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Developing stretchable strain sensors with high sensitivity and stability is crucial for various applications such as prosthetic hands, human health monitoring, and human‐machine interactions. However, achieving these qualities simultaneously remains challenging. Here, an inherently stretchable strain sensor is presented that integrates ultrahigh sensitivity and robust stability, enabling stretch, press, or bend sensing capabilities. This sensor employs a softer elastomeric channel filled with liquid metal (LM) as the conductive path. A stiffer elastomer convex integrated into the channel serves as a strain‐manipulated gate, controlling opening gap of electrical current flow path. During deformation, the softer elastomer undergoes cross sectional reduction due to the Poisson effect, while the stiffer convex gate retains its geometry. This heterogeneous deformation behavior leads to significant contraction or closure of the LM channel, resulting in increased resistance and a remarkable enhancement in sensitivity by more than two orders of magnitude. The all‐soft design maintains exceptional stability even under extended or repetitive substantial deformations. With the ability to monitor subtle and large human body movements, detect grip actions of soft grippers reliably, and monitor the gradual and extended growth process of plants, this sensor holds significant potential for advancements in flexible electronics. [ABSTRACT FROM AUTHOR]

Stochastic computing is a non‐traditional computing approach that utilizes stochastic bitstreams to represent numerical values. This representation enables the implementation of circuits using basic logic gates, named stochastic circuits. This work proposes a versatile architecture with correlated input bitstreams for biased accumulation. The design offers a notable reduction in the reliance on random number generators, resulting in lower hardware costs and higher computing accuracy when compared with the existing designs. Experimental results show that the application of Gaussian smoothing has a reduction in area by at least 45% and an improvement in peak signal‐to‐noise ratio of at least 30%. [ABSTRACT FROM AUTHOR]

The on‐chip near‐infrared (NIR) lasing devices based on van der Waals (vdW) layered materials are highly desired owing to their widespread applications in optoelectronic communication, computing, and sensing. However, the single‐mode NIR lasing devices with superior performance based on vdW layered materials are hard to obtain because of complex and meticulous microcavity structure and the damage to layered materials during preparation. Here, a high‐quality NIR single‐mode lasing device in γ‐phase indium selenide (γ‐InSe) is achieved by using a transferrable planar microcavity. The single‐mode lasing devices based on distributed Bragg reflectors microcavity and super Tamm structure can be simply prepared with quality factors up to 5710 and 3526, respectively. And angle‐resolved spectra show that the lasing device has high directionality with divergence angle <5°. Moreover, the wavelength of lasing device can be tuned ≈30 nm by varying the cavity length via thickness control of γ‐InSe layer. These results not only suggest that γ‐InSe is a promising material for NIR lasing devices, but also present a simple and effective approach for preparing high‐quality lasing devices utilizing other vdW layered materials. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction and myocardial remodeling have been reported to be the main underlying molecular mechanisms of doxorubicin‐induced cardiotoxicity. SIRT6 is a nicotinamide adenine dinucleotide‐dependent enzyme that plays a vital role in cardiac protection against various stresses. Moreover, previous studies have demonstrated that FSTL1 could alleviate doxorubicin‐induced cardiotoxicity by inhibiting autophagy. The present study investigated the probable mechanisms of FSTL1 on doxorubicin‐induced cardiotoxicity in vivo and in vitro. We confirmed that FSTL1 exerted a pivotal protective role on cardiac tissue in vivo and on doxorubicin‐induced cell injury in vitro. Furthermore, FSTL1 can alleviate doxorubicin‐induced mitochondrial dysfunction by inhibiting autophagy and apoptosis. Further studies demonstrated that FSTL1 can activate SIRT6 signaling by restoring the SIRT6 protein expression in doxorubicin‐induced myocardial injury. SIRT6 activation elevated the protein expression of Nrf2 in doxorubicin‐induced H9C2 injury. Treatment with the Nrf2 inhibitor ML385 partially antagonized the cardioprotective role of SIRT6 on doxorubicin‐induced autophagy or apoptosis. These results suggested that the protective mechanism of FSTL1 on doxorubicin‐induced cardiotoxicity may be related with the inhibition of autophagy and apoptosis, partly through the activation of SIRT6/Nrf2. [ABSTRACT FROM AUTHOR]

Cyclobutanes with a gem‐dimethyl group are common motifs in natural products. However, strategies for constructing enantioenriched gem‐dimethyl cyclobutanes are still underdeveloped. Herein, we report an enantioselective approach to synthesize a broad group of chiral 2,3‐disubstituted cyclobutanones through sequential 1,4‐conjugate addition/trapping/cross‐coupling of readily available cyclobutenones. The intermediate 2‐bromocyclobutanone provides a valuable synthetic handle for further coupling transformations. In addition, this strategy was successfully utilized to synthesize gem‐dimethyl cyclobutane‐containing natural products, including (+)‐β‐caryophyllene, (−)‐raikovenal, (−)‐1β,9αH‐5‐linoleoyloxy‐4,5‐secocaryophyllen‐4‐one, and (−)‐rumphellanones A−C. [ABSTRACT FROM AUTHOR]

Perfluorotetradecanoic acid (PFTeDA) is a novel perfluoroalkyl substance that ubiquitously exists in the environment. However, whether PFTeDA affects adrenal cortex function remains unclear. Male Sprague–Dawley rats (age of 60 days) were daily administered with PFTeDA (0, 1, 5, and 10 mg/kg body weight) through gavage for 28 days. PFTeDA did not change body and adrenal gland weights. PFTeDA markedly elevated serum corticosterone level at 10 mg/kg but lowering serum aldosterone level at this dosage without influencing serum adrenocorticotropic hormone level. PFTeDA thickened zona fasciculata without affecting zona glomerulosa. PFTeDA remarkably upregulated the expression of corticosterone biosynthetic genes (Mc2r, Scarb1, Star, Cyp21, Cyp11b1, and Hsd11b1) and their proteins, whereas downregulating aldosterone biosynthetic enzyme Cyp11b2 and its protein, thereby distinctly altering their serum levels. PFTeDA markedly downregulated the expression of antioxidant genes (Sod1 and Sod2) and their proteins at 10 mg/kg. PFTeDA significantly decreased SIRT1/PGC1α and AMPK signaling while stimulating AKT1/mTOR signaling. Corticosterone significantly inhibited testosterone production by adult Leydig cells at >0.1 μM in vitro; however aldosterone significantly stimulated testosterone production at 0.1 nM. In conclusion, exposure to PFTeDA at male rat adulthood causes corticosterone excess and aldosterone deficiency via SIRT1/PGC1α, AMPK, and AKT1/mTOR signals, which in turn additively leads to testosterone deficiency. [ABSTRACT FROM AUTHOR]

