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Obtaining new materials, industrial chemicals, and energy from the conversion of agricultural and forestry biomass to fill the gap of non-renewable fossil energy has become a growing trend. As a waste biomass, the G. sinensispods (GSP) after saponin extraction are always discarded due to lack of industrial/high value-added utilization. Herein, in order to lay a foundation for the selection of pretreatment strategies of GSP and the valorization of GSP lignin, the lignins from the different varieties of GSP were isolated by double enzymatic method and quantitatively characterized. Results indicated that GSP lignin was of the GS-type (S/G, 1.1–1.4) and the interunit linkages were mainly β-O-4′ linkage, along with a certain amount of carbon-carbon linkages (≈35/Ar). L1 showed higher β-O-4′ linkage content (61.3/100 Ar) and relative molar mass (12190 mol/g). Some atypical lignin units, such as cinnamyl aldehyde end-group, cinnamyl alcohol end-groups, and ferulates, were also revealed in GSP lignins. Finally, the potential molecular structure graphs of the GSP lignin were depicted on the basis of the quantitative results. Overall, comprehensive research of the structural characteristics of GSP lignin is essential for efficiently deconstructing GSP and transforming the utilization of the cell wall components.

Food-derived α-glucosidase inhibitory peptides have gained significant interest in treating type 2 diabetes mellitus (T2DM) owing to their favorable safety profiles. Molecular docking combined with molecular dynamics simulation was performed to screen α-glucosidase inhibitory peptides from Ginkgo bilobaseed cake (GBSC), and two novel peptides (Met-Pro-Gly-Pro-Pro (MPGPP) and Phe-Ala-Pro-Ser-Trp (FAPSW)) were acquired. The results of molecular docking and molecular dynamics simulation suggested that FAPSW and MPGPP could generate stable complexes with 3wy1, and the electrostatic and van der Waals forces played contributory roles in FAPSW and MPGPP binding to 3wy1. The α-glucosidase inhibition assay corroborated that FAPSW and MPGPP had good α-glucosidase inhibition capacity, with IC50values of 445.34 ± 49.48 and 1025.68 ± 140.78 μM, respectively. In vitrosimulated digestion results demonstrated that FAPSW and MPGPP strongly resisted digestion. These findings lay a theoretical foundation for FAPSW and MPGPP in treating T2DM.

Constant output characteristics, zero phase angle (ZPA), and coupler voltage stresses as low as possible are practical requirements for high power and large air-gap capacitive power transfer (CPT) applications. This article derives conditions of load-independent constant voltage output, ZPA, and minimum coupler voltages for general CPT systems, respectively. Minimum degrees of freedom (DOF) for the above performance are analyzed. Given performance requirements, a systematic circuit design method based on DOF analysis is proposed to design compensation circuits with fewer components to simplify complexity and decrease costs. The proposed method can predict feasible topologies, and application considerations are provided to guide topology selection. A 3LC-compensated CPT system is proposed to realize the constant voltage output with ZPA, minimum coupler voltages, and efficiency optimization. A 2.2 kW CPT prototype has been prepared with a 250 mm air-gap distance and dc–dc efficiency is 87.2%. Rms values of coupler voltages are about 5 kV at the rated power.

•Precious and representative Fanhongcaisamples with different colors are analyzed.•The coloring effect of Fanghongcaiare in-situ non-destructively investigated.•The hue of Fanhongcaiis determined mainly by different crystal forms of iron oxide.•α-Fe2O3displays red color, while γ-Fe2O3and Fe3O4yield orange and dark red colors.•Presence of γ-Fe2O3&Fe3O4are relatedto subtle differences in processing and firing.

