AuNi bimetallic aerogel with ultra-high stability applied in smart and portable biosensing.

Glucose detection is of significant importance in providing information to the human health management. However, conventional enzymatic glucose sensors suffer from a limited long-term stability due to the losing activity of the enzymes. In this work, the AuNi bimetallic aerogel with a well-defined nanowire network is synthesized and applied as the sensing nanomaterial in the non-enzymatic glucose detection. The three-dimensional (3D) hierarchical porous structure of the AuNi bimetallic aerogel ensures the high sensitivity of the sensor (40.34 µA mM-1 cm-2). Theoretical investigation unveiled the mechanism of the boosting electrocatalytic activity of the AuNi bimetallic aerogel toward glucose. A better adhesion between the sensing nanomaterial and the screen-printing electrodes (SPEs) is obtained after the introduction of Ni. On the basis of a wide linearity in the range of 0.1-5 mM, an excellent selectivity, an outstanding long-term stability (90 days) as well as the help of the signal processing circuit and an M5stack development board, the as-prepared glucose sensor successfully realizes remote monitoring of the glucose concentration. We speculate that this work is favorable to motivating the technological innovations of the non-enzymatic glucose sensors and intelligent sensing devices.

Whole-protein enteral nutrition formula supplementation reduces Escherichia and improves intestinal barrier function in HIV-infected immunological nonresponders.

People living with human immunodeficiency virus (PLWH) have persistent malnutrition, intestinal barrier dysfunction, and gut microbial imbalance. The interplay between gut microbiota and nutrients is involved in the immune reconstitution of PLWH. To evaluate the effects of whole-protein enteral nutrition formula supplementation on T-cell levels, intestinal barrier function, nutritional status, and gut microbiota composition in human immunodeficiency virus (HIV)-infected immunological nonresponders (INRs) who failed to normalize CD4+ T-cell counts, with a number <350 cells/µL, a pilot study was carried out in 13 HIV-infected INRs undergoing antiretroviral therapy who received a 3-month phase supplementation of 200 mL/200 kcal/45 g whole-protein enteral nutrition formula once daily. Our primary endpoint was increased CD4+ T-cell counts. Secondary outcome parameters were changes in intestinal barrier function, nutritional status, and gut microbiota composition. We showed that CD4+ T-cell counts of HIV-infected INRs increased significantly after the 3-month supplementation. Dietary supplementation for 3 months improved the intestinal barrier function and nutritional status of HIV-infected INRs. Furthermore, the enteral nutrition formula significantly decreased the relative abundance of Escherichia at the genus level and increased the alpha diversity of gut microbiota in HIV-infected INRs. The findings demonstrated that the whole-protein enteral nutrition formula aids in reducing Escherichia and improving intestinal barrier function in HIV-infected INRs. This study provides insight into the role of nutrients in the improvement of immune reconstitution in HIV-infected INRs. This study is registered in the Chinese Clinical Trial Registry (Document No. ChiCTR2000037839; http://www.chictr.org.cn/index.aspx).

Portable visual and electrochemical detection of hydrogen peroxide release from living cells based on dual-functional Pt-Ni hydrogels.

It is important to monitor the intra-/extracellular concentration of hydrogen peroxide (H2O2) in biological processes. However, miniaturized devices that enable portable and accurate H2O2 measurement are still in their infancy because of the difficulty of developing facile sensing strategies and highly integrated sensing devices. In this work, portable H2O2 sensors based on Pt-Ni hydrogels with excellent peroxidase-like and electrocatalytic activities are demonstrated. Thus, simple and sensitive H2O2 sensing is achieved through both colorimetric and electrochemical strategies. The as-fabricated H2O2 sensing chips exhibit favorable performance, with low detection limits (0.030 µM & 0.15 µM), wide linearity ranges (0.10 µM-10.0 mM & 0.50 µM-5.0 mM), outstanding long-term stability (up to 60 days), and excellent selectivity. With the aid of an M5stack development board, portable visual and electrochemical H2O2 sensors are successfully constructed without complicated and expensive equipment or professional operators. When applied to the detection of H2O2 released from HeLa cells, the results obtained by the developed sensors are in good agreement with those from an ultraviolet‒visible spectrophotometer (UV‒vis) (1.97 µM vs. 2.08 µM) and electrochemical station (1.77 µM vs. 1.84 µM).

