Iterative Design of Near-Infrared Fluorescent Probes for Early Diagnosis of Alzheimer's Disease by Targeting Aß Oligomers.

Amyloid-ß oligomers (AßOs), crucial toxic proteins in early Alzheimer's disease (AD), precede the formation of Aß plaques and cognitive impairment. In this context, we present our iterative process for developing novel near-infrared fluorescent (NIRF) probes specifically targeting AßOs, aimed at early AD diagnosis. An initial screening identified compound 18 as being highly selective for AßOs. Subsequent analysis revealed that compound 20 improved serum stability while retaining affinity for AßOs. The most promising iteration, compound 37, demonstrated exceptional qualities: a high affinity for AßOs, emission in the near-infrared region, and good biocompatibility. Significantly, ex vivo double staining indicated that compound 37 detected AßOs in AD mouse brain and in vivo imaging experiments showed that compound 37 could differentiate between 4-month-old AD mice and age-matched wild-type mice. Therefore, compound 37 has emerged as a valuable NIRF probe for early detection of AD and a useful tool in exploring AD's pathological mechanisms.

Rational Design of Nitride Phosphor-In-Glass with Robust Stability and Photoluminescence Performance.

Phosphor-in-glass represents a promising avenue for merging the luminous efficiency of high-quality phosphor and the thermal stability of a glass matrix. Undoubtedly, the glass matrix system and its preparation are pivotal factors in achieving high stability and preserving the original performance of embedded phosphor particles. In contrast to the well-established commercial Y3Al5O12:Ce3+ oxide phosphor, red nitride phosphor, which plays a critical role in high-quality lighting, exhibits greater structural instability during the high-temperature synthesis of inorganic glasses. A telluride glass with a refractive index (RI = 2.15@615 nm) akin to that of nitride phosphor (∼2.19) has been devised, demonstrating high efficiency in photon utilization. The lower glass-transition temperature plays a crucial role in safeguarding phosphor particles against erosion resulting from exposure to high-temperature melts. Phosphor-in-glass retains 93% of the quantum efficiency observed for pure phosphor. The assembled white light-emitting diodes module has precise color tuning capabilities, achieving an optimal color rendering index of 93.7, a luminous efficacy of 80.4 lm/W, and a correlated color temperature of 5850 K. These outcomes hold potential for advancing the realm of inorganic package and high-quality white light illumination.

Differences in Glycemic Control for Inpatients with Type 1 Diabetes on Insulin Pump Versus Subcutaneous Insulin Therapy.

BACKGROUND: Inpatient use of insulin pump therapy has been increasing due to greater availability of this technology, however there is a paucity of research that investigates glycemic control of inpatient insulin pump users. OBJECTIVE: To compare the glycemic control of hospitalized patients with type 1 diabetes (T1D) who used insulin pump vs. multiple daily injections (MDI). DESIGN: Retrospective chart review. PARTICIPANTS: Patients with T1D who were hospitalized between January 1, 2017, and December 31, 2019, in an academic medical center in the New York metropolitan area. MAIN MEASURES: Patients were categorized into three groups based on their method of insulin administration: "pump only" group used insulin pump exclusively, "MDI only" group used MDI only, and "intermittent pump" group used a combination of both methods. The primary endpoints are mean blood glucose, rates of hypoglycemic events (blood glucose < 70 mg/dL), and rates of hyperglycemic events (blood glucose > 250 mg/dL). Separate multivariable Poisson regressions were performed to determine the association between the type of insulin administration and rate outcomes (i.e., rate of hypoglycemic events and rate of hyperglycemic events). RESULTS: The study included 78 patients with a mean age of 51, who were mostly male (54%), and white (72%). The average proportion of glucose measurements that were hyperglycemic for the "pump only", "MDI only", and "intermittent pump" groups were 0.11 (SD = 0.11), 0.25 (SD = 0.19), and 0.24 (SD = 0.25), respectively. The "pump only" group has a significantly lower proportion of hyperglycemic events as compared to the "MDI only" group (p = 0.0227). CONCLUSIONS: In this sample, patients who exclusively used their insulin pump while inpatient had a lower rate of hyperglycemic events than patients who used MDI only; suggesting that select patients can safely continue their insulin pump therapy in the inpatient setting.

Decomposition of an odorant in olfactory perception and neural representation.