Chlorinated bisphenol A (BPA) derivatives are formed during chlorination process of drinking water, whereas bisphenol S (BPS) and brominated BPA and BPS (TBBPA and TBBPS) were synthesized for many industrial uses such as fire retardants. However, the effect of halogenated BPA and BPS derivatives on glucocorticoid metabolizing enzyme 11β‐hydroxysteroid dehydrogenase 1 (11β‐HSD1) remains unclear. The inhibitory effects of 6 BPA derivatives in the inhibition of human and rat 11β‐HSD1 were investigated. The potencies for inhibition on human 11β‐HSD1 were TBBPA (IC50, 3.87 μM) = monochloro BPA (MCBPA, 4.08 μM) = trichloro BPA (TrCBPA, 4.41 μM) > tetrachloro BPA (TCBPA, 9.75 μM) > TBBPS (>100 μM) = BPS (>100 μM), and those for rat 11β‐HSD1 were TrCBPA (IC50, 2.76 μM) = MCBPA (3.75 μM) > TBBPA (39.58 μM) > TCBPA = TBBPS = BPS. All these BPA derivatives are mixed/competitive inhibitors of both human and rat enzymes. Molecular docking studies predict that MCBPA, TrCBPA, TCBPA, and TBBPA all bind to the active site of human 11β‐HSD1, forming hydrogen bonds with catalytic residue Ser170 except TCBPA. Regression of the lowest binding energy with IC50 values revealed a significant inverse linear regression. In conclusion, halogenated BPA derivatives are mostly potent inhibitors of human and rat 11β‐HSD1, and there is structure‐dependent inhibition. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) enters host cells by first engaging its cellular receptor angiotensin converting enzyme 2 (ACE2) to induce conformational changes in the virus‐encoded spike protein and fusion between the viral and target cell membranes. Here, we report that certain monoclonal neutralizing antibodies against distinct epitopic regions of the receptor‐binding domain of the spike can replace ACE2 to serve as a receptor and efficiently support membrane fusion and viral infectivity in vitro. These receptor‐like antibodies can function in the form of a complex of their soluble immunoglobulin G with Fc‐gamma receptor I, a chimera of their antigen‐binding fragment with the transmembrane domain of ACE2 or a membrane‐bound B cell receptor, indicating that ACE2 and its specific interaction with the spike protein are dispensable for SARS‐CoV‐2 entry. These results suggest that antibody responses against SARS‐CoV‐2 may help expand the viral tropism to otherwise nonpermissive cell types with potential implications for viral transmission and pathogenesis. Synopsis: SARS‐CoV‐2 enters host cells by first engaging its cellular receptor to induce membrane fusion. Certain monoclonal neutralizing antibodies can independently function as a receptor to support viral infectivity in cultured cells.Monoclonal neutralizing antibodies can serve as an entry receptor for SARS‐CoV‐2 in cell culture.Receptor‐like antibodies can function in three different membrane‐bound forms.The cognate receptor ACE2 is dispensable for SARS‐CoV‐2 entry in vitro. [ABSTRACT FROM AUTHOR]

In this study, the effect of agglomerate sizes for a fractal dimension (Df) of 2.5 on the hydrodynamics at intermediate Reynolds numbers (Re) of 1–120 was assessed. The results show that a core behaves like a solid sphere that exists in the central region inside the agglomerate. In addition, increasing the agglomerate diameter represents adding an extra permeable layer outside the agglomerate. For a larger Re or a smaller agglomerate diameter, the fluid can enter and penetrate through the agglomerate more easily, and the hydrodynamic characteristics of agglomerates deviate more from those of solid spheres. The effect of diameters on the velocity and pressure profiles becomes less significant with the increase in the diameter. Based on the simulated results, the drag ratio has an approximately linear relationship with Re, and its intercept has an exponential relationship with the dimensionless agglomerate diameter. Compared with homogeneous porous spheres, the drag ratio of the agglomerate is different. The effect of diameters on the drag ratio decreases as the diameter increases. It should be noted that the effect of radially varying permeability on inhomogeneous agglomerates should not be ignored and that the effect weakens as Re increases. [ABSTRACT FROM AUTHOR]

Background: Increased brain docosahexaenoic acid (DHA) uptake reflects a compensatory mechanism for maintaining brain DHA homeostasis and can be captured through PET‐MRI scan uptake studies using radiolabeled DHA. It has been previously shown that APOE4 status and alcohol intake alter brain DHA uptake in mice. Whether a change in DHA intake affects the brain DHA incorporation coefficient (K*) however is not known. Method: Four‐month‐old C57BL/6J mice were fed either a diet rich in DHA (15 kcal% Fat, 1.7 g/kg ALA, and 7g/kg DHA) or deficient in DHA (15 kcal% Fat and 0.9 mg/kg ALA) for 4 months. At 8 months, anesthetized mice were subjected to dynamic PET‐MRI for 30 min following i.v. injection of 22‐[18F]fluorodocosahexaenoic acid ([18F]FDHA), prepared in‐house through radiosynthesis. Using an image‐derived cardiac input function, brain uptake was assessed by estimating [18F]FDHA K* values using both the Patlak model approach and the irreversible two‐tissue compartmental model (Irr2TCM) with and without correction of the brain radioactivity for radioactive spillover from the skull. Mice were then sacrificed, and the plasma and brains were analyzed using liquid chromatography‐mass spectrometry (LC‐MS) to evaluate differences in the unlabeled concentrations of fatty acids into phospholipids, triglycerides, and other lipids. Result: There was no significant difference in the [18F]FDHA K* estimates (with either Patlak or Irr2TCM) between mice fed a DHA‐rich or a DHA‐deficient diet. LC‐MS based lipidomic analysis showed that the DHA‐rich diet significantly increased DHA concentration in triglycerides in plasma and in phosphatidylethanolamine in the brain. Conclusion: These results suggest that under physiological conditions, increased dietary intake of DHA in wild‐type mice increases DHA in brain phosphatidylethanolamine and in plasma triglycerides without changing the DHA K*. The net effect likely is increased brain DHA uptake, equal to the product of unesterified DHA plasma concentration and K*. Imaging brain DHA with dynamic [18F]FDHA PET‐MRI is a potentially useful tool not only to investigate the APOE4 phenotype, which promotes DHA dysregulation, but also to assess dietary and pharmacological interventions that affect brain DHA homeostasis as well as to guide future treatments. [ABSTRACT FROM AUTHOR]

Background: Neuroprotective nutritional interventions involving greater consumption of polyunsaturated fats (Mediterranean diet, fish consumption or DHA supplements) are less effective in APOE4 carriers with dementia compared to non‐carriers. We recently demonstrated greater activation of calcium dependent phospholipase A2 (cPLA2) in APOE4 compared with non‐APOE4 using both postmortem human brains and in brain tissues from APOE4 animal models. Activation of cPLA2 is associated with lower omega‐3 brain levels and lower measures of blood‐brain barrier (BBB) integrity as assessed using 7T DCE MRI to derive contrast transfer values (K trans). Method: Here, we present new data on aging (18 months) old APOE mouse models on a low DHA diet, APOE4‐TR mice treated with LPS and APOE knock out mice as a model of lower BBB integrity. All models were treated with the brain penetrant cPLA2 inhibitor ASB14780 at 10 mg/kg IP daily over 8 weeks in the aging model and acutely (7 days) in the younger LPS and APOE KO models. Result: cPLA2 inhibition was associated with increased brain omega‐3 levels in both the aging APOE4 model and in the younger APOE4 mice treated acutely with LPS. In the aging APOE4 mouse model, cPLA2 inhibition associated with better performance on novel object recognition, improved synaptic markers, and lower microglial activation. In the APOE KO model, treatment was associated with improved measures of BBB with lower K trans following treatment (Figure). Conclusion: The results here demonstrate how neuroinflammation associated with APOE4 depletes brain omega‐3s via activation of cPLA2 and how reducing cPLA2 activity can rescue this phenotype. The development of specific and potent brain penetrant cPLA2 inhibitors promises to enhance the brain effects of omega‐3 enriched diets by limiting the effects of neuroinflammation on the aging APOE4 brain. [ABSTRACT FROM AUTHOR]

