GPR124 promotes trophoblast proliferation, migration, and invasion and inhibits trophoblast cell apoptosis and inflammation via JNK and P38 MAPK pathways.

Early-onset preeclampsia, which occurrs before 34 weeks of gestation, is the most dangerous classification of preeclampsia, which is a pregnancy-specific disease that causes 1% of maternal deaths. G protein-coupled receptor 124 (GPR124) is significantly expressed at various stages of the human reproductive process, particularly during embryogenesis and angiogenesis. Our prior investigation demonstrated a notable decrease in GPR124 expression in the placentas of patients with early-onset preeclampsia compared to that in normal pregnancy placentas. However, there is a lack of extensive investigation into the molecular processes that contribute to the role of GPR124 in placenta development. This study aimed to examine the mechanisms by which GPR124 affects the occurrence of early-onset preeclampsia and its function in trophoblast. Proliferative, invasive, migratory, apoptotic, and inflammatory processes were identified in GPR124 knockdown, GPR124 overexpression, and normal HTR8/SVneo cells. The mechanism of GPR124-mediated cell function in GPR124 knockdown HTR8/SVneo cells was examined using inhibitors of the JNK or P38 MAPK pathway. Downregulation of GPR124 was found to significantly inhibit proliferation, invasion and migration, and promote apoptosis of HTR8/SVneo cells when compared to the control and GPR124 overexpression groups. This observation is consistent with the pathological characteristics of preeclampsia. In addition, GPR124 overexpression inhibits the secretion of pro-inflammatory cytokines interleukin (IL)-8 and interferon-γ (IFN-γ) while enhancing the secretion of the anti-inflammatory cytokine interleukin (IL)-4. Furthermore, GPR124 suppresses the activation of P-JNK and P-P38 within the JNK/P38 MAPK pathway. The invasion, apoptosis, and inflammation mediated by GPR124 were partially restored by suppressing the JNK and P38 MAPK pathways in HTR8/SVneo cells. GPR124 plays a crucial role in regulating trophoblast proliferation, invasion, migration, apoptosis, and inflammation via the JNK and P38 MAPK pathways. Furthermore, the effect of GPR124 on trophoblast suggests its involvement in the pathogenesis of early-onset preeclampsia.

Down-regulated Wnt7a and GPR124 in early-onset preeclampsia placentas reduce invasion and migration of trophoblast cells.

OBJECTIVES: Preeclampsia (PE) is a disease specific to pregnancy that causes 9-10 % of maternal deaths. Early-onset PE (<34 weeks' gestation) is the most dangerous category of PE. Wnt7a and GPR124 (G protein-coupled receptor 124) are widely expressed in the human reproductive process. Especially during embryogenesis and tumorigenesis, Wnt7a plays a crucial role. However, few studies have examined the association between Wnt7a-GPR124 and early-onset PE. The aim of this study was to examine the significance of Wnt7a and GPR124 in early-onset PE as well as Wnt7a's role in trophoblast cells. METHODS: Immunohistochemistry (IHC), real-time PCR, and western blotting (WB) were used to investigate Wnt7a and GPR124 expression in normal and early-onset PE placentas. Additionally, FACS, Transwell, and CCK-8 assays were used to diagnose Wnt7a involvement in migration, invasion, and proliferation. RESULTS: In the early-onset PE group, Wnt7a and GPR124 expression was significantly lower than in the normal group, especially in the area of syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). A negative correlation was found between Wnt7a RNA and GPR124 expression (r=-0.42, p<0.01). However, the Wnt7a RNA expression level was positive correlated with PE severity. In further cellular functional experiments, knockdown of Wnt7a inhibits HTR8/SVeno cells invasion and migration but has little effect on proliferation and apoptosis. CONCLUSIONS: Through the Wnt pathway, Wnt7a regulates trophoblast cell invasion and migration, and may contribute to early-onset preeclampsia pathogenesis. A molecular level study of Wnt7a will be needed to find downstream proteins and mechanisms of interaction.

Protective effects of Bifidobacterium bifidum FL-228.1 on dextran sulfate sodium-induced intestinal damage in mice.