Nonenzymatic Sweat Wearable Uric Acid Sensor Based on N-Doped Reduced Graphene Oxide/Au Dual Aerogels.

Sweat wearable sensors enable noninvasive and real-time metabolite monitoring in human health management but lack accuracy and wearable applicability. The rational design of sensing electrode materials will be critical yet challenging. Herein, we report a dual aerogel-based nonenzymatic wearable sensor for the sensitive and selective detection of uric acid (UA) in human sweat. The three-dimensional porous dual-structural aerogels composed of Au nanowires and N-doped graphene nanosheets (noted as N-rGO/Au DAs) provide a large active surface, abundant access to the target, rapid electron transfer pathways, and a high intrinsic activity. Thus, a direct UA electro-oxidation is demonstrated at the N-rGO/Au DAs with a much higher activity than those at the individual gels (i.e., Au and N-rGO). Moreover, the resulting sensing chip displays high performance with a good anti-interfering ability, long-term stability, and excellent flexibility toward the UA detection. With the assistance of a wireless circuit, a wearable sensor is successfully applied in the real-time UA monitoring on human skin. The obtained result is comparable to that evaluated by high-performance liquid chromatography. This dual aerogel-based nonenzymatic biosensing platform not only holds considerable promise for the reliable sweat metabolite monitoring but also opens an avenue for metal-based aerogels as flexible electrodes in wearable sensing.

Naïve B cells with low differentiation improve the immune reconstitution of HIV-infected patients.

Incomplete immune reconstitution happens in some HIV-infected patients who have achieved persistent viral suppression under antiretroviral therapy (ART). We performed single-cell RNA sequencing for peripheral blood mononuclear cells to analyze B cell receptor (BCR) repertoire and B cell subtypes in health controls (non-HIV-infected, HCs), HIV-infected immunological responders (IRs), and immunological nonresponders (INRs). We found that the dominant usage of IGHV gene segments of naïve B cells and memory B cells were IGHV3 and IGHV4, and the diversity of BCR repertoire was decreased in INRs. Differentiation trajectory analysis showed that the low differentiation of naïve B cells was related to satisfactory immune status. The cell cycle of B cells with immune-specific genes of IgD+ B cells was degraded in INRs, which was mediated by the anaphase-promoting complex/cyclosome pathway in the phase of G2/M checkpoints. These findings provide significant insights to understand the function of B cell-mediated immune response in immune reconstitution after HIV infection.

Whole-transcriptome analyses of sheep embryonic testicular cells infected with the bluetongue virus.

Introduction: bluetongue virus (BTV) infection triggers dramatic and complex changes in the host's transcriptional profile to favor its own survival and reproduction. However, there is no whole-transcriptome study of susceptible animal cells with BTV infection, which impedes the in-depth and systematical understanding of the comprehensive characterization of BTV-host interactome, as well as BTV infection and pathogenic mechanisms. Methods: to systematically understand these changes, we performed whole-transcriptome sequencing in BTV serotype 1 (BTV-1)-infected and mock-infected sheep embryonic testicular cells, and subsequently conducted bioinformatics differential analyses. Results: there were 1504 differentially expressed mRNAs, 78 differentially expressed microRNAs, 872 differentially expressed long non-coding RNAs, and 59 differentially expressed circular RNAs identified in total. Annotation from the Gene Ontology, enrichment from the Kyoto Encyclopedia of Genes and Genomes, and construction of competing endogenous RNA networks revealed differentially expressed RNAs primarily related to virus-sensing and signaling transduction pathways, antiviral and immune responses, inflammation, and development and metabolism related pathways. Furthermore, a protein-protein interaction network analysis found that BTV may contribute to abnormal spermatogenesis by reducing steroid biosynthesis. Finally, real-time quantitative PCR and western blotting results showed that the expression trends of differentially expressed RNAs were consistent with the whole-transcriptome sequencing data. Discussion: this study provides more insights of comprehensive characterization of BTV-host interactome, and BTV infection and pathogenic mechanisms.