Mid‐infrared (MIR) semiconductor laser sources are essential for applications in gas detection, infrared imaging, and high‐speed free space optical communications. At present, the dynamic wavelength tunability of MIR lasers based on lead salt, antimonide, and quantum cascade lasers is limited and their compact size as well as heterogeneous integration are still challenging. Two‐dimensional (2D) materials, used as optical gain materials, have the flexible tunability and compatible van der Waals integrations—providing many new possibilities for constructing MIR laser sources of large tunability and high integration. Here, wide‐wavelength tunable MIR vertical cavity surface emitting lasers (VCSELs) integrated on silicon substrates are realized based on 2D black arsenic phosphorus (b‐AsxP1−x). The emission wavelength of the optically pumped laser device is demonstrated to be tuned from 3.42 to 4.65 µm at room temperature, which could be controlled by adjusting the alloy composition and thickness of the gain media b‐AsxP1−x. The tunable MIR VCSEL device would pave the way for further exploration of 2D materials‐based IR lasers working as on‐chip light sources. [ABSTRACT FROM AUTHOR]

Integrated multiwavelength nanolasers are important in the practical development of optical circuitry for optical information processing and optical data storage. Herein, a new method for on‐chip integrated lasers is proposed, which can integrate single‐mode lasers with multiple wavelengths at room temperature. A four‐wavelength single‐mode nanoribbon laser chip is fabricated for demonstration. The mode of different laser units is controlled by the thickness of dielectric microcavity layers to select the resonant modes of excitation. Therefore, multiwavelength lasing can be coupled out based on the integrated cavity which is realized using combinatorial etching technique and can integrate tens of different‐wavelength lasers on a chip. The lasing modes of this device are all single‐mode lasing because of the short cavity length. Its lowest lasing threshold is only 5.4 kW cm−2. The gain material and the dielectric microcavity can be controlled and fabricated separately, which have strong controllability and flexibility. This new laser chip paves the way for a new class of hybrid nanolasers for chip‐integrated applications. [ABSTRACT FROM AUTHOR]

Stochastic computing (SC) encodes numerical values into probabilistic binary bitstreams to enable complex arithmetic operations to be transformed into simple bit operations. Different operations can be performed through the same SC element by adjusting the correlation between bitstreams. In this work, two stochastic mean circuits (MCs) are proposed by manipulating positively and negatively correlated bitstreams, respectively named PCMC and NCMC, to improve computing accuracy, lower area, and power consumption. Furthermore, a general structure for MCs, denoted as GMC, is also proposed to generalize their design approach. Compared with the existing multiplexer (MUX)‐based stochastic MCs, the proposed circuits have approximately 50%, 59%, 61%, and 64% reduction in area, and 100×, 10×, 151×, and 12 × improvement in MSE, for 2‐, 3‐, 4‐, and 5‐input situations, respectively. With applications to edge detection and mean filtering, the proposed designs are superior to the existing counterparts in terms of accuracy and hardware cost. [ABSTRACT FROM AUTHOR]

Inorganic perovskites have become a widely investigated candidate for fabrication of high‐performance micro‐devices due to their excellent optoelectronic properties and stability to the environment. Especially, their excellent lasing characteristics as a micro/nanolaser source, combined with flexible substrates, have great potential in the field of wearable or foldable photonic device applications. Here, the high‐quality CsPbBr3 perovskite microsheets with stress‐induced grooves are directly prepared on the ultrathin fluorine mica by the chemical vapor deposition method, and the single‐mode lasers are realized in these large‐size (>15 × 15 µm) microsheets. Thanks to the flexibility of mica, bending induced tensile strain on CsPbBr3 microsheet causes the laser mode blueshift continuously and reversibly with 15.3 meV %−1, this can be well explained by the Lorentz oscillator model under lasing conditions. Furthermore, by using the first‐principles calculation, it is clarified that the bandedge blueshift originates from the distortion of {PbBr6}4− octahedra and the consequential increase of the bond length of Pb‐Br3 and the Pb‐Br3‐Pb bond angle. This work opens up a new way to realize on‐chip single‐mode lasers with microstructures, and is helpful for the application of flexible photonic device in the fields of integrated on‐chip sensors. [ABSTRACT FROM AUTHOR]

Short‐wave infrared (SWIR) information is critical for material analysis, imaging sensing, and other fields. To acquire SWIR spectrum with compact devices, strategies for reconstructive microspectrometer have emerged, such as photonic crystal and quantum dot filter. However, the current SWIR microspectrometer needs many filters with insufficient resolution. In this work, the authors develop a SWIR chip‐spectrometer based on Fabry–Perot microcavities array which can be fabricated by using fast and low‐cost UV laser direct‐writing grayscale lithography. The ultra‐compact chip‐spectrometer can work in a very wide range from 900 to 1700 nm with only 20 detector pixels and a reconstruction algorithm. The spectral resolution achieves 2 nm by 50 pixels set and 5 nm by 20 pixels set at SWIR range, which is 3 times higher, with 3.9 times less units number, than for recently reported SWIR quantum dot spectrometers. To the best of our knowledge, this is a minimum high‐resolution SWIR InGaAs detector based chip‐spectrometer which can work in the whole SWIR band with only 20 detector pixels. It has great potential for applications in smart‐phone or other miniature portable spectrometers. [ABSTRACT FROM AUTHOR]

Image binarization algorithms in document image analysis divide pixel values into two groups, including white as background and black as foreground. Among others, the local contrast and mean (LCM)‐based thresholding algorithm offers excellent performance in processing degraded documents. This algorithm, however, is susceptible to noise and requires significant hardware resources. In this paper, an energy‐efficient and fault‐tolerant architecture is proposed for implementing the LCM algorithm in stochastic computing (SC). Leveraging correlated input bitstreams, this architecture saves energy and improves the fault tolerance of the implementation. Experimental results show that the proposed LCM stochastic architecture significantly outperforms the stochastic implementation of the Sauvola algorithm in terms of both binarization accuracy and hardware overhead and energy consumption. Even using 16‐bit streams, the proposed circuit produces an error rate lower than 5%. The stochastic implementation of the LCM algorithm using a 16‐bit length FSM‐based LD sequence is 22 times less in area, 26 times less in total power, 28 times less in energy consumption and more fault‐tolerant than the conventional 8‐bit bit‐width weighted binary with the same frequency constraints. [ABSTRACT FROM AUTHOR]

