Quercetin, a bioflavonoid derived from vegetables and fruits, exerts anti-inflammatory effects in various diseases. Our previous study revealed that quercetin could suppress the expression of matrix metalloprotease-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) to achieve anti-inflammatory effects in tumor necrosis factor-α (TNF-α)-stimulated human retinal pigment epithelial (ARPE-19) cells. The present study explored whether quercetin can inhibit the interleukin-1β (IL-1β)-induced production of inflammatory cytokines and chemokines in ARPE-19 cells. Prior to stimulation by IL-1β, ARPE-19 cells were pretreated with quercetin at various concentrations (2.5-20 µM). The results showed that quercetin could dose-dependently decrease the mRNA and protein levels of ICAM-1, IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1). It also attenuated the adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. We also demonstrated that quercetin inhibited signaling pathways related to the inflammatory process, including phosphorylation of mitogen-activated protein kinases (MAPKs), inhibitor of nuclear factor κ-B kinase (IKK)α/β, c-Jun, cAMP response element-binding protein (CREB), activating transcription factor 2 (ATF2) and nuclear factor (NF)-κB p65, and blocked the translocation of NF-κB p65 into the nucleus. Furthermore, MAPK inhibitors including an extracellular signal-regulated kinase (ERK) 1/2 inhibitor (U0126), a p38 inhibitor (SB202190) and a c-Jun N-terminal kinase (JNK) inhibitor (SP600125) decreased the expression of soluble ICAM-1 (sICAM-1), but not ICAM-1. U0126 and SB202190 could inhibit the expression of IL-6, IL-8 and MCP-1, but SP600125 could not. An NF-κB inhibitor (Bay 11-7082) also reduced the expression of ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1. Taken together, these results provide evidence that quercetin protects ARPE-19 cells from the IL-1β-stimulated increase in ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways to ameliorate the inflammatory response.

Inorganic phosphate-solubilizing bacteria (IPB) are an important component of microbial populations in lake sediments. The phosphate that they decompose and release becomes an important source of phosphorus for eutrophic algae. The IPB strains were screened and isolated from the sediments of Sancha Lake using National Botanical Research Institute's phosphate (NBRIP) plates. Their taxonomy was further determined by the 16S rDNA technique. The tricalcium phosphate-solubilizing ability of obtained IPB strains was evaluated using NBRIP- bromophenol blue (BPB) plates and Pikovskaya (PVK) liquid medium. Then, the ability of IPB strains to release phosphorus from the sediments were investigated by mimicking the lake environment. In this study, a total of 43 IPB strains were screened and isolated from the sediments of Sancha Lake, belonging to three phyla, eight families, and ten genera. Among them, two potentially new strains, SWSI1728 and SWSI1734, belonged to genus Bacillus, and a potentially new strain, SWSI1719, belonged to family Micromonosporaceae. Overall, the IBP strains were highly diverse and Bacillus and Paenibacillus were the dominant genera. In the tricalcium phosphate-solubilizing experiment, only 30 of the 43 IPB strains exhibited clear halo zones on plates, while in the liquid culture experiment, all strains were able to dissolve tricalcium phosphate. The phosphate-solubilizing abilities of the strains varied significantly, and the strain SWSI1725 of the Bacillus genus showed the strongest ability with a phosphate-solubilizing content of 103.57 mg/L. The sterilized systems demonstrated significantly elevated phosphorus hydrochloride (HCl-P) decomposition and release from the sediments after the inoculation of IPB strains, whereas no significant effect was demonstrated on the phosphonium hydroxide (NaOH-P). Thus, the IPB strains in the sediments of Sancha Lake possessed rich diversity and the ability to release phosphorus in sediments.