Dynamics and correlations in multiplex immune profiling reveal persistent immune inflammation in male drug users after withdrawal.

Drug withdrawal elicits immune responses that contribute to the development of withdrawal symptoms and relapse. The understanding of the immunologic dynamics after drug withdrawal is limited, precluding the finding of promising immune intervention measures. Here, we performed cytokine and multiplex immune profiling in heroin, methamphetamine (METH) and ephedrine users after withdrawal and identified the correlation between cytokines and other immune parameters. We showed that broad and strong inflammatory responses occurred at the early stage after drug withdrawal, and the inflammatory responses showed a downtrend with the extension of withdrawal time. Notably, immune dysregulation remained through and may last longer than 12 months after withdrawal in heroin and METH users. Our findings suggest that cytokines, immune cells, complement and immunoglobulin form a complex immune network that regulates immune responses after withdrawal. These data provide a reference for future scientific research and drug research and development.

Association between CD4+ T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders.

BACKGROUND: CD4+ T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflammatory cytokines production and an altered intestinal microbiome profile. Changes in gut bacterial composition have been linked to low CD4+ T cell counts in HIV-infected individuals. However, the association between CD4+ T cell counts and gut microbiota community composition and cytokines levels in INRs (CD4+ T cell counts < 500 cells/µL) from Yunnan Province, China, has not been previously investigated. METHODS: To address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count > 200 cells/µL group and CD4 count < 200 cells/µL group. The gut microbiota composition of each subject was analyzed by 16S rRNA gene sequencing. We also compared CD8+ T cell counts, pro-inflammatory cytokines levels, and nutritional status between the two groups. RESULTS: Compared to INRs with CD4 count > 200 cells/µL, those with CD4 count < 200 cells/µL had a lower CD4/CD8 ratio, lower nutritional status and higher serum levels of tumor necrosis factor (TNF)-α, interferon-γ-inducible protein (IP)-10 and interleukin (IL)-1α. Ruminococcaceae was less abundant in the CD4 count < 200 cells/µL group than in the CD4 count > 200 cells/µL group, and difference in alpha diversity was observed between the two groups. Moreover, CD4+ T cell counts were negatively associated with TNF-α and IL-1α levels and positively associated with the relative abundance of Ruminococcaceae. CONCLUSIONS: Our study demonstrated that lower CD4+ T cell counts in INRs are associated with a reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. Thus, interventions targeting gut microbiota to increase CD4+ T cell counts are a potential strategy for promoting immune reconstitution in HIV-infected INRs.

Bluetongue virus non-structural protein 3 (NS3) and NS4 coordinatively antagonize type â interferon signaling by targeting STAT1.

Previous studies have pointed out that bluetongue virus (BTV) down-regulates the expression levels of type Ⅰ interferon (IFN-Ⅰ) and inhibits IFN-Ⅰ signaling by targeting on the Janus tyrosine kinase (JAK)-signal transducer and activator of transcription protein (STAT) pathway. However, individual viral protein could not effectively block IFN-Ⅰ signaling. There is a need to explore the underlying mechanisms by which viral proteins of BTV coordinate to antagonize the IFN-Ⅰ signaling. We investigated the coordinative role of BTV-1 nonstructural protein 3 (NS3) and NS4 in counteracting IFN-Ⅰ signaling in the JAK-STAT pathway by directly interacting with STAT1. The NS3 and NS4 targeted the SH2 domain of STAT1 to inhibit its phosphorylation, heterodimerization, nuclear translocation, as well as activation of downstream genes of the JAK-STAT pathway. NS3 and NS4 impaired STAT1 phosphorylation induced by IFN-Ⅰ in a dose dependent manner. Overall, this study confirmed that NS3 and NS4 of BTV participate in interfering with IFN-Ⅰ signaling process. Also, a new mechanism employed by BTV to evade host innate immune responses was revealed.