Objectives: The prevalence of human papillomavirus (HPV) infection and HPV genotypes varies in different regions. However, there is little data on HPV prevalence and genotyping in Guangxi Province, South China. This study conducted a 10‐year survey in a health center, to estimate the prevalence characteristics of HPV genotypes. Methods: By using polymerase chain reaction (PCR) amplification and nucleic acid molecular hybridization, the HPV genotypes were detected from 77,756 females who were patients of the Department of Obstetrics and Gynecology and those who visited the Health Management Center for a physical examination between August 2011 and November 2020. The prevalence, genotypes, age‐related HPV infections, as well as chronological change of HPV prevalence, and the HPV genotype distribution were analyzed. Results: The overall prevalence of HPV infection was 21.14% (16,439/77,756). The HPV infection rate differed significantly between the patients of the Department of Obstetrics and Gynecology and the women who underwent a physical examination (22.98% vs. 9.88%, p < 0.05). The prevalence rates of high‐risk HPV, low‐risk HPV, mixed HPV (mixed high‐risk, and low‐risk HPV infection), and multiple HPV infections were 18.96% (14,739/77,756), 4.09% (3178/77,756), 1.90% (1478/77,756), and 4.94% (3838/77,756), respectively. The most prevalent genotypes were HPV 52, 16, and 58. The age‐associated HPV prevalence showed bimodal curves, with the first peak at <25 years and the second peak at >56 years. Conclusions: This study provides baseline data on the HPV prevalence in the general female population of Nanning, Guangxi Province. Women <25 and >56 years old faced the greatest threat of HPV infection, and HPV 52, 16, and 58 were the most common genotypes. [ABSTRACT FROM AUTHOR]

Stochastic computing (SC) is an approximate computing paradigm using probabilities and aims at realizing circuits with low hardware cost. Basic operations (such as addition) have been comprehensively studied, whereas there are few studies on nonlinear operations (such as division and square root) in SC. In this paper, a stochastic division circuit is proposed by using maximally correlated input bitstreams to eliminate the necessity for distinguishing the divisor and dividend. Additionally, four stochastic square root circuits are designed with improved accuracy by decreasing the correlation between intermediate bitstreams via inserting delay elements. Experimental results show that both the proposed division and square root circuits achieve lower mean squared errors (MSEs) while requiring nearly the same hardware resources, compared with the state‐of‐the‐art designs. This result shows the potential in exploiting signal correlation in SC circuit design for high accuracy. [ABSTRACT FROM AUTHOR]

Background: Polyunsaturated fatty acids (PUFAs) are the precursors of various lipid mediators of inflammation. Brain imaging techniques for monitoring the brain's uptake of PUFAs would not only uncover the effects of risk factors for excessive neuroinflammation associated with Alzheimer's disease (AD) and related dementia but also direct the development of methods to prevent or treat AD. Radiosynthesized 11C‐docosahexaenoic acid (DHA) and 11C‐arachidonic acid (AA) have already been utilized in positron emission tomography (PET) studies in humans [1, 2]. Because 18F has a longer half‐life than 11C, fluorinated PUFA derivatives would be more favorable alternatives for PET studies of brain uptake. Methods: We prepared 18F‐fluorinated analogues of DHA (18F‐FDHA) and AA (18F‐FAA) as PUFA PET tracers. Radiosynthesis was performed via a nucleophilic fluorination scheme using the tosylate ester derivatives as precursors. We then performed bolus injection of each tracer into 16‐month‐old APOE4 knock‐in mice and scanned them by dynamic PET‐MRI over 45 min to assess region‐specific uptake. PUFA uptake kinetics in the cerebral region was evaluated using the time‐dependent activity in the lumen of the right ventricle as the image‐derived input function and using an irreversible two‐tissue compartment model to calculate the incorporation coefficient (Ki). Results: Both 18F‐FDHA and 18F‐FAA were successfully synthesized in high radiochemical purity (≥98%) and were found to be stable in the formulation and mouse serum for 2 hr. The mean Ki values for the cerebral region were determined to be 6.31 ± 0.98 µL mL‐1 min‐1 for 18F‐FDHA (n = 4) and 6.75 ± 0.68 µL mL‐1 min‐1 for 18F‐FAA (n = 5). Conclusion: Using an image‐based method with 18F‐fluorinated PUFA tracers, we were able to determine Ki values for both AA and DHA. The use of these PUFA PET tracers has the potential to elucidate deleterious changes in PUFA metabolism during various phases of AD as well as effects due to dietary interventions and drug treatment. References 1. Yassine, H.N. et al. (2017). DHA brain uptake and APOE4 status: a PET study with [1‐11C]‐DHA. Alzheimers Res Ther 9, 23. 2. Zanderigo, F. et al. (2018). [11C]arachidonic acid incorporation measurement in human brain: Optimization for clinical use. Synapse 72. [ABSTRACT FROM AUTHOR]

Nanocrystals (NCs) are widely used in optoelectronics, photocatalysis, and bioimaging. As the surface area to volume ratio increases with a decrease in the size of NCs, strategies to control the size of NCs are highly valuable for many applications. Given the importance of photoluminescent dyes, especially those with aggregation‐induced emission, the transformation from an amorphous to a crystalline state can yield a drastic enhancement in their optical properties, which is of significance for biomedical applications. Till now, there is no general method available for the synthesis of small NCs with accurate control over the size and uniformity. Herein, a simple and general approach of ouzo nanocrystallization is presented for the synthesis of small (<100 nm) and highly uniform (polydispersity index~0.1) NCs with good control over the size. The process of nanoprecipitation is used to synthesize uniform nanoparticles (NPs) with different size, which is followed by solvent addition to form swollen NPs. Further, the amorphous core of swollen NPs is converted into NCs within polymer shell under Ouzo zone, which restricts NCs to grow above certain size. To demonstrate the general applicability of ouzo nanocrystallization, two different classes of luminescent materials are used as examples to fabricate small and highly uniform NCs. [ABSTRACT FROM AUTHOR]

Background: Carrying the apolipoprotein E ε4 (APOE4) allele is the highest known genetic risk factor for late‐onset Alzheimer's disease (LOAD). Although how APOE4 leads to LOAD is not known, dysregulated endo‐lysosomal trafficking and lipid metabolism are key defects associated with APOE4. Cholesterol accumulation in glia instigates intracellular trafficking defects, increases cellular stress, and disrupts secretion. Additionally, enlarged endosomes were observed in the frontal lobes of APOE4‐carrying individuals, decades before the appearance of Aβ fibrilization. Therefore, we asked if cholesterol and endo‐lysosomal trafficking dysregulation in APOE4 carriers were due to differential lipidation of APOE3 and APOE4. Method: Localization of ATP Binding Cassette Subfamily A Member 1 (ABCA1) in early, late, and recycling endosomal compartments were analyzed in human isogenic induced pluripotent stem cell (iPSC)‐derived neural cells and in cell lines treated with recombinant APOE in microscopic images. Membrane and cytoplasmic ABCA1 were compared using Western blots. Secreted high‐density lipoprotein (HDL) particles containing fluorescently tagged APOE3 or APOE4 were analyzed using ion‐mobility spectrometry. CS‐6253, an ABCA1 agonist peptide, was used to increase APOE lipidation. Result: The protein levels of ABCA1, which mediates cholesterol and phospholipid efflux to the nascent apolipoprotein particles, were lower in APOE4/4 iPSC‐derived astrocytes compared to astrocytes derived from isogenic APOE3/3 iPSCs. Advanced image analysis revealed lower ABCA1 protein levels in Rab11+ recycling endosomes and less colocalization between ABCA1 and Rab7, a late endosome marker, in APOE4/4 astrocytes than APOE3/3 astrocytes. Consequently, less ABCA1 was detected at the cell membrane. Combined with previous data, these findings suggest APOE4 lipidation was reduced due to reduced ABCA1 activity. Additionally, BHK cells treated with recombinant APOE3 or APOE4 showed differences in ABCA1 localization that were altered by increasing APOE lipidation by activating ABCA1 via CS‐6253. Finally, fluorescently tagged APOE3 and APOE4 were incorporated in HDL particles and were secreted whose sizes were altered after CS‐6253 treatment, suggesting differences in lipidation levels. Conclusion: We demonstrated that diminished APOE4 lipidation is, at least in part, due to dysregulation of endo‐lysosomal trafficking of ABCA1 and that increasing APOE4 lipidation could alleviate cellular defects. [ABSTRACT FROM AUTHOR]