Biodegradable materials made from cereal arabinoxylan could provide an alternative source of packaging to replace current nonbiodegradable plastics. The main purpose of this research was to determine how arabinoxylan (AX) films made from wheat bran (WB) AX, maize bran (MB) AX, and dried distillers grain (DDG) AX made with either glycerol or sorbitol at varying levels (10, 25 or 50%) interacts with soil and water. The biodegradability of all films ranged from 49.4% biodegradable (DDG AX with 10% sorbitol) to 67.7% biodegradable (MB AX with 50% glycerol). In addition, the MB AX films with 25% sorbitol had the lowest moisture content at 9.7%, the MB AX films with 10% glycerol had the highest water solubility at 95.6%, and the MB AX films with 50% glycerol had the highest water vapor transmission rate (WVTR) at 90.8 g h-1 m-2. Despite these extreme trends in the MB AX films, the WB AX films were the least hydrophilic on average while the DDG AX films were the most hydrophilic on average. The 18 materials developed in this research demonstrate varying affinities for water and biodegradation. These materials can be used for many different packaging materials, based on their unique characteristics.

Vitamin C (ascorbate) is important for neutrophil function and immune health. Studies showing improved immune function have primarily used cells from scorbutic animals or from individuals with infectious conditions or immune cell disorders. Few studies have focused on the requirements of neutrophils from healthy adults. Therefore, we have investigated the role of vitamin C, at concentrations equivalent to those obtained in plasma from oral intakes (i.e., 50-200 µmol/L), on key functions of neutrophils isolated from healthy individuals. Cells were either pre-loaded with dehydroascorbic acid, which is rapidly reduced intracellularly to ascorbate, or the cells were activated in the presence of extracellular ascorbate. We measured the effects of enhanced ascorbate uptake on the essential functions of chemotaxis, oxidant production, programmed cell death and neutrophil extracellular trap (NET) formation. We found that neutrophils isolated from healthy individuals already had replete ascorbate status (0.35 nmol/106 cells), therefore they did not uptake additional ascorbate. However, they readily took up dehydroascorbic acid, thus significantly increasing their intracellular ascorbate concentrations, although this was found to have no additional effect on superoxide production or chemotaxis. Interestingly, extracellular ascorbate appeared to enhance directional mobilityin the presence of the chemoattractant formyl-methionyl-leucyl-phenylalanine (fMLP). Stimulation of the cells in the presence of ascorbate significantly increased intracellular ascorbate concentrations and, although this exhibited a non-significant increase in phosphatidylserine exposure, NET formation was significantly attenuated. Our findings demonstrate the ability of neutrophils to regulate their uptake of ascorbate from the plasma of healthy humans to maintain an optimal level within the cell for proper functioning. Higher oral intakes, however, may help reduce tissue damage and inflammatory pathologies associated with NET formation.

Prunus spp. is one of the most recalcitrant fruit tree species in terms of in vitro regeneration and transformation, mostly when mature tissues are used as explants. The present study describes the in vitro regeneration via indirect organogenesis, and Agrobacterium tumefaciens-mediated transformation of the peach rootstock Hansen 536 (Prunus persica × Prunus amygdalus) through the use of meristematic bulks (MBs) as starting explants. Efficient adventitious shoot regeneration was obtained when Hansen 536 MBs were cultured on an optimized medium consisting of modified McCown Woody Plant medium (WPM) enriched with 4.4 M 6-Benzyladenine (BA), 0.1 M 1-Naphthaleneacetic acid (NAA) and 6.0 g L-1 plant agar S1000 (B&V). MB slices were used later as starting explants for Agrobacterium-mediated transformation to introduce an RNAi construct "ihp35S-PPV194" against PPV virus. Transgenic events were identified by both green fluorescent protein (GFP) screening and kanamycin selection at different concentrations (0, 17 or 42 M). GFP-fluorescent proliferating callus lines were selected and confirmed to stably express the ihp35S-PPV194::eGFP gene construct by molecular analysis. Although shoot regeneration from these transgenic calli has not been obtained yet, this represents one of the few examples of successful attempts in peach genetic transformation from somatic tissues, and also serves as a useful in vitro system for future gene functional analysis in peach.

