Modular Access to Functionalized Oxetanes as Benzoyl Bioisosteres.

Bioisosterism is a valuable principle exploited in drug discovery to fine-tune physicochemical properties of bioactive compounds. Functionalized 3-aryl oxetanes, as an important class of bioisosteres for benzoyl groups (highly prevalent structures in approved drugs), have been rarely utilized in agrochemicals and pharmaceuticals due to significant synthetic challenges. Here, we present a modular synthetic strategy based on the unexplored yet readily available reagents, oxetanyl trichloroacetimidates, inspired by Schmidt glycosylation, enabling easy access to a library of functionalized oxetanes. This operationally simple protocol leverages the vast existing libraries of aryl halides and various nucleophiles. The power and generality of this approach is demonstrated by late-stage functionalization of complex molecules, as well as the rapid synthesis of oxetane analogues of bioactive molecules and marketed drugs. Preliminary mechanistic study suggests that the oxygen atom in the oxetane ring plays a crucial role in stabilizing the carbocation intermediates.

Small random library method combined with local searching in optical critical dimension measurements.

The critical dimensions (CDs) of gratings significantly influence their optical performances and require high-resolution measurements. To avoid damaging the gratings, a model-based optical critical dimension (OCD) measurement method utilizing ellipsometry or scatterometry was applied by matching the simulated and experimental values. However, online CD measurements during grating fabrication require a bulky presimulated library containing the condition points with various CDs, making it time consuming and resource intensive to build with large dimension ranges to account for grating fabrication errors. In this study, we proposed a smaller random library with an unevenly distributed resolution, offering finer resolution when the grating to be measured is close to the reference grating. This approach, validated using a home-constructed spectroscopic ellipsometer, resulted in better results. Finally, a local search algorithm based on a random library was applied to further improve the measurement accuracy. This approach extraordinarily reduced the preparation time for OCD measurements and achieved better performance, significantly improving the efficiency of grating development and fabrication inspection.

Acteoside protects podocyte against apoptosis through regulating AKT/GSK-3ß signaling pathway in db/db mice.

BACKGROUND: Podocyte apoptosis is one of the important pathological mechanisms of diabetic kidney disease (DKD). Acteoside (Act), a major active component of Rehmannia glutinosa leaves total glycoside, has a strong renoprotective action. Our study aims to demonstrate Act's renoprotective actions in db/db mice. METHODS: We adopted C57BLKS/J db/db mice as DKD animal models. After 8 weeks of Act administration, the 24-hour urine albumin, renal function index, and blood lipid levels were quantified using matching kits. Renal pathology was evaluated by HE and PAS staining. The podocyte damage and apoptosis-related signaling pathway were observed by using immunohistochemistry, western blot, and TUNEL staining. RESULTS: The albuminuria of db/db mice was reduced from 391 ug/24 h to 152 ug/24 h, and renal pathology changes were alleviated after Act administration. The western blot and immunohistochemistry showed that Act treatment upregulated the synaptopodin and podocin expression compared with db/db mice, while the TUNEL staining indicated podocyte apoptosis was inhibited. The B-cell lymphoma-2 (Bcl-2) level was upregulated in the Act group, but cleaved caspase-3 and Bcl-2 associated X protein (Bax) expression declined, while the protein kinase B/glycogen synthase kinase-3ß (AKT/GSK-3ß) signaling pathway was repressed. CONCLUSIONS: By inhibiting the AKT/GSK-3ß signaling pathway, Act protected podocytes from apoptosis, decreasing the urine albumin of db/db mice and delaying the course of DKD.

Multi-omics methods reveal that putrescine and cadaverine cause different degrees of enrichment of high-risk resistomes and opportunistic pathogens in the water and sediment of the Yellow River.

