector machine or RIPPER to find the optimal gene features and rules that can divide epithelial cells into four clusters with different cell subtypes like basal and luminal cells and different phases like pregnancy and virginity. As representations, the feature genes Cldn7, Gjb6, Sparc, Cldn3, Cited1, Krt17, Spp1, Cldn4, Gjb2 and Cldn19 might play an important role in classifying the epithelial mammary cells. Notably, seven most important rules based on the combination of cell-specific and tissue-specific expressions of feature genes effectively classify the epithelial mammary cells in a quantitative and interpretable manner.

The Association Between the Albumin and Viral Negative Conversion Rate in Patients Infected with Novel Coronavirus Disease 2019 (COVID-19).

Purpose: The novel coronavirus disease 2019 (COVID-19) epidemic is the severe global pandemic with large numbers of infected cases and deaths in recent decades. The previous studies were all about the influence of albumin (ALB) for the severity and mortality of in-patients infected with COVID-19. But few studies exist about the influence factors to achieve viral negative conversion. Therefore, this study conducted an exploratory study to investigate the effect of albumin on negative conversion rate. Methods: Among the 190 hospitalized patients with moderate COVID-19 who had a course of disease longer than 30 days, 102 achieved viral negative conversion in 30-45 days and 88 not after 45 days. Taking other variables as concomitant variable, Cox proportional hazard regression model was applied to explore the influence of albumin to negative conversion rate under various factors. Results: By comparing patients who could and could not achieve the finally viral negative conversion, a possible nonlinear relationship between the continuous variables and clinical outcomes was examined by a restricted cubic spline regression model. An association was found between albumin levels and hazard ratio of viral negative conversion rate (P = 0.027). The increase of albumin was accompanied with decreases of hazard ratio of viral negative conversion rate (the value of albumin <38 g/L). But when the value of albumin was higher than 38 g/L, the hazard ratio of viral negative conversion rate approached 1, it means that albumin is not a risk factor for the viral negative conversion rate of COVID-19 disease. Conclusion: For patients with COVID-19, albumin is a common and observed laboratory parameter. It is associated with final viral negative conversion rate although its underlying mechanism and relationship with the viral negative conversion rate still need to be clarified.

A proton-conductive metal-organic framework based on imidazole and sulphate ligands.

A metal-organic framework (MOF) built from a combination of metal cations, neutral azole ligands and sulphate anions, [Cu2(DHBDI)3(SO4)2]n (1, DHBDI = 1H,5H-benzo[1,2-d:4,5-d']diimidazole), was synthesized. MOF 1 exhibits good chemical stability in acids, bases and boiling water while showing high hydrophilicity. Meanwhile, MOF 1 exhibits a proton conductivity of 1.14 × 10-3 S cm-1 at 90 °C and 98% RH, among the best for MOF materials with uncoordinated N sites. Temperature-dependent conductivity measurements suggest a vehicle mechanism (Ea = 0.64 eV) for proton transport.

The gene knockout of ATlaR improves insulin resistance induced by high-fat diet in rats / 中国药理学通报

Aim To explore the role of angiotensin U type 1 a reeeptor ( AT 1 aR ) , an important component of HAS, in obesity-induced insulin resistance.Methods Wild type ( WT) and ATlaR gene knockout (ATlaR ) SD rats were fed with normal diet and 60% high-fat diet for 12 weeks, respectively.After 12 weeks, blood was collected from the abdominal aorta of rats to obtain serum, and the serum insulin level was measured by ELISA.The epididvmal adipose tissue was obtained, and gene expressions of peroxisome pro- liferator-activated receptor -y ( PPAR7) and sterol reg¬ulator}' element binding protein lc (SREBP-lc) in ad¬ipose tissue were detected by RT-PCR method.The protein expressions of insulin signaling pathway and protein kinase C (PKC) in adipose tissue were detec¬ted by Western blot.Results ATI aR knockout signif¬icantly reduced HOMA-IR and improved insulin resist¬ance induced by high-fat diet.In ATlaR rats fed with high-fat, the protein expressions of insulin signa¬ling pathway were much higher than those of WT rats, indicating that ATlaR gene knockout improved the in¬sulin signaling pathway in high-fat diet.In addition, the PKCa, PKCe and PKCr| expressions of ATlaR rats were significantly lower than those of WT rats.And the gene expressions of PPAR-y and SREBP-lc, which promoted adipogenic differentiation, significantly increased in ATlaR rats fed with a high-fat diet, demonstrating that ATlaR knockout promoted adipo¬genic differentiation.Conclusions ATlaR knockout significantly improves high-fat diet induced 1R by en¬hancing protein expressions of insulin signaling path¬way, inhibiting PKC expression and promoting adipo¬genic differentiation.

Isolation of Microvesicles from Human Circulating Neutrophils.

Neutrophil-derived microvesicles (NDMVs) are liberated by neutrophils upon cell activation by molecules. Once activated, neutrophils are primarily involved in acute inflammation; however, the microvesicles they produce are largely anti-inflammatory. NDMVs have been shown to protect cartilage during inflammatory arthritis. They exert these effects by inhibiting or affecting the function of target cells, including macrophages. NDMVs have the potential to act as disease-modifying agents, especially for inflammatory diseases. This protocol describes a method using differential centrifugation to separate neutrophils from whole human blood. Subsequently, neutrophils are identified by cytospin and Wright's staining, and then the NDMVs are isolated using differential centrifugation.

Suppressing Sulfite Dimerization at a Polarized Gold Electrode/Water Solution Interface for High-Quality Gold Electrodeposition.

