Proteomics Platform Reveals Broad-Spectrum Nanobodies for SARS-CoV-2 Variant Neutralization.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of different variants of concerns with immune evasion that have been prevalent over the past three years. Nanobodies, the functional variable regions of camelid heavy-chain-only antibodies, have garnered interest in developing neutralizing antibodies due to their smaller size, structural stability, ease of production, high affinity, and low immunogenicity, among other characteristics. In this work, we describe an integrated proteomics platform for the high-throughput screening of nanobodies against different SARS-CoV-2 spike variants. To demonstrate this platform, we immunized a camel with subunit 1 (S1) of the wild-type spike protein and constructed a nanobody phage library. The binding and neutralizing activities of the nanobodies against 72 spike variants were then measured, resulting in the identification of two nanobodies (C-282 and C-39) with broad neutralizing activity against six non-Omicron variants (D614G, Alpha, Beta, Gamma, Delta, Kappa) and five Omicron variants (BA.1-5). Their neutralizing capability was validated using in vitro pseudovirus-based neutralization assays. All these results demonstrate the utility of our proteomics platform to identify new nanobodies with broad neutralizing capability and to develop a treatment for patients with SARS-CoV-2 variant infection in the future.

Unidirectional coupled chiral fiber grating.

We investigate a unidirectional coupled chiral fiber grating (UCFG) with both helical refractive index (RI) and loss modulation. The two modulations form a π/2 phase difference in the fiber cross-sectional azimuth angle, which "breaks" the mode coupled reciprocity of the forward and backward propagation. The forward propagation fundamental mode coupling is forbidden, while the backward propagation fundamental mode is coupled to the vortex mode. A simulation model based on the beam propagation method (BPM) is utilized to confirm the unidirectional coupling. Using the coupled mode analysis, we find that the key to the coupling difference lies in the non-Hermitian coupling matrix. In addition, the UCFG design involving mixed modulation is also discussed. The UCFG demonstrates its potential as a passive vortex beam generator, filter, and detector, with a transmittance difference of up to 30 dB between the coupled and uncoupled vortex modes.

Circulating cytokines and alcoholic liver disease: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: Increased inflammation in the liver during ethanol exposure is a major feature of alcoholic liver disease (ALD). An important contributing component to the development of ALD is the inflammatory response brought on by immunological response, however the connection between individual circulating cytokines and ALD is still unclear. To ascertain the causation, we conducted a two-sample bidirectional Mendelian randomization research. METHODS: We extracted 41 cytokines and growth factors of 8293 Europeans and ALD cases of the same ethnicity (1416 cases and 217,376 controls) from the Genome-Wide Association Studies (GWAS) database for two-sample bidirectional MR analysis. RESULTS: Our analyses suggest that higher interleukin-7 (IL-7) levels are associated with an increased risk of ALD (p = 0.028, OR = 1.191,95% CI = 1.019-1.392), while tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a protective factor for ALD (p = 0.032, OR = 0.863, 95% CI = 0.754-0.988) which can reduce the risk of disease occurrence. In addition, genetically predicted ALD does not affect the expression of circulating cytokines regulators. CONCLUSIONS: Our study supports that cytokines play a pivotal role in the pathogenesis of ALD. To determine the mechanisms and pathways of action of these biomarkers, further basic research is required to ensure their clinical suitability for preventing and treating ALD.

Probe-Type Multi-Core Fiber Optic Sensor for Simultaneous Measurement of Seawater Salinity, Pressure, and Temperature.