Molecules-the elementary units of substances-are commonly considered the units of processing in olfactory perception, giving rise to undifferentiated odour objects invariant to environmental variations. By selectively perturbing the processing of chemical substructures with adaptation ('the psychologist's microelectrode') in a series of psychophysical and neuroimaging experiments (458 participants), we show that two perceptually distinct odorants sharing part of their structural features become significantly less discernible following adaptation to a third odorant containing their non-shared structural features, in manners independent of olfactory intensity, valence, quality or general olfactory adaptation. The effect is accompanied by reorganizations of ensemble activity patterns in the posterior piriform cortex that parallel subjective odour quality changes, in addition to substructure-based neural adaptations in the anterior piriform cortex and amygdala. Central representations of odour quality and the perceptual outcome thus embed submolecular structural information and are malleable by recent olfactory encounters.

NIR-enhanced Pt single atom/g-C3N4 nanozymes as SOD/CAT mimics to rescue ATP energy crisis by regulating oxidative phosphorylation pathway for delaying osteoarthritis progression.

Osteoarthritis (OA) progresses due to the excessive generation of reactive oxygen and nitrogen species (ROS/RNS) and abnormal ATP energy metabolism related to the oxidative phosphorylation pathway in the mitochondria. Highly active single-atom nanozymes (SAzymes) can help regulate the redox balance and have shown their potential in the treatment of inflammatory diseases. In this study, we innovatively utilised ligand-mediated strategies to chelate Pt4+ with modified g-C3N4 by π-π interaction to prepare g-C3N4-loaded Pt single-atom (Pt SA/C3N4) nanozymes that serve as superoxide dismutase (SOD)/catalase (CAT) mimics to scavenge ROS/RNS and regulate mitochondrial ATP production, ultimately delaying the progression of OA. Pt SA/C3N4 exhibited a high loading of Pt single atoms (2.45 wt%), with an excellent photothermal conversion efficiency (54.71%), resulting in tunable catalytic activities under near-infrared light (NIR) irradiation. Interestingly, the Pt-N6 active centres in Pt SA/C3N4 formed electron capture sites for electron holes, in which g-C3N4 regulated the d-band centre of Pt, and the N-rich sites transferred electrons to Pt, leading to the enhanced adsorption of free radicals and thus higher SOD- and CAT-like activities compared with pure g-C3N4 and g-C3N4-loaded Pt nanoparticles (Pt NPs/C3N4). Based on the use of H2O2-induced chondrocytes to simulate ROS-injured cartilage invitro and an OA joint model invivo, the results showed that Pt SA/C3N4 could reduce oxidative stress-induced damage, protect mitochondrial function, inhibit inflammation progression, and rebuild the OA microenvironment, thereby delaying the progression of OA. In particular, under NIR light irradiation, Pt SA/C3N4 could help reverse the oxidative stress-induced joint cartilage damage, bringing it closer to the state of the normal cartilage. Mechanistically, Pt SA/C3N4 regulated the expression of mitochondrial respiratory chain complexes, mainly NDUFV2 of complex 1 and MT-ATP6 of ATP synthase, to reduce ROS/RNS and promote ATP production. This study provides novel insights into the design of artificial nanozymes for treating oxidative stress-induced inflammatory diseases.

Periodic Folded Gold Nanostructures with a Sub-10 nm Nanogap for Surface-Enhanced Raman Spectroscopy.

Surface-enhanced Raman spectroscopy has emerged as a powerful spectroscopy technique for detection with its capacity for label-free, nondestructive analysis, and ultrasensitive characterization. High-performance surface-enhanced Raman scattering (SERS) substrates with homogeneity and low cost are the key factors in chemical and biomedical analysis. In this study, we propose the technique of atomic force microscopy (AFM) scratching and nanoskiving to prepare periodic folded gold (Au) nanostructures as SERS substrates. Initially, folded Au nanostructures with tunable nanogaps and periodic structures are created through the scratching of Au films by AFM, the deposition of Ag/Au films, and the cutting of epoxy resin, reducing fabrication cost and operational complexity. Periodic folded Au nanostructures show the three-dimensional nanofocusing effect, hotspot effect, and standing wave effect to generate an extremely high electromagnetic field. As a typical molecule to be tested, p-aminothiophenol has the lowest detection limit of up to 10-9 M, owing to the balance between the electromagnetic field energy concentration and the transmission loss in periodic folded Au nanostructures. Finally, by precisely controlling the periods and nanogap widths of the folded Au nanostructures, the synergistic effect of surface plasmon resonance is optimized and shows good SERS properties, providing a new strategy for the preparation of plasmonic nanostructures.

Demographic Variables Associated With Diabetes Technology Awareness or Use in Adults With Type 2 Diabetes.