Pre-Digested Protein Enteral Nutritional Supplementation Enhances Recovery of CD4+ T Cells and Repair of Intestinal Barrier in HIV-Infected Immunological Non-Responders.

AIDS patients with immune non-response are prone to malnutrition, intestinal barrier damage, thus aggravating chronic immune activation and inflammation. However, nutritional interventions targeting malnutrition may be beneficial to restore immune function, improve clinical outcomes, and reduce mortality remains largely unclear. This work aimed to evaluate the efficacy of a nutritional supplement in HIV-infected immune non-responders (INRs). The subjects received oral supplementation of a pre-digested protein nutrition formula for three months. We show that the CD4+ T and CD8+ T cell counts were significantly increased after supplementation of the pre-digested enteral nutritional supplement. Among all pro-inflammatory cytokines in the serum, only IL-1ß level was significantly decreased, while TNF-ß was significantly increased (P < 0.05). The levels of intestinal mucosal damage markers, diamine oxidase (DAO), D-lactic acid (D-lactate), and lipopolysaccharide (LPS), decreased significantly (P < 0.05) after the nutritional intervention. Moreover, at month 3 after the intervention, the body weight, body mass index, albumin, and hemoglobin of all subjects were significantly increased (P < 0.05). The correlation analysis demonstrated a significantly negative correlation of CD4+ T cell count with levels of DAO (r = -0.343, P = 0.004), D-lactate (r = -0.250, P = 0.037), respectively, and a significantly positive correlation of IL-1ß level with levels of DAO (r = 0.445, P < 0.001), D-lactate (r = 0.523, P < 0.001), and LPS (r = 0.622, P < 0.001). We conclude that the pre-digested enteral nutrition supplement is effective for HIV-infected INRs.

Regulation of Gut Microbiota on Immune Reconstitution in Patients With Acquired Immunodeficiency Syndrome.

Human immunodeficiency virus type 1 (HIV-1) infection of CD4+ T cells in the gut plays an insidious role in acquired immunodeficiency syndrome (AIDS) pathogenesis. Host immune function is closely related to gut microbiota. Changes in the gut microbiota cause a different immune response. Previous studies revealed that HIV-1 infection caused changes in gut microbiota, which induced immune deficiency. HIV-1 infection results in an abnormal composition and function of the gut microbiota, which may disrupt the intestinal epithelial barrier and microbial translocation, leading to long-term immune activation, including inflammation and metabolic disorders. At the same time, an abnormal gut microbiota also hinders the effect of antiviral therapy and affects the immune reconstruction of patients. However, studies on the impact of the gut microbiota on immune reconstitution in patients with HIV/AIDS are still limited. In this review, we focus on changes in the gut microbiota caused by HIV infection, as well as the impact and regulation of the gut microbiota on immune function and immune reconstitution, while we also discuss the potential impact of probiotics/prebiotics and fecal microbiota transplantation (FMT) on immune reconstitution.

Self-heated fiber thermal lever sensor based on the temperature gradient inside a hermetic chamber.

A thermal convection-based fiber lever sensor is proposed and experimentally demonstrated. Instead of the solid or liquid mass found in a conventional lever sensor, a Co2+-doped microfiber is self-heated with a pump laser as the heat source, generating a symmetrical temperature profile inside a hermetic chamber due to thermal convection. The convection current generated by the temperature gradient remains in the opposite direction to gravity with different tilt angles, due to a natural convection effect acting as a "gas pendulum". However, the locations of two micro-single mode fibers are asymmetric, corresponding to the central axis of the temperature gradient. Therefore, the tilt angle can be detected by interrogating the wavelength shift of the Michelson interferometer induced by the temperature difference. The experimental results show that a tilt-angle sensitivity of 95 pm/deg can be achieved. The proposed fiber-optic lever sensor possesses large dynamic range, low cost, and high sensitivity.

Dual-optofluidic waveguide in-line fiber biosensor for real-time label-free detection of interferon-gamma with temperature compensation.