PURPOSE: Numerous studies have found that probiotics benefit the intestinal barrier. However, the prophylactic effects of probiotics on the intestinal barrier, i.e., if probiotics exert protective effects in healthy individuals to defend them against harmful elements, have seldomly been reported. The present study aimed to investigate the possible mechanisms of potential strains with the function of preventing intestinal barrier damage. METHODS: This study investigated nine potential probiotic strains using in vitro and in vivo models on their intestinal barrier-protecting properties. Transcriptomic was then employed to decipher the underlying mechanisms of action of the strains. RESULTS: The results showed that the strains, to varying degrees, regulated the ratio of interleukin (IL)-10 and IL-12 in peripheral blood mononuclear cells (PBMCs), increased the transepithelial electrical resistance (TEER) values, and decreased Caco-2 cell monolayers permeability. Correspondingly, the strains showed different prophylactic efficacies in protecting mice from dextran sulfate sodium (DSS)-induced intestinal barrier damage. Remarkably, Bifidobacterium bifidum FL-228.1 (FL-228.1) showed the best prophylactic efficacies in protecting mice from DSS-induced intestinal barrier damage. Further research suggested that FL-228.1 exerted its prophylactic effects by enhancing mucin 2 (Muc2) production and Claudin (Cldn)-4 in the colon. Furthermore, the transcriptomic and protein-protein interactions (PPI) analyses indicated that the inhibition of NLRP3 and the activation of PPARγ and TLR2 could be involved in protecting the intestinal barrier by FL-228.1. CONCLUSION: Bifidobacterium bifidum FL-228.1 may be developed as a promising probiotic for the prevention of intestinal barrier damage via PPARγ/NLRP3/ TLR2 pathways by enhancing Muc2 and Cldn-4.

3-Dimensional electrical impedance spectroscopy for in situ endoluminal mapping of metabolically active plaques.

Electrical impedance spectroscopy (EIS) has been recognized to characterize oxidized low-density lipoprotein (oxLDL) in the metabolically active plaque. However, intravascular deployment of 3-D EIS-derived electrical impedance tomography (EIT) for endoluminal mapping of oxLDL-laden arterial walls remains an unmet clinical challenge. To this end, we designed the 6-point microelectrode arrays that were circumferentially configurated onto the balloon catheter for 15 intravascular EIS permutations. In parallel, we created the metabolically active plaques by performing partial ligation of right carotid artery in Yorkshire mini-pigs (n = 6 males), followed by demonstrating the plaque progression at baseline, 8 weeks, and 16 weeks of high-fat diet via computed tomography (CT) angiogram. Next, we deployed the 3-D EIS sensors to the right and left carotid arteries, and we demonstrated 3-D EIS mapping of metabolically active endolumen in the right but not left carotid arteries as evidenced by the positive E06 immunostaining for oxLDL-laden regions. By considering electrical conductivity (σ) and permittivity (ε) properties of collagen, lipid, and smooth muscle presence in the arterial wall, we further validated the 3-D EIS-derived EIT by reconstructing the histology of right and left carotid arteries for the finite element modeling of the oxLDL-laden endolumen, and we accurately predicted 3-D EIS mapping. Thus, we establish the capability of 3-D EIS-derived EIT to detect oxLDL-laden arterial walls with translational implication to predict metabolically active plaques prone to acute coronary syndromes or stroke.

Comparison of microbiomes in ulcerative and normal mucosa of recurrent aphthous stomatitis (RAS)-affected patients.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is the most common form of oral ulcerative disease, whose cause is still unknown. Researchers have found the association of many factors with the occurrence of RAS, and proposed oral bacterial infection could be a cause for this disease. METHODS: To investigate whether the occurrence of RAS is associated with oral bacterial infection, we performed high throughput sequencing analysis of bacterial samples collected from the normal oral mucosa and aphthous ulcers of 24 patients. RESULTS: Firmicutes, Proteobacteria and Bacteriodetes were the most abundant phyla in the microbiomes analysed. The alpha diversities of the oral mucosa and aphthous ulcer microbiomes were similar, suggesting a similar richness and diversity. The NMDS analysis showed the oral mucosa and aphthous ulcer microbiomes are significantly different. This suggestion is further supported by Anosim, MRPP, and Adonis analyses. More detailed comparison of the two groups of microbiomes suggested that the occurrence of RAS is significantly associated with the increase of Escherichia coli and Alloprevotella, as well as the decrease of Streptococcus. CONCLUSIONS: Considering E. coli is a very common intestinal bacterium, we propose that E. coli colonization could be a cause for RAS, and controlling E. coli colonization could help curing RAS.

