Operando probing and adjusting of the complicated electrode process of multivalent metals at extreme temperature.

Nearly half of the elements in the periodic table are extracted, refined, or plated using electrodeposition in high-temperature melts. However, operando observations and tuning of the electrodeposition process during realistic electrolysis operations are extremely difficult due to severe reaction conditions and complicated electrolytic cell, which makes the improvement of the process very blind and inefficient. Here, we developed a multipurpose operando high-temperature electrochemical instrument that combines operando Raman microspectroscopy analysis, optical microscopy imaging, and a tunable magnetic field. Subsequently, the electrodeposition of Ti-which is a typical polyvalent metal and generally shows a very complex electrode process-was used to verify the stability of the instrument. The complex multistep cathodic process of Ti in the molten salt at 823 K was systematically analyzed by a multidimensional operando analysis strategy involving multiple experimental studies, theoretical calculations, etc. The regulatory effect and its corresponding scale-span mechanism of the magnetic field on the electrodeposition process of Ti were also elucidated, which would be inaccessible with existing experimental techniques and is significant for the real-time and rational optimization of the process. Overall, this work established a powerful and universal methodology for in-depth analysis of high-temperature electrochemistry.

Ultra-Stable Ti Vacancies-Pt Atomic Clusters Structure on Titanium Oxycarbide Supports for High Current Density Hydrogen Evolution Reaction.

Electrocatalysts with low Pt loading mass to achieve high current density (≥1 A cm-2) for hydrogen evolution reaction (HER) are still extremely challenging due to the limited intrinsic activity and weak stability of catalytic sites. The modulation of the electronic microenvironment of the support-Pt structure is crucial to enhance the intrinsic activity and stability of catalytic sites. Herein, an innovative titanium oxycarbide (TiVCO) solid solution with Ti vacancies (TiV) is proposed as support to anchor sub-nanoscale Pt atomic clusters (Pt ACs) and a stable "TiV-Pt ACs" structure is carefully designed. The electronic microenvironment of "TiV-Pt ACs" is indirectly optimized by an unsaturated C/O site near TiV. Thanks to this, novel "TiV-Pt ACs" structure (Pt@TiVCO) with low Pt loading mass (2.44 wt.%) exhibits excellent HER activity in acidic solution and the mass activity is more than ten times that of commercial 20% Pt/C at the overpotentials of 50 and 100 mV. Particularly, Pt@TiVCO shows amazing stability at high and fluctuating current density of 1-2 A cm-2 for 120 h. This work provides a novel and promising method to develop stable and low-loading Pt-based catalysts adapting to high current density.

The influence of iron on bone metabolism disorders.

Iron is a necessary trace element in the human body, and it participates in many physiological processes. Disorders of iron metabolism can cause lesions in many tissues and organs, including bone. Recently, iron has gained attention as an independent factor influencing bone metabolism disorders, especially the involvement of iron overload in osteoporosis. The aim of this review was to summarize the findings from clinical and animal model research regarding the involvement of iron in bone metabolism disorders and to elucidate the mechanisms behind iron overload and osteoporosis. Lastly, we aimed to describe the association between bone loss and iron overload. We believe that a reduction in iron accumulation can be used as an alternative treatment to assist in the treatment of osteoporosis, to improve bone mass, and to improve the quality of life of patients.

The Reverse of Electrostatic Interaction Force for Ultrahigh-Energy Al-Ion batteries.