Sepsis, defined as life-threatening organ failure caused by a dysregulated host response to severe infection, is a major cause of death among intensive care unit patients. Therapies targeting on immunomodulatory is a new research field in sepsis treatment. B- and T-lymphocyte attenuator (BTLA) is an inhibitory costimulatory factor molecule of B and T lymphocytes. Studies have shown that elevated expression of BTLA in lymphocytes can reduce mortality in sepsis, but its regulatory compounds and the underlying mechanism remains to be elucidated. Here, we show that treatment with CP-673451 significantly decreases mortality of septic mouse. CP-673451 is a PDGFR kinase inhibitor which can promote the expression of BTLA, inhibit the release of chemokines such as CXCL13, and reduce first the chemotaxis of B cells to the peripheral blood and vital organs. CP-673451 also inhibits both the release of cytokines and chemokines such as IL-1β, IL-6, IL-10, TNF-α, CCL1, CCL2 and CCL7 and reduces both the chemotactic ability of T cells. This suggests that CP-673451 may prevent septic death by inhibiting lymphocyte chemotaxis and alleviating “cytokine storm”. In conclusion, our study provides a new therapeutic target and an effective compound for sepsis treatment.

ABSTRACTFerroptosis is a form of inflammatory cell death for which key mediators remain obscure. Here, we report that the proteoglycan decorin (DCN) is released by cells that are dying from ferroptosis and then acts as an alarm signal to trigger innate and adaptive immune responses. The early release of DCN during ferroptosis is an active process that involves secretory macroautophagy/autophagy and lysosomal exocytosis. Once released, extracellular DCN binds to the receptor advanced glycosylation end-product-specific receptor (AGER) on macrophages to trigger the production of pro-inflammatory cytokines in an NFKB/NF-κB-dependent manner. Pharmacological and genetic inhibition of the DCN-AGER axis protects against ferroptotic death-related acute pancreatitis and limits the capacity of ferroptotic cancer cells to induce a tumor-protective immune response. Thus, DCN is an essential mediator of the inflammatory and immune consequences of ferroptosis.

Developing a green and three energy-driven portable small electronic device that not only relies on electricity is becoming an imperative trend and symbolizing the critical development direction in the future electronic equipment field. To actualize the breakthrough of multifunctional materials in the development path of integrated electronic technology, we insightfully propose an innovative scheme, ingeniously combining the lightweight nano-membrane and high elastomer hydrogel and imaginatively fabricated a “membrane-hydrogel” dual-module structure in coaxial electrospinning, liquid-phase polymerization, and eco-friendly freeze-thaw cycle methods, gathering thermal energy, solar energy, and piezoresistive sensing thanks to phase-transition paraffin, polypyrrole (PPy), and Silver nanowires (AgNWs), respectively. AgNWs collaborate with PPy to increase thermal conduction pathways, enhance photothermal conversion ability, and remarkably improve the conductivity of PW/PPy/Pg@Ag (σ=0.148 S m−1), in particular, the microarray structure at the hydrogel bottom endows it an ultra-high piezoresistive response range (440.6 kPa), tremendously inspiring the advanced dual-module material design strategy and paving the way for the multifunctional expanding of electronic devices that can attach thermal energy, solar energy, and electrical energy.

Immunosuppression in response to severe sepsis remains a serious human health concern. Evidence of sepsis-induced immunosuppression includes impaired T lymphocyte function, T lymphocyte depletion or exhaustion, increased susceptibility to opportunistic nosocomial infection, and imbalanced cytokine secretion. CD4 T cells play a critical role in cellular and humoral immune responses during sepsis. Here, using an RNA sequencing assay, we found that the expression of T cell-containing immunoglobulin and mucin domain-3 (Tim-3) on CD4 T cells in sepsis-induced immunosuppression patients was significantly elevated. Furthermore, the percentage of Tim-3+CD4 T cells from sepsis patients was correlated with the mortality of sepsis-induced immunosuppression. Conditional deletion of Tim-3 in CD4 T cells and systemic Tim-3 deletion both reduced mortality in response to sepsis in mice by preserving organ function. Tim-3+CD4 T cells exhibited reduced proliferative ability and elevated expression of inhibitory markers compared with Tim-3−CD4 T cells. Colocalization analyses indicated that HMGB1 was a ligand that binds to Tim-3 on CD4 T cells and that its binding inhibited the NF-κB signaling pathway in Tim-3+CD4 T cells during sepsis-induced immunosuppression. Together, our findings reveal the mechanism of Tim-3 in regulating sepsis-induced immunosuppression and provide a novel therapeutic target for this condition.

