Trained immunity as a potential target for therapeutic immunomodulation in Duchenne muscular dystrophy.

Dysregulated inflammation involving innate immune cells, particularly of the monocyte/macrophage lineage, is a key contributor to the pathogenesis of Duchenne muscular dystrophy (DMD). Trained immunity is an evolutionarily ancient protective mechanism against infection, in which epigenetic and metabolic alterations confer non-specific hyperresponsiveness of innate immune cells to various stimuli. Recent work in an animal model of DMD (mdx mice) has shown that macrophages exhibit cardinal features of trained immunity, including the presence of innate immune system "memory". The latter is reflected by epigenetic changes and durable transmissibility of the trained phenotype to healthy non-dystrophic mice by bone marrow transplantation. Mechanistically, it is suggested that a Toll-like receptor (TLR) 4-regulated, memory-like capacity of innate immunity is induced at the level of the bone marrow by factors released from the damaged muscles, leading to exaggerated upregulation of both pro- and anti-inflammatory genes. Here we propose a conceptual framework for the involvement of trained immunity in DMD pathogenesis and its potential to serve as a new therapeutic target.

Amygdala neural ensemble mediates mouse social investigation behaviors.

Innate social investigation behaviors are critical for animal survival and are regulated by both neural circuits and neuroendocrine factors. Our understanding of how neuropeptides regulate social interest, however, is incomplete at the current stage. In this study, we identified the expression of secretin (SCT) in a subpopulation of excitatory neurons in the basolateral amygdala. With distinct molecular and physiological features, BLASCT+ cells projected to the medial prefrontal cortex and were necessary and sufficient for promoting social investigation behaviors, whilst other basolateral amygdala neurons were anxiogenic and antagonized social behaviors. Moreover, the exogenous application of secretin effectively promoted social interest in both healthy and autism spectrum disorder model mice. These results collectively demonstrate a previously unrecognized group of amygdala neurons for mediating social behaviors and suggest promising strategies for social deficits.

Novel Network Method Major Minor Variation Clustering Enables Identification of Poliovirus Clusters with High-Resolution Linkages.

The Global Polio Eradication Initiative uses an outbreak response protocol that defines type 2 Sabin or Sabin-like virus as those with 0-5 nucleotides diverging from their parental strain in the complete VP1 genomic region. Sabin or Sabin-like viruses share highly similar genome sequences, regardless of their origin. Thus, it is challenging to distinguish viruses at a higher resolution to detect polio clusters or trace sources for local transmissions of viruses at an early stage. To identify type 2 Sabin or Sabin-like sources and improve our ability to map viral sources to campaigns during the polio endgame, we investigated the feasibility of a new method for genetic sequence analysis. We named the method Major Minor Variation Clustering (MMVC), which uses a network model to simultaneously incorporate sequence similarity in major and minor variants in addition to onset dates to detect fine-scale polio clusters. Each identified cluster represents a collection of sequences that are highly similar in both major and minor variants, enabling the discovery of new links between viruses. By applying the method to a published data set collected in Nigeria during 2009-2012, we found that clusters identified using this method have several improvements over clusters derived from a phylogenetic tree approach. Integrative data analysis reveals that sequences in the same cluster have greater genomic similarities and better agreement with onset dates. As a complement to current phylogenetic tree approaches, MMVC has the potential to improve epidemiological surveillance and investigation precision to guide polio eradication.

Real-Time Monitoring Renal Impairment Due to Drug-Induced AKI and Diabetes-Caused CKD Using an NAG-Activatable NIR-II Nanoprobe.

Real-time in vivo optical imaging of kidney function is important for the diagnosis of renal diseases, such as acute kidney injury (AKI) and chronic kidney disease (CKD), with high morbidity and mortality worldwide. However, the reported optical imaging agents still have limitations for identifying AKI or CKD in the early stage due to their low sensitivity, poor tissue penetration, and significant background interference. Herein, an N-acetyl-ß-d-glucosaminidase (NAG)-activatable second near-infrared (NIR-II) fluorescent nanoprobe (BOD-II-NAG-NP) is developed for monitoring the progression of drug-induced AKI and in vivo imaging of diabetes-caused CKD. NAG, as a biomarker of renal diseases, is able to specifically activate BOD-II-NAG-NP to release NIR-II fluorescence signals, enabling in vivo imaging of kidney dysfunctions in living mice. Importantly, such an active imaging mechanism allows BOD-II-NAG-NP to noninvasively detect the onset of drug-induced AKI at least 32 h earlier than the most existing assays, which indicates that BOD-II-NAG-NP has the potential to be an optical imaging agent for the early diagnosis of AKI. Moreover, NIR-II fluorescence produced by BOD-II-NAG-NP could deeply penetrate into the relatively thick layers of fat in diabetic nephropathy mice and provide in vivo imaging with high resolution, indicating that BOD-II-NAG-NP has clinical potential for precision diagnosis of CKD.