The two-dimensional (2D) MXenes with sufficient interlayer spacing are promising cathode materials for aluminum-ion batteries (AIBs), yet the electrostatic repulsion effect between the surface negative charges and the active anions (AlCl4 - ) hinders the intercalation of AlCl4 - and is usually ignored. Here, we propose a charge regulation strategy for MXene cathodes to overcome this challenge. By doping N and Co, the zeta potential is gradually transformed from negative (Ti3 C2 Tx ) to near-neutral (Ti3 CNTx ), and finally positive (Ti3 CNTx @Co). Therefore, the electrostatic repulsion force can be greatly weakened between Ti3 CNTx and AlCl4 - , or even formed a strong electrostatic attraction between Ti3 CNTx @Co and AlCl4 - , which can not only accommodate more AlCl4 - ions in the Ti3 CNTx @Co interlayers to increase the capacity, but also solve the stacking and expansion problems. As a result, the optimized Al-MXene battery exhibits an ultrahigh capacity of up to 240 mAh g-1 (2-4 times the capacity of graphite cathode, 60-120 mAh g-1 ) and a potential ultrahigh energy density (432 Wh kg-1 , 2-4 times the value of graphite, 110-220 Wh kg-1 ) based on the mass of cathode materials, comparable to LiFePO4 -based lithium-ion batteries (350-450 Wh kg-1 , based on the mass of LiFePO4 ).

Fluorescence Noise Eliminating Fiber-Enhanced Raman Spectroscopy for Simultaneous and Multiprocess Analysis of Intermediate Compositions for C2H2 and H2 Production.

C2H2 and H2, as important chemical and energy raw materials, can be produced effectively and environmentally friendly by the partial oxidation (POX) of CH4. Simultaneous analysis of intermediate gas compositions in the multiprocess (cracking, recovery, degassing, etc) of POX can regulate product generation and improve production efficiency. To overcome the disadvantage of common gas chromatography, we propose a fluorescence noise eliminating fiber-enhanced Raman spectroscopy (FNEFERS) technique for simultaneous and multiprocess analysis of the POX process, in which the fluorescence noise eliminating (FNE) method can effectively eliminate the horizontal and vertical spatial noise to ensure ppm level limits of detection (LOD). The vibration modes of gas compositions related to each POX process such as cracked gas, synthesis gas, and product acetylene are analyzed. Meanwhile, the composition of three-process intermediate sample gases from Sinopec Chongqing SVW Chemical Co., Ltd is quantitatively and qualitatively analyzed simultaneously, along with the ppm level LODs (H2: 11.2 ppm, C2H2: 3.1 ppm, CO2: 9.4 ppm, C2H4: 4.8 ppm, CH4: 1.5 ppm, CO: 17.9 ppm, allene: 1.5 ppm, methyl acetylene: 2.6 ppm, 1,3-butadiene: 2.8 ppm) with a laser power of 180 mW, exposure time of 30 s, and accuracy of higher than 95.2%. This study fully demonstrates the ability of FNEFERS to replace gas chromatography to achieve simultaneous and multiprocess analysis of intermediate compositions for C2H2 and H2 production and to monitor other chemical and energy production processes.

Nonaqueous Rechargeable Aluminum Batteries: Progresses, Challenges, and Perspectives.

For significantly increasing the energy densities to satisfy the growing demands, new battery materials and electrochemical chemistry beyond conventional rocking-chair based Li-ion batteries should be developed urgently. Rechargeable aluminum batteries (RABs) with the features of low cost, high safety, easy fabrication, environmental friendliness, and long cycling life have gained increasing attention. Although there are pronounced advantages of utilizing earth-abundant Al metals as negative electrodes for high energy density, such RAB technologies are still in the preliminary stage and considerable efforts will be made to further promote the fundamental and practical issues. For providing a full scope in this review, we summarize the development history of Al batteries and analyze the thermodynamics and electrode kinetics of nonaqueous RABs. The progresses on the cutting-edge of the nonaqueous RABs as well as the advanced characterizations and simulation technologies for understanding the mechanism are discussed. Furthermore, major challenges of the critical battery components and the corresponding feasible strategies toward addressing these issues are proposed, aiming to guide for promoting electrochemical performance (high voltage, high capacity, large rate capability, and long cycling life) and safety of RABs. Finally, the perspectives for the possible future efforts in this field are analyzed to thrust the progresses of the state-of-the-art RABs, with expectation of bridging the gap between laboratory exploration and practical applications.

Design Strategies of High-Performance Positive Materials for Nonaqueous Rechargeable Aluminum Batteries: From Crystal Control to Battery Configuration.