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated systems (Cas) are efficient tools for targeting specific genes for laboratory research, agricultural engineering, biotechnology, and human disease treatment. Cas9, by far the most extensively used gene-editing nuclease, has shown great promise for the treatment of hereditary diseases, viral infection, cancers, and so on. Recent reports have revealed that some other types of CRISPR-Cas systems may also have surprising potential to join the fray as gene-editing tools for various applications. Despite the rapid progress in basic research and clinical tests, some underlying problems present continuous, significant challenges, such as editing efficiency, relative difficulty in delivery, off-target effects, immunogenicity, etc. This article summarizes the applications of CRISPR-Cas from bench to bedside and highlights the current obstacles that may limit the usage of CRISPR-Cas systems as gene-editing toolkits in precision medicine and offer some viewpoints that may help to tackle these challenges and facilitate technical development. CRISPR-Cas systems, as a powerful gene-editing approach, will offer great hopes in clinical treatments for many individuals with currently incurable diseases.

The poor mechanical properties and disadvantages of catalysts limit the application of self-healing materials. To address these issues, catalyst-free self-healing bio-based polymers (AESO–EMPA polymers) with robust mechanical properties were prepared using epoxidized maleopimaric anhydride (EMPA) and aminated epoxidized soybean oil (AESO). The AESO–EMPA polymers are recyclable and exhibit self-healing and shape memory because of the dual-dynamic network of multiple H-bonds and dynamic ester bonds in the structure. Under the synergistic catalysis of the tertiary amines and hydroxyl groups originated from the polymers, the polymers in this study achieve network rearrangement without the need for additional catalysts. The polymers also exhibit excellent mechanical properties with a tensile strength of 29.1 ± 0.25 MPa and a Tgof 80.2 °C owing to the unique rigid backbone of rosin and the dual-dynamic network. The AESO–EMPA polymers can be used as reusable adhesives and exhibit excellent shear strength and repair rates.

Introduction: Vanin-1 plays a pivotal role in oxidative stress and the inflammatory response. However, its relationship with traumatic sepsis remains unknown. The aim of our study was to evaluate whether plasma vanin-1 could be used for the early prediction of traumatic sepsis. Methods: In this three-stage prospective cohort study, severe trauma patients admitted from January 2015 to October 2018 at two hospitals were enrolled. Plasma vanin-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). The associations among variables and traumatic sepsis were identified by logistic regression models and the receiver operating characteristic (ROC) curve was analyzed to evaluate the diagnostic efficiency. Results: A total of 426 trauma patients (22 in the discovery cohort, 283 in the internal test cohort, and 121 in the external validation cohort) and 16 healthy volunteers were recruited. The plasma vanin-1 of trauma patients was significantly higher than that of healthy volunteers (P< 0.05). Patients with sepsis had higher plasma vanin-1 than patients without sepsis in the discovery trauma cohort (P< 0.05). In the internal test cohort, plasma vanin-1 at day 1 after trauma was significantly associated with the incidence of sepsis (OR = 3.92, 95% CI 2.68–5.72, P= 1.62 × 10−12). As a predictive biomarker, vanin-1 afforded a better area under the curve (AUC) (0.82, 95% CI 0.77–0.87) than C-reaction protein (CRP) (0.62, 95% CI 0.56–0.68, P< 0.0001), procalcitonin (PCT) (0.66, 95% CI 0.60–0.71, P< 0.0001), and Acute Physiology and Chronic Health Evaluation II (APACHE II) (0.71, 95% CI 0.65–0.76, P= 6.70 × 10−3). The relevance was further validated in the external validation cohort (OR = 4.26, 95% CI 2.22–8.17, P= 1.28 × 10−5), with an AUC of 0.83 (95% CI 0.75–0.89). Vanin-1 could also improve the diagnostic efficiency of APACHE II (AUC = 0.85). Conclusions: Our study demonstrated that plasma vanin-1 increased among trauma patients and was independently associated with the risk of sepsis. Vanin-1 might be a potential biomarker for the early prediction of traumatic sepsis. Trial Registration: Clinicaltrials.gov Identifier, NCT01713205.