An electron-deficiency-based framework for NIR-II fluorescence probes.

Fluorescent probes in the NIR-II region provide high bioimaging quality. Optimizing the probe structure to achieve NIR-II imaging is ongoing, but remains challenging. Herein, increasing the electron withdrawing ability of the substituent in monochlorinated BODIPY greatly adjusted the emission wavelength from the NIR-I to NIR-II region, giving an efficient design strategy of NIR-II probes.

The sugar transporter system of strawberry: genome-wide identification and expression correlation with fruit soluble sugar-related traits in a Fragaria × ananassa germplasm collection.

Sugar from plant photosynthesis is a basic requirement for life activities. Sugar transporters are the proteins that mediate sugar allocation among or within source/sink organs. The transporters of the major facilitator superfamily (MFS) targeting carbohydrates represent the largest family of sugar transporters in many plants. Strawberry (Fragaria × ananassa Duchesne) is an important crop appreciated worldwide for its unique fruit flavor. The involvement of MFS sugar transporters (STs) in cultivated strawberry fruit sugar accumulation is largely unknown. In this work, we characterized the genetic variation associated with fruit soluble sugars in a collection including 154 varieties. Then, a total of 67 ST genes were identified in the v4.0 genome integrated with the v4.0.a2 protein database of F. vesca, the dominant subgenome provider for modern cultivated strawberry. Phylogenetic analysis updated the nomenclature of strawberry ST homoeologs. Both the chromosomal distribution and structural characteristics of the ST family were improved. Semi-RT-PCR analysis in nine tissues from cv. Benihoppe screened 34 highly expressed ST genes in fruits. In three varieties with dramatically differing fruit sugar levels, qPCR integrated with correlation analysis between ST transcript abundance and sugar content identified 13 sugar-correlated genes. The correlations were re-evaluated across 19 varieties, including major commercial cultivars grown in China. Finally, a model of the contribution of the sugar transporter system to subcellular sugar allocation in strawberry fruits was proposed. Our work highlights the involvement of STs in controlling strawberry fruit soluble sugars and provides candidates for the future functional study of STs in strawberry development and responses and a new approach for strawberry genetic engineering and molecular breeding.

In Vivo Imaging of Senescent Vascular Cells in Atherosclerotic Mice Using a ß-Galactosidase-Activatable Nanoprobe.

Senescence-associated diseases have severely diminished the quality of life and health of patients. However, a sensitive assay of these diseases remains limited due to a lack of straightforward methods. Considering that senescence-associated ß-galactosidase (SA-ß-Gal) is overexpressed in senescent cells, the detection of SA-ß-Gal in senescent cells and tissues might be a feasible strategy for the early diagnosis of SA diseases. In this study, a ß-galactosidase-activatable nanoprobe BOD-L-ßGal-NPs was developed for the imaging of senescent cells and vasculature in atherosclerotic mice via real-time monitoring of ß-Gal. BOD-L-ßGal-NPs was fabricated by encapsulating a newly designed NIR ratiometric probe BOD-L-ßGal within a poly(lactic-co-glycolic) acid (PLGA) core. Nanoprobe BOD-L-ßGal-NPs showed good accumulation in arteries, thus successfully visualizing senescent cells and vasculature in atherosclerotic mice by tail vein injection. Our findings indicated that nanoprobe BOD-L-ßGal-NPs holds great potential for the early diagnosis and therapy of atherosclerosis and other aging-associated diseases.

Precise imaging of mitochondria in cancer cells by real-time monitoring of nitroreductase activity with a targetable and activatable fluorescent probe.

An activatable and mitochondrial-targetable fluorescent probe was developed. This designed probe showed ratiometric fluorescence and light-up near-infrared emission responsiveness to nitroreductase, achieving precise imaging of mitochondria in cancer cells by real-time monitoring of nitroreductase activity.

Rational design of fluorescent probes for targeted in vivo nitroreductase visualization.

Nitroreductase (NTR) has been recognized as a biomarker for identifying the hypoxic status of cancers. Therefore, it is of high scientific interest to design effective fluorescent probes for tracking NTR activity. However, studies on elucidation of the structure-performance relationship of fluorescent probes and those providing valuable insight into optimized probe design have rarely been reported. Three BODIPY based fluorescent probes were made by conjugation of para-, ortho-, and meta-nitrobenzene to the BODIPY core via a thiolether bond, respectively. Our study revealed that the linkage and nitro substituent position significantly influence the capability of nitroreductase detection.

Rational design of water-dispersible and biocompatible nanoprobes with H2S-triggered NIR emission for cancer cell imaging.