Rechargeable aluminum batteries (RABs) have been paid considerable attention in the field of electrochemical energy storage batteries due to their advantages of low cost, good safety, high capacity, long cycle life, and good wide-temperature performance. Unlike traditional single-ion rocking chair batteries, more than two kinds of active ions are electrochemically participated in the reaction processes on the positive and negative electrodes for nonaqueous RABs, so the reaction kinetics and battery electrochemistries need to be given more comprehensive assessments. In addition, although nonaqueous RABs have made significant breakthroughs in recent years, they are still facing great challenges in insufficient reaction kinetics, low energy density, and serious capacity attenuation. Here, the research progresses of positive materials are comprehensively summarized, including carbonaceous materials, oxides, elemental S/Se/Te and chalcogenides, as well as organic materials. Later, different modification strategies are discussed to improve the reaction kinetics and battery performance, including crystal structure control, morphology and architecture regulation, as well as flexible design. Finally, in view of the current research challenges faced by nonaqueous RABs, the future development trend is proposed. More importantly, it is expected to gain key insights into the development of high-performance positive materials for nonaqueous RABs to meet practical energy storage requirements.

Prevalence and distribution of human papillomavirus genotypes among women attending gynecology clinics in northern Henan Province of China.

BACKGROUND: Human papillomavirus (HPV) infection can cause cervical and other cancers, including vulva, vagina, penis, anus, or oropharynx. However, in China's northern Henan Province, data on the prevalence and genotype distribution of HPV among women attending gynecology clinics is limited. This study aimed to investigate the current prevalence and genotype distribution of HPV among women attending gynecology clinics in northern Henan Province. METHODS: This study included 15,616 women aged 16-81 years old who visited the Xinxiang central hospital's gynecology department between January 2018 and December 2019. HPV DNA was detected by a conventional PCR method followed by HPV type-specific hybridization, which was designed to detect 17 high-risk HPV (HR-HPV) genotypes and 20 low-risk HPV (LR-HPV) genotypes. HPV prevalence and corresponding 95% confidence intervals (95% CI) were calculated using SPSS 18.0. RESULTS: The overall HPV prevalence was 19.7% among women in northern Henan Province. Single, double, and multiple HPV infections accounted for 13.7%, 4.3%, and 1.8% of the total cases. Most infections were caused by HR-HPV (71.8%), and single genotype HPV infection (13.7%) was the most common pattern. The most common HR-HPV genotype was HPV16 (4.3%), followed by HPV52 (3.5%) and HPV58 (2.0%). The most common LR-HPV genotype was HPV6 (1.4%), followed by HPV61 (1.1%) and HPV81 (1.1%). CONCLUSIONS: HPV infection is high among women attending gynecology clinics in northern Henan Province. The highest prevalence was found in women less than 20 years old. In northern Henan Province, the 9-valent HPV vaccine is strongly recommended for regular immunization.

Prevalence and molecular subtyping of Blastocystis in domestic pigeons in Henan Province, Central China.

Blastocystis is an anaerobic intestinal protozoan parasite found in humans and many kinds of animals that mainly causes diarrhea, abdominal pain, and other clinical symptoms. At present, research on the prevalence and subtype diversity of Blastocystis in domestic pigeons is very limited. The purpose of this study was to detect the infection rate and gene subtype distribution of Blastocystis in domestic pigeons in Henan Province, Central China, to provide a foundation for preventing and controlling Blastocystis in domestic pigeons. Fecal DNA was extracted from 504 fresh fecal samples of pigeons collected from four areas in Henan Province, Central China. All DNA samples were investigated by polymerase chain reaction, and positive samples were sequenced to analyze the gene subtypes based on small ribosomal subunit (SSU rRNA) gene. The overall infection rate of Blastocystis in pigeons in Henan Province was 7.7% (39/504). Four subtypes (STs) of Blastocystis were identified including ST1 (2/39, 5.1%), ST3 (16/39, 41%), ST4 (1/39, 2.6%), and ST7 (20/39, 51.3%), all of which belonged to zoonotic subtypes, and ST7 was the dominant gene subtype. The results show that Blastocystis infection is common in domestic pigeons in Henan Province, Central China, and the pathogens were zoonotic subtypes. Particular attention should be given to reducing the risk of transmission of Blastocystis from domestic pigeons to humans.