Background: Apolipoprotein E4 (ApoE4) dysregulates cholesterol metabolism in the brain promoting the accumulation of lipid droplets, synaptic dysfunction and associates with a greater Alzheimer's disease risk. We previously demonstrated that ApoE4 reduces the function of ATP‐binding cassette transporters A1 (ABCA1) which has important roles in cholesterol transport. The mechanisms of how ApoE4 induces less ABCA1 activity are poorly understood. Method: ABCA1 binding proteins were analyzed with mass spectrum after immunoprecipitation. Immortalized astrocytes, primary astrocytes, mouse brain and human postmortem brain samples were used to test the association of ABCA1 and caveolin‐1 levels. Small interfere RNA was used to knockdown caveolin‐1 expression and 3H labelled cholesterol was used to test the cholesterol efflux of ABCA1. Result: Here, we enriched ABCA1 binding protein complexes from ABCA1‐overexpressing cells treated with recombinant ApoE3 or ApoE4 proteins for a proteomic screen implicating endocytosis as a major pathway differentiating ApoE3 from ApoE4. Among the protein targets discovered, caveolin‐1 expression increased after ApoE4 treatment. Caveolin‐1 and ABCA1 interactions were confirmed using immunoprecipitation experiments. Cholesterol accumulation in astrocytes induced caveolin‐1 expression and promoted ABCA1 degradation. Greater caveolin‐1 and lower ABCA1 expression was observed in brains of 8, 18 and 22 months‐old ApoE4‐TR mice compared with the corresponding ApoE3‐TR mice. Isolation of single cell types from adult mouse ApoE‐TR brains confirmed lower ABCA1 and greater caveolin‐1 expression was largely driven by astrocytes and not microglia or neurons enriched fractions. Conclusion: In conclusion, cholesterol accumulation induced by ApoE4 promotes ABCA1 degradation in astrocytes partly through a caveolin‐1 dependent endocytosis pathway. [ABSTRACT FROM AUTHOR]

In this paper, the hierarchical solid structures and multiscale pore structures inside fluidized nanoparticle agglomerates (FNPAs) are qualitatively revealed in the transmission electron microscope (TEM) images of ultrathin slices of solidified FNPAs from the bottom of the bed. The micromorphology of aggregates and simple agglomerates, the porosities of pores intra and inter simple agglomerates, and pore size distributions inside FNPAs are quantitatively analyzed by image analysis. The average fractal dimensions of aggregates of about 300 nm‐1000 nm and simple agglomerates of several micrometres are around 1.9 and 2.6 respectively. The pore structure of FNPAs is complex and heterogeneous and displays a multiscale feature. Nearly 50% of the pores intra simple agglomerates have sizes of tens of nanometers and more than half the pores between simple agglomerates are of micrometre scale. The porosities of the pores intra and inter simple agglomerates are about 0.82 and 0.85 respectively. [ABSTRACT FROM AUTHOR]

The direct growth of semiconductor nanowire (NW) arrays horizontally aligned on a substrate is critically important for the applications of NWs in electronic or optoelectronic devices at the circuit level. The strict requirement of lattice matching between a substrate and a material in the covalent epitaxy of crystals makes the wire arrays be grown on the substrates only with similar lattice parameters. Herein, a van der Waals epitaxy route is developed to realize the in‐plane growth of large‐scale Bi2S3 NW arrays on mica with a large lattice mismatch. The orthorhombic Bi2S3 NWs grow epitaxially with the axial direction of ⟨001⟩Bi2S3 along the six symmetric directions of the mica. Transmission electron microscope measurements show that the epitaxial relationships are [001]Bi2S3||[100]mica and [32¯0]Bi2S3||[010]mica along the length and width directions of the wires, respectively. More importantly, photodetectors based on Bi2S3 NWs show a wide photoresponse spectrum range from 500 to 980 nm. A high responsivity (5233 A W−1) and a specific detectivity (1.8 × 1012 Jones) are achieved under 830 nm light irradiation with ultralow intensity (64 nW cm−2). In addition, the photodetectors exhibit high stability with at least 48 day storage in ambient atmosphere or with 1000 times bending. [ABSTRACT FROM AUTHOR]

Near infrared (NIR) light excitable photosensitizers are highly desirable for photodynamic therapy with deep penetration. Herein, a NIR‐II light (1200 nm) activated photosensitizer TQ‐BTPE is designed with aggregation‐induced singlet oxygen (1O2) generation for two‐photon photodynamic cancer cell ablation. TQ‐BTPE shows good two‐photon absorption and bright aggregation‐induced NIR‐I emission upon NIR‐II laser excitation. The 1O2 produced by TQ‐BTPE in an aqueous medium is much more efficient than that of commercial photosensitizer Ce6 under white light irradiation. Upon NIR‐II excitation, the two‐photon photosensitization of TQ‐BTPE is sevenfold higher than that of Ce6. The TQ‐BTPE molecules internalized by HeLa cells are mostly located in lysosomes as small aggregate dots with homogeneous distribution inside the cells, which favors efficient photodynamic cell ablation. The two‐photon photosensitization of TQ‐BTPE upon NIR‐I and NIR‐II excitation shows higher 1O2 generation efficiency than under NIR‐I excitation owing to the larger two‐photon absorption cross section at 920 nm. However, NIR‐II light exhibits better biological tissue penetration capability after passing through a fresh pork tissue, which facilitates stronger two‐photon photosensitization and better cancer cell ablation performance. This work highlights the promise of NIR‐II light excitable photosensitizers for deep‐tissue photodynamic therapy. [ABSTRACT FROM AUTHOR]

A novel visible‐light‐induced radical cascade trifluoromethylation/cyclization of N‐benzamides with CF3SO2Na has been achieved. This protocol provides an efficient strategy for the synthesis of CF3‐containing isoquinoline‐1,3‐diones under mild reaction conditions. The reaction features metal‐free, air oxidation, CF3SO2Na as CF3 source, additives free and operational simplicity. Moreover, the representative products displayed significant potencial antifungal activities in vitro. [ABSTRACT FROM AUTHOR]