We present an approach for constructing a H2S-specific nanoprobe by the entrapment of a small molecule probe within the hydrophobic interior of surface cross-linked micelles (SCMs), endowing the designed nanoprobes with good water solubility and biocompatibility. Importantly, the obtained nanoprobes displayed good responsiveness to H2S in both ratiometric fluorescence and light-up NIR emission modes, thus enabling accurate identification of H2S-rich colorectal cancer cells.

Imaging of ovarian cancers using enzyme activatable probes with second near-infrared window emission.

We herein develop two ß-galactosidase (ß-Gal) activatable NIR fluorescent probes for visualizing ovarian cancers. Particularly, probe BOD-M-ßGal produced NIR-II emission light at 900-1300 nm upon ß-Gal activation. By using our activatable and target specific NIR-II probe for deep-tissue imaging of ß-Gal overexpressed ovarian cancer cells, rapid and accurate imaging of ovarian tumors in nude mice was achieved.

Relieving the Photosensitivity of Organic Field-Effect Transistors.

It is generally believed that the photoresponse behavior of organic field-effect transistors (OFETs) reflects the intrinsic property of organic semiconductors. However, this photoresponse hinders the application of OFETs in transparent displays as driven circuits due to the current instability resulting from the threshold voltage shift under light illumination. It is necessary to relieve the photosensitivity of OFETs to keep the devices stable. 2,6-diphenyl anthracene thin-film and single-crystal OFETs are fabricated on different substrates, and it is found that the degree of molecular order in the conducting channels and the defects at the dielectric/semiconductor interface play important roles in determining the phototransistor performance. When highly ordered single-crystal OFETs are fabricated on polymeric substrates with low defects, the photosensitivity (P) decreases by more than 105 times and the threshold voltage shift (ΔVT ) is almost eliminated compared with the corresponding thin-film OFETs. This phenomenon is further verified by using another three organic semiconductors for similar characterizations. The decreased P and ΔVT of OFETs ensure a good current stability for OFETs to drive organic light-emitting diodes efficiently, which is essential to the application of OFETs in flexible and transparent displays.

The Influence of Culture on Attitudes Towards Humorous Advertising.

Humor has been widely used in advertising in recent decades. Various studies found that humor could significantly improve advertising performance. However, most of these studies were conducted in a Eastern context and did not consider cultural factors. In a cross-cultural research framework, the current study explored the effects of advertisement characteristics (i.e., brand nationality and humor tactics) on Chinese and United States audiences' attitudes toward humorous advertisements. Results showed that the attitudinal differences between Chinese audiences and United States audiences was not significant at the aggregate level. Instead, the differences lie in an audience's responsiveness to characteristics of the ads. Specifically, while United States audiences showed a strong preference for ads featuring Chinese brands compared to those of United States brands, Chinese audiences did not differentiate them. United States audiences preferred ads using self-enhancing tactics to those using affiliative tactics, whereas, again Chinese audiences did not differentiate. We also explored whether individual differences in cultural values could account for the effect of audience nationality. Results suggest that differences embedded in culture groups, as indicated by audience nationality, could not be explained or substituted by individual variance in humor tolerance and uncertainty avoidance. Limitations and future directions were discussed.

Is perceived force an accurate method of regulating exercise load for the neck?

OBJECTIVE: Patient perceived level of force is commonly used to regulate exercise load. This study determined the accuracy of perceived force as a method of regulating exercise load for the cervical flexors and extensors. METHODS: Thirty healthy individuals performed submaximal isometric cervical flexion and extension exercise at perceived intensities (25%, 50%, and 75%) of their maximal voluntary contraction (MVC) with no feedback in a neck dynamometer. Measurements of "actual" versus "perceived" force levels were compared before and after the performance of an MVC. Data were analyzed descriptively and the relationship between performance error, test, and participant factors examined. RESULTS: With the exception of the 25% MVC extension trials post-MVC, an underestimation of force was observed over all conditions that worsened as the target force increased (50% and 75%) with only some improvement following the experience of an MVC (p < 0.001). Linear mixed modeling indicated participants familiar with exercise may have better accuracy (p = 0.07). CONCLUSION: Regulating isometric resistance exercise load of the neck based on a perceived proportion of MVC force may only be accurate at low intensities (25% MVC) but not for moderate to high (50-75%) intensities.

Aberrant Development and Synaptic Transmission of Cerebellar Cortex in a VPA Induced Mouse Autism Model.