Live birth from a blastocyst derived from a conjoined oocyte in a frozen embryo transfer cycle: a case report and a literature review.

The significance of conjoined oocytes in the clinical in vitro fertilization (IVF) laboratory setting has been questionable due to the extremely limited data available. This issue is discussed by presenting one case for conjoined oocyte observed in the program of the assisted reproduction and by including a review of corresponding literature. This report describes a successful clinical pregnancy with subsequent live birth from a conjoined oocyte. To our knowledge, there are only three reported cases of successful live birth from conjoined oocytes, but this is the first case of live birth from a blastocyst derived from a conjoined oocyte fertilized using intracytoplasmic sperm injection (ICSI) in a frozen embryo transfer cycle. Moreover, this study reports the first time that live birth of a conjoined oocyte is achieved without removing the degenerated immature oocyte prior to transfer. It demonstrates that the degenerated immature oocyte has no adverse effect on subsequent embryo development and pregnancy outcome. In addition, we reviewed the literature to evaluate the origin, incidence, safety, and significance of conjoined oocytes in reproductive health. We further confirm previous reports that demonstrate that a mature oocyte from conjoined-oocyte complexes can be fertilized by standard IVF or ICSI and lead to the development of a blastocyst, subsequent pregnancy, and live birth.

Seizures in PPT1 Knock-In Mice Are Associated with Inflammatory Activation of Microglia.

Infantile neuronal ceroid lipofuscinosis (INCL), the most severe form of neuronal ceroid lipofuscinoses, is caused by mutations in the lysosomal enzyme palmitoyl protein thioesterase 1 (PPT1). Typical symptoms of this disease include progressive psychomotor developmental retardation, visual failure, seizures, and premature death. Here, we investigated seizure activity and relevant pathological changes in PPT1 knock-in mice (PPT1 KI). The behavior studies in this study demonstrated that PPT1 KI mice had no significant seizure activity until 7 months of age, and local field potentials also displayed epileptiform activity at the same age. The expression levels of Iba-1 and CD68 demonstrated, by Western blot analysis, the inflammatory cytokine TNF-α content measured with enzyme-linked immunosorbent assay, and the number of microglia demonstrated by immunohistochemistry (IHC) were significantly increased at age of 7 months, all of which indicate microglia activation at an age of seizure onset. The increased expression of GFAP were seen at an earlier age of 4 months, and such an increase reached its peak at age of 6 months, indicating that astrocyte activation precedes microglia. The purinergic P2X7 receptor (P2X7R) is an ATP-sensitive ionic channel that is highly expressed in microglia and is fundamental to microglial activation, proliferation, cytokines release and epilepsy. We show that the ATP concentration in hippocampal tissue in PPT1 KI mice was increased using an enhanced ATP assay kit and demonstrated that the antagonist of P2X7R, A-438079, significantly reduced seizures in PPT1 KI mice. In contrast to glial cell activation and proliferation, a significant reduction in synaptic proteins GABAAR was seen in PPT1 KI mice. These results indicate that seizure in PPT1 KI mice may be associated with microglial activation involved in ATP-sensitive P2X7R signaling and impaired inhibitory neurotransmission.

Ultra-High Temperature Molten Oxide Electrochemistry.

Recently, the ultra-high temperature electrochemistry (UTE, about >1000 °C) has emerged, which represents an exploration to extend the temperature limit of human technology in electrochemical engineering. UTE has far-reaching impact on revolutionary low-carbon metal extraction and the in situ production of oxygen for deep-space exploration. It is hence of urgency to systematically summarize the development of UTE. In this Review, the basic concepts of UTE and the physicochemical properties of molten oxides are analyzed. The principles in the design of inert anodes for the oxygen evolution reaction in molten oxides are discussed, which forms a solid basis for the in situ production of oxygen from simulated lunar regolith by UTE. Furthermore, liquid metal cathodes for revolutionary titanium extraction and ironmaking/steelmaking are highlighted. With emphasis on the key challenges and perspectives, the Review can provide valuable inspiration for the rapid advancement of UTE.