Contamination of antibiotic resistomes due to animal carcass decay has become a serious environmental concern. However, the relationship between main metabolite compounds of corpse decomposition (i.e., putrescine and cadaverine) and antibiotic resistomes remains unclear. To tackle this issue, the response of antibiotic resistance genes (ARGs) and microbiome in aquatic environment to excess putrescine, cadaverine and a mixture of both based on laboratory simulation experiment was investigated by high-throughput quantitative PCR and amplicon sequencing methods. Our results showed putrescine and cadaverine led to the increasing of TC (total carbon) and TN (total nitrogen) both in water and sediment. Under the exposure of putrescine and cadaverine, the total abundance of mobile genetic elements (MGEs) and most ARGs in water was higher than in sediment. In particular, putrescine and cadaverine caused significantly different decreases in alpha diversity of microbial community in water and sediment compared with the control group. Microbial community structures both in water and sediment were also significantly affected by cadaverine and putrescine. Furthermore, putrescine and cadaverine led to different degrees of increases of high-risk ARGs (like mecA) and opportunistic pathogens (like Delftia) in sediment, promoting the prevalence of antibiotic resistant bacteria. In conclusion, our findings revealed the influences of main metabolites of carcass decay on microbiome and resistomes, providing references for risk assessment and pollution management.

Yunnan Baiyao-loaded multifunctional microneedle patches for rapid hemostasis and cutaneous wound healing.

Microneedle patches have been extensively employed for wound healing, while the lack of rapid hemostasis efficiency and multiple tissue-repair properties restrict their values in hemorrhagic wound applications. Herein, we propose a Yunnan Baiyao-loaded multifunctional microneedle patch, namely (BY + EGF)@MN, with deep tissue penetration, hemostasis efficiency and regenerative properties for hemorrhagic wound healing. The (BY + EGF)@MNs are designed with a BY-loaded Bletilla striata polysaccharide (BSP) base for rapid hemostasis and epidermal growth factor (EGF)-loaded GelMA tips for subsequent wound healing. As the BSP base can be fastly dissolved and completely release BY in 6 min to promote platelet adhesion and activate coagulation system, while the EGF can achieve a controlled and sustained release behavior in 7 days with the gradual degradation of the GelMA tips, the (BY + EGF)@MNs exhibit strong pro-coagulability and satisfactory hemostatic effect in a rat hepatic hemorrhage wound model. Based on the multifunctional characteristics, we have verified that when applied in rat cutaneous wounds, the proposed MNs can accelerate the wound healing process by enhancing neovascularization, fibroblast density, and collagen deposition. Thus, we believe that such (BY + EGF)@MNs are promising candidates for rapid hemostasis and diverse wound healing applications.

Body mass index affects the association between plasma lipids and peripheral eosinophils in a general chinese population: a cross-sectional survey.

BACKGROUND: Lipid metabolism affects type 2 immunity; however, the association between plasma lipids and eosinophilic inflammation in humans is uncertain. This study analysed the relationship between plasma lipids and peripheral eosinophils and whether patterns differ with different body mass indexes (BMI). METHODS: A cross-sectional survey including 62,441 healthy participants recruited from a regular health screening programme was conducted. Participants were divided into normal weight, overweight and obese subgroups according to BMI. RESULTS: Multiple linear regression analysis revealed that elevated logarithmic-transformed eosinophil counts (log(EOS)) significantly correlated with high total cholesterol(TC), triglyceride(TG), low-density lipoprotein-cholesterol (LDL-C), and low high-density lipoprotein-cholesterol (HDL-C)levels in the overall population, as well as in men and women, while certain associations between peripheral blood eosinophil percentage and serum lipids varied by gender. These correlations existed across almost all BMI subgroups, and standardised ß values decreased sequentially with increasing BMI. HDL-C had the most significant effect on eosinophils in obese women. Two-factor analysis of variance showed log(EOS) increased with higher BMI and hyperlipidemia whether in male or female and a synergistic effect exists of lipid levels (TG and LDL-C) and BMI in men. CONCLUSIONS: Blood eosinophil counts were correlated with blood lipid levels and modified by body mass index status. The effects of lipid levels and body mass index on blood eosinophil counts were synergistic. Therefore, lipid metabolism may be involved in systemic eosinophil inflammation.

Microneedle-Integrated Sensors for Extraction of Skin Interstitial Fluid and Metabolic Analysis.