The effects of silicon (Si) on root development, mineral content, and expression of Si transporter genes in Euphorbia pulcherrima Willd. 'Flame', 'Mable Bell', 'Green Star', 'Pink Bell', and 'Peach Bowl' cultivars were investigated in this study. Stem cuttings in a propagation bench were drenched regularly with a solution containing either 0 (control) or 50 ppm of silicon (Si treatment) from potassium silicate (K2SiO3), with a 25 °C mean air temperature and 80% relative humidity (RH) under 70% shading. The results showed that the 'Flame' treated with Si had a significantly higher survival ratio as compared with that of the control (P ≤ 0.05) and that the Si treatment improved number of roots, length of longest root, fresh root weight, and dry root weight in all cultivars except 'Mable Bell'. Supplementary Si increased the content of magnesium (Mg) and decreased the content of boron (B) and zinc (Zn) in the roots. The content of sulfur (S) in the shoots was increased by supplementary Si. The relative expression of Lsi1 and Lsi2 was higher in 'Peach Bowl', while it was lower in 'Mable Bell' and 'Green Star', which may be caused by the differing accumulation of Si in the shoot. Overall, supplementary Si had beneficial effects during cutting propagation of poinsettia cultivars, although these effects were cultivar-dependent.

It is quite intriguing that bovines were largely unaffected by influenza A, even though most of the domesticated and wild animals/birds at the human-animal interface succumbed to infection over the past few decades. Influenza A occurs on a very infrequent basis in bovine species and hence bovines were not considered to be susceptible hosts for influenza until the emergence of influenza D. This review describes a multifaceted chronological review of literature on influenza in cattle which comprises mainly of the natural infections/outbreaks, experimental studies, and pathological and seroepidemiological aspects of influenza A that have occurred in the past. The review also sheds light on the bovine models used in vitro and in vivo for influenza-related studies over recent years. Despite a few natural cases in the mid-twentieth century and seroprevalence of human, swine, and avian influenza viruses in bovines, the evolution and host adaptation of influenza A virus (IAV) in this species suffered a serious hindrance until the novel influenza D virus (IDV) emerged recently in cattle across the world. Supposedly, certain bovine host factors, particularly some serum components and secretory proteins, were reported to have anti-influenza properties, which could be an attributing factor for the resilient nature of bovines to IAV. Further studies are needed to identify the host-specific factors contributing to the differential pathogenetic mechanisms and disease progression of IAV in bovines compared to other susceptible mammalian hosts.

Background Orexin and its receptors are critical regulating sympathetic vasomotor tone under physiological and pathophysiological conditions. Orexin receptor 1 ( OXR 1) is upregulated in the paraventricular nucleus ( PVN ) in the hypothalamus and contributes to increased sympathetic outflow in obese Zucker rats ( OZR s). We hypothesized that silencing OXR 1 expression in the PVN decreases heightened blood pressure and elevated sympathetic outflow in OZR s. Methods and Results An adeno-associated virus ( AAV ) vector containing a short hairpin RNA (sh RNA ) targeting rat OXR 1 was designed to silence OXR 1 expression in the PVN . The AAV - OXR 1-sh RNA or scrambled sh RNA was injected into the PVN in OZR s. The arterial blood pressure in free-moving OZR s was continuously monitored by using a telemetry approach. The firing activity of spinally projecting PVN neurons in rat brain slices was recorded 3 to 4 weeks after injection of viral vectors. The free-moving OZR s treated with AAV - OXR 1-sh RNA had markedly lower OXR 1 expression and lower mean arterial blood pressure, heart rate, and ratio of low- to high-frequency components of heart rate variability compared with OZR s treated with scrambled sh RNA . Furthermore, AAV - OXR 1-sh RNA treatment markedly reduced renal sympathetic nerve activity and attenuated sympathoexcitatory response induced by microinjection of orexin A into the PVN . In addition, treatment with AAV - OXR 1-sh RNA substantially decreased the basal firing activity of spinally projecting PVN neurons in OZR s and attenuated the excitatory effect of orexin A on the firing activity of these neurons. Conclusions These data suggest that chronic downregulation of OXR 1 expression in the PVN reduces sympathetic vasomotor tone in obesity-related hypertension.

The combination of pexidartinib and binimetinib was safe and tolerable and demonstrated encouraging signs of efficacy in two patients with advanced gastrointestinal stromal tumor (GIST) refractory to tyrosine kinase inhibitors (TKIs).Molecular profiling of GISTs at diagnosis and upon progression may provide insight into the mechanisms of response or resistance to targeted therapies.Additional trials are needed to further explore combined KIT and MEK inhibition in treatment-naïve and TKI-refractory patients with advanced GIST.