In this article, we propose and demonstrate a probe-type multi-core fiber (MCF) sensor for the multi-parameter measurement of seawater. The sensor comprises an MCF and two capillary optical fibers (COFs) with distinct inner diameters, in which a 45° symmetric core reflection (SCR) structure and a step-like inner diameter capillary (SIDC) structure filled with polydimethylsiloxane (PDMS) are fabricated at the fiber end. The sensor is equipped with three channels for different measurements. The surface plasmon resonance (SPR) channel (CHSPR) based on the side-polished MCF is utilized for salinity measurement. The fiber end air cavity, forming the Fabry-Pérot interference (FPI) channel (CHFPI), is utilized for pressure and temperature measurement. Additionally, the fiber Bragg grating (FBG) channel (CHFBG), which is inscribed in the central core, serves as temperature compensation for the measurement results. By combining three sensing principles with space division multiplexing (SDM) technology, the sensor overcomes the common challenges faced by multi-parameter sensors, such as channel crosstalk and signal demodulation difficulties. The experimental results indicate that the sensor has sensitivities of 0.36 nm/‱, -10.62 nm/MPa, and -0.19 nm/°C for salinity, pressure, and temperature, respectively. As a highly integrated and easily demodulated probe-type optical fiber sensor, it can serve as a valuable reference for the development of multi-parameter fiber optic sensors.

Human Autoantigen Atlas: Searching for the Hallmarks of Autoantigens.

Understanding autoimmunity to endogenous proteins is crucial in diagnosing and treating autoimmune diseases. In this work, we developed a user-friendly AAgAtlas portal (http://biokb.ncpsb.org.cn/aagatlas_portal/index.php#), which can be used to search for 8045 non-redundant autoantigens (AAgs) and 47 post-translationally modified AAgs against 1073 human diseases that are prioritized by a credential score developed by multisource evidence. Using AAgAtlas, the immunogenic properties of human AAgs was systematically elucidated according to their genetic, biophysical, cytological, expression profile, and evolutionary characteristics. The results indicated that human AAgs are evolutionally conserved in protein sequence and enriched in three hydrophilic and polar amino acid residues (K, D, and E) that are located at the protein surface. AAgs are enriched in proteins that are involved in nucleic acid binding, transferase, and the cytoskeleton. Genome, transcriptome, and proteome analyses further indicated that AAb production is associated with gene variance and abnormal protein expression related to the pathological activities of different tumors. Collectively, our data outlines the hallmarks of human AAgs that facilitate the understanding of humoral autoimmunity and the identification of biomarkers of human diseases.

High-order mixed vortex beam generator.

A mixed multi-order vortex beam generator, based on a Reuleaux triangle core fiber chiral grating (RCFG), is proposed. The triangular perturbation and off-axis effects induced by core shape, result in the simultaneous coupling of the core mode with the 1st- and 3rd-order vortex modes. To the best of our knowledge, this is the first time that a mixed vortex beam was generated in a single chiral fiber. The phase matching conditions required for the co-coupling of multi-order vortex beams are analyzed based on the coupled mode theory. Additionally, a cladding shrinkage method is proposed to flexibly adjust the co-coupling wavelength. We found that the key to co-coupling lies in balancing the different order perturbations of the Reuleaux triangle core fiber (RTF). The proposed method offers a new approach for the design of mixed multi-order vortex beam generators, with potential applications in fields such as fiber OAM communications, optical tweezers, and super-resolution imaging.

A systematic review and meta-analysis of glucocorticoids treatment in severe COVID-19: methylprednisolone versus dexamethasone.