Skin interstitial fluid (ISF) has emerged as a fungible biofluid sample for blood serum and plasma for disease diagnosis and therapy. The sampling of skin ISF is highly desirable considering its easy accessibility, no damage to blood vessels, and reduced risk of infection. Particularly, skin ISF can be sampled using microneedle (MN)-based platforms in the skin tissues, which exhibit multiple advantages including minimal invasion of the skin tissues, less pain, ease of carrying, capacity for continuous monitoring, etc. In this review, we focus on the current development of microneedle-integrated transdermal sensors for collecting ISF and detecting specific disease biomarkers. Firstly, we discussed and classified microneedles according to their structural design, including solid MNs, hollow MNs, porous MNs, and coated MNs. Subsequently, we elaborate on the construction of MN-integrated sensors for metabolic analysis with highlights on the electrochemical, fluorescent, chemical chromogenic, immunodiagnostic, and molecular diagnostic MN-integrated sensors. Finally, we discuss the current challenges and future direction for developing MN-based platforms for ISF extraction and sensing applications.

How habitat heterogeneity shapes bacterial and protistan communities in temperate coastal areas near estuaries.

In this study, we investigated microbial communities (bacteria and protist) in two coastal areas near the estuaries of the Liaohe (LH) River and Yalujiang (YLJ) River in the Northwestern Pacific Ocean. Due to the existence of Liaodong Peninsula and different levels of urbanization, geographical segregation and significant environmental heterogeneity were observed between these two areas. There were significantly different regional species pools and biogeographic patterns for both bacterial and protistan communities between LH and YLJ coastal areas. Species turnover was the main mechanism driving ß-diversity patterns of both bacterial and protistan communities in each area. In addition, the contributed ratio of nestedness to the ß-diversity patterns was significantly higher for protists compared to bacteria. Variation in regional species pools was found to be the dominant driver of differences of bacterial and protistan communities between the LH and YLJ coastal areas. For a single-studied area, local community assembly mechanisms, including heterogeneous selection and dispersal limitation, were found to shape the bacterial and protistan communities through calculation of the ß-deviation index. Among them, the relative importance of heterogeneous selection and dispersal limitation on the community assembly varied according to microorganism type and habitat.

Programmable Knot Microfibers from Piezoelectric Microfluidics.

Microfibers have demonstrated significant application values in a large number of areas. Current efforts focus on developing new technologies to prepare microfibers with controllable morphological and structural features to enhance their functions. Here, a piezoelectric microfluidic platform is presented for consecutive spinning of functional microfibers with programmable spindle-knots. In this platform, a jet of a pregel-solution flowing in the channel can be subjected to a programmable piezoelectric signal and vibrates synchronously. Following a rapid polymerization of the wavy jet, microfibers with corresponding morphologies can be generated, including uniform, gradient, and symmetrical knots. Such a unique knot structure contributes to a water-collection mechanism. Thus, it has been observed that microfibers with programmed knots enable even more flexible droplet handling and active water transport. In addition, by constructing higher-order knot fiber networks, practical applications including spray reaction, lab-on-a-chip vapor detection, etc., can also be demonstrated. it is believed that this platform opens a new avenue for fiber spinning, and the programmable microfibers would be highly applicable in chemical, biomedical, and environmental areas.

Application of Variational Mode Decomposition and Whale Optimization Algorithm to Laser Ultrasonic Signal Denoising.

Laser ultrasound signal echoes are easily drowned out by the surrounding environmental noise in industrial field applications, and it is worthwhile to study methods of retaining the weak ultrasound signal during signal processing. To address this problem, this paper proposes to adopt the parameters optimized by the whale optimization algorithm to the variational mode decomposition (VMD) of laser ultrasound signals. The optimized parameters can avoid the frequency mixing and incomplete noise separation caused by the choice of artificial VMD parameters. The Hausdorff distance is applied in the process of reconstructing the signal to help accurately select the relevant modes and improve the signal-to-noise ratio. Simulation and experimental results show that the proposed method is feasible and effective compared with the other three available denoising methods.

Identification of a lncRNA prognostic signature-related to stem cell index and its significance in colorectal cancer.