Electrocatalysis for Continuous Multi-Step Reactions in Quasi-Solid-State Electrolytes Towards High-Energy and Long-Life Aluminum-Sulfur Batteries.

Aluminum-sulfur (Al-S) batteries of ultrahigh energy-to-price ratios are a promising energy storage technology, while they suffer from a large voltage gap and short lifespan. Herein, we propose an electrocatalyst-boosting quasi-solid-state Al-S battery, which involves a sulfur-anchored cobalt/nitrogen co-doped graphene (S@CoNG) positive electrode and an ionic-liquid-impregnated metal-organic framework (IL@MOF) electrolyte. The Co-N4 sites in CoNG continuously catalyze the breaking of Al-Cl and S-S bonds and accelerate the sulfur conversion, endowing the Al-S battery with a shortened voltage gap of 0.43 V and a high discharge voltage plateau of 0.9 V. In the quasi-solid-state IL@MOF electrolytes, the shuttle effect of polysulfides has been inhibited, which stabilizes the reversible sulfur reaction, enabling the Al-S battery to deliver 820 mAh g-1 specific capacity and 78 % capacity retention after 300 cycles. This finding offers novel insights to design Al-S batteries for stable energy storage.

Adipocyte-specific deletion of Depdc5 exacerbates insulin resistance and adipose tissue inflammation in mice.

The mammalian target of rapamycin complex 1 (mTORC1) is a crucial regulator of adipogenesis and systemic energy metabolism. Its dysregulation leads to a diversity of metabolic diseases, including obesity and type 2 diabetes. DEP-domain containing 5 (DEPDC5) is a critical component of GATOR1 complex that functions as a key inhibitor of mTORC1. So far, its function in adipose tissue remains largely unknown. Herein we evaluated how persistent mTORC1 activation in adipocyte via Depdc5 knockout modulates adiposity in vivo. Our data indicated that adipocyte-specific knockout of Depdc5 in aged mice led to reduced visceral fat, aggravated insulin resistance and enhanced adipose tissue inflammation. Moreover, we found that Depdc5 ablation resulted in upregulation of adipose triglyceride lipase (ATGL) in adipocytes and elevated levels of serum free fatty acids (FFAs). Intriguingly, rapamycin treatment did not reverse insulin resistance but alleviated adipose tissue inflammation caused by Depdc5 deletion. Taken together, our findings revealed that mTORC1 activation caused by Depdc5 deletion promotes lipolysis process and further exacerbates insulin resistance and adipose tissue inflammation in mice.

The molecular characterization and immune protection of adhesion protein 65 (AP65) of Trichomonas vaginalis.

BACKGROUND: Adherence to the surface of the host cell is the precondition for T. vaginalis parasitism and pathogenicity, causing urogenital infection. The AP65 of T. vaginalis (TvAP65) involves in the process of adhesion. So, the present study was aimed at investigating the molecular characterization and vaccine candidacy of TvAP65 for protecting the host from the onset of Trichomoniasis. METHODS: The open reading frame (ORF) of TvAP65 was amplified and then inserted into pET-32a (+) to clone recombinant TvAP65 (rTvAP65). The immunoblotting determined the immunogenicity and molecular size of TvAP65, while immunofluorescence staining visualized and the precise localization of TvAP65 in T. vaginalis trophozoites. Animal challenge and enzyme-linked immunosorbent assay (ELISA) test were used to evaluate the immunoprotection and the types of the immune response of TvAP65. RESULTS: By the sequence analysis, TvAP65 encoded a 63.13 kDa protein that consisted 567 amino acid residues with a high antigenic index. The western blotting revealed that rTvAP65 and native TvAP65 could interact with the antibodies in the rat serums post hoc rTvAP65 immunization and the serums from the mice that were experimentally infected with T. vaginalis, respectively. Immunofluorescence stained TvAP65 on the surface of T. vaginalis trophozoites. Moreover, following emulsification with Freund's adjuvant, rTvAP65 was subsequently administered to BALB/c mice three times at 0, 2, and 4 weeks and the results from this animal challenge experiments showed significant increases in immunoglobulins of IgG2a, IgG1, and IgG, and cytokine of IFN-γ, and IL-2, and 10. Lastly, rTvAP65 vaccinated animals had a prolonged survival time (26.80 ± 4.05) after challenged by T. vaginalis. CONCLUSIONS: TvAP65 mediated the adhesion of T. vaginalis to the host epithelia for the pathogenesis of the parasite and can be considered as a candidate protein for designing a functional vaccine that induces cell-mediated and humoral immunity against the T. vaginalis infection.