Thermosetting foams have limited capabilities for recycling, reprocessing, or reshaping. Moreover, most of the foaming agents currently employed in these foams are derived from organic compounds sourced from petrochemicals, thereby posing a significant environmental threat due to heightened pollution. To solve these problems, a fully biobased degradable vitrimer foam (EPC-X) was fabricated using an environmentally friendly all-in-one foaming strategy by cross-linking epoxidized malepimaric anhydride (EMPA), 1,5-diaminopentane (PDA), and 1,5-diaminopentane carbamate (PDAC) as a latent curing-blowing agent. To our delight, the vitrimer foams exhibit excellent mechanical properties (2.86 ± 0.11 MPa compressive strength) owing to their unique rigid rosin backbone and cross-linking networks. The presence of dynamic β-hydroxy ester bonds and the self-catalytic behavior of tertiary amine groups facilitate network rearrangement without requiring additional catalysts, thereby resulting in the development of EPC-X with rapid self-healing and shape memory properties. The self-healing foam could support a weight of 500 g (approximately 562 times its own mass). Moreover, these high-performance vitrimer foams can also be easily degraded in an ethanolamine (EA) or NaOH solution under mild conditions. Such a design strategy offers an alternative approach for developing superior degradable and thermal stimuli-responsive thermosetting foams.

Cellulose is a biodegradable and renewable natural material that it is naturally resistant to breaking and modification. Moreover, the crystalline structure of cellulose is a major factor restricting its industrial utilization. In this study, cellulose polymorphs were prepared from natural cellulose, and their solvability and thermal response were investigated. Using liquid- and solid-state NMR signals, the distinct types and dissolving states of cellulose polymorphs were identified. The thermal behavior of the polymorphic forms of cellulose-d was also evaluated, and cellulose II exhibited the poorest thermal stability and a unique exothermic reaction.

Sepsis and septic shock are associated with life-threatening organ dysfunction caused by an impaired host response to infections. Although circadian clock disturbance impairs the early inflammatory response, its impact on post-septic immunosuppression remains poorly elucidated. Here, we show that Bmal1, a core circadian clock gene, plays a role in the regulation of host immune responses in experimental sepsis. Mechanistically, Bmal1deficiency in macrophages increases PKM2 expression and lactate production, which is required for expression of the immune checkpoint protein PD-L1 in a STAT1-dependent manner. Consequently, targeted ablation of Pkm2in myeloid cells or administration of anti-PD-L1-neutralizing antibody or supplementation with recombinant interleukin-7 (IL-7) facilitates microbial clearance, inhibits T cell apoptosis, reduces multiple organ dysfunction, and reduces septic death in Bmal1-deficient mice. Collectively, these findings suggest that the circadian clock controls the immune checkpoint pathway in macrophages and therefore represents a potential therapeutic target for lethal infection.