Background: The relationship between long noncoding RNAs (lncRNAs) and the mRNA stemness index (mRNAsi) in colorectal cancer (CRC) is still unclear. Materials & methods: The mRNAsi, mRNAsi-related lncRNAs and their clinical significance were analyzed by bioinformatic approaches in The Cancer Genome Atlas (TCGA)-COREAD dataset. Results: mRNAsi was negatively related to pathological features but positively related to overall survival and recurrence-free survival in CRC. A five mRNAsi-related lncRNAs prognostic signature was further developed and showed independent prognostic factors related to overall survival in CRC patients, due to the five mRNAsi-related lncRNAs involved in several pathways of the cancer stem cells and malignant cancer cell phenotypes. Conclusion: The present study highlights the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.

Lay abstract Previous evidence has indicated that the mRNA stem index (mRNAsi) is representative of the stemness of cancer stem cells (CSCs), whereas long noncoding RNAs (lncRNAs) may be crucial regulators in CSC phenotype. Nevertheless, the relationship between lncRNAs and mRNAsi in CRC is still unclear. Our results show that the mRNAsi was negatively related to pathological features and positively related to prognosis in CRC. Five mRNAsi-related lncRNAs were further identified and developed as a prognostic signature that could independently predict survival in CRC patients due to the five mRNAsi-related lncRNAs being involved in several pathways of CSCs and malignant cancer cell phenotypes, indicating the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.

Gelatin methacryloyl-based tactile sensors for medical wearables.

Gelatin methacryloyl (GelMA) is a widely used hydrogel with skin-derived gelatin acting as the main constituent. However, GelMA has not been used in the development of wearable biosensors, which are emerging devices that enable personalized healthcare monitoring. This work highlights the potential of GelMA for wearable biosensing applications by demonstrating a fully solution-processable and transparent capacitive tactile sensor with microstructured GelMA as the core dielectric layer. A robust chemical bonding and a reliable encapsulation approach are introduced to overcome detachment and water-evaporation issues in hydrogel biosensors. The resultant GelMA tactile sensor shows a high-pressure sensitivity of 0.19 kPa-1 and one order of magnitude lower limit of detection (0.1 Pa) compared to previous hydrogel pressure sensors owing to its excellent mechanical and electrical properties (dielectric constant). Furthermore, it shows durability up to 3000 test cycles because of tough chemical bonding, and long-term stability of 3 days due to the inclusion of an encapsulation layer, which prevents water evaporation (80% water content). Successful monitoring of various human physiological and motion signals demonstrates the potential of these GelMA tactile sensors for wearable biosensing applications.

Endosymbionts of Metazoans Dwelling in the PACManus Hydrothermal Vent: Diversity and Potential Adaptive Features Revealed by Genome Analysis.

Deep-sea hydrothermal vent communities are dominated by invertebrates, namely, bathymodiolin mussels, siboglinid tubeworms, and provannid snails. Symbiosis is considered key to successful colonization by these sedentary species in such extreme environments. In the PACManus vent fields, snails, tubeworms, and mussels each colonized a niche with distinct geochemical characteristics. To better understand the metabolic potentials and genomic features contributing to host-environment adaptation, we compared the genomes of the symbionts of Bathymodiolus manusensis, Arcovestia ivanovi, and Alviniconcha boucheti sampled at PACManus, and we discuss their environmentally adaptive features. We found that B. manusensis and A. ivanovi are colonized by Gammaproteobacteria from distinct clades, whereas endosymbionts of B. manusensis feature high intraspecific heterogeneity with differing metabolic potentials. A. boucheti harbored three novel Epsilonproteobacteria symbionts, suggesting potential species-level diversity of snail symbionts. Genome comparisons revealed that the relative abundance of gene families related to low-pH homeostasis, metal resistance, oxidative stress resistance, environmental sensing/responses, and chemotaxis and motility was the highest in A. ivanovi's symbiont, followed by symbionts of the vent-mouth-dwelling snail A. boucheti, and was relatively low in the symbiont of the vent-periphery-dwelling mussel B. manusensis, which is consistent with their environmental adaptations and host-symbiont interactions. Gene families classified as encoding host interaction/attachment, virulence factors/toxins, and eukaryotic-like proteins were most abundant in symbionts of mussels and least abundant in those of snails, indicating that these symbionts may differ in their host colonization strategies. Comparison of Epsilonproteobacteria symbionts to nonsymbionts demonstrated that the expanded gene families in symbionts were related to vitamin B12 synthesis, toxin-antitoxin systems, methylation, and lipopolysaccharide biosynthesis, suggesting that these are vital to symbiont establishment and development in EpsilonproteobacteriaIMPORTANCE Deep-sea hydrothermal vents are dominated by several invertebrate species. The establishment of symbiosis has long been thought to be the key to successful colonization by these sedentary species in such harsh environments. However, the relationships between symbiotic bacteria and their hosts and their role in environmental adaptations generally remain unclear. In this paper, we show that the distribution of three host species showed characteristic niche partitioning in the Manus Basin, giving us the opportunity to understand how they adapt to their particular habitats. This study also revealed three novel genomes of symbionts from the snails of A. boucheti Combined with a data set on other ectosymbiont and free-living bacteria, genome comparisons for the snail endosymbionts pointed to several genetic traits that may have contributed to the lifestyle shift of Epsilonproteobacteria into the epithelial cells. These findings could increase our understanding of invertebrate-endosymbiont relationships in deep-sea ecosystems.