OBJECTIVE: The preferred agent of glucocorticoids in the treatment of patients with severe COVID-19 is still controversial. This study aimed to compare the efficacy and safety of methylprednisolone and dexamethasone in the treatment of patients with severe COVID-19. METHODS: By searching the electronic literature database including PubMed, Cochrane Central Register of Controlled Trials, and Web of Science, the clinical studies comparing methylprednisolone and dexamethasone in the treatment of severe COVID-19 were selected according to the inclusion criteria and exclusion criteria. Relevant data were extracted and literature quality was assessed. The primary outcome was short-term mortality. The secondary outcomes were the rates of ICU admission and mechanical ventilation, PaO2/FiO2 ratio, plasma levels of C-reactive protein (CRP), ferritin, and neutrophil/lymphocyte ratio, hospital stay, and the incidence of severe adverse events. Statistical pooling applied the fixed or random effects model and reported as risk ratio (RR) or mean difference (MD) with the corresponding 95% confidence interval (CI). Meta-analysis was performed using Review Manager 5.1.0. RESULTS: Twelve clinical studies were eligible, including three randomized controlled trials (RCTs) and nine non-RCTs. A total of 2506 patients with COVID-19 were analyzed, of which 1242 (49.6%) received methylprednisolone and 1264 (50.4%) received dexamethasone treatment. In general, the heterogeneity across studies was significant, and the equivalent doses of methylprednisolone were higher than that of dexamethasone. Our meta-analysis showed that methylprednisolone treatment in severe COVID-19 patients was related to significantly reduced plasma ferritin and neutrophil/lymphocyte ratio compared with dexamethasone, and that no significant difference in other clinical outcomes between the two groups was found. However, subgroup analyses of RCTs demonstrated that methylprednisolone treatment was associated with reduced short-term mortality, and decreased CRP level compared with dexamethasone. Moreover, subgroup analyses observed that severe COVID-19 patients treated with a moderate dose (2 mg/kg/day) of methylprednisolone were related to a better prognosis than those treated with dexamethasone. CONCLUSIONS: This study showed that compared with dexamethasone, methylprednisolone could reduce the systemic inflammatory response in severe COVID-19, and its effect was equivalent to that of dexamethasone on other clinical outcomes. It should be noted that the equivalent dose of methylprednisolone used was higher. Based on the evidence of subgroup analyses of RCTs, methylprednisolone, preferably at a moderate dose, has an advantage over dexamethasone in the treatment of patients with severe COVID-19.

Survival of Listeria monocytogenes and Salmonella in citrus storage waxes or on lemons held under common commercial storage conditions.

To prolong cold storage, diluted storage waxes are applied to washed lemons after harvest and before packing, without drying steps, to reduce premature rotting and water loss. The survival of Listeria monocytogenes and Salmonella in undiluted and diluted storage waxes (S1-S4), and on lemon surfaces under common commercial storage were investigated. Populations of L. monocytogenes declined more slowly than Salmonella in undiluted storage waxes over 24 h of storage at 4 or 22 °C. L. monocytogenes (inoculated at ∼6 log CFU/mL) was detected by enrichment in undiluted waxes S2, S3, and S4 after 75-135 days at 4 °C but not after 30, 10, or 105 days, respectively at 22 °C. L. monocytogenes survived better in diluted than in undiluted storage waxes at 22 °C. Populations of L. monocytogenes (∼6 log CFU/lemon) declined by 0.64-1.62 log on lemon surfaces right after waxing. Populations of L. monocytogenes decreased to <1.30 log CFU/lemon after 28 days (1:9 S1) or 75 days (other treatments) at 12 °C and ≥93% RH. Except for 1:9 S1, L. monocytogenes was detected by enrichment in all lemon samples over 87 days of storage. Packinghouses should consider the survival of L. monocytogenes and Salmonella in citrus storage waxes in their food safety programs.

Isolation and characterization of competitive exclusion microorganisms from animal wastes-based composts against Listeria monocytogenes.

AIM: To isolate the slow-growing or viable but non-culturable competitive exclusion (CE) microorganisms from composts and then verify the anti-Listeria monocytogenes activities of those CE isolates in compost. METHODS AND RESULTS: CE strains were isolated from composts using double- or triple-layer agar methods, purified, and then characterized. Both compost extracts and solid compost samples were spiked with a cocktail of 3 L. monocytogenes strains which were co-inoculated with or without CE strain cocktail and incubated at both 22 and 35°C for 168 h. Results indicated that the addition of resuscitation promoting factor (Rpf) promoted the growth of slow-growing species from composts. About 50% of the isolated CE strains (n = 40) were identified as Bacillus spp., 17 strains can inhibit more than 10 tested L. monocytogenes strains, and nine strains were motile and competitive biofilm formers. In compost extracts, the growth potentials of L. monocytogenes were reduced up to 2.2 logs when co-culturing with CE strains. In compost samples, the addition of CE strains reduced L. monocytogenes population by ca. 1.3 log CFU/g at 22°C after 24-168 h incubation. CONCLUSION: Our modified double/triple-layer agar procedure with Rpf as growth supplement coupled with spot-on-lawn testing can be a quick and efficient method for isolating CE candidates from composts. The efficacy of CE strains against L. monocytogenes in compost extracts and compost samples was affected by compost type, nutrient level, and incubation temperature. SIGNIFICANCE AND IMPACT OF THE STUDY: Compost is a rich source of CE microorganisms, and compost-adapted CE microorganisms have the potential as a biological agent to control L. monocytogenes in agricultural environments.