Background: Studies in populations with type 1 diabetes highlight racial/ethnic disparities in the use of diabetes technology; however, little is known about disparities among those with type 2 diabetes. This project investigates the racial/ethnic and socioeconomic disparities in diabetes technology awareness and use in adults with type 2 diabetes in the ambulatory setting. Methods: Adults ≥40 years of age with type 2 diabetes in ambulatory care were invited to participate via an e-mail link to a de-identified REDCap (Research Electronic Data Capture) questionnaire. Variables, including awareness and use of continuous glucose monitoring (CGM) and insulin pumps, were summarized descriptively using frequencies and percentages and were compared across racial/ethnic groups, education level, and income using Pearson χ2 or Fisher exact tests. Results: The study included 116 participants, most of whom (62%) were White, elderly Medicare recipients. Compared with White participants, those of racially/ethnically minoritized groups were less likely to be aware of CGM (P = 0.013) or insulin pumps (P = 0.001). Participants with a high school education or less were also less likely to be aware of insulin pumps (P = 0.041). Interestingly, neither awareness nor use of CGM or insulin pumps was found to be associated with income. Conclusion: This cross-sectional analysis suggests that racially/ethnically minoritized groups and individuals with lower education have less awareness of CGM or insulin pumps.

Structure and optical limiting effects of heterometallic Ag6@Ti12 and Ag8@Ti12 oxo clusters regulated by alkynyl ligands.

Heterometallic Ag6@Ti12 and Ag8@Ti12 oxo clusters were prepared through a strategy of protecting polynuclear silver cores by a hollow Ti-O module. The introduction of alkyne ligands has shown significant influence on their structures and optical limiting effects.

c-Fos regulated by TMPO/ERK axis promotes 5-FU resistance via inducing NANOG transcription in colon cancer.

Acquired drug resistance is one of the most common limitations for the clinical response of colon cancer to 5-Fluorouracil (5-FU)-based chemotherapy. The relevant molecular mechanisms might be diversity, but still not be elucidated clearly. In this study, we aimed to investigate the potential mechanisms of c-Fos, a subfamily of activator protein-1, in 5-FU chemoresistance. We determined that phosphorylated c-Fos promoted colon cancer cells resistance to 5-FU by facilitating the cancer stemness. Mechanically, 5-FU treatment induced autolysosome-dependent degradation of TMPO, which subsequently triggered ERK-mediated phosphorylation of c-Fos. Additionally, c-Fos was found to bind to the promoter of NANOG and phosphorylation of c-Fos at Ser 374 was required for its regulation of NANOG expression. NANOG ablation impaired c-Fos/p-c-Fos induced 5-FU resistance and stemness. Taken together, these findings revealed that TMPO-mediated phosphorylation of c-Fos conferred 5-FU resistance by regulating NANOG expression and promoting cell stemness in colon cancer cells. c-Fos could be as a therapeutic target for colon cancer.

PET/NIR Fluorescence Bimodal Imaging for Targeted Tumor Detection.

Cancer is one of the greatest threats to human health due to late diagnosis and incomplete resection. The bimodal probe combines positron emission tomography (PET) imaging for noninvasive whole-body scanning with intraoperative near-infrared fluorescence (NIRF) surgical guidance for preoperative tumor detection, tumor resection during surgery, and postoperative monitoring. We developed a new PET/NIRF bimodal imaging agent, [68Ga]Ga-DOTA-NPC, covalently coupled to DCDSTCY and DOTA via ethylenediamine and radiolabeled with gallium-68, and investigated it in vitro and in vivo. The probe was found to be preferential for colon cancer cells due to the organic anion-transporting polypeptide1B3 (OATP1B3). PET/NIRF imaging allowed us to confirm [68Ga]Ga-DOTA-NPC as a promising probe for tumor detection, as it provides good biosafety and high-contrast tumor accumulation. Orthotopic and subcutaneous colon tumors were successfully resected under real-time NIRF guidance. [68Ga]Ga-DOTA-NPC provides highly sensitive and unlimited tissue-penetrating PET/NIRF imaging, helping to visualize and differentiate tumors from adjacent tissue.

Graphene/silicon heterojunction for reconfigurable phase-relevant activation function in coherent optical neural networks.

