Polysaccharide from Panax japonicus C.A. Mey prevents non-alcoholic fatty liver disease development based on regulating liver metabolism and gut microbiota in mice.

In this study, a new polysaccharide (PSPJ) with specific molecular weight and monosaccharide compositions was isolated and purified from the water extract of Panacis Japonici Rhizoma (PJR). 16S rRNA analysis and untargeted metabolomic analysis were used to assess PSPJ's efficacy in averting non-alcoholic fatty liver disease (NAFLD). This study indicated that PSPJ significantly reduced liver fat accumulation, the increase in blood lipids and ALT caused by HFD, indicating that PSPJ can prevent NAFLD. We demonstrated through cell experiments that PSPJ does not directly affect liver cells. The gut microbiota disorder and alterations in short-chain fatty acids (SCFAs) induced by the high-fat diet (HFD) were ameliorated by PSPJ, as evidenced by the analysis of 16S rRNA. In particular, supplementing PSPJ reduced the abundance of Turicibacter, Dubosiella, and Staphylococcus, and increased the abundance of Bacteroides, Blautia, and Lactobacillus. Untargeted metabolomic analysis shows that PSPJ improves liver metabolic disorders by regulating arachidonic acid metabolism, carbohydrate digestion and absorption, fatty acid biosynthesis, fatty acid metabolism and retinol metabolism. The findings of our investigation indicate that PSPJ has the potential to modulate liver metabolism through alterations in the composition of intestinal bacteria, hence preventing NAFLD.

Discovery of Peptidic Ligands against the SARS-CoV-2 Spike Protein and Their Use in the Development of a Highly Sensitive Personal Use Colorimetric COVID-19 Biosensor.

In addition to efficacious vaccines and antiviral therapeutics, reliable and flexible in-home personal use diagnostics for the detection of viral antigens are needed for effective control of the COVID-19 pandemic. Despite the approval of several PCR-based and affinity-based in-home COVID-19 testing kits, many of them suffer from problems such as a high false-negative rate, long waiting time, and short storage period. Using the enabling one-bead-one-compound (OBOC) combinatorial technology, several peptidic ligands with a nanomolar binding affinity toward the SARS-CoV-2 spike protein (S-protein) were successfully discovered. Taking advantage of the high surface area of porous nanofibers, immobilization of these ligands on nanofibrous membranes allows the development of personal use sensors that can achieve low nanomolar sensitivity in the detection of the S-protein in saliva. This simple biosensor employing naked-eye reading exhibits detection sensitivity comparable to some of the current FDA-approved home detection kits. Furthermore, the ligand used in the biosensor was found to detect the S-protein derived from both the original strain and the Delta variant. The workflow reported here may enable us to rapidly respond to the development of home-based biosensors against future viral outbreaks.

Site-Specific Albumin-Selective Ligation to Human Serum Albumin under Physiological Conditions.

Human serum albumin (HSA) is the most abundant protein in human blood plasma. It plays a critical role in the native transportation of numerous drugs, metabolites, nutrients, and small molecules. HSA has been successfully used clinically as a noncovalent carrier for insulin (e.g., Levemir), GLP-1 (e.g., Liraglutide), and paclitaxel (e.g., Abraxane). Site-specific bioconjugation strategies for HSA only would greatly expand its role as the biocompatible, non-toxic platform for theranostics purposes. Using the enabling one-bead one-compound (OBOC) technology, we generated combinatorial peptide libraries containing myristic acid, a well-known binder to HSA at Sudlow I and II binding pockets, and an acrylamide. We then used HSA as a probe to screen the OBOC myristylated peptide libraries for reactive affinity elements (RAEs) that can specifically and covalently ligate to the lysine residue at the proximity of these pockets. Several RAEs have been identified and confirmed to be able to conjugate to HSA covalently. The conjugation can occur at physiological pH and proceed with a high yield within 1 h at room temperature. Tryptic peptide profiling of derivatized HSA has revealed two lysine residues (K225 and K414) as the conjugation sites, which is much more specific than the conventional lysine labeling strategy with N-hydroxysuccinimide ester. The RAE-driven site-specific ligation to HSA was found to occur even in the presence of other prevalent blood proteins such as immunoglobulin or whole serum. Furthermore, these RAEs are orthogonal to the maleimide-based conjugation strategy for Cys34 of HSA. Together, these attributes make the RAEs the promising leads to further develop in vitro and in vivo HSA bioconjugation strategies for numerous biomedical applications.