Serum Protein Profiling Reveals a Landscape of Inflammation and Immune Signaling in Early-stage COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n = 15) and influenza (n = 13) patients. We identified a large set of differentially expressed proteins (n = 132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.

Effects of different doses of methylprednisolone therapy on acute respiratory distress syndrome: results from animal and clinical studies.

BACKGROUND: The optimal dose of glucocorticoids for acute respiratory distress syndrome (ARDS) is uncertain. This study aimed to evaluate the effects of different doses of methylprednisolone on sepsis-induced acute lung injury (ALI) rats and a cohort of moderate and severe ARDS patients. METHODS: ALI rats, challenged with lipopolysaccharide, were randomly received intraperitoneal injection of normal saline (model group) and different doses of methylprednisolone (0.5, 2, 8 mg/kg, named as low-, moderate- and high-dose group, respectively) for 5 days. The body weight changes of rats, inflammatory factors in bronchoalveolar lavage fluid (BALF), lung wet/dry ratio, histopathological score, and the mRNA expressions of glucocorticoid receptor α (GRα), GRß and nuclear factor-κB (NF-κB) were measured. Forty moderate and severe ARDS patients were treated with standard of care or plus different doses of methylprednisolone (40, 80, 120 mg/day, named as low-, moderate- and high-dose group, respectively) for 5 days. Clinical outcomes were PaO2/FiO2 ratio and C-reactive protein (CRP) level at day 5, intubation rate, hospital stay, 28-day mortality, and adverse events rate. RESULTS: In animal experiment, different doses of methylprednisolone could increase the body weight of rats, and reduce inflammatory factors in BALF and the degree of lung injury compared with model group. The efficacy of methylprednisolone at moderate-dose was better than that at low-dose, but was equivalent to that at high-dose, which was consistent with the differential changes in the mRNA expression of GRα, GRß and NF-κB. In clinical study, the moderate-dose group was associated with higher PaO2/FiO2 ratio and lower CRP level. No significant difference in other clinical outcomes among groups was detected. CONCLUSIONS: This study showed that the efficacy of methylprednisolone in ARDS treatment was not always dose-dependent due to the differential regulation of related receptors. The moderate-dose of methylprednisolone may be the potential optimal dose for ARDS treatment, which needs to be further verified by larger clinical trials.

The longitudinal relationship between BOLD signal variability changes and white matter maturation during early childhood.

Intra-individual transient temporal fluctuations in brain signal, as measured by fMRI blood oxygenation level dependent (BOLD) variability, is increasingly considered an important signal rather than measurement noise. Evidence from computational and cognitive neuroscience suggests that signal variability is a good proxy-measure of brain functional integrity and information processing capacity. Here, we sought to explore across-participant and longitudinal relationships between BOLD variability, age, and white matter structure in early childhood. We measured standard deviation of BOLD signal, total white matter volume, global fractional anisotropy (FA) and mean diffusivity (MD) during passive movie viewing in a sample of healthy children (aged 2-8 years; N = 83). We investigated how age and white matter development related to changes in BOLD variability both across- and within-participants. Our across-participant analyses using behavioural partial least squares (bPLS) revealed that the influence of age and white matter maturation on BOLD variability was highly interrelated. BOLD variability increased in widespread frontal, temporal and parietal regions, and decreased in the hippocampus and parahippocampal gyrus with age and white matter development. Our longitudinal analyses using linear mixed effects modelling revealed significant associations between BOLD variability, age and white matter microstructure. Analyses using artificial neural networks demonstrated that BOLD variability and white matter micro and macro-structure at earlier ages were strong predictors of BOLD variability at later ages. By characterizing the across-participant and longitudinal features of the association between BOLD variability and white matter micro- and macrostructure in early childhood, our results provide a novel perspective to understand structure-function relationships in the developing brain.