We determined the effect on gene transcription of laser-mediated, long-wavelength UV-irradiation of Saccharomyces cerevisiae by RNAseq analysis at times T15, T30, and T60 min after recovery in growth medium. Laser-irradiated cells were viable, and the transcriptional response was transient, with over 400 genes differentially expressed at T15 or T30, returning to basal level transcription by T60. Identification of transcripts exhibiting enhanced differential expression that were unique to UV laser-irradiation were identified by imposing a stringent significance cut-off (P < 0.05, log2 difference >2) then filtering out genes known as environmental stress response (ESR) genes. Using these rigorous criteria, 56 genes were differentially expressed at T15; at T30 differential expression was observed for 57 genes, some of which persisted from T15. Among the highly up-regulated genes were those supporting amino acid metabolic processes sulfur amino acids, methionine, aspartate, cysteine, serine), sulfur regulation (hydrogen sulfite metabolic processes, sulfate assimilation, sulfate reduction), proteasome components, amino acid transporters, and the iron regulon. At T30, the expression profile shifted to expression of transcripts related to catabolic processes (oxidoreductase activity, peptidase activity). Transcripts common to both T15 and T30 suggested an up-regulation of catabolic events, including UV damage response genes, and protein catabolism via proteasome and peptidase activity. Specific genes encoding tRNAs were among the down-regulated genes adding to the suggestion that control of protein biosynthesis was a major response to long-wave UV laser irradiation. These transcriptional responses highlight the remarkable ability of the yeast cell to respond to a UV-induced environmental insult.

Filamentous fungi are remarkable producers of enzymes dedicated to the degradation of sugar polymers found in the plant cell wall. Here, we integrated transcriptomic data to identify novel transcription factors (TFs) related to the control of gene expression of lignocellulosic hydrolases in Trichoderma reesei and Aspergillus nidulans Using various sets of differentially expressed genes, we identified some putative cis-regulatory elements that were related to known binding sites for Saccharomyces cerevisiae TFs. Comparative genomics allowed the identification of six transcriptional factors in filamentous fungi that have corresponding S. cerevisiae homologs. Additionally, a knockout strain of T. reesei lacking one of these TFs (S. cerevisiae AZF1 homolog) displayed strong reductions in the levels of expression of several cellulase-encoding genes in response to both Avicel and sugarcane bagasse, revealing a new player in the complex regulatory network operating in filamentous fungi during plant biomass degradation. Finally, RNA sequencing (RNA-seq) analysis showed the scope of the AZF1 homologue in regulating a number of processes in T. reesei, and chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) provided evidence for the direct interaction of this TF in the promoter regions of cel7a, cel45a, and swo Therefore, we identified here a novel TF which plays a positive effect in the expression of cellulase-encoding genes in T. reesei IMPORTANCE In this work, we used a systems biology approach to map new regulatory interactions in Trichoderma reesei controlling the expression of genes encoding cellulase and hemicellulase. By integrating transcriptomics related to complex biomass degradation, we were able to identify a novel transcriptional regulator which is able to activate the expression of these genes in response to two different cellulose sources. In vivo experimental validation confirmed the role of this new regulator in several other processes related to carbon source utilization and nutrient transport. Therefore, this work revealed novel forms of regulatory interaction in this model system for plant biomass deconstruction and also represented a new approach that could be easy applied to other organisms.