The diversity of glycosylation of cellobiohydrolase I from Trichoderma reesei determined with mass spectrometry.

Cellulases are glycosylated enzymes that have wide applications in fields like biofuels. It has been widely accepted that glycosylation of cellulases impact their performance. Trichoderma reesei is the most important cellulase-producer and cellobiohydrolase I (CBHI) is the most important cellulase from T. reesei. Therefore, the glycosylation of T. reesei CBHI has been a focus of research. However, investigations have been focused on N-glycosylation of three of the four potential glycosylation sites, as well as O-glycosylation on the linker region, while a full picture of glycosylation of T. reesei CBHI is still needed. In this work, with extensive mass spectrometric investigations on CBHI from two T. reesei strains grown under three conditions, several new discoveries were made: 1) N45 and N64 are N-glycosylated with high mannose type glycans; 2) the catalytic domain of CBHI is extensively O-glycosylated with hexoses and N-acetylhexosamines; 3) experimental evidence on the mannosylation of carbohydrate binding domain (other than the linker adjacent region) was found. With structural analysis, we found several glycosylation sites (such as T383, S8, and S46) are located at the openings of the substrate-binding tunnel, and potentially involve in the binding of cellulose. These investigations provide a full and comprehensive picture on the glycosylation of CBHI from T. reesei, which benefits the engineering of CBHI by raising potential sites for modification.

Changes in optical characteristics induced by polymer blending in printed colloidal quantum dots microlasers.

On-chip microlasers are desirable to meet the different control requirements and unique demands in different application scenarios. In this work, we obtained the on-chip microlaser by printing pixelated CdSe/ZnS colloidal quantum dots (CQDs), incorporating the quantum dot self-assembly mechanism and the external cavity-free configuration. The spectral purity of the microlaser can be significantly improved by slightly blending polymer into the CQD matrix. The quasitoroid profile was gradually changed to microdisks as the polystyrene (PS) concentration increased from 0 wt.% to 10 wt.%. Specially, when the PS solution varied from 0 wt.% to 1 wt.%, the lasing threshold of 1.4 µJ/mm2 was increased up to 14 µJ/mm2, meanwhile the emission wavelength range showed a 25 nm blue-shift approximately. The easy printing technologies and the low-cost polymer blending method employed in the obtained microlasers will further facilitate the development of printing photonics and electronics, especially in the high-performance microlaser displays and high-precision sensors.

Chemical Profiling and Screening of the Marker Components in the Fruit of Cassia fistula by HPLC and UHPLC/LTQ-Orbitrap MSn with Chemometrics.

Cassia fistula L. which is known as "Golden Shower", is used as an ornamental plant due to its flowers, and fruit parts of this plant have a high medicinal value. There are few reports providing a comprehensive overview of the chemical composition of its fruit or explaining the differences between samples from different sources because of the complexity of its chemical components. The purpose of the present study was to establish a fingerprint evaluation system based on Similarity Analysis (SA), Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA) for the composition identification and quality control of this herb. Twelve samples from Xinjiang and Sichuan provinces in China and India were analyzed by HPLC, and there were fifteen common peaks in the twelve batches. Molecular weight and formula information can be derived from thirty-one peaks by UHPLC/LTQ-Orbitrap MSn, molecular structure information of twenty components was obtained, of which ten compounds were identified by comparison with standard materials. Samples of twelve batches were divided according to their similarity into four groups, which were basically consistent with three different C.fistula fruit-producing areas. Five compounds were finally considered to be chemical markers to determine the quality of this herb. A fingerprints method combined with chemometrics was established to differentiate the origin of the fruit of C. fistula which has the advantages of effectivity and convenience, laying the foundation for the quality evaluation of this herb from different sources.