Ezh2 promotes clock function and hematopoiesis independent of histone methyltransferase activity in zebrafish.

EZH2 is a subunit of polycomb repressive complex 2 (PRC2) that silences gene transcription via H3K27me3 and was shown to be essential for mammalian liver circadian regulation and hematopoiesis through gene silencing. Much less, however, is known about how Ezh2 acts in live zebrafish. Here, we show that zebrafish ezh2 is regulated directly by the circadian clock via both E-box and RORE motif, while core circadian clock genes per1a, per1b, cry1aa and cry1ab are down-regulated in ezh2 null mutant and ezh2 morphant zebrafish, and either knockdown or overexpression of ezh2 alters locomotor rhythms, indicating that Ezh2 is required for zebrafish circadian regulation. In contrast to its canonical silencing function, zebrafish Ezh2 up-regulates these key circadian clock genes independent of histone methyltransferase activity by directly binding to key circadian clock proteins. Similarly, Ezh2 contributes to hematopoiesis by enhancing expression of hematopoietic genes such as cmyb and lck. Together, our findings demonstrate for the first time that Ezh2 acts in both circadian regulation and hematopoiesis independent of silencing PRC2.

Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota.

Phloretin, extracted from the pericarp and velamen of apples or pears, is a dihydrochalcone flavonoid with anti-bacterial and anti-inflammatory activities. It has been reported that phloretin has anti-inflammatory effects in ulcerative colitis (UC) mice. However, the role of the gut microbiota in the phloretin anti-UC process remains unclear. In this study, we observed that the anti-UC effect of phloretin was affected by co-housing, probably because of the transmissible nature of the gut micobiota. Through fecal micobiota transplantation (FMT), the effects of the gut microbiota on the anti-UC of phloretin were further confirmed. UC was induced in mice by administrating 3% dextran sulfate sodium (DSS) in drinking water for 7 days. Phloretin (60 mg/kg) was administered by gavage every day during the experiment. Fecal microbes (109 CFU/mL) from phloretin-treated UC mice were administered by gavage to non-phloretin-treated UC mice for 7 days. The results showed that FMT, like phloretin, ameliorated UC by improving disease symptoms and colon inflammation, balancing inflammatory cytokines, maintaining intestinal barrier integrity, restoring systemic immune function, inhibiting NF-κB and NLRP3 inflammasome activation and ameliorating the oxidant stress. Both FMT and phloretin treatment increased the levels of Bacteroidetes, Alistipes and Lactobacillus and decreased those of Firmicutes, Oscillibacter and Ruminiclostridium_6. Correlation analysis between gut microbes and micro-environmental factors revealed that Alistipes abundance was negatively correlated with DAI, pathological score, and TNF-α, IL-6 and IL-1ß levels, and Alistipes was more abundant in phloretin or FMT treated UC mice. Oscillibacter abundance was significantly positively correlated with IL-6 and IL-1ß levels and pathological score, and Oscillibacter was increased in UC mice. Furthermore, network analysis of the dominant genera revealed that Alistipes abundance was negatively related to Oscillibacter abundance. In conclusion, this study suggests that the anti-UC effects of phloretin are achieved through regulation of the gut microbiota and phloretin has the potential to be developed as a promising agent for the treatment of UC.

The potential application of black and blue phosphorene as cathode materials in rechargeable aluminum batteries: a first-principles study.