A full bio-based cured resin was synthesized by copolymerization of acrylated-epoxidized soybean oil (AESO) and 2-acrylamidoethyl dehydroabietic acid (DHA-HEMAA). The rigid rosin-based monomer 2-acrylamidoethyl dehydroabietic acid was first prepared from dehydroabietic acid and N-hydroxyethylacrylamide, which was characterized by nuclear magnetic resonance and Fourier transform infrared (FTIR) spectrometry techniques. The cured resin was then synthesized and characterized by FTIR spectroscopy, differential scanning calorimetry, dynamic thermomechanical analysis, and thermogravimetric analysis, as well as using a Kruss tensiometer and a universal testing machine. The results indicated that the resin cured with rosin-based monomer exhibited excellent thermomechanical properties. The crosslink density and thermal stability of cured samples containing DHA-HEMAA at molar ratio between 10 and 30% were higher than those of AESO/DHA-HEMAA0 sample. With increasing DHA-HEMAA content, the glass transition temperature (Tg), elongation-at-break, and tensile strength of samples increased, in the stated order, from 16 to 38 °C, from 24 to 45.8%, and from 1.7 to 6.5 MPa. Due to DHA-HEMAA with a hydrophenanthrene structure, the θvalues increased with the increase of DHA-HEMAA molar ratios. The full bio-based rosin thermosetting resins may have great potentials in practical application fields, such as coating, adhesive, and packaging materials.

Airway epithelial cells play a significant role in the pathogenesis of asthma. Although the structural and functional defects of airway epithelial cells have been postulated to increase asthma susceptibility and exacerbate asthma severity, the mechanism and implication of these defects remain uncertain. Integrin β4 (ITGB4) is a structural adhesion molecule that is downregulated in the airway epithelium of asthma patients. In this study, we demonstrated that ITGB4 deficiency leads to severe allergy‐induced airway inflammation and airway hyper‐responsiveness (AHR) in mice. After house dust mite (HDM) challenge, epithelial cell‐specific ITGB4‐deleted mice showed increased lymphocyte, eosinophil, and neutrophil infiltration into lung compared with that of the wild‐type mice. ITGB4 deficiency also resulted in increased expression of the Th2 cytokine IL‐4, IL‐13, and the Th17 cytokine IL‐17A in the lung tissue and in the T cells after HDM challenge. The aggravated inflammation in ITGB4 defect mice was partly caused by enhanced disrupted epithelial barrier integrity after HDM stress, which induced the increased thymic stromal lymphopoietin secretion from airway epithelial cells. This study therefore demonstrates that ITGB4 plays a pivotal role in containing allergen‐mediated lung inflammation and airway hyper‐responsiveness in allergic asthma. ITGB4 defects conferred airway inflammation by disrupting barrier function and altering TSLP secretion.

Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems in bacteria and archaea provide adaptive immunity against invading foreign nucleic acids. Previous studies suggest that certain bacteria employ their Type II CRISPR-Cas systems to target their own genes, thus evading host immunity. However, whether other CRISPR-Cas systems have similar functions during bacterial invasion of host cells remains unknown. Here we identify a novel role for Type I CRISPR-Cas systems in evading host defenses in Pseudomonas aeruginosa strain UCBPP-PA14. The Type I CRISPR-Cas system of PA14 targets the mRNA of the bacterial quorum-sensing regulator LasR to dampen the recognition by toll-like receptor 4, thus diminishing the pro-inflammatory responses of the host in cell and mouse models. Mechanistically, this nuclease-mediated RNA degradation requires a “5′-GGN-3′” recognition motif in the target mRNA, and HD and DExD/H domains in Cas3 of the Type I CRISPR-Cas system. As LasR and Type I CRISPR-Cas systems are ubiquitously present in bacteria, our findings elucidate an important common mechanism underlying bacterial virulence.