Temperature cross-sensitivity is a long-standing challenge for most of the in-line fiber optofluidic waveguide biosensors. In this paper, we propose a dual-optofluidic waveguide antiresonant reflecting optical waveguide (ARROW) biosensor for the detection of interferon-gamma (IFN-γ) concentration with temperature compensation. Two Fabry-Perot resonators infiltrated with IFN-γ and NaCl were formed in a hollow core fiber, which generate two resonance dips based on the ARROW model. The optical biosensor for the detection of interferon-gamma (IFN-γ) has been a key research interest in recent years because IFN-γ is an important early biomarker for many serious human diseases. Based on the dual-optofluidic waveguide ARROW biosensor, the IFN-γ concentration can be measured through the modulation of the resonance condition of the ARROW, while the temperature fluctuation can be eliminated due to same thermo-optic coefficients of two infiltration liquids. The experimental results show that the response of the ARROW biosensor can be amplified significantly with the signal-enhanced streptavidin, and the limit of detection of 0.5 ng/ml can be achieved for the IFN-γ concentration. More importantly, the influence of the temperature could be compensated through the referenced resonance dip. The proposed fiber biosensor has a great potential for the real-time detection of IFN-γ concentrations in the fields of health monitoring, cancer prevention, biological engineering, etc.

Temperature compensated three-dimension fiber optic vector magnetic field sensor based on an elliptical core micro fiber Bragg grating.

In this paper, a temperature-compensated three-dimension vector fiber optic magnetic field sensor based on an elliptical core micro fiber Bragg grating (FBG) has been proposed and experimentally demonstrated. The elliptical core fiber was tapered to form a microfiber, in which a FBG was inscribed. Due to the magnetism-manipulation of the anisotropic aggregation of ferromagnetism nanoparticles around the fiber surface, the effective refractive index of the evanescent field for two orthogonal polarization modes was modulated, and the magnetic field orientation can be detected by interrogating the wavelength interval between two reflection peaks. However, two reflection peaks show the identical response to ambient temperature. Hence the proposed sensor can achieve the measurements of the magnetic field intensity and the orientation simultaneously without the temperature cross-sensitivity. The experimental results show that the magnetic field orientation sensitivity of 15 pm/deg and intensity sensitivity of 81 pm/mT can be achieved, and the maximum standard variation of the temperature cross-sensitivity is only 0.02 nm. The proposed elliptical core micro FBG appears to have potential applications in navigation, vehicle detection, and current sensing.

Temperature compensated fiber optic anemometer based on graphene-coated elliptical core micro-fiber Bragg grating.

The ambient temperature fluctuation is a long-standing challenge for the hot wire anemometer due to the strong cross-talk. Here, a graphene-coated elliptical core micro-fiber Bragg grating has been proposed for the detection of flow rate with the temperature compensation. With the strong interaction between the graphene layers and the heating light, the graphene coat on the surface of the microfiber can be heated, acting as a heater. The flow rate can be measured through the different responses of two orthogonal polarization modes to the refractive index change of the graphene layer induced by the heat transfer. More importantly, due to the identical response of two polarization modes to the ambient temperature, the fiber-optic anemometer could compensate the temperature cross-talk effectively. The experimental results show that the sensitivity of the 0.42 nm/(m/s) for the fiber anemometer can be achieved, and the temperature standard variation is only 0.084 nm with the range from 20°C to 50°C. The proposed fiber-optic anemometer is very attractive in the fields of various industries for the temperature self-compensation detection of gas flow.

The PLATZ Transcription Factor GL6 Affects Grain Length and Number in Rice.

