PKM2: A Potential Regulator of Cardiac Injury Through Glycolytic and Non-glycolytic Pathways.

Adult animals are unable to regenerate heart cells due to postnatal cardiomyocyte cycle arrest, leading to higher mortality rates in cardiomyopathy. However, reprogramming of energy metabolism in cardiomyocytes provides a new perspective on the contribution of glycolysis to repair, regeneration, and fibrosis after cardiac injury. Pyruvate kinase (PK) is a key enzyme in the glycolysis process. This review focuses on the glycolysis function of PKM2, although PKM1 and PKM2 both play significant roles in the process after cardiac injury. PKM2 exists in both a low-activity dimer and a high-activity tetramer form. PKM2 dimers promote aerobic glycolysis but have low catalytic activity, leading to the accumulation of glycolytic intermediates. These intermediates enter the PPP pathway to promote cardiomyocyte proliferation and heart regeneration. Additionally, they activate KATP channels, protecting the heart against ischemic damage. PKM2 tetramers function similarly to PKM1 in glycolysis, promoting pyruvate oxidation and subsequently ATP generation to protect the heart from ischemic damage. They also activate KDM5 through the accumulation of αKG, thereby promoting cardiomyocyte proliferation and cardiac regeneration. Apart from glycolysis, PKM2 interacts with transcription factors like Jmjd4, RAC1, ß-catenin, and HIF-1α, playing various roles in homeostasis maintenance, remodeling, survival regulation, and neovascularization promotion. However, PKM2 has also been implicated in promoting cardiac fibrosis through mechanisms like SIRT3 deletion, TG2 expression enhancement, and activation of TGF-ß1/Smad2/3 and Jak2/Stat3 signals. Overall, PKM2 shows promising potential as a therapeutic target for promoting cardiomyocyte proliferation and cardiac regeneration, as well as addressing cardiac fibrosis after injury.

Dual-channel snapshot imaging spectrometer with wide spectrum and high resolution.

The comprehensive analysis of dynamic targets brings about the demand for capturing spatial and spectral dimensions of visual information instantaneously, which leads to the emergence of snapshot spectral imaging technologies. While current snapshot systems face major challenges in the development of wide working band range as well as high resolution, our novel dual-channel snapshot imaging spectrometer (DSIS), to the best of our knowlledge, demonstrates the capability to achieve both wide spectrum and high resolution in a compact structure. By dint of the interaction between the working band range and field of view (FOV), reasonable limits on FOV are set to avoid spectral overlap. Further, we develop a dual-channel imaging method specifically for DSIS to separate the whole spectral range into two parts, alleviating the spectral overlap on each image surface, improving the tolerance of the system for a wider working band range, and breaking through structural constraints. In addition, an optimal FOV perpendicular to the dispersion direction is determined by the trade-off between FOV and astigmatism. DSIS enables the acquisition of 53×11 spatial elements with up to 250 spectral channels in a wide spectrum from 400 to 795 nm. The theoretical study and optimal design of DSIS are further evaluated through the simulation experiments of spectral imaging.

Spatial-spectral resolution tunable snapshot imaging spectrometer: analytical design and implementation.

A snapshot imaging spectrometer is a powerful tool for dynamic target tracking and real-time recognition compared with a scanning imaging spectrometer. However, all the current snapshot spectral imaging techniques suffer from a major trade-off between the spatial and spectral resolutions. In this paper, an integral field snapshot imaging spectrometer (TIF-SIS) with a continuously tunable spatial-spectral resolution and light throughput is proposed and demonstrated. The proposed TIF-SIS is formed by a fore optics, a lenslet array, and a collimated dispersive subsystem. Theoretical analyses indicate that the spatial-spectral resolution and light throughput of the system can be continuously tuned through adjusting the F number of the fore optics, the rotation angle of the lenslet array, or the focal length of the collimating lens. Analytical relationships between the spatial and spectral resolutions and the first-order parameters of the system with different geometric arrangements of the lenslet unit are obtained. An experimental TIF-SIS consisting of a self-fabricated lenslet array with a pixelated scale of 100×100 and a fill factor of 0.716 is built. The experimental results show that the spectral resolution of the system can be steadily improved from 4.17 to 0.82 nm with a data cube (N x×N y×N λ) continuously tuned from 35×35×36 to 40×40×183 in the visible wavelength range from 500 to 650 nm, which is consistent with the theoretical prediction. The proposed method for real-time tuning of the spatial-spectral resolution and light throughput opens new possibilities for broader applications, especially for recognition of things with weak spectral signature and biomedical investigations where a high light throughput and tunable resolution are needed.

Non-uniformity correction of wide field of view imaging system.

Requirements for wide field of view (FOV) imaging system reflect the need for both uniform illumination as well as excellent image quality across the entire FOV. As the monocentric lens combined with a parallel array of relay imagers achieves a wide-FOV while maintaining a high resolution, we studied the monocentric cascade imaging system (MCIS). However, the imaging experiment of the prototype shows two issues, including vignetting and non-uniform image quality over the full FOV. They affect the image stitching which is necessary for wide-FOV image acquisition. This paper studies how the position of the aperture stop affects the vignetting and the local aberrations in MCIS. Moving laws of the aperture stop and its relationship with the local aberrations are presented. Moreover, aspheric surfaces on