ABSTRACTAlthough the PINK1-PARK2 pathway contributes to the pathogenesis of Parkinson disease, its roles in sepsis (a major challenge for critical care) were previously unknown. Here, we show that pink1−/−and park2−/−mice are more sensitive to polymicrobial sepsis-induced multiple organ failure and death. The decrease in the circulating level of the neurotransmitter dopamine in pink1−/−and park2−/−mice accelerates the release of a late sepsis mediator, HMGB1, via HIF1A-dependent anaerobic glycolysis and subsequent NLRP3-dependent inflammasome activation. Genetic depletion of Nlrp3 or Hif1ain pink1−/−and park2−/−mice confers protection against lethal polymicrobial sepsis. Moreover, pharmacological administration of dopamine agonist (e.g., pramipexole), HMGB1-inhibitor (e.g., neutralizing antibody or glycyrrhizin), or NLRP3-inhibitor (e.g., MCC950) reduces septic death in pink1−/−and park2−/−mice. The mRNA expression of HIF1Aand NLRP3is upregulated, whereas the mRNA expression of PINK1and PARK2is downregulated in peripheral blood mononuclear cells of patients with sepsis. Thus, an impaired PINK1-PARK2-mediated neuroimmunology pathway contributes to septic death and may represent a novel therapeutic target in critical care medicine.

Natural small molecules have demonstrated tremendous potential for the construction of supramolecular chiral nanostructures owing to their unique molecular structures and chirality. In this study, novel CO2-responsive supramolecular hydrogels were constructed using a series of rosin-based surfactants (CnMPAN, n= 10, 12, and 14). The macroscopic properties, rheological properties, nanostructures, and intermolecular interactions of the hydrogels were investigated using differential scanning calorimetry, rotational rheometry, cryogenic transmission electron microscopy, and Fourier transform infrared spectroscopy. Interestingly, diverse nanostructures containing helical nanofibers, interwoven nanofibers, and twisted nanoribbons were formed in the hydrogels, which were rarely observed in reported supramolecular hydrogels, and the strength of the hydrogels was significantly enhanced by increasing the CnMPAN concentration and the alkyl chain length. The obtained hydrogels exhibited excellent CO2-responsiveness, with no obvious variation in the nanostructures and rheological properties after response to CO2/N2for five cycles. Taking advantage of the chiral nanostructures of hydrogels, gold nanoparticles (GNPs) were further prepared. The average particle sizes of the resulting GNPs were as low as 2.5 nm, and the GNPs also had a chiral structure. It is worth noting that no additional reductants and UV-light irradiation were used during the reduction process of GNPs. This study emphasizes that the unique molecular structure and chirality of rosin are critical for the preparation of hydrogels with chiral nanostructures. In addition, this study enriches the applications of forest resources.

ABSTRACTIn contrast to normal tissue, cancer cells display profound alterations in protein synthesis and degradation. Therefore, proteins that regulate endoplasmic reticulum (ER) homeostasis are being increasingly recognized as potential therapeutic targets. The ubiquitin-proteasome system and autophagy are crucially important for proteostasis in cells. However, interactions between autophagy, the proteasome, and ER stress pathways in cancer remain largely undefined. This study demonstrated that withaferin-A (WA), the biologically active withanolide extracted from Withania somnifera, significantly increased autophagosomes, but blocked the degradation of autophagic cargo by inhibiting SNARE-mediated fusion of autophagosomes and lysosomes in human pancreatic cancer (PC) cells. WA specifically induced proteasome inhibition and promoted the accumulation of ubiquitinated proteins, which resulted in ER stress-mediated apoptosis. Meanwhile, the impaired autophagy at early stage induced by WA was likely activated in response to ER stress. Importantly, combining WA with a series of ER stress aggravators enhanced apoptosis synergistically. WA was well tolerated in mice, and displayed synergism with ER stress aggravators to inhibit tumor growth in PC xenografts. Taken together, these findings indicate that simultaneous suppression of 2 key intracellular protein degradation systems rendered PC cells vulnerable to ER stress, which may represent an avenue for new therapeutic combinations for this disease.