Solid/liquid interfacial structure occupies great importance in chemistry, biology, and materials. In this paper, by combining EC-SERS study and DFT calculation, we reveal the adsorption and dimerization of sulfite (SO32-) at a gold electrode/water solution interface, and establish an adsorption displacement strategy to suppress the dimerization of sulfite. At the gold electrode/sodium sulfite solution interface, at least two layers of SO32- anions are adsorbed on the electrode surface. As the applied potential shifts negatively, the adsorption strength of the first SO32- layer is weakened gradually and then is dimerized with the second orientated SO32- layer to form S2O52-, and S2O52- is further reduced to S2O32-. After hydroxyethylene disphosphonic acid (HEDP) is introduced to the gold electrode/sodium sulfite solution interface, the second oriented SO32- layer is replaced by a HEDP coadsorption layer. This results in the first layer of SO32- being desorbed directly without any structural transformation or chemical reaction as the potential shifts negatively. The suppression of sulfite dimerization by HEDP is more clear at the gold electrode/gold sulfite solution interface owing to the electroreduction of gold ions. Furthermore, the electrochemical studies and electrodeposition experiments show that as the sulfite dimerization reaction is suppressed, the electroreduction of gold ions is accelerated, and the deposited gold coating is bright and dense with finer grains.

Internalization of Neutrophil-Derived Microvesicles Modulates TNFα-Stimulated Proinflammatory Cytokine Production in Human Fibroblast-Like Synoviocytes.

Neutrophil-derived microvesicles (NDMVs) have the potential to exert anti-inflammatory effects. Our study aimed to explore the effects of NDMVs on proinflammatory cytokines expressed by tumor necrosis factor α (TNFα)-stimulated fibroblast-like synoviocytes (FLS). FLS were isolated from the synovium of knee osteoarthritis (OA) patients undergoing surgery. NDMVs, isolated from TNFα-stimulated healthy neutrophils, were characterized by electron microscopy and nanoparticle tracking analysis. MTT and scratch wound healing assays were used to measure FLS viability and migration after treatment with NDMVs, while internalization of fluorescently labeled NDMVs was appraised by flow cytometry and confocal microscopy. Levels of proinflammatory cytokines in supernatants were quantified by the Bio-Plex system. Incubation of FLS with NDMVs at a vesicle/cell ratio of 100 resulted in a time-dependent uptake, with 35% of synoviocytes containing microvesicles over a 6-24 h time period, with no significant change in cell viability. TNFα stimulated the cytokine expression in FLS, and NDMVs down-regulated TNFα-induced expression of IL-5, IL-6, IL-8, MCP-1, IFNγ and MIP-1ß. However, this down-regulation was selective, as NDMVs had no significant effects on TNFα-stimulated expression of IL-2 or IL-4. NDMVs were internalized by FLS to inhibit TNFα-stimulated broad-spectrum proinflammatory cytokine secretion. NDMVs, therefore, may exhibit an anti-inflammatory role in the regulation of the FLS function.

Isomaltulose Exhibits Prebiotic Activity, and Modulates Gut Microbiota, the Production of Short Chain Fatty Acids, and Secondary Bile Acids in Rats.

In vitro experiments have indicated prebiotic activity of isomaltulose, which stimulates the growth of probiotics and the production of short chain fatty acids (SCFAs). However, the absence of in vivo trials undermines these results. This study aims to investigate the effect of isomaltulose on composition and functionality of gut microbiota in rats. Twelve Sprague-Dawley rats were divided into two groups: the IsoMTL group was given free access to water containing 10% isomaltulose (w/w), and the control group was treated with normal water for five weeks. Moreover, 16S rRNA sequencing showed that ingestion of isomaltulose increased the abundances of beneficial microbiota, such as Faecalibacterium and Phascolarctobacterium, and decreased levels of pathogens, including Shuttleworthia. Bacterial functional prediction showed that isomaltulose affected gut microbial functionalities, including secondary bile acid biosynthesis. Targeted metabolomics demonstrated that isomaltulose supplementation enhanced cholic acid concentration, and reduced levels of lithocholic acid, deoxycholic acid, dehydrocholic acid, and hyodeoxycholic acid. Moreover, the concentrations of propionate and butyrate were elevated in the rats administered with isomaltulose. This work suggests that isomaltulose modulates gut microbiota and the production of SCFAs and secondary bile acids in rats, which provides a scientific basis on the use of isomaltulose as a prebiotic.

Habitat hierarchies distribution of Sargassum muticum in Lidao bay, Shandong, China based on habitat suitability index model.

We used the habitat suitability index (HSI) model to determine the habitat suitability of Sargassum muticum in Lidao bay, Shandong Province. Eight environmental factors, including temperature, salinity, depth, turbidity, sediment, inorganic nitrogen concentration, phosphate concentration, distance from seaweed bed, were used as input variables for HSI model. The weight of each factor was defined by the analytic hierarchy process (AHP). We implemented the distribution of S. muticum suitable habitat along the coast of Lidao bay with the HSI model, based on the investigation of the environmental factors in spring and autumn 2018. The results showed that most of the S. muticum natural habitats were identified as excellent habitat and suitable habitat, accounting for 14.2% in spring and 18.6% in autumn. The distribution of habitat hierarchies varied across seasons, while habitat hierarchies showed spatial intersections in different seasons. There were significant seasonal differences in the factor suitability indices of temperature and phosphate concentration, which accounted for the seasonal HSI variations of S. muticum in Lidao bay. The S. muticum HSI model could be used to detect the habitat hierarchies distribution of S. muticum, and also to find its potential suitable habitat, which could provide a reference for future resource conservation and artificial proliferation of S. muticum.