Effect of refractive index of packaging materials on the light extraction efficiency of COB-LEDs with millilens array.

Lens arrays are introduced to diminish the total internal reflection (TIR) that happens at chip-encapsulant and encapsulant-air interfaces of chip-on-board light-emitting diodes (COB-LEDs), so as to improve the light extraction efficiency (LEE) of the COB-LEDs. However, the LEE of COB-LEDs with lens array depends on the refractive index of the encapsulant layer nencap and lens array nlens, which was rarely concerned so far. Optical simulations based on a Monte Carlo ray tracing method, and experiments were conducted to investigate the effect of nencap and nlens on the LEE of COB-LEDs with millilens array. The simulated results show that the TIR at chip-encapsulant, encapsulant-lens, and lens-air interfaces can be significantly diminished by regulating the nencap and nlens, and the LEE of COB-LEDs decreases as the refractive difference of encapsulant layer and lens array |nlens-nencap| increases. Compared to the COB-LEDs with only a flat encapsulant layer, the LEEs of blue and white COB-LEDs with nlens=nencap=nITO=2 are enhanced by 246.2% and 50.6%, where nITO is the refractive index of the top layer of the conventional LED chip. The experimental results agree well with the simulated results with normalized LEE deviation within 7.3%.

Tumor Receptor-Mediated In Vivo Modulation of the Morphology, Phototherapeutic Properties, and Pharmacokinetics of Smart Nanomaterials.

To be clinically efficacious, nanotherapeutic drugs need to reach disease tissues reliably and cause limited side effects to normal organs and tissues. Here, we report a proof-of-concept study on the development of a smart peptidic nanophototherapeutic agent in line with clinical requirements, which can transform its morphology from nanoparticles to nanofibrils at the tumor sites. This in vivo receptor-mediated transformation process resulted in the formation and prolonged tumor-retention of highly ordered (J-aggregate type of photosensitizer) photosensitive peptide nanofibrillar network with greatly enhanced photothermal and photodynamic properties. This strategy of "multiple daily low-intensity laser radiation after each intravenous injection of significantly low-dose of nanomaterials" demonstrated effective elimination of 4T1 orthotopic syngeneic breast cancer in mice. The technology for nanomaterial modulation based on living cell surface receptors, in this case tumor-associated α3ß1 integrin, has great potential for clinical translation and is expected to improve the therapeutic efficacy against many cancers.

Explosive bouncing on heated silicon surfaces under low ambient pressure.

Droplet impingement on heated surfaces has been investigated by varying the surface textures, temperature, and droplet properties with demonstration of various phenomenological behaviors, such as evaporation, boiling, splashing, and Leidenfrost bouncing. However, the ambient pressure dependence has not been well explored, especially for ambient pressures lower than 5 kPa. By examining the ambient pressure (from 0.2 to 20 kPa) and surface temperature (from 20 to 200 °C) simultaneously, we found a novel explosive bouncing behavior which is different from Leidenfrost bouncing and only occurs at extremely low ambient pressure (≤6 kPa). Through experimental validation and mechanical analysis, we found that the explosive bouncing is caused by the dramatic explosion of the local vapor bubble and reducing the ambient pressure benefits the formation and explosion of the vapor bubble.

A Meshfree Representation for Cardiac Medical Image Computing.