Highly Active Electrochemiluminescence of Ruthenium Complex Co-assembled Chalcogenide Nanoclusters and the Application for Label-Free Detection of Alkaline Phosphatase.

Rational design of electrochemiluminescence (ECL) reagents is essential for the development of ECL biosensors with superior performances. In this work, the assembly of tris(1,10-phenanthroline)ruthenium(II) [Ru(phen)32+] and tetrahedral chalcogenide nanoclusters of [Cd32S14(SC6H5)38]2- in the formation of complex nanoclusters (CdS-Ru) was developed, in which Ru(phen)32+ was uniformly encapsulated and dispersed at a molecular level in the chalcogenide nanocluster via multiple noncovalent interactions. It was observed that the promoted ECL emission was realized by the charge transfer between the tetrahedral CdS nanocluster and Ru(phen)32+ by the formation of the assembly complex, which was elucidated by cyclic voltammetry curves, ECL-potential curves, and in situ dynamic ECL spectra. Taking advantages of the facile charge transfer in the open framework CdS-Ru, a high ECL efficiency has been achieved with remarkable stability. Moreover, a solid-state ECL sensor based on the CdS-Ru modified electrode was fabricated for label-free detection of alkaline phosphatase (ALP) activity with a detection limit as low as 0.35 U/L and superior reproducibility. This solid-state ECL sensor also displayed favorable selectivity among various interferences and was applied for ALP activity analysis in human serum samples. These results implicated the potential applications of CdS-Ru for sensitive ECL analysis in complicated reaction systems and enlightened the rational design for self-enhanced and highly efficient ECL materials.

Plant-Scale Validation of Physical Heat Treatment of Poultry Litter Composts Using Surrogate and Indicator Microorganisms for Salmonella.

This study selected and used indicator and surrogate microorganisms for Salmonella to validate the processes for physically heat-treated poultry litter compost in litter processing plants. Initially laboratory validation studies indicated that 1.2- to 2.7-log or more reductions of desiccation-adapted Enterococcus faecium NRRL B-2354 were equivalent to > 5-log reductions of desiccation-adapted Salmonella Senftenberg 775/W in poultry litter compost, depending on treatment conditions and compost types. Plant validation studies were performed in one turkey litter compost processor and one laying hen litter compost processor. E. faecium was inoculated at ca.7 log CFU g-1 into the turkey litter compost and at ca. 5 log CFU g-1 into laying hen litter compost with respectively targeted moisture contents. The thermal processes in the two plants yielded 2.8 - > 6.4 log CFU g-1 (> 99.86%) reductions E. faecium of the inoculated. Similarly, for the processing control samples, reductions of presumptive indigenous enterococci were in the order of 1.8-3.7 log CFU g-1 (98.22% to 99.98%) of the total naturally present. In contrast, there were less reductions of indigenous mesophiles (1.7-2.9 log CFU) and thermophiles (0.4-3.2 log CFU g-1). More indigenous enterococci were inactivated in the presence of higher moisture in the poultry litter compost. Based on the data collected under the laboratory conditions, the processing conditions in both plants were adequate to reduce any potential Salmonella contamination of processed poultry litter compost by at least 5 logs, even though the processing conditions varied among trials and plants.IMPORTANCE Poultry litter compost, commonly used as a biological soil amendment, is subjected to a physical heat-treatment in industry setting to reduce pathogenic bacteria such as Salmonella and produce a dry product. According to the FDA Food Safety Modernization Act (FSMA) Produce Safety Rule, the thermal process for poultry litter compost should be scientifically validated to satisfy the microbial standard requirement. To the best of our knowledge, this is the first validation study in commercial poultry litter compost processing plants, and our results indicated that Salmonella levels, if present, could be reduced by at least 5 logs based on the reductions of surrogate and indicator microorganisms, even though the processing conditions in these commercial plants varied greatly. Furthermore, both indicator and surrogate microorganisms along with the custom-designed sampler can serve as practical tools for poultry litter compost processors to routinely monitor or validate their thermal processes without introducing pathogens into the industrial environments.