Background: APOE4 is the strongest genetic risk factor for late‐onset Alzheimer's disease (AD) and is associated with increased susceptibility to neuroinflammation, however the reasons for this association are not very clear. Increased phosphorylation of calcium‐dependent cytosolic PLA2 (cPLA2) is evident in amyloid plaques of human brains. Enhanced cPLA2 activity promotes the release of arachidonic acid (AA) and prostaglandin E₂ (PGE2) to initiate an inflammatory response. Our primary aim is to determine if ApoE4 increases cPLA2 activity. Method: Cellular, animal models and human brain tissue were employed Result: We found greater cPLA2 expression and phosphorylation in ApoE4 immortalized and primary astrocytes compared to ApoE3. Greater levels of phosphorylated cPLA2 and higher cPLA2 activity were found in the brains of ApoE4‐TR mice (vs ApoE3) at 8‐months of age. In addition, phosphorylated cPLA2 level was increased in hippocampus of APOE4/E4 carriers with AD compared to cognitive healthy APOE3/E3 carriers. To examine the mechanisms for phosphorylation of cPLA2, we examined its regulation by the mitogen‐activated protein kinase (MAPK) pathway. We found that the p38 pathway (but not ERKs pathway) was more activated in cells, mouse and human brain samples with ApoE4 genotype compared to ApoE3. Conclusion: Our research implicates an ApoE4‐driven cPLA2 activation as a mechanism for the increased susceptibility to neuroinflammation in AD and a potential target for treatment. [ABSTRACT FROM AUTHOR]

Background: The activation of calcium‐dependent cytosolic phospholipase A2 (cPLA2) is involved in inflammatory signaling by promoting the conversion of arachidonic acid (AA) into eicosanoids, while catabolizing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We previously found higher cPLA2 activation correlated with increased pro‐inflammatory lipid metabolites in APOE4 brains. However, it is not known whether the inhibition cPLA2 will decrease neuroinflammation ApoE4‐mice. Method: First, ApoE4 targeted replacement mice (ApoE4‐TR, n = 3, male, 4 months old) were treated daily with vehicle or the specific cPLA2 inhibitor ASB14780 (10 mg/kg, intraperitoneal) for three days. The brains were collected and analyzed using LC‐MS based lipidomics. Second, ApoE2‐TR (n = 14, 8M/6F), ApoE3‐TR (n = 12, 5M/7F) and ApoE4‐TR (n = 17, 8M/9F) mice were fed a low‐DHA diet starting at 6 months old. ApoE4 mice were treated daily for three weeks with vehicle (n = 8, 4M/4F) or 10mg/kg/day ASB14780 IP (n = 9, 5M/4F) starting at 14 months old. Behavioral tests were subsequently conducted on the mice, after which the brains were collected for lipidomic and biochemical analyses. Result: IP ASB14780 was detected in brain tissue corresponding with decreases in pro‐inflammatory metabolites of AA after only 3 days treatment in ApoE4‐TR mice. In addition, long term ASB14780 treatment decreased brain cPLA2 phosphorylation levels and significantly increased brain EPA and DHA levels (p<0.01 for both) but did not change brain AA levels in ApoE4‐TR mice. Compared to ApoE3‐TR mice, untreated ApoE4‐TR mice had higher levels of inflammatory eicosanoids (e.g., prostaglandin E2, PGE2) resulting from AA metabolism. However, ASB14780 treatment decreased inflammatory metabolites in ApoE4‐TR mice. Additionally, ASB14780‐treatment was able to reduce microglia activation in ApoE4‐TR mice (p = 0.04 for hippocampus and p<0.01 for cortex). For behavioral experiments, ApoE4‐TR mice had significantly lower discrimination index compared to ApoE3‐TR mice at 15 months using the novel object recognition test (p = 0.029). Treatment with ASB14780 ameliorated the recognition deficits of ApoE4‐TR mice but the effects did not reach statistical significance (p = 0.15). Conclusion: Our findings reveal inhibition of cPLA2 with ASB14780 could ameliorate eicosanoid‐driven neuroinflammation in ApoE4 mice, restoring synaptic dysfunction, and preventing behavioral deficits. cPLA2 represents a potential drug target to mitigate increased neuroinflammation with APOE4 and AD. [ABSTRACT FROM AUTHOR]

Background: The Apolipoprotein E4 (APOE4) allele has been associated with an accentuated response to brain inflammation and increases the risk of AD dementia progression. Among inflammation signaling pathways, eicosanoids play a prominent role in neurodegeneration. Method: This study compared measures of the eicosanoid lipidome from patients with AD dementia compared to age and sex‐matched controls with no cognitive impairment (NCI), stratified by APOE genotypes using postmortem brain tissues from the Religious Order Study (n = 42). Result: Targeted lipidomic analysis by mass spectrometry of the dorsolateral prefrontal cortex demonstrated lower levels of omega‐3 fatty acids eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), and DHA‐derived neuroprotectin D1 (NPD‐1) in persons with lower global cognitive function, independent of age, sex and education years. APOE4 was associated with greater pro‐inflammatory lipids (e.g., PGD2, PGE2, 12‐HHT, LTB4 and 5‐HETE) and pro‐resolving lipids (eg. lipoxins, resolvins and EETs) in patients with dementia (Figure 1). Pathway analysis implicates greater activation of calcium dependent phospholipase A2 (cPLA2), 5‐lipoxygenase (5‐LOX) and soluble epoxide hydrolase (sEH) underlying the observed lipidomic profile. Conclusion: These results confirm a chronic state of unresolved inflammation in the AD dementia brain that is accentuated in carriers of the APOE4 allele and identify novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Blood‐brain barrier (BBB) is essential for neural health and function. Degradation of BBB is observed in Alzheimer's disease (AD) and is more pronounced in individuals carrying the apolipoprotein E4 (ApoE4) allele, which is a major genetic risk factor for AD. ApoE4 increases the activation of calcium‐dependent phospholipase A2 (cPLA2), which is linked to BBB function. Here, we asked if cPLA2 inhibition in ApoE4 carrying mice could repair BBB integrity and if the changes could be observed in vivo by dynamic contrast‐enhanced MRI (DCE‐MRI). Method: 16‐month‐old ApoE4 targeted replacement (ApoE4‐TR) mice were divided into a control group treated with vehicle (n=4) and an experimental group treated with a cPLA2 inhibitor ASB‐14780 (n=4). All imaging was performed using a 7T MRI scanner. DCE‐MRI protocol involved acquisition of baseline images (5min), mice receiving a bolus of gadolinium diethylenetriaminepentaacetic acid (Gd‐DTPA, 0.3mmol/kg, i.v.)) and followed by post‐bolus scans for 20min. Regions of interest (ROIs), such as the hippocampus and isocortex, were manually defined using T2‐weighted (FSE) anatomical scans in ImageJ. Volume transfer constants (KTrans) of the contrast agent uptake were calculated for each subject from the dynamic DCE‐MRI scan using the Patlak model on the Rocketship software (MATLAB). Result: KTrans values for the isocortex and the hippocampus were calculated for two animals from the control group and three animals from the experimental group. The mean KTrans value in the hippocampus region was 60% lower for the mice treated with cPLA2 inhibitor than controls (p=0.056), 0.0459 ± 0.0168 min‐1 and 0.117 ± 0.030 min‐1 respectively. Similarly, the mean KTrans value in the isocortex for the treated mice was 50% lower than the controls (p=0.89), 0.0554 ± 0.018 min‐1 and 0.110 ± 0.028 min‐1 respectively. Conclusion: We observed that cPLA2 inhibition decreased KTrans values implying increased BBB function. Thus, cPLA2 inhibition can be a possible therapeutic path towards reversing some of the damage to the brain due to AD. Currently, we are validating this observation with larger sample sizes and by analyzing the brains of these mice for changes in molecular signatures of BBB. [ABSTRACT FROM AUTHOR]