The prominent advantage of meshfree method, is the way to build the representation of computational domain, based on the nodal points without any explicit meshing connectivity. Therefore, meshfree method can conveniently process the numerical computation inside interested domains with large deformation or inhomogeneity. In this paper, we adopt the idea of meshfree representation into cardiac medical image analysis in order to overcome the difficulties caused by large deformation and inhomogeneous materials of the heart. In our implementation, as element-free Galerkin method can efficiently build a meshfree representation using its shape function with moving least square fitting, we apply this meshfree method to handle large deformation or inhomogeneity for solving cardiac segmentation and motion tracking problems. We evaluate the performance of meshfree representation on a synthetic heart data and an in-vivo cardiac MRI image sequence. Results showed that the error of our framework against the ground truth was 0.1189 ± 0.0672 while the error of the traditional FEM was 0.1793 ± 0.1166. The proposed framework has minimal consistency constraints, handling large deformation and material discontinuities are simple and efficient, and it provides a way to avoid the complicated meshing procedures while preserving the accuracy with a relatively small number of nodes.

Metal-free direct alkylation of unfunctionalized allylic/benzylic sp3 C-H bonds via photoredox induced radical cation deprotonation.

Despite notable recent efforts, a catalytic and convenient strategy for the direct alkylation of unactivated allylic or benzylic sp3 C-H bonds remains a formidable challenge facing the synthesis community. We herein report an unprecedented allylic/benzylic alkylation using only an organo-photoredox catalyst, which enables coupling of a broad scope of alkenes/arenes and electron-deficient alkenes in an atom- and redox-economic manner. A photoredox induced alkene/arene radical cation deprotonation is proposed to smoothly generate the key allylic and benzylic radical intermediates. It represents the first C-C bond formation via radical cation deprotonation under visible light conditions. The resulting products can be easily scaled up and directly converted to γ,δ-unsaturated or α,ß-diaryl-acids, -esters, -amides, -pyrazoles, -isoxazoles, as well as lactones, which enables this mild and selective sp3 C-H alkylation to rapidly access complex bioactive molecules.

Low Dose PET Image Reconstruction with Total Variation Using Alternating Direction Method.

In this paper, a total variation (TV) minimization strategy is proposed to overcome the problem of sparse spatial resolution and large amounts of noise in low dose positron emission tomography (PET) imaging reconstruction. Two types of objective function were established based on two statistical models of measured PET data, least-square (LS) TV for the Gaussian distribution and Poisson-TV for the Poisson distribution. To efficiently obtain high quality reconstructed images, the alternating direction method (ADM) is used to solve these objective functions. As compared with the iterative shrinkage/thresholding (IST) based algorithms, the proposed ADM can make full use of the TV constraint and its convergence rate is faster. The performance of the proposed approach is validated through comparisons with the expectation-maximization (EM) method using synthetic and experimental biological data. In the comparisons, the results of both LS-TV and Poisson-TV are taken into consideration to find which models are more suitable for PET imaging, in particular low-dose PET. To evaluate the results quantitatively, we computed bias, variance, and the contrast recovery coefficient (CRC) and drew profiles of the reconstructed images produced by the different methods. The results show that both Poisson-TV and LS-TV can provide a high visual quality at a low dose level. The bias and variance of the proposed LS-TV and Poisson-TV methods are 20% to 74% less at all counting levels than those of the EM method. Poisson-TV gives the best performance in terms of high-accuracy reconstruction with the lowest bias and variance as compared to the ground truth (14.3% less bias and 21.9% less variance). In contrast, LS-TV gives the best performance in terms of the high contrast of the reconstruction with the highest CRC.

Novel crystal timing calibration method based on total variation.