Developing a suitable cathode material for rechargeable aluminum-ion batteries (AIBs) is currently recognized as a key challenge in pushing AIBs from lab-level to industrial application. Herein, detailed density functional theory (DFT) calculations are carried out to investigate the potential application of black and blue phosphorus monolayers as cathode materials for AIBs. It can be found that AlCl4- ions can strongly bind with both phosphorene allotropes, along with significant charge transfer. For black P, a semiconducting-to-metallic transition is realized in the (AlCl4)8P16 compound. Likewise, the band gap of blue P is reduced from 1.971 eV (pristine blue P) to 0.817 eV. Moreover, both phosphorene allotropes show excellent structural integrity with increased AlCl4- concentration, while delivering competitive theoretical capacities of 432.29 and 384.25 mA h g-1 for black ((AlCl4)8P16) and blue phosphorene ((AlCl4)8P18), respectively. Kinetic calculations present modest energy barriers of 0.19 and 0.39 eV for AlCl4- ions migrating on the surface of black and blue P, and an anisotropic migration nature is also found in both phosphorene allotropes. Based on our results, black and blue phosphorene show great potential as cathode materials for AIBs with robust ion-adsorption, insignificant deformation, self-improved conductivity, and fast kinetic performance.

Mannan-Binding Lectin Suppresses Peptidoglycan-Induced TLR2 Activation and Inflammatory Responses.

Peptidoglycan (PGN), as the major components of the bacterial cell wall, is known to cause excessive proinflammatory cytokine production. Toll-like receptor 2 (TLR2) is abundantly expressed on immune cells and has been shown to be involved in PGN-induced signaling. Although more and more evidences have indicated that PGN is recognized by TLR2, the role of TLR2 PGN recognition is controversial. Mannan-binding lectin (MBL), a plasma C-type lectin, plays a key role in innate immunity. More and more evidences show that MBL could suppress the amplification of inflammatory signals. Whether MBL can alter PGN-elicited cellular responses through TLR2 in macrophages is still unknown, and possible mechanism underlying it should be investigated. In this study, we found that MBL significantly attenuated PGN-induced inflammatory cytokine production, including TNF-α and IL-6, in PMA-stimulated THP-1 cells at both mRNA and protein levels. The expression of TLR2 was strongly induced by PGN stimulation. Furthermore, the administration of TLR2-neutralized antibody effectively suppressed PGN-induced TNF-α and IL-6 expression. These results supplied the evidence that PGN from Saccharomyces cerevisiae could be recognized by TLR2. In addition, we also found that MBL decreased PGN-induced TLR2 expression and suppressed TLR2-mediated downstream signaling, including the phosphorylation of IκBα, nuclear translocation of NF-κBp65, and phosphorylation of MAPK p38 and ERK1/2. Administration of MBL alone did not have an effect on the expression of TLR2. Finally, our data showed that PGN-mediated immune responses were more severely suppressed by preincubation with MBL and indicated that MBL can combine with both TLR2 and PGN to block the inflammation cytokine expression induced by PGN. All these data suggest that MBL could downregulate inflammation by modulating PGN/TLR2 signaling pathways. This study supports an important role for MBL in immune regulation and signaling pathways involved in inflammatory responses.

Alteration of DACH1 methylation patterns in lung cancer contributes to cell proliferation and migration.

Lung cancer is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of total lung cancer cases. Dachshund homolog 1 (DACH1), is a protein encoded by the DACH1 gene in humans. DACH1 inhibits lung adenocarcinoma invasion and tumor growth but has a lower expression in NSCLC. To investigate the mechanisms of decreased DACH1 expression, its DNA methylation patterns were investigated. The results showed a higher methylation rate in NSCLC compared with the adjacent normal lung tissues. Cell transfection experiments showed that increased methylation impaired transcription factor transactivation. In vivo demethylation treatment and overexpression of DACH1 increased apoptosis and decreased migration and invasion in NSCLC A549 cells. Our research provides new insight into NSCLC pathogenesis and identifies a new therapeutic target.