Sepsis is a challenging clinical syndrome caused by a dysregulated host response to infection. Here, we identified an unexpected proseptic activity of aconitate decarboxylase 1 (ACOD1) in monocytes and macrophages. Previous studies have suggested that ACOD1, also known as immune-responsive gene 1, is an immunometabolic regulator that favors itaconate production to inhibit bacterial lipopolysaccharide-induced innate immunity. We used next-generation sequencing of lipopolysaccharide-activated THP1 cells to demonstrate that ACOD1 accumulation confers a robust proinflammation response by activating a cytokine storm, predominantly through the tumor necrosis factor signaling pathway. We further revealed that the phosphorylation of cyclin-dependent kinase 2 (CDK2) on threonine-160 mediates the activation of mitogen-activated protein kinase 8 through receptor for activated C kinase 1, leading to JUN-dependent transcription of ACOD1in human and mouse macrophages or monocytes. Genetic deletion of CDK2or ACOD1in myeloid cells, or the administration of the CDK inhibitor dinaciclib, protected mice against polymicrobial sepsis and was associated with improved survival and decreased cytokine storm. The expression of the CDK2-ACOD1 axis also correlated with severity of illness in a cohort of 40 patients with bacterial sepsis. Thus, our findings provide evidence for a previously unrecognized function of ACOD1 in innate immunity and suggest it as a potential therapeutic target for the treatment of sepsis.

To investigate the relationship of protein expression of hypoxia-inducible factor-1 alpha (HIF-1α) with clinicopathological factors and prognosis of hepatocellular carcinoma (HCC).

Furfural residue (FR) is a waste lignocellulosic material with enormous potential for bioethanol production. In this study, bioethanol production from FR after delignification was compared. Hydrophilic variation was measured by conductometric titration to detect the relationship between hydrophilicity and bioethanol production. It was found that ethanol yield increased as delignification enhanced, and it reached up to 75.6% of theoretical yield for samples with 8.7% lignin. The amount of by-products decreased as delignification increased. New inflection points appeared in conductometric titration curves of samples that were partially delignified, but they vanished in the curves of the highly delignified samples. Total charges and carboxyl levels increased after slight delignification, and they decreased upon further delignification. These phenomena suggested some new hydrophilic groups were formed during pretreated delignification, which would be beneficial to enzymatic hydrolysis. However, some newly formed groups may act as toxicant to the yeast during simultaneous saccharification and fermentation.

Cancer stem cells (CSCs)/tumor-initiating cells have been defined as a subset of tumor cells responsible for initiating and sustaining tumor development. Emerging evidence strongly supports the existence of CSCs in various solid tumors, but they have not yet been identified in human gallbladder carcinomas (GBC). In this study, we identified CSCs in primary GBC and in the cell line GBC-SD using the cell surface markers CD44 and CD133. The percentages of CD44+CD133+ cells were 1.76-3.05% in primary tumors and 40.29% in GBC-SD cells. These cells showed stem cell properties, including self-renewal, differentiation potential, and high tumorigenicity. In vitro culture experiments revealed that CD44+CD133+ GBC cells possessed a higher spheroid-colony forming ability in serum-free media than other subpopulations. When injected into nonobese diabetic/severe combined immunodeficient mice, these cells formed new tumors and generated CD44+CD133+, CD44-, and CD133- progeny. CD44+CD133+ cells also showed a high degree of chemoresistance, possibly due to upregulation of the breast cancer resistance protein (ABCG2) and the transcription factor Gli1 in these highly tumorigenic cells. These results suggest that the CD44+CD133+ population exhibited CSC-like characteristics and may thus provide a novel approach to the diagnosis and treatment of GBC.