Morula transfer achieves better clinical outcomes than post-thawed cleavage embryos after overnight culture in frozen embryo transfer (FET) cycles.

PURPOSE: This study aimed to investigate the clinical outcomes of morula stage transfer derived from post-thawed cleavage embryos undergoing overnight culture in frozen embryo transfer (FET) cycles. METHODS: We performed a retrospective study that included 392 FET cycles with 784 thawed embryos undergoing overnight culture between January 2014 and December 2018. Embryos were divided into three groups in terms of their status: 8-16 cells without morula (group I), one morula (group II), and two morulae (group III). The clinical outcomes of these cycles were then compared between the three groups. Logistic regression analysis was performed to control for confounders. RESULTS: Group III was associated with a significantly higher clinical pregnancy rate (odds ratio [OR] 2.35; 95% confidence interval [CI] 1.29-4.27; P = 0.005), implantation rate (OR 3.00; CI 1.75-5.16; P < 0.001), multiple pregnancy rate (OR 4.91; CI 2.11-11.40; P < 0.001), and live birth rate (OR 1.96; CI 1.10-3.49; P = 0.022) than group I. Group II had a higher live birth rate than group I after adjustment (OR 1.70; CI 1.04-2.79; P = 0.035). There was no difference in the rate of premature delivery when compared across the three groups after adjustment. CONCLUSION: The transfer of morula stage embryos following the overnight culture of post-thawed cleavage embryos led to an improvement in the clinical outcomes of FET cycles. It is important to reduce the number of morula embryos transferred in order to achieve a singleton pregnancy.

Defective Black Nano-Titania Thermogels for Cutaneous Tumor-Induced Therapy and Healing.

Current challenges in cutaneous tumor therapy are healing the skin wounds resulting from surgical resection and eliminating possible residual tumor cells to prevent recurrence. To address this issue, bifunctional biomaterials equipped with effective tumor therapeutic capacity for skin cancers and simultaneous tissue regenerative ability for wound closure are highly recommended. Herein, we report an injectable thermosensitive hydrogel (named BT-CTS thermogel) with the integration of nanosized black titania (B-TiO2- x, ∼50 nm) nanoparticles into a chitosan (CTS) matrix. The B-TiO2- x nanocrystal exhibits a crystalline/amorphous core-shell structure with abundant oxygen vacancies, which endows the BT-CTS thermogels with simultaneous photothermal therapy (PTT) and photodynamic therapy (PDT) effects under single-wavelength near-infrared laser irradiation, leading to an excellent therapeutic effect on skin tumors in vitro and in vivo. Moreover, the BT-CTS thermogel not only supports the adhesion, proliferation, and migration of normal skin cells but also facilitates skin tissue regeneration in a murine chronic wound model. Therefore, such BT-CTS thermogels with easy injectability, excellent thermostability, and simultaneous PTT and PDT efficacy as well as tissue regenerative activity offers a promising pathway for the healing of cutaneous tumor-induced wounds.