A novel crystal timing calibration method based on total variation (TV), abbreviated as 'TV merge', has been developed for a high-resolution positron emission tomography (PET) system. The proposed method was developed for a system with a large number of crystals, it can provide timing calibration at the crystal level. In the proposed method, the timing calibration process was formulated as a linear problem. To robustly optimize the timing resolution, a TV constraint was added to the linear equation. Moreover, to solve the computer memory problem associated with the calculation of the timing calibration factors for systems with a large number of crystals, the merge component was used for obtaining the crystal level timing calibration values. Compared with other conventional methods, the data measured from a standard cylindrical phantom filled with a radioisotope solution was sufficient for performing a high-precision crystal-level timing calibration. In this paper, both simulation and experimental studies were performed to demonstrate the effectiveness and robustness of the TV merge method. We compare the timing resolutions of a 22Na point source, which was located in the field of view (FOV) of the brain PET system, with various calibration techniques. After implementing the TV merge method, the timing resolution improved from 3.34 ns at full width at half maximum (FWHM) to 2.31 ns FWHM.

Structural optimization for remote white light-emitting diodes with quantum dots and phosphor: packaging sequence matters.

White light-emitting diodes (WLEDs) with quantum dots (QDs) and phosphor have attracted tremendous attentions due to their excellent color rendering ability. In the packaging process, QDs layer and phosphor-silicone layer tend to be separated to reduce the reabsorption losses, and to maintain the stability of QDs surface ligands. This study investigated the packaging sequence between QDs and phosphor on the optical and thermal performances of WLEDs. The output optical power and PL spectra were measured and analyzed, and the temperature fields were simulated and validated experimentally by infrared thermal imager. It was found that when driven by 60 mA, the QDs-on-phosphor type WLEDs achieved luminous efficiency (LE) of 110 lm/W, with color rendering index (CRI) of Ra = 92 and R9 = 80, while the phosphor-on-QDs type WLEDs demonstrated lower LE of 68 lm/W, with Ra = 57 and R9 = 24. Moreover, the QDs-on-phosphor type WLEDs generated less heat than that of another, consequently the highest temperature in the QDs-on-phosphor type was lower than another, and the temperature difference can reach 12.3°C. Therefore, in terms of packaging sequence, the QDs-on-phosphor type is an optimal packaging architecture for higher optical efficiency, better color rendering ability and lower device temperature.

Sparse/Low Rank Constrained Reconstruction for Dynamic PET Imaging.

In dynamic Positron Emission Tomography (PET), an estimate of the radio activity concentration is obtained from a series of frames of sinogram data taken at ranging in duration from 10 seconds to minutes under some criteria. So far, all the well-known reconstruction algorithms require known data statistical properties. It limits the speed of data acquisition, besides, it is unable to afford the separated information about the structure and the variation of shape and rate of metabolism which play a major role in improving the visualization of contrast for some requirement of the diagnosing in application. This paper presents a novel low rank-based activity map reconstruction scheme from emission sinograms of dynamic PET, termed as SLCR representing Sparse/Low Rank Constrained Reconstruction for Dynamic PET Imaging. In this method, the stationary background is formulated as a low rank component while variations between successive frames are abstracted to the sparse. The resulting nuclear norm and l1 norm related minimization problem can also be efficiently solved by many recently developed numerical methods. In this paper, the linearized alternating direction method is applied. The effectiveness of the proposed scheme is illustrated on three data sets.

Design of a brightness-enhancement-film-adaptive freeform lens to enhance overall performance in direct-lit light-emitting diode backlighting.

In this study, a brightness-enhancement-film- (BEF) adaptive method is proposed to design freeform lenses for enhancing brightness performance in a direct-lit light-emitting diode (LED) backlight system. A detailed design algorithm is presented based on the analysis of the output optical properties of the BEF. By introducing a constriction factor, we can control the light intensity distribution curve at will to adapt to the characteristics of the BEF and make more light transmit through the BEF. Compared with an LED backlight system without a freeform lens, the BEF-adaptive lens method can improve axial luminance by 20.67% and output efficiency by 6.02%.