Abstract: Red/near‐infrared dyes are highly demanded for biological applications but most of them are far from satisfactory. In this work, a series of red/near‐infrared fluorophores based on electron‐withdrawing benzo[1,2‐b:4,5‐b′]dithiophene 1,1,5,5‐tetraoxide (BDTO) are synthesized and characterized. They possess both aggregation‐induced emission, and hybridized local and charge‐transfer characteristics. Crystallographic, spectroscopic, electrochemical and computational results reveal that the oxidation of benzo[1,2‐b:4,5‐b′]dithiophene to BDTO can endow the fluorophores with greatly red‐shifted emission, enhanced emission efficiency, reduced energy levels, enlarged two‐photon absorption cross section, and increased reactive oxygen species generation efficiency. The nanoparticles fabricated with a near‐infrared fluorophore TPA‐BDTO show high photostability and biocompatibility with good performance in targeted photodynamic ablation of cancer cells and two‐photon fluorescence imaging of intravital mouse brain vasculature. [ABSTRACT FROM AUTHOR]

During the evolution of a software system, a large number of bug reports are submitted. Locating the source code files that need to be fixed to resolve the bugs is a challenging problem. Thus, there is a need for a technique that can automatically figure out these buggy files. A number of bug localization solutions that take in a bug report and output a ranked list of files sorted based on their likelihood to be buggy have been proposed in the literature. However, the accuracy of these tools still needs to be improved. In this paper, to address this need, we propose AmaLgam+, which is a method for locating relevant buggy files that puts together fives sources of information, namely, version history, similar reports, structure, stack traces, and reporter information. We perform a large-scale experiment on four open source projects, namely, AspectJ, Eclipse, SWT, and ZXing to localize more than 3000 bugs. We compare AmaLgam + with several state-of-the-art approaches including AmaLgam, BLUiR+, BRtracer+, BugLocator, and TFIDF-DHbPd. These approaches leverage one or several of the sources of information analyzed by AmaLgam+, but not all of them. On average, AmaLgam + achieves a 6.0% improvement over AmaLgam, which merges three sources of information, in terms of Mean Average Precision (MAP). For AspectJ and Eclipse datasets, in which there are many bug reports with stack traces and many reporters submit multiple bug reports, AmaLgam + achieves a 12.0% improvement over AmaLgam in terms of MAP. Compared with the other state-of-the-art approaches, AmaLgam + achieves an improvement of 20.3%, 22.5%, 33.1%, and 73.9% over BLUiR+, BRtracer+, BugLocator, and TFIDF-DHbPd in terms of MAP, respectively. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Lipid poor apolipoprotein E (ApoE) aggregates are central to the pathogenesis of Alzheimer's disease (AD), promoting cerebral amyloid‐β plaques formation, and altering endosomal recycling of apoE complexed proteins. Activating the ATP binding cassette A1 (ABCA1) to lipidate ApoE reduces its aggregation, promotes ApoE recycling and presents an attractive mechanism to rescue AD pathology. Method: ABCA1 was immunoprecipitated using anti‐GFP beads (Chromotek) from ApoE3/ApoE4 treated Hela‐ABCA1GFP cell lysates. A unbiased proteomics (LC‐MS) screen was employed to indentify ABCA1 binding proteins from the immunoprecipitated samples. E3/E4 AD (n=9, cogdx=4) and E3/E3 AD (n=11, cogdx=4) patient inferior frontal cortex from the Religious Order Study and the Memory and Aging Project (ROSMAP) were lysed and analyzed by Western blot for targets from proteomics screen. Result: ApoE4 was associated with lower astrocytic ABCA1 activity. We identified caveolin‐1 (Cav‐1), an integral membrane protein in plasma membrane lipid rafts, as one of the ABCA1‐binding proteins that regulate ABCA1 cell surface level. Using multiple models, we observed elevated Cav‐1 in primary astrocytes and brains of ApoE4‐ targeted replacement (TR) mice. Knockdown Cav‐1 through siRNA treatment restored ABCA1 surface expression level, underscoring the importance of Cav‐1 in ABCA1 trafficking. In AD patient samples from ROSMAP, Cav‐1 protein expression in E3/E4 AD inferior frontal cortex (n=9) demonstrated non‐significant increase from 1.2 to 2.6 (normalized to β‐actin) compared to E3/E3 AD (n=11). Ongoing efforts are planned to expand the human study sample size. Conclusion: ApoE4 is associated with elevated Cav‐1 level and knockdown of Cav‐1 can restore ABCA1 surface expression. Our work provides a deeper understanding of the critical mechanisms that define the pathogenicity of ApoE4 and can ultimately identify key pathways that regulate endosomal dysregulation in ApoE4. [ABSTRACT FROM AUTHOR]

SUMMARY Considering the effect of non-Darcy flow, the perturbation theory and normal mode method are introduced to analyze the linear stability of one-dimensional non-Darcy flow of gases in broken rocks. A stability criterion for linear systems is obtained theoretically when the steady states of pressure and velocity fields are perturbed, and the effects of the physical parameters on the linear governing system are studied theoretically and numerically. It is pointed out that the deviation coefficient from Darcy's law plays an important role in the governing system; the increasing absolute value of deviation coefficient from Darcy's law stabilizes the system, and the numerical results are shown graphically. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective. To determine if supplemental intraarticular α2-macroglobulin (α2M) has a chondroprotective effect in a rat model of osteoarthritis (OA). Methods. Using Western blotting, mass spectrometry, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry, α2M was identified as a potential therapeutic agent through a comparison of α2M concentrations in serum, synovial fluid (SF), and cartilage from normal subjects and patients with OA. In cultured chondrocytes, the effects of α2M on interleukin-1 (IL-1)-induced cartilage catabolic enzymes were evaluated by Luminex assay and ELISA. In vivo effects on cartilage degeneration and matrix metalloproteinase 13 (MMP-13) concentration were evaluated in male rats (n =120) randomized to 1 of 4 treatments: 1) anterior cruciate ligament transection (ACLT) and saline injections, 2) ACLT and 1 IU/kg injections of α2M, 3) ACLT and 2 IU/kg injections of α2M, or 4) sham operation and saline injections. Rats were administered intraarticular injections for 6 weeks. The concentration of MMP-13 in SF lavage fluid was measured using ELISA. OA-related gene expression was quantified by real-time quantitative polymerase chain reaction. The extent of OA progression was graded by histologic examination. Results. In both normal subjects and OA patients, α2M levels were lower in SF as compared to serum, and in OA patients, MMP-13 levels were higher in SF than in serum. In vitro, α2M inhibited the induction of MMP-13 by IL-1 in a dose-dependent manner in human chondrocytes. In the rat model of ACLT OA, supplemental intraarticular injection of α2M reduced the concentration of MMP-13 in SF, had a favorable effect on OA-related gene expression, and attenuated OA progression. Conclusion. The plasma protease inhibitor α2M is not present in sufficient concentrations to inactivate the high concentrations of catabolic factors found in OA SF. Our findings suggest that supplemental intraarticular α2M provides chondral protection in posttraumatic OA. [ABSTRACT FROM AUTHOR]