Optical neural networks (ONNs) herald a new era in information and communication technologies and have implemented various intelligent applications. In an ONN, the activation function (AF) is a crucial component determining the network performances and on-chip AF devices are still in development. Here, we first demonstrate on-chip reconfigurable AF devices with phase activation fulfilled by dual-functional graphene/silicon (Gra/Si) heterojunctions. With optical modulation and detection in one device, time delays are shorter, energy consumption is lower, reconfigurability is higher and the device footprint is smaller than other on-chip AF strategies. The experimental modulation voltage (power) of our Gra/Si heterojunction achieves as low as 1 V (0.5 mW), superior to many pure silicon counterparts. In the photodetection aspect, a high responsivity of over 200 mA/W is realized. Special nonlinear functions generated are fed into a complex-valued ONN to challenge handwritten letters and image recognition tasks, showing improved accuracy and potential of high-efficient, all-component-integration on-chip ONN. Our results offer new insights for on-chip ONN devices and pave the way to high-performance integrated optoelectronic computing circuits.

Reversible Thermally Driven Phase Change of Layered In2Se3 for Integrated Photonics.

Two-dimensional In2Se3, an unconventional phase-change material, has drawn considerable attention for polymorphic phase transitions and electronic device applications. However, its reversible thermally driven phase transitions and potential use in photonic devices have yet to be explored. In this study, we observe the thermally driven reversible phase transitions between α and ß' phases with the assistance of local strain from surface wrinkles and ripples, as well as reversible phase changes within the ß phase family. These transitions lead to changes in the refractive index and other optoelectronic properties with minimal optical loss at telecommunication bands, which are crucial in integrated photonic applications such as postfabrication phase trimming. Additionally, multilayer ß'-In2Se3 working as a transparent microheater proves to be a viable option for efficient thermo-optic modulation. This prototype design for layered In2Se3 offers immense potential for integrated photonics and paves the way for multilevel, nonvolatile optical memory applications.

Multivariate analysis differentiates intertemporal choices in both value and cognitive control network.

Choices between immediate smaller reward and long-term larger reward are referred to as intertemporal choice. Numerous functional magnetic resonance imaging (fMRI) studies have investigated the neural substrates of intertemporal choice via conventional univariate analytical approaches, revealing dissociable activations of decisions involving immediately available rewards and decisions involving delayed rewards in value network. With the help of multivariate analyses, which is more sensitive for evaluating information encoded in spatially distributed patterns, we showed that fMRI activity patterns represent viable signatures of intertemporal choice, as well as individual differences while controlling for age. Notably, in addition to value network, regions from cognitive control network play prominent roles in differentiating between different intertemporal choices as well as individuals with distinct discount rates. These findings provide clear evidence that substantiates the important role of value and cognitive control networks in the neural representation of one's intertemporal decisions.

Sex-specific effects of human chemosignal on perception of angry but not fearful faces.

Androsta-4,16,-dien-3-one (androstadienone), a steroids implicated as a human social chemosignal, has been reported to impact one's emotional perception along the valence axis. The current study takes a step further to examine whether it modulates the perception of angry and fearful faces, two negative emotions that are similar with respect to valence and arousal, but signal different social values. Systematic comparisons of psychophysical data collected from 40 heterosexual men and 45 heterosexual women revealed that androstadienone subconsciously biased heterosexual men toward perceiving the male faces as less angry, while it biased the heterosexual women toward perceiving the female faces as angrier. Meanwhile, androstadienone did not affect the perception of fearful faces in either men or women. These findings indicate that the modulation of androstadienone on negative emotional perceptions is not uniform, suggesting that it alters the perception of specific rather than general negative emotions. In particular, it impacts one's perception of anger, which signals impending aggression, and hence could further impact an individual's social interaction in a sex-specific manner.

Androstadienone modulates human aggression in a sex-dependent manner.

Chemosensory communication is ubiquitous in human social interaction. Androstadienone is a potential candidate human sex pheromone that is associated with social dominance and competition. The aim of the present study was to investigate the effects of androstadienone on aggression. We specifically distinguished two types of aggression, namely proactive and reactive aggression. Two hundred and six male and female participants received either androstadienone or a control carrier in a double-blind, placebo-controlled, between-participants design. Participants performed two aggression tasks, one on reactive aggression and the other on proactive aggression, while they were exposed to the olfactory stimuli. The results revealed that for men, smelling androstadienone reduced both reactive and proactive aggression, whereas it increased reactive aggression in women. These effects were present despite the olfactory stimuli not being explicitly discriminable. These findings provide direct evidence that androstadienone modulates human aggression in a sex-dependent manner.

Genome Sequence Resource of Serratia ureilytica HNU47: A Strain with Biocontrol Potential Against Bacterial Wilt Pathogen Ralstonia solanacearum.