Suckling Piglet Intestinal Enterocyte Nutrient Metabolism Changes.

BACKGROUND/AIMS: Intestinal morphology and the types of enterocytes are changed in piglets during the suckling period, but it is unclear whether these changes are associated with metabolic changes in epithelium. The present study was conducted to test the hypothesis that glucose, fatty acids, and amino acid metabolism in differentiated piglet enterocytes changed during suckling. METHODS: Twenty-four piglets (Duroc × [Landrace × Yorkshire]) from 8 litters (3 piglets/litter) were selected. A single piglet from each litter was randomly selected and euthanized at days 7, 14, and 21. Differentiated enterocytes (DE) were isolated from their mid-jejunum. Isobaric tags for relative and absolute quantification and subsequent liquid chromatography-tandem mass spectrometry were used to identify and measure protein synthesis. RESULTS: The results showed that various activities, including: cellular processes; metabolic processes; biological regulation; pigmentation; and, localization, in DEs changed during suckling. Metabolic process analyses revealed that protein expression related to glycolysis and citrate cycle was decreased from day 7 to day 14. The number of differentiated enterocytes of 21 d piglets increased compared to 7 d piglets. Most of the proteins involved in fatty acid and amino acids metabolism had decreased DE expression between day 7 and day 14. Some, but not all, detected proteins down-regulated in DEs of 21 day piglets compared to 7 day piglets. CONCLUSION: These results indicate that glucose, fatty acids, and amino acids metabolism changed during suckling. This may provide useful information for designing feed formulas and regulating piglet intestinal growth and development.

Distribution of a phase-stabilized 100.02 GHz millimeter-wave signal over a 160 km optical fiber with 4.1 × 10-17 instability.

We report a long-distance phase-stabilized millimeter-wave distribution over optical fibers, where the optical-link-induced phase noise is compensated with a high-precision photonic-generated millimeter-wave (mm-wave) voltage-controlled oscillator (VCO). The mm-wave VCO is realized based on pre-filtering and re-modulating optical spectral lines of an optical frequency comb (OFC). By adjusting the frequency spacing of the optical spectral lines extracted from the OFC, the phase error of the transmitted optical mm-wave signal can be compensated precisely. Using the mm-wave VCO, we demonstrate a distribution of a 100.02 GHz signal over spooled optical fibers and the fractional frequency instability of the system at different transmission distances is exhibited. The residual phase noise of the remote mm-wave signal after being transferred through a 160-km fiber link is measured to be -59 dBc/Hz at 1 Hz frequency offset from the carrier, and the RMS timing jitter in the frequency range from 0.01 Hz to 1 MHz reaches 62 fs. The long-term fractional frequency instability of 4.1 × 10-17 at 10000 s averaging time is achieved, and the maximum timing drift is within 0.93 ps (peak to peak) during 4 hours.

Effects of Post-Treatment Hydrogen Gas Inhalation on Uveitis Induced by Endotoxin in Rats.

BACKGROUND Molecular hydrogen (H2) has been widely reported to have benefiicial effects in diverse animal models and human disease through reduction of oxidative stress and inflammation. The aim of this study was to investigate whether hydrogen gas could ameliorate endotoxin-induced uveitis (EIU) in rats. MATERIAL AND METHODS Male Sprague-Dawley rats were divided into a normal group, a model group, a nitrogen-oxygen (N-O) group, and a hydrogen-oxygen (H-O) group. EIU was induced in rats of the latter 3 groups by injection of lipopolysaccharide (LPS). After that, rats in the N-O group inhaled a gas mixture of 67% N2 and 33% O2, while those in the H-O group inhaled a gas mixture of 67% H2 and 33% O2. All rats were graded according to the signs of uveitis after electroretinography (ERG) examination. Protein concentration in the aqueous humor (AqH) was measured. Furthermore, hematoxylin-eosin staining and immunostaining of anti-ionized calcium-binding adapter molecule 1 (Iba1) in the iris and ciliary body (ICB) were carried out. RESULTS No statistically significant differences existed in the graded score of uveitis and the b-wave peak time in the Dark-adapted 3.0 ERG among the model, N-O, and H-O groups (P>0.05), while rats of the H-O group showed a lower concentration of AqH protein than that of the model or N-O group (P<0.05). The number of the infiltrating cells in the ICB of rats from the H-O group was not significantly different from that of the model or N-O group (P>0.05), while the activation of microglia cells in the H-O group was somewhat reduced (P<0.05). CONCLUSIONS Post-treatment hydrogen gas inhalation did not ameliorate the clinical signs, or reduce the infiltrating cells of EIU. However, it inhibited the elevation of protein in the AqH and reduced the microglia activation.