Vaccination with live Hirame novirhabdovirus (HIRRV) at temperature-controlled condition induced protective immunity in flounder (Paralichthys olivaceus).

Hirame novirhabdovirus (HIRRV) is a severe viral pathogen of flounder resulting in significant losses to the aquaculture industry. However, the mortality due to the disease would be significantly reduced when the water temperature was increased from 10 to 20 °C. In this study, we examined the potentiality of vaccination with live HIRRV under a temperature-controlled culture condition for development of protective immunity in flounder. Flounders were infected with HIRRV at 10 °C and maintained for 2 days, and then the temperature was shift up to 20 °C. When the temperature was further shift down to 10 °C at 7 (S-7 group), 14 (S-14 group) or 21 (S-21 group) days post infection (dpi), mortality rates of 60%, 13.33% and 0 were observed, respectively. To investigate the development of protective immunity of survived flounder, a re-challenge was performed and a highest survival rate of 80% was found in S-21 group, which was significantly higher than S-14 group (65%) and S-7 group (45%). Moreover, it was found that a lower viral load was detected in the flounder maintained at 20 °C for a longer time, and a longer maintaining of survived flounder at 20 °C would also elicit higher percentages of IgM + B lymphocytes and specific antibodies levels. Notably, a significantly higher levels of specific antibodies were detected post re-challenge compared with the first peak level after initial infection. Therefore, these demonstrated that the initial infection with live HIRRV under a temperature-controlled condition elicited an effective protective immune response against HIRRV, and maintaining at 20 °C for a long enough time would allow the HIRRV-infected flounder to eliminate the virus completely and acquired a protective immunity against HIRRV infection. This is the first study showing the possibility of developing an effective preventive measure against HIRRV by vaccination with live virus under controlled water temperature.

The first third-generation HIV-1 circulating recombinant form (CRF114_0155) identified in central China.

A novel circulating recombinant form (CRF) was identified in eight HIV-1-infected patients without direct epidemiological relationships in Henan Province, Central China. Recombination analysis indicated that the genome of this novel CRF comprises five segments: three inherited from CRF01_AE cluster-4 and two from CRF55_01B. Therefore, the CRF was designated CRF114_0155. It is not only the first novel CRF identified in Henan Province but also the first third-generation CRF of HIV-1 and the first CRF descendant of CRF55_01B. Bayesian inference of phylogeny dated the most recent common ancestor of the CRF114_0155 cluster to 2010. The emergence of CRF114_0155 reflects that the genotype constitution of HIV-1 has become more complex and that stricter intervention measures should be implemented in central China.

Molecular Cages Self-Assembled by Imine Condensation in Water.

Self-assembly by imine condensation in aqueous media is a formidable task because of the labile nature of imines in the presence of water. Here, by taking advantage of multivalence and ligand preorganization, basket-shaped triscationic cage molecules are self-assembled in high yields in both water and organic solvent, by condensing a hexaformyl and bisamine. These cages, especially the chiral ones, are stable or inert in aqueous solution, that is, no decomposition was observed upon dilution, precipitation, or exposure to competitive amines or aldehydes. Such water-compatibility allows the hosts to take advantage of the hydrophobic effect to accommodate hydrophobic guests. The chiral cage S-23+ selectively binds and distinguishes one of two enantiomers, opening up opportunities for applications such as chiral compound separation. Chiral narcissistic self-sorting and sergeants-and-soldiers effects occur during cage formation when two amino precursors are involved in self-assembly.