Autistic spectral disorder (ASD) is a prevalent neurodevelopmental disease that affects multiple brain regions. Both clinical and animal studies have revealed the possible involvement of the cerebellum in ASD pathology. In this study, we generated a rodent ASD model through a single prenatal administration of valproic acid (VPA) into pregnant mice, followed by cerebellar morphological and functional studies of the offspring. Behavioral studies showed that VPA exposure led to retardation of critical motor reflexes in juveniles and impaired learning in a tone-conditioned complex motor task in adults. These behavioral phenotypes were associated with premature migration and excess apoptosis of the granular cell (GC) precursor in the cerebellar cortex during the early postnatal period, and the decreased cell density and impaired dendritic arborization of the Purkinje neurons. On acute cerebellar slices, suppressed synaptic transmission of the Purkinje cells were reported in the VPA-treated mice. In summary, converging evidence from anatomical, electrophysiological and behavioral abnormalities in the VPA-treated mice suggest cerebellar pathology in ASD and indicate the potential values of motor dysfunction in the early diagnosis of ASD.

Soft-Etching Copper and Silver Electrodes for Significant Device Performance Improvement toward Facile, Cost-Effective, Bottom-Contacted, Organic Field-Effect Transistors.

Poor charge injection and transport at the electrode/semiconductor contacts has been so far a severe performance hurdle for bottom-contact bottom-gate (BCBG) organic field-effect transistors (OFETs). Here, we have developed a simple, economic, and effective method to improve the carrier injection efficiency and obtained high-performance devices with low cost and widely used source/drain (S/D) electrodes (Ag/Cu). Through the simple electrode etching process, the work function of the electrodes is more aligned with the semiconductors, which reduces the energy barrier and facilitates the charge injection. Besides, the formation of the thinned electrode edge with desirable micro/nanostructures not only leads to the enlarged contact side area beneficial for the carrier injection but also is in favor of the molecular self-organization for continuous crystal growth at the contact/active channel interface, which is better for the charge injection and transport. These effects give rise to the great reduction of contact resistance and the amazing improvement of the low-cost bottom-contact configuration OFETs performance.

Fabrication of uniform 4H-SiC mesopores by pulsed electrochemical etching.

In this letter, the uniform 4H silicon carbide (SiC) mesopores was fabricated by pulsed electrochemical etching method. The length of the mesopores is about 19 µm with a diameter of about 19 nm. The introduction of pause time (T off) is crucial to form the uniform 4H-SiC mesopores. The pore diameter will not change if etching goes with T off. The hole concentration decreasing at the pore tips during the T off is the main reason for uniformity.

Direct synthesis of phosphorus and nitrogen co-doped monolayer graphene with air-stable n-type characteristics.

Large-area substitutional phosphorus-nitrogen co-doped monolayer graphene is directly synthesized on a Cu surface by chemical vapor deposition using molecules of phosphonitrilic chloride trimer as the phosphorus and nitrogen sources. The doping levels of both phosphorus and nitrogen atoms decrease as a function of the growth temperature. In contrast, the doping effect is enhanced with temperature because of the formation of more stable bond configurations for dopants at higher temperatures. Moreover, the doping amount of nitrogen atoms is always higher than that of phosphorus atoms at all used temperatures. The phosphorus and nitrogen co-doped graphene exhibits remarkable air-stable n-type characteristics. This work demonstrates the critical role of phosphorus atoms in achieving enhanced electron donation compared to nitrogen atom doping of graphene, and is important for various applications associated with the need for air-stable n-type graphene materials.

Topological structural transformations of nanoparticle self-assemblies mediated by phase transfer and their application as organic-inorganic hybrid photodetectors.

Nanoparticle (NP) self-assemblies have attracted an increasing amount of attention in recent years because of their potential application in the construction of novel nanodevices. The controllable transformation of NP self-assemblies (NPS) between a polar and nonpolar environment is required for many specific applications because of their different properties in different environments. In this article, water-soluble luminescent CdS/CdTe NPS were synthesized using thioglycolic acid as a capping agent. The stiff and straight NPS bundles became loose after phase transfer from an aqueous to an organic phase. Subsequently, the NPS transferred to the aqueous phase. The loose structure transformed into many twisted nanoribbons. Additionally, hybrid photodetectors made using the organic-soluble NPS and P3HT polymers were fabricated, and we found that the NPS/P3HT blend may be perfect for light detection. The organic-soluble NPS are potentially useful for the fabrication of semiconductor nanojunctions.

Fullerene/sulfur-bridged annulene cocrystals: two-dimensional segregated heterojunctions with ambipolar transport properties and photoresponsivity.

Fullerene/sulfur-bridged annulene cocrystals with a two-dimensional segregated alternating layer structure were prepared by a simple solution process. Single-crystal analysis revealed the existence of continuing π-π interactions in both the donor and acceptor layers, which serve as transport paths for holes and electrons separately. The ambipolar transport behaviors were demonstrated with single-crystal field-effect transistors and rationalized by quantum calculations. Meanwhile, preliminary photoresponsivity was observed with the transistor configuration.