Insights into deep-sea adaptations and host-symbiont interactions: A comparative transcriptome study on Bathymodiolus mussels and their coastal relatives.

Mussels (Bivalve: Mytilidae) have adapted to various habitats, from fresh water to the deep sea. To understand their adaptive characteristics in different habitats, particularly in the bathymodiolin mussels in deep-sea chemosynthetic ecosystems, we conducted a comparative transcriptomic analysis between deep-sea bathymodiolin mussels and their shallow-water relatives. A number of gene families related to stress responses were shared across all mussels, without specific or significantly expanded families in deep-sea species, indicating that all mussels are capable of adapting to diverse harsh environments, but that different members of the same gene family may be preferentially utilized by different species. One of the most extraordinary trait of bathymodiolin mussels is their endosymbiosis. Lineage-specific and positively selected TLRs and highly expressed C1QDC proteins were identified in the gills of the bathymodiolins, suggesting their possible functions in symbiont recognition. However, pattern recognition receptors of the bathymodiolins were globally reduced, facilitating the invasion and maintenance of the symbionts obtained by either endocytosis or phagocytosis. Additionally, various transporters were positively selected or more highly expressed in the deep-sea mussels, indicating a means by which necessary materials could be provided for the symbionts. Key genes supporting lysosomal activity were also positively selected or more highly expressed in the deep-sea mussels, suggesting that nutrition fixed by the symbionts can be absorbed in a "farming" way wherein the symbionts are digested by lysosomes. Regulation of key physiological processes including lysosome activity, apoptosis and immune reactions is needed to maintain a stable host-symbiont relationship, but the mechanisms are still unclear.

Inhibition of JAK/STAT pathway restrains TSLP-activated dendritic cells mediated inflammatory T helper type 2 cell response in allergic rhinitis.

Thymic stromal lymphopoietin (TSLP) has recently been implicated as a key molecule for initiating allergic rhinitis (AR) at the cell-dendritic cell (DC) interface. Previous studies demonstrated that TSLP activated DCs to express more OX40 ligand (OX40L), which is associated with the initiation of T helper type 2 (Th2) cell responses. STAT phosphorylation has been reported to be promoted by TSLP. Thus, we investigated if the JAK/STAT pathway inhibitor CYT387 could affect TSLP-DC-mediated Th2 cell response in naive T cell and AR mice model. Western blot showed that the levels of phosphorylated JAK1, JAK2, STAT1, STAT3, and STAT5 were increased in TSLP-DCs, which can be offset by CYT387. Flow cytometry indicated that CYT387 had obviously down-regulated the surface maturation co-stimulatory molecules (CD11c, CD80, CD86, and MHCII) in DCs, which were increased by TSLP. Moreover, CYT387 markedly reduced the ability of TSLP-DCs to promote the differentiation of naive CD4+ T cells into IL-4-expressing Th2 cells. The histological examination showed that the CYT387-treated group showed less epithelial disruption, epithelial cell proliferation, and reduced eosinophil infiltration compared with AR group. Western blot and RT-PCR demonstrated that the expression of OX40L was increased in AR mice, but that it was decreased by CYT387. Furthermore, CYT387 treatment resulted in the reduction of IL-4 and IL-5 expression and increased IFN-γ level in AR mice, which was consistent with the levels of intracellular cytokine in Th2 cell. In conclusion, we suggest that blockading the JAK/STAT pathway restrains inflammatory Th2 cell response induced by TSLP-DCs in AR.