Grain size is one of the key determinants of grain yield. Although a number of genes that control grain size in rice (Oryza sativa) have been identified, the overall regulatory networks behind this process remain poorly understood. Here, we report the map-based cloning and functional characterization of the quantitative trait locus GL6, which encodes a plant-specific plant AT-rich sequence- and zinc-binding transcription factor that regulates rice grain length and spikelet number. GL6 positively controls grain length by promoting cell proliferation in young panicles and grains. The null gl6 mutant possesses short grains, whereas overexpression of GL6 results in large grains and decreased grain number per panicle. We demonstrate that GL6 participates in RNA polymerase III transcription machinery by interacting with RNA polymerase III subunit C53 and transcription factor class C1 to regulate the expression of genes involved in rice grain development. Our findings reveal a further player involved in the regulation of rice grain size that may be exploited in future rice breeding.

The Ubx Polycomb response element bypasses an unpaired Fab-8 insulator via cis transvection in Drosophila.

Chromatin insulators or boundary elements protect genes from regulatory activities from neighboring genes or chromatin domains. In the Drosophila Abdominal-B (Abd-B) locus, the deletion of such elements, such as Frontabdominal-7 (Fab-7) or Fab-8 led to dominant gain of function phenotypes, presumably due to the loss of chromatin barriers. Homologous chromosomes are paired in Drosophila, creating a number of pairing dependent phenomena including transvection, and whether transvection may affect the function of Polycomb response elements (PREs) and thus contribute to the phenotypes are not known. Here, we studied the chromatin barrier activity of Fab-8 and how it is affected by the zygosity of the transgene, and found that Fab-8 is able to block the silencing effect of the Ubx PRE on the DsRed reporter gene in a CTCF binding sites dependent manner. However, the blocking also depends on the zygosity of the transgene in that the barrier activity is present when the transgene is homozygous, but absent when the transgene is heterozygous. To analyze this effect, we performed chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR) experiments on homozygous transgenic embryos, and found that H3K27me3 and H3K9me3 marks are restricted by Fab-8, but they spread beyond Fab-8 into the DsRed gene when the two CTCF binding sites within Fab-8 were mutated. Consistent with this, the mutation reduced H3K4me3 and RNA Pol II binding to the DsRed gene, and consequently, DsRed expression. Importantly, in heterozygous embryos, Fab-8 is unable to prevent the spread of H3K27me3 and H3K9me3 marks from crossing Fab-8 into DsRed, suggesting an insulator bypass. These results suggest that in the Abd-B locus, deletion of the insulator in one copy of the chromosome could lead to the loss of insulator activity on the homologous chromosome, and in other loci where chromosomal deletion created hemizygous regions of the genome, the chromatin barrier could be compromised. This study highlights a role of homologous chromosome pairing in the regulation of gene expression in the Drosophila genome.

CTCF prevents genomic instability by promoting homologous recombination-directed DNA double-strand break repair.

CTCF is an essential epigenetic regulator mediating chromatin insulation, long-range regulatory interactions, and the organization of large topological domains in the nucleus. Phenotypes of CTCF haploinsufficient mutations in humans, knockout in mice, and depletion in cells are often consistent with impaired genome stability, but a role of CTCF in genome maintenance has not been fully investigated. Here, we report that CTCF maintains genome stability, is recruited to sites of DNA damage, and promotes homologous recombination repair of DNA double-strand breaks (DSBs). CTCF depletion increased chromosomal instability, marked by chromosome breakage and end fusions, elevated genotoxic stress-induced genomic DNA fragmentation, and activated the ataxia telangiectasia mutated (ATM) kinase. We show that CTCF could be recruited to drug-induced 53BP1 foci and known fragile sites, as well as to I-SceI endonuclease-induced DSBs. Laser irradiation analysis revealed that this recruitment depends on ATM, Nijmegen breakage syndrome (NBS), and the zinc finger DNA-binding domain of CTCF. We demonstrate that CTCF knockdown impaired homologous recombination (HR) repair of DSBs. Consistent with this, CTCF knockdown reduced the formation of γ-radiation-induced Rad51 foci, as well as the recruitment of Rad51 to laser-irradiated sites of DNA lesions and to I-SceI-induced DSBs. We further show that CTCF is associated with DNA HR repair factors MDC1 and AGO2, and directly interacts with Rad51 via its C terminus. These analyses establish a direct, functional role of CTCF in DNA repair and provide a potential link between genome organization and genome stability.