SUMMARY In this paper, we study the adaptive resource allocation in multiuser orthogonal frequency division multiplexing (OFDM) systems. We try to maximize the sum capacity of an OFDM system with given transmission power budget, while meeting users' minimal rate requirements. Unlike other resource allocation schemes, which generally separate subchannel allocation and power distribution into independent procedures, our proposed algorithm implements joint subchannel and power allocation. Given a set of subchannels, the required power to satisfy a user's minimal rate constraint is calculated by water-filling policy. Then, the user who requires the maximum power to meet the rate requirement has a priority to obtain an additional subchannel. The procedure continues until all subchannels are consumed, by which time the consumed power to meet all users' rate requirements is also worked out. Finally, the margin power is allocated among all subchannels in an optimal manner to maximize the sum capacity of the OFDM system. Simulation results show that our proposed algorithm performs better than other existing ones. The solution produced by our proposed algorithm is close to the upper bound, while its complexity is relatively lower compared with other methods, which makes it attractive for applications. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

SUMMARY In this paper we study the resource allocation problem for the multiuser orthogonal frequency division multiplexing (OFDM)-based cognitive radio (CR) systems with proportional rate constraints. The mutual interference introduced by primary user (PU) and cognitive radio user (also referred to secondary user, SU) makes the optimization problem of CR systems more complex. Moreover, the interference introduced to PUs must be kept under a given threshold. In this paper, the highest achievable rate of each OFDM subchannel is calculated by jointly considering the channel gain and interference level. First, a subchannel is assigned to the SU with the highest achievable rate. The remaining subchannels are always allocated to the SU that suffers the severest unjustness. Second, an efficient bit allocation algorithm is developed to maximize the sum capacity, which is again based on the highest achievable rate of each subchannel. Finally, an adjustment procedure is designed to maintain proportional fairness. Simulation results show that the proposed algorithm maximizes the sum capacity while keeping the proportional rate constraints satisfied. The algorithm exhibits a good tradeoff between sum capacity maximization and proportional fairness. Furthermore, the proposed algorithm has lower complexity compared with other algorithms, rendering it promising for practical applications. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Two‐photon fluorescence imaging allows in vivo study of biological structures and activities in deep tissues, in which bright fluorophores with high photostability and good biocompatibility are highly desirable. Herein, a small‐molecule fluorogen with aggregation‐induced emission (AIEgen) is complexed with fetal bovine serum (FBS) proteins to develop a protein‐sized AIEgen–protein hybrid nanocomposite (TPEPy‐FBS) with bright far‐red/near‐infrared (NIR) emission, excellent photostability, and low phototoxicity for deep and high‐resolution in vivo two‐photon brain vasculature imaging. Upon complexation with FBS, the fluorescence of TPEPy is greatly intensified and a sixfold enhancement is observed with 10% FBS in aqueous media. The yielded TPEPy‐FBS shows good physical stability in aqueous media and the phototoxicity of TPEPy is dramatically inhibited after complexation with FBS. Moreover, TPEPy‐FBS exhibits bright two‐photon fluorescence in far‐red/NIR region and good photostability upon femtosecond laser excitation, which facilitates high performance in vivo imaging. A large imaging depth of 656 µm is obtained in brain vasculature network imaging with a high signal‐to‐background ratio of 234, where a small blood capillary of 1.05 µm can be resolved at an imaging depth of 656 µm. Highlighted is a simple and versatile strategy to develop efficient two‐photon probes for in vivo biological imaging. [ABSTRACT FROM AUTHOR]

Perfect absorbers with extremely high absorption are of crucial importance for many applications such as harvesting solar energy and eliminating stray light. A key point for their applications is ultralow photon escaping rate (PER) with easy fabrication process, which enables to maximize energy utilization or minimize the influence of stray light. An ultrathin perfect absorber (total thickness of 226 nm) is reported in this work with dielectric plasmonic nanocomposite (titanium nitride (TiN) embedded in aluminum nitride (AlN)) and antireflective coating (ARC). It can be fabricated by low‐cost one‐step sputtering approach in a very large area (200 × 200 mm2 for demonstration) on almost any substrates, including flexible polyethylene‐terephthalate. The average PER is only 0.4% in the whole visible range of 400–750 nm. As an example, the absorber is used in a laser scanning confocal microscope to eliminate the strong laser stray light and enhance the signal‐to‐noise ratio, which improves the clarity and contrast of imaging remarkably. It can not only match the requirement of harvesting solar energy, but also is suitable for stray light elimination of weak signal detection instruments, etc. [ABSTRACT FROM AUTHOR]

In article number 1808365, Bin Liu and co‐workers report NIR‐II light (1200 nm) excitable single‐chain conjugated polymer dots with bright NIR‐I emission (peak at ≈725 nm and quantum yield of 20.6%) for deep in vivo two‐photon imaging of an intact brain. High contrast images clearly reveal brain vasculature structure through the intact skull with a large depth of 400 μm. [ABSTRACT FROM AUTHOR]

Methods for noninvasive brain imaging are highly desirable to study brain structures in neuroscience. Two‐photon fluorescence microscopy (2PFM) with near‐infrared (NIR) light excitation is a relatively noninvasive approach commonly used to study brain with high spatial resolution and large imaging depth. However, most of the current studies require cranial window implantation or skull‐thinning methods due to attenuation of excitation light. 2PFM through intact mouse skull is challenging due to strong scattering induced by skull bone. Herein, NIR‐II light excitable single‐chain conjugated polymer dots (CPdots) with bright fluorescence in NIR‐I region (peak at ≈725 nm and quantum yield of 20.6 ± 1.0%) are developed for deep in vivo two‐photon fluorescence (2PF) imaging of intact mouse brain. The synthesized CPdots exhibit good biocompatibility, high photostability, and large two‐photon absorption cross section. The CPdots allow 2PF images acquired upon excitation at 800, 1040 and 1200 nm with the highest signal‐to‐background ratio of 208 demonstrated for 1200 nm excitation. Moreover, a 3D reconstruction of the brain blood vessel network is obtained with a large vertical depth of 400 µm through intact skull. This work demonstrates great potential of bright NIR fluorophores for in vivo deep tissue imaging. NIR‐II light (1200 nm) excitable single‐chain conjugated polymer dots with bright NIR‐I emission (peak at ≈725 nm and quantum yield of 20.6%) is developed for deep in vivo two‐photon imaging of intact mouse brain. High contrast images clearly reveal brain vasculature structure through intact skull with a large depth of 400 µm. [ABSTRACT FROM AUTHOR]