Constraining Homo- and Heteroanion Dimers in Ultraclose Proximity within a Self-Assembled Hexacationic Cage.

A hexacationic cage 36+ was synthesized via hydrazone condensation in aqueous acid. Cage 36+ bears three biscationic arms, each of which contains four relatively acidic protons, including one NH and three CH protons. These hydrogen bond donors, as well as its intrinsic cationic nature, enable cage 36+ to encapsulate two anions concurrently within its cavity. The axial asymmetrical nature of the biscationic arms allow the cage to recognize two different anions in a selective manner, to encompass bound heteroanion dimers, such as Cl-·NO3- and Cl-·Br-. Single crystal X-ray diffraction analyses reveal that in the solid state the two anions are constrained in ultraclose proximity within the cage; e.g., the Cl-···Cl- and Cl-···Br- distances are 3.2 and 2.9 Å, respectively, which are shorter than the sum of their van der Waals radii. Evidence consistent with the sequential binding of two identical or disparate anions in CD3CN is also presented.

In Situ Formation of Gold Nanoparticles Decorated Ti3C2 MXenes Nanoprobe for Highly Sensitive Electrogenerated Chemiluminescence Detection of Exosomes and Their Surface Proteins.

In this work, an ultrasensitive electrogenerated chemiluminescence (ECL) biosensor for exosomes and their surface proteins was developed by the in situ formation of gold nanoparticles (AuNPs) decorated Ti3C2 MXenes hybrid with aptamer modification (AuNPs-MXenes-Apt). In this strategy, the exosomes were efficiently captured on an exosome recognized CD63 aptamer modified electrode interface. Meanwhile, in situ formation of gold nanoparticles on single layer Ti3C2MXenes with aptamer (MXenes-Apt) modification was obtained, in which MXenes acted as both reductants and stabilizer, and no additional reductant and stabilizer involved. The in situ formed AuNPs-MXenes-Apt hybrid not only presented highly efficient recognition of exosomes specifically, but also provide naked catalytic surface with high electrocatalytic activity of gold nanoparticles with predominated (111) facets that significantly improved the ECL signal of luminol. In this way, a highly sensitive ECL biosensor for exosomes detection was constructed ascribing to the synergistic effects of large surface area, excellent conductivity, and catalytic effects of the AuNPs-MXenes-Apt. The detection limit is 30 particles µL-1 for exosomes derived from HeLa cell line, which was over 1000 times lower than that of conventional ELISA method and the linear range was from 102 particles µL-1 to 105 particles µL-1. This ECL sensing platform possessed high selectivity toward exosomes and their surface proteins derived different kinds of tumor cell lines (HeLa cells, OVCAR cells and HepG2 cells), and enabled sensitive and accurate detection of exosomes from human serum, which implied that the ECL biosensor provided a feasible, sensitive, and reliable tool for exosomes detection in exosomes-related clinical diagnostic.

MiR-124 attenuates doxorubicin-induced cardiac injury via inhibiting p66Shc-mediated oxidative stress.

Previous studies showed that miR-124 had a protective role by reducing oxidant stress and preventing cell apoptosis and autophagy. However, its role in doxorubicin-induced cardiomyopathy was less known. In our study, we confirmed increased ROS and decreased expression of miR-124 in doxorubicin-treated heart tissues and primary cardiomyocytes. The oxidative stress and cell apoptosis were alleviated by overexpressing miR-124, characterized by decreased activity of MDA and increased activity of SOD. While inhibiting miR-124 generated opposed effects. Mechanistically, our bioinformatic prediction and luciferase assay confirmed that miR-124 inhibited the expression of p66Shc, a proapoptotic signaling pathway. Our results suggested that miR-124 was hopeful to become a therapeutic target in doxorubicin-related cardiomyopathy.