The properties and physiological function of pore-forming α-subunits of large conductance calcium- and voltage-activated potassium (BK) channels are potently modified by their functional coupling with regulatory subunits in many tissues. However, mechanisms that might control functional coupling are very poorly understood. Here we show that S-acylation, a dynamic post-translational lipid modification of proteins, of the intracellular S0-S1 loop of the BK channel pore-forming α-subunit controls functional coupling to regulatory β1-subunits. In HEK293 cells, α-subunits that cannot be S-acylated show attenuated cell surface expression, but expression was restored by co-expression with the β1-subunit. However, we also found that nonacylation of the S0-S1 loop reduces functional coupling between α- and β1-subunits by attenuating the β1-subunit-induced left shift in the voltage for half-maximal activation. In mouse vascular smooth muscle cells expressing both α- and β1-subunits, BK channel α-subunits were endogenously S-acylated. We further noted that S-acylation is significantly reduced in mice with a genetic deletion of the palmitoyl acyltransferase (Zdhhc23) that controls S-acylation of the S0-S1 loop. Genetic deletion of Zdhhc23 or broad-spectrum pharmacological inhibition of S-acylation attenuated endogenous BK channel currents independently of changes in cell surface expression of the α-subunit. We conclude that functional effects of S-acylation on BK channels depend on the presence of β1-subunits. In the absence of β1-subunits, S-acylation promotes cell surface expression, whereas in its presence, S-acylation controls functional coupling. S-Acylation thus provides a mechanism that dynamically regulates the functional coupling with β1-subunits, enabling an additional level of conditional, cell-specific control of ion-channel physiology.

Fungal and bacterial populations coexist in the oral cavity, frequently forming mixed-species biofilms that complicate treatment against polymicrobial infections. However, despite relevance to oral health, the bidirectional interactions between these microbial populations are poorly understood. In this study, we aimed to elucidate the mechanisms underlying the interactions between the fungal species Candida albicans and the bacterial species Streptococcus gordonii as they coexist in mixed-species biofilms. Specifically, the interactions of different C. albicans mutant strains deficient in filamentation (efg1Δ/Δ and brg1Δ/Δ), adhesive interactions (als3Δ/Δ and bcr1Δ/Δ), and production of matrix exopolymeric substances (EPS) (kre5Δ/Δ, mnn9Δ/Δ, rlm1Δ/Δ, and zap1Δ/Δ) were evaluated with S. gordonii under different conditions mimicking the environment in the oral cavity. Interestingly, our results revealed that growth of the biofilm-deficient C. albicansals3Δ/Δ and bcr1Δ/Δ mutant strains in synthetic saliva or with S. gordonii restored their biofilm-forming ability. Moreover, challenging previous observations indicating an important role of morphogenetic conversions in the interactions between these two species, our results indicated a highly synergistic interaction between S. gordonii and the C. albicans filamentation-deficient efg1Δ/Δ and brg1Δ/Δ deletion mutants, which was particularly noticeable when the mixed biofilms were grown in synthetic saliva. Importantly, dual-species biofilms were found to exhibit increase in antimicrobial resistance, indicating that components of the fungal exopolymeric material confer protection to streptococcal cells against antibacterial treatment. Collectively, these findings unravel a high degree of complexity in the interactions between C. albicans and S. gordonii in mixed-species biofilms, which may impact homeostasis in the oral cavity.IMPORTANCE Microbial communities have a great impact in health and disease. C. albicans interacts with multiple microorganisms in the oral cavity, frequently forming polymicrobial biofilms. We report on the synergistic interactions between C. albicans and the Gram-positive bacterium S. gordonii, for which we have examined the different contributions of adhesive interactions, filamentation, and the extracellular matrix to the formation of dual-species biofilms. Our results demonstrate that growth in the presence of the bacterium can restore the biofilm-forming ability of different C. albicans mutant strains with defects in adhesion and filamentation. The mixed-species biofilms also show high levels of resistance to antibacterial and antifungal antibiotics, and our results indicate that the fungal biofilm matrix protects bacterial cells within these mixed-species biofilms. Our observations add to a growing body of evidence indicating a high level of complexity in the reciprocal interactions and consortial behavior of fungal/bacterial biofilms.