Our objective was to investigate the expression of scavenger receptor SR and CD14 in the liver and their relationship with local antiinflammatory and proinflammatory responses in endotoxemia in order to uncover the mechanism for the liver to turn into effector organ from defense one at the level of cell receptors in sepsis. Mouse models of endotoxemia of different severity were reproduced by injection of different doses of lipopolysaccharide LPS via tail vein. Expression of SR and CD14 in the liver was assayed by immunohistochemistry and was then analyzed with an image analysis system. The levels of TNF, IL6, IL4, and IL10 in liver tissue were determined with ELISA. Expression of SR in the liver in the highdose group was markedly decreased 1 h after injection of LPS, and also in low and mediumdose groups at 3 h. The expression of SR in the liver in the three groups was shown to be progressively decreased with the time prolonged. There was significant difference in average optical density OD values of SR among the three groups. The expression of CD14 in the liver in the three groups was shown to be significantly increased 1 h after injection of LPS, and much more with the time prolonged. But there was no significant difference in OD values of CD14 among the three groups. The contents of intrahepatic proinflammatory mediators TNF and IL6 and antiinflammatory mediators IL4 and IL10 were successively significantly increased after injection of LPS. The release of antiinflammatory mediators was shown to be later than that of proinflammatory mediators. Correlation analysis indicated that there was negative correlation between expression of SR and CD14, and that changes of TNF, IL6, IL4, and IL10 levels in liver tissues were correlated significantly positively with OD values of CD14 and negatively with OD values of SR. Expression of SR in the liver was shown to be progressively decreased, and that of CD14 increased in endotoxemia, which was closely related to the uncontrolled inflammatory response in liver. This might be an important mechanism for the liver to turn into effector organ from defense one in sepsis.

We present a simple diffusion model for investigation of the effect of a post-growth thermal history on growth-zoned minerals. The model treats the mineral as a chemically closed system. Our treatment incorporates the effects of any thermal history into one essential parameter. We then demonstrate that the usability of zoned minerals in metamorphic P-T history calculations depends on the mineral grain size and the post-growth thermal history. Using garnet as an example, we show that while large garnets (>1 mm) are safe to use, garnets smaller than that that have experienced temperatures characteristic of upper greenschist or lower amphibolite facies metamorphism will yield seriously misleading information. The deviation of the calculated growth history from the true growth history can be greater than 100° C and is the greatest for the early part of the garnet history.

Feedback inhibition of the microRNA decoy activity of lncRNA MEG3 tempers inflammation during lung infection.

FDA-approved ALK-inhibiting drugs protect mice against sepsis through attenuating STING signaling activation in innate immune cells.

A screen in Dictyosteliumreveals that mTORC2 signaling participates in electrotaxis, as well as chemotaxis.

A novel cellulose-chitosan gel was successfully prepared in three steps: (1) ferrocene- (Fc-) cellulose with degrees of substitution (DS) of 0.5 wt% was synthesised by ferrocenecarboxylic acid and cellulose within dimethylacetamide/lithium chloride (DMAc/LiCl); (2) the β-cyclodextrin (β-CD) groups were introduced onto the chitosan chains by reacting chitosan with epichlorohydrin in dimethyl sulphoxide and a DS of 0.35 wt%; (3) thus, the cellulose-chitosan gel was obtained via an intermolecular inclusion interaction of Fc-cellulose and β-CD-chitosan in DMA/LiCl, that is, by an intermolecular inclusion interaction, between the Fc groups of cellulose and the β-CD groups on the chitosan backbone at room temperature. The successful synthesis of Fc-cellulose and β-CD-chitosan was characterised by 13C-NMR spectroscopy. The gel based on β-CD-chitosan and Fc-cellulose was formed under mild conditions which can engender autonomous healing between cut surfaces after 24 hours: the gel cannot self-heal while the cut surfaces were coated with a solution of a competitive guest (adamantane acid). The cellulose-chitosan complex made by this method underwent self-healing. Therefore, this study provided a novel method of expanding the application of chitosan by binding it with another polymer.

An excessive inflammatory response is thought to account for the pathogenesis of sepsis and multiple organ dysfunction syndrome (MODS) after severe trauma. The interleukin-10 (IL-10) is a potent anti-inflammatory cytokine. The objectives of this prospective study were to investigate the distribution of IL-10 promoter polymorphisms in a cohort of 308 Chinese Han patients with major trauma, and to identify associations of IL-10 promoter polymorphisms with IL-10 production and incidence of sepsis and MODS.