Effect of Interfacial Molecular Orientation on Power Conversion Efficiency of Perovskite Solar Cells.

A wide variety of charge carrier dynamics, such as transport, separation, and extraction, occur at the interfaces of planar heterojunction solar cells. Such factors can affect the overall device performance. Therefore, understanding the buried interfacial molecular structure in various devices and the correlation between interfacial structure and function has become increasingly important. Current characterization techniques for thin films such as X-ray diffraction, cross section scanning electronmicroscopy, and UV-visible absorption spectroscopy are unable to provide the needed molecular structural information at buried interfaces. In this study, by controlling the structure of the hole transport layer (HTL) in a perovskite solar cell and applying a surface/interface-sensitive nonlinear vibrational spectroscopic technique (sum frequency generation vibrational spectroscopy (SFG)), we successfully probed the molecular structure at the buried interface and correlated its structural characteristics to solar cell performance. Here, an edge-on (normal to the interface) polythiophene (PT) interfacial molecular orientation at the buried perovskite (photoactive layer)/PT (HTL) interface showed more than two times the power conversion efficiency (PCE) of a lying down (tangential) PT interfacial orientation. The difference in interfacial molecular structure was achieved by altering the alkyl side chain length of the PT derivatives, where PT with a shorter alkyl side chain showed an edge-on interfacial orientation with a higher PCE than that of PT with a longer alkyl side chain. With similar band gap alignment and bulk structure within the PT layer, it is believed that the interfacial molecular structural variation (i.e., the orientation difference) of the various PT derivatives is the underlying cause of the difference in perovskite solar cell PCE.

Elevated MMP1 Expression in Carcinoma-Associated Fibroblasts of Breast Cancer Contributes to Tumor Progression and Unfavorable Prognosis.

OBJECTIVE: Previous studies have shown that cancer-associated fibroblasts (CAFs) may play a role in tumor growth and development through paracrine action. Several studies reported upregulated matrix metallopeptidase 1 (MMP1) expression in various cancers. The aim is to investigate the role of elevated MMP1 expression in CAFs of breast cancer. METHODS: A total of 203 cases were used for immunohistochemical analysis based on multiple clinical parameters. Tissues for primary cultures of CAFs were collected from 10 breast cancer patients who underwent complete surgical resection of their tumors. MMP1 expression in primary CAFs was detected using reverse transcription-quantitative PCR and western blotting. MMP1-overexpressing CAFs were established via lentiviral transfection, followed by cell functional assays and animal xenograft experiments. RESULTS: MMP1 expression in CAFs of breast cancer was significantly associated with T stage, triple-negative breast cancer status, neoadjuvant chemotherapy status and Ki67 expression. Additionally, MMP1 expression was closely correlated with unfavorable prognosis based on overall survival and disease-free survival analyses. Elevated MMP1 expression in CAFs was verified to promote cell adhesion, invasion, proliferation abilities and attenuate chemosensitivity to Taxotere treatment. CONCLUSION: The results indicated that MMP1 expression in CAFs may participate in the malignant phenotype and unfavorable prognosis of breast cancer.

Metabolites 13,14-Dihydro-15-keto-PGE2 Participates in Bifidobacterium animalis F1-7 to Alleviate Opioid-Induced Constipation by 5-HT Pathway.

SCOPE: People suffer from constipation caused by many factors, including constipation (Opioid-Induced Constipation, OIC) during analgesic treatment. Microorganisms may be a potent solution to this problem, but the mechanism is still unclear. METHODS AND RESULTS: Based on models in vivo and in vitro, the potential mechanism involving Bifidobacterium animalis F1-7 (B. animalis F1-7), screened in the previous studies, is explored through non-targeted metabonomics, electrophysiological experiment and molecular level docking. The results showed that B. animalis F1-7 effectively alleviates OIC and promotes the expression of chromogranin A (CGA) and 5-hydroxytryptamine (5-HT). The metabolite 13,14-dihydro-15-keto-PGE2 related to B. animalis F1-7 is found, which has a potential improvement effect on OIC at 20 mg kg BW-1 in vivo. At 30 ng mL-1 it effectively stimulates secretion of CGA/5-HT (408.95 ± 1.18 ng mL-1 ) by PC-12 cells and changes the membrane potential potassium ion current without affecting the sodium ion current in vitro. It upregulates the target of free fatty acid receptor-4 protein(FFAR4/ß-actin, 0.81 ± 0.02). CONCLUSION: The results demonstrate that metabolite 13,14-dihydro-15-keto-PGE2 participated in B. animalis F1-7 to alleviate OIC via the 5-HT pathway.