Serratia ureilytica HNU47 was originally isolated from rhizosphere soil of stock in a continuous cropping tomato-planting field, which has excellent antagonistic ability against Ralstonia solanacearum. Here, we sequenced the genome of HNU47 to gain insights into the underlying basis of its antagonistic activity. Results of phylogenetic analysis of the whole genomic sequence demonstrated that HNU47 belongs to S. ureilytica. Through antiSMASH analysis, 10 secondary metabolite biosynthesis gene clusters were predicted. There were only two gene clusters with similarity higher than 95% with known compounds' gene clusters and the similarities of the other eight gene clusters were lower than 30%, including three gene clusters with no homology. In addition, biocontrol experiments confirmed that HNU47 could decrease the incidence of bacterial wilt caused by R. solanacearum on tomato. These findings support the potential of developing S. ureilytica HNU47 as a biocontrol agent against R. solanacearum by producing some unknown active compounds. The genome sequence reported here is also useful for revealing the modulation mechanisms underlying biosynthesis of active compounds.

De novo ulcerative colitis and Takotsubo cardiomyopathy following sleeve gastrectomy.

The increasing prevalence of severe obesity is a major public health concern. Bariatric surgery is an important treatment option for severe obesity due to its long-term sustained result. Multiple studies have shown that patients have an increased risk of developing inflammatory bowel disease following bariatric surgery. Takotsubo syndrome usually presents as acute left ventricular systolic dysfunction without corresponding obstructive coronary artery disease after an acute stress episode. We describe a unique case of a patient who developed de novo ulcerative colitis and takotsubo cardiomyopathy shortly after sleeve gastrectomy. The patient made a successful recovery due to prompt recognition and appropriate treatment.

Narrow Complex Tachycardia With Intermittent 2:1 Atrioventricular Relationship.

Narrow QRS complex tachycardia has a broad differential diagnosis. We present a series of rhythm strips with representative onset, transition from 2:1 AV conduction to 1:1 AV conduction, and offset of tachycardia. By analyzing these rhythm strips, we can identify the electrophysiologic mechanism and diagnosis. (Level of Difficulty: Intermediate.).

Estratetraenol increases preference for large sexual reward but not impulsivity among heterosexual males.

There is increasing evidence suggesting that estratetraenol, a human chemosignal deemed a putative sex pheromone, affects social cognition and sexual behavior. The present study investigates the effects of estratetraenol on preference for sexual rewards in heterosexual males. Seventy-six male participants received either estratetraenol or a control carrier in a double-blind, placebo-controlled, within-participant design. Participants underwent a sexual delay discounting task, in which they were asked to make a choice between a variable larger-later option (i.e., waiting longer to view a sexual picture for a longer duration) and a smaller-sooner option (i.e., waiting for a fixed shorter period of time to view the same picture for a shorter duration). Results revealed that, compared to the control solution, estratetraenol selectively increases preference for larger-later sexual rewards. Computational modelling showed that estratetraenol has no observable influence on impulsivity, as indexed by the discounting rate. These findings suggest that estratetraenol could increase men's sexual motivation, possibly facilitating behavioral processes associated with the pursuit of a sexual partner.

A comprehensive mouse brain acetylome-the cellular-specific distribution of acetylated brain proteins.

Nε-lysine acetylation is a reversible posttranslational modification (PTM) involved in multiple physiological functions. Genetic and animal studies have documented the critical roles of protein acetylation in brain development, functions, and various neurological disorders. However, the underlying cellular and molecular mechanism are still partially understood. Here, we profiled and characterized the mouse brain acetylome and investigated the cellular distribution of acetylated brain proteins. We identified 1,818 acetylated proteins, including 5,196 acetylation modification sites, using a modified workflow comprising filter-aided sample preparation (FSAP), acetylated peptides enrichment, and MS analysis without pre- or post-fraction. Bioinformatics analysis indicated these acetylated mouse brain proteins were mainly located in the myelin sheath, mitochondrial inner membrane, and synapse, as well as their involvement in multiple neurological disorders. Manual annotation revealed that a set of brain-specific proteins were acetylation-modified. The acetylation of three brain-specific proteins was verified, including neurofilament light polypeptide (NEFL), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP), and neuromodulin (GAP43). Further immunofluorescence staining illustrated that acetylated proteins were mainly distributed in the nuclei of cortex neurons and axons of hippocampal neurons, sparsely distributed in the nuclei of microglia and astrocytes, and the lack of distribution in both cytoplasm and nuclei of cerebrovascular endothelial cells. Together, this study provided a comprehensive mouse brain acetylome and illustrated the cellular-specific distribution of acetylated proteins in the mouse brain. These data will contribute to understanding and deciphering the molecular and cellular mechanisms of protein acetylation in brain development and neurological disorders. Besides, we proposed some problems that need to be solved in future brain acetylome research.