Bacterial surface attachment is mediated by filamentous appendages called pili. Here, we describe the role of Tad pili during surface colonization of Caulobacter crescentus Using an optical trap and microfluidic controlled flow conditions to mimic natural environments, we demonstrated that Tad pili undergo repeated dynamic cycles of extension and retraction. Within seconds after establishing surface contact, pilus retraction reorients cells into an upright position, promoting walking-like movements against the medium flow. Pilus-mediated positioning of the flagellate pole close to the surface facilitates motor-mediated mechanical sensing and promotes anchoring of the holdfast, an adhesive substance that affords long-term attachment. We present evidence that the second messenger c-di-GMP regulates pilus dynamics during surface encounter in distinct ways, promoting increased activity at intermediate levels and retraction of pili at peak concentrations. We propose a model in which flagellum and Tad pili functionally interact and together impose a ratchet-like mechanism that progressively drives C. crescentus cells toward permanent surface attachment.IMPORTANCE Bacteria are able to colonize surfaces in environmental, industrial, and medical settings, where they form resilient communities called biofilms. In order to control bacterial surface colonization, microbiologists need to gain a detailed understanding of the processes that bacteria use to live at the liquid-surface interface and that allow them to adhere to and move on surfaces and eventually grow and persist on solid media. To facilitate these processes, bacteria are equipped with adhesive structures such as flagella and pili and with matrix components such as exopolysaccharides. How these cellular organelles are coordinated to optimize surface processes is currently subject to intense investigations. Here we used the model organism Caulobacter crescentus to demonstrate that polar pili are highly dynamic structures that are functionally interconnected with the flagellar motor to mediate surface sensing, thereby enforcing rapid and permanent surface attachment. These studies provide an entry point for an in-depth molecular analysis of bacterial surface colonization.

The level of expression of long non-coding RNA (LncRNA) X-inactive specific transcript (XIST) is up-regulated in pancreatic cancer (PC). However, the role of XIST in PC and the underlying mechanism are still unknown. The present study aimed to elucidate how XIST participates in PC and its potential target, miR-141-3p. We detected the XIST expression in PC tissues and cells by qRT-PCR. Cell proliferation was measured using a CCK8 kit, and the migration and invasion of cells was measured by Transwell assay. Silencing XIST and miR-141-3p was performed with transfection by Lipofectamine kit. Binding assay was conducted by luciferase reporter assay. Protein expression was examined by Western blot. These results indicate that (i) XIST is highly expressed in tumor tissues while miR-141-3p is down-regulated. (ii) Silencing XIST inhibits the pancreatic cell proliferation, migration and invasion. (iii) MiR-141-3p inhibitor alleviates the inhibitory effect by siXIST in PC cell lines. (iv) MiR-141-3p directly interacts with XIST and also negatively regulates transforming growth factor-β 2 (TGF-β2) expression. (v) Overexpression of XIST attenuates the inhibition of TGF-β2 expression by miR-141-3p. The conclusion, is that XIST could promote proliferation, migration and invasion of PC cells via miR-141-5p/TGF-β2 axis.

Objective: This research aimed to explore the function of protease activated receptor 2 (PAR-2) in oral squamous cell carcinoma (OSCC) development and progression, as well as underlying molecular mechanism.Methods: Tissue samples were collected from 115 OSCC patients. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of PAR-2 mRNA in OSCC tissues and cells. MTT and Transwell assays were used to detect the proliferation, migration, and invasion of OSCC cells, respectively. Western blot was performed to determine protein expression.Results: The expression of PAR-2 mRNA was up-regulated in OSCC tissue and cells (P<0.01), and its mRNA level was obviously correlated to tumor differentiation and TNM stage in OSCC (P<0.05 for both). The activation of PAR-2 with PAR-2AP (PAR-2 agonist) significantly promoted the proliferation, migration, and invasion of OSCC cells, while its knockout could inhibit malignant behaviors of OSCC cells (P<0.05). Excessive activation of PAR-2 enhanced phosphorylation level of PI3K, AKT, and mTOR revealing the activation of PI3K/AKT pathway. Moreover, LY294002, the inhibitor of PI3K/AKT pathway, could reverse oncogenic action caused by PAR-2 activation.Conclusion:PAR-2 can promote OSCC growth and progression via activating PI3K/AKT signaling pathway.