Machine learning-directed electrical impedance tomography to predict metabolically vulnerable plaques.

The characterization of atherosclerotic plaques to predict their vulnerability to rupture remains a diagnostic challenge. Despite existing imaging modalities, none have proven their abilities to identify metabolically active oxidized low-density lipoprotein (oxLDL), a marker of plaque vulnerability. To this end, we developed a machine learning-directed electrochemical impedance spectroscopy (EIS) platform to analyze oxLDL-rich plaques, with immunohistology serving as the ground truth. We fabricated the EIS sensor by affixing a six-point microelectrode configuration onto a silicone balloon catheter and electroplating the surface with platinum black (PtB) to improve the charge transfer efficiency at the electrochemical interface. To demonstrate clinical translation, we deployed the EIS sensor to the coronary arteries of an explanted human heart from a patient undergoing heart transplant and interrogated the atherosclerotic lesions to reconstruct the 3D EIS profiles of oxLDL-rich atherosclerotic plaques in both right coronary and left descending coronary arteries. To establish effective generalization of our methods, we repeated the reconstruction and training process on the common carotid arteries of an unembalmed human cadaver specimen. Our findings indicated that our DenseNet model achieves the most reliable predictions for metabolically vulnerable plaque, yielding an accuracy of 92.59% after 100 epochs of training.

Metagenomic insights into bacterial communities and functional genes associated with texture characteristics of Kazakh artisanal fermented milk Ayran in Xinjiang, China.

The complex microflora of traditional fermented milk is crucial to milk coagulation mainly through acid and protease production; however, it is still unclear which microbes and proteases significantly influence the texture of Ayran, a Kazakh artisanal fermented milk in Xinjiang, China. In this study, fifty-nine samples of Ayran were collected and investigated on texture properties. Finally, six Ayran samples with different texture features were screened out, and the taxonomic and functional attributes of their microbiota were characterized by metagenomics. The results showed that the hardness of the fermented milk in Yili Kazakh Autonomous Prefecture was significantly higher than that in other pasture areas. Lactobacillus and Lactococcus were the core genera that affected the coagulation quality of milk. Furthermore, we found that the proline iminopeptidase pip (EC 3.4.11.5) gene of Lactobacillus helveticus and Limosilactobacillus fermentum and the dipeptidase E pepE (EC 3.4.13.21) gene of Lactococcus lactis were most associated with the coagulation quality of fermented milk. Furthermore, positive correlations were observed among the hardness of fermented milk, the activity of the proteases, and the corresponding functional gene expressions.

Probiotics Alleviate Food Protein Allergy in Mice by Activating TLR4 Signaling Pathway.

SCOPE: Food allergy has become a world recognized public health problem due to its versatility and lack of efficacious methods for its treatment. Probiotics supplement is a potential way to prevent food allergy. METHODS AND RESULTS: In this study, potential strains are screen out by peripheral blood mononuclear cells (PBMCs), and their abilities of alleviating food allergy are examined using a mouse model induced by ovalbumin (OVA). The results show that six strains increase ratio of interferon-γ (IFN-γ)/interleukin (IL)-4 secreted by PBMCs with good abilities in intestinal adhesion and gastrointestinal tolerance. Oral administration of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) attenuates allergic responses in allergy mice, including allergic symptoms, mast cells aggregation and activity, serum OVA-special-immunoglobulins E (OVA-sIgE) production. KV9 and FN3 upregulate the production of IFN-γ/IL-4 in splenocytes, increase the genes and proteins expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (Myd88) and interferon regulatory factor (IRF)-1 in allergic mice spleen, and decrease the IRF-4. CONCLUSION: The study demonstrates that KV9 and FN3 possess anti-allergic activities via activation of TLR4 pathway and modulating the expression of IRF-1 and IRF-4 which leads to T helper type 1 (Th1)/T helper type 2 (Th2) cell immunology balance.