There is growing evidence for GABA and glutamate-glutamine dysfunction in the pathogenesis of mood and anxiety disorders. It is important to study this pathology in the early phases of the illness in order to develop new approaches to secondary prevention. New magnetic resonance spectroscopy (MRS) measures allow determining glutamine, the principal metabolite of synaptic glutamate that is directly related to glutamate levels in the synaptic cleft, as well as glutamate and GABA. In contrast to previous investigations, this study used community-based recruitment methods and a combined categorical and dimensional approach to psychopathology. In the study protocol, neuroticism was defined as the primary outcome. Neuroticism shares a large proportion of its genetic variance with mood and anxiety disorders. We examined young adult participants recruited from the general population in a cross-sectional study using 3-T 1H-MRS with one voxel in the left dorsolateral prefrontal cortex (DLPFC). The total sample of N = 110 (61 females) included 18 individuals suffering from MDD and 19 individuals suffering from DSM-IV anxiety disorders. We found that glutamine and glutamine-to-glutamate ratio were correlated with neuroticism in the whole sample (r = 0.263, p = 0.005, and n = 110; respectively, r = 0.252, p = 0.008, and n = 110), even when controlling for depression and anxiety disorder diagnoses (for glutamine: beta = 0.220, p = 0.047, and n = 110). Glutamate and GABA were not significantly correlated with neuroticism (r = 0.087, p = 0.365, and n = 110; r = -0.044, p = 0.645, and n = 110). Lack of self-confidence and emotional instability were the clinical correlates of glutamate-glutamine dysfunction. In conclusion, this study suggests that prefrontal glutamine is increased in early phases of mood and anxiety disorders. Further understanding of glutamate-glutamine dysfunction in stress-related disorders may lead to new therapeutic strategies to prevent and treat these disorders.

Flexible and skin-attachable vibration sensors have been studied for use as wearable voice-recognition electronics. However, the development of vibration sensors to recognize the human voice accurately with a flat frequency response, a high sensitivity, and a flexible/conformable form factor has proved a major challenge. Here, we present an ultrathin, conformable, and vibration-responsive electronic skin that detects skin acceleration, which is highly and linearly correlated with voice pressure. This device consists of a crosslinked ultrathin polymer film and a hole-patterned diaphragm structure, and senses voices quantitatively with an outstanding sensitivity of 5.5 V Pa-1 over the voice frequency range. Moreover, this ultrathin device (<5 μm) exhibits superior skin conformity, which enables exact voice recognition because it eliminates vibrational distortion on rough and curved skin surfaces. Our device is suitable for several promising voice-recognition applications, such as security authentication, remote control systems and vocal healthcare.

Wearable and skin electronics benefit from mechanically soft and stretchable materials to conform to curved and dynamic surfaces, thereby enabling seamless integration with the human body. However, such materials are challenging to process using traditional microelectronics techniques. Here, stretchable transistor arrays are patterned exclusively from solution by inkjet printing of polymers and carbon nanotubes. The additive, non-contact and maskless nature of inkjet printing provides a simple, inexpensive and scalable route for stacking and patterning these chemically-sensitive materials over large areas. The transistors, which are stable at ambient conditions, display mobilities as high as 30 cm2 V-1 s-1 and currents per channel width of 0.2 mA cm-1 at operation voltages as low as 1 V, owing to the ionic character of their printed gate dielectric. Furthermore, these transistors with double-layer capacitive dielectric can mimic the synaptic behavior of neurons, making them interesting for conformal brain-machine interfaces and other wearable bioelectronics.

Although chimeric antigen receptor (CAR) T cell therapies have demonstrated considerable success in treating hematologic malignancies, they have simultaneously been plagued by a cytokine release syndrome (CRS) that can harm or even kill the cancer patient. We describe a CAR T cell strategy in which CAR T cell activation and cancer cell killing can be sensitively regulated by adjusting the dose of a low molecular weight adapter that must bridge between the CAR T cell and cancer cell to initiate tumor eradication. By controlling the concentration and dosing schedule of adapter administration, we document two methods that can rapidly terminate (<3 h) a pre-existing CRS-like toxicity and two unrelated methods that can pre-emptively prevent a CRS-like toxicity that would have otherwise occurred. Because all four methods concurrently enhance CAR T cell potency, we conclude that proper use of bispecific adapters could potentially avoid a life-threatening CRS while enhancing CAR T cell tumoricidal activity.