A self-assembled implantable microtubular pacemaker for wireless cardiac electrotherapy.

The current cardiac pacemakers are battery dependent, and the pacing leads are prone to introduce valve damage and infection, plus a complete pacemaker retrieval is needed for battery replacement. Despite the reported wireless bioelectronics to pace the epicardium, open-chest surgery (thoracotomy) is required to implant the device, and the procedure is invasive, requiring prolonged wound healing and health care burden. We hereby demonstrate a fully biocompatible wireless microelectronics with a self-assembled design that can be rolled into a lightweight microtubular pacemaker for intravascular implantation and pacing. The radio frequency was used to transfer energy to the microtubular pacemaker for electrical stimulation. We show that this pacemaker provides effective pacing to restore cardiac contraction from a nonbeating heart and have the capacity to perform overdrive pacing to augment blood circulation in an anesthetized pig model. Thus, this microtubular pacemaker paves the way for the minimally invasive implantation of leadless and battery-free microelectronics.

Bifidobacterium bifidum Ameliorates DSS-Induced Colitis in Mice by Regulating AHR/NRF2/NLRP3 Inflammasome Pathways through Indole-3-lactic Acid Production.

In this study, the effectors and mechanisms of Bifidobacterium bifidum FL-276.1 and B. bifidum FL-228.1 in alleviating dextran sulfate sodium (DSS)-induced colitis were investigated. Both FL-276.1 and FL-228.1 significantly alleviated DSS-induced colitis, whether they were supplemented from the beginning of the experiment (whole course intervention) or after the DSS induction started (partial intervention). Aryl hydrocarbon receptor (AHR) and the nuclear factor erythroid 2-related factor 2 (NRF2) pathways were activated in mice colons, while the NLR family pyrin domain containing 3 (NLRP3) was downregulated under the whole course intervention modes. Indole-3-lactic acid, an AHR ligand produced by FL-276.1 and FL-228.1, could regulate the AHR/NRF2/NLRP3 pathway in Caco-2 monolayers, thus upregulating the tight junction proteins and protecting the integrity of the epithelial barrier. These results are conducive to promoting clinical trials and product development of probiotics for alleviating colitis.

Phage_UniR_LGBM: Phage Virion Proteins Classification with UniRep Features and LightGBM Model.

Phage, the most prevalent creature on the planet, serves a variety of critical roles. Phage's primary role is to facilitate gene-to-gene communication. The phage proteins can be defined as the virion proteins and the nonvirion ones. Nowadays, experimental identification is a difficult process that necessitates a significant amount of laboratory time and expense. Considering such situation, it is critical to design practical calculating techniques and develop well-performance tools. In this work, the Phage_UniR_LGBM has been proposed to classify the virion proteins. In detailed, such model utilizes the UniRep as the feature and the LightGBM algorithm as the classification model. And then, the training data train the model, and the testing data test the model with the cross-validation. The Phage_UniR_LGBM was compared with the several state-of-the-art features and classification algorithms. The performances of the Phage_UniR_LGBM are 88.51% in Sp,89.89% in Sn, 89.18% in Acc, 0.7873 in MCC, and 0.8925 in F1 score.

New Mutations in cls Lead to Daptomycin Resistance in a Clinical Vancomycin- and Daptomycin-Resistant Enterococcus faecium Strain.

Daptomycin (DAP), a last-resort antibiotic for treating Gram-positive bacterial infection, has been widely used in the treatment of vancomycin-resistant enterococci (VRE). Resistance to both daptomycin and vancomycin leads to difficulties in controlling infections of enterococci. A clinical multidrug-resistant Enterococcus faecium EF332 strain that shows resistance to both daptomycin and vancomycin was identified, for which resistance mechanisms were investigated in this work. Whole-genome sequencing and comparative genomic analysis were performed by third-generation PacBio sequencing, showing that E. faecium EF332 contains four plasmids, including a new multidrug-resistant pEF332-2 plasmid. Two vancomycin resistance-conferring gene clusters vanA and vanM were found on this plasmid, making it the second reported vancomycin-resistant plasmid containing both clusters. New mutations in chromosomal genes cls and gdpD that, respectively, encode cardiolipin synthase and glycerophosphoryl diester phosphodiesterase were identified. Their potential roles in leading to daptomycin resistance were further investigated. Through molecular cloning and phenotypic screening, two-dimensional thin-layer chromatography, fluorescence surface charge test, and analysis of cardiolipin distribution patterns, we found that mutations in cls decrease surface negative charges of the cell membrane (CM) and led to redistribution of lipids of CM. Both events contribute to the DAP resistance of E. faecium EF332. Mutation in gdpD leads to changes in CM phospholipid compositions, but cannot confer DAP resistance. Neither mutation could result in changes in cellular septa. Therefore, we conclude that the daptomycin resistance of E. faecium EF332 is conferred by new cls mutations. This work reports the genetic basis for vancomycin and daptomycin resistance of a multidrug-resistant E. faecium strain, with the finding of new mutations of cls that leads to daptomycin resistance.

Room-Temperature Annealing-Free Gold Printing via Anion-Assisted Photochemical Deposition.

Metal patterning via additive manufacturing has been phasing-in to broad applications in many medical, electronics, aerospace, and automotive industries. While previous efforts have produced various promising metal-patterning strategies, their complexity and high cost have limited their practical application in rapid production and prototyping. Herein, a one-step gold printing technique based on anion-assisted photochemical deposition (APD), which can directly print highly conductive gold patterns (1.08 × 107 S m-1 ) under ambient conditions without post-annealing treatment, is introduced. Uniquely, the APD uses specific ion effects with projection lithography to pattern Au nanoparticles and simultaneously sinter them into tunable porous gold structures. The significant influence of kosmotropic or chaotropic anions in the precursor ink on tuning the morphologies and conductivities of the printed patterns by employing a series of different ions, including Cl- ions, in the printing process is presented. Additionally, the resistance stabilities and the electrochemical properties of the APD-printed gold patterns are carefully investigated. The high conductivity and excellent conformability of the printed Au electrodes are demonstrated with reliable performance in electrophysiological signal delivery and acquisition for biomedical applications. This work exploits the potential of photochemical-deposition-based metal patterning in flexible electronic manufacturing.

Bifidobacterium bifidum relieved DSS-induced colitis in mice potentially by activating the aryl hydrocarbon receptor.

Inflammatory bowel disease (IBD) characterized by relapsed intestinal inflammation and barrier function disruption is still a great therapeutic challenge. This study aimed to screen probiotics that have the potential to help alleviate IBD and further elucidate their mechanism of action. Caco-2 cell differentiated monolayers and RAW264.7 cells stimulated by lipopolysaccharide (LPS) were used for probiotic screening in vitro, and then the efficacies of the obtained six bacterial strains were evaluated in mice with dextran sulfate sodium (DSS)-induced colitis. The results showed that all of the strains at varying degrees could increase the transepithelial electrical resistance (TEER) value, decrease the influx of FITC-dextran in Caco-2 cell monolayers and attenuate the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-stimulated RAW264.7 cells. In vivo experiments indicated that Bifidobacterium bifidum FL-276.1 (FL-276.1) and Bifidobacterium bifidum FL-228.1 (FL-228.1) showed the best efficacies to ameliorate body weight loss, colon shortening, and intestinal barrier disruption. Accordingly, in FL-276.1 and FL-228.1 groups, the genes of zonula occludens-1 (ZO-1), claudin-4, occludin and mucin 2 (Muc2) in mouse colonic tissues were significantly upregulated, while TNF-α, IL-1ß and IL-6 were downregulated. Further results showed that strains FL-276.1 and FL-228.1 could activate the aryl hydrocarbon receptor (AhR) in the intestine. Our study showed that the two Bifidobacterium bifidum strains, FL-276.1 and FL-228.1, ameliorated DSS-induced colitis by enhancing the intestinal barrier and anti-inflammation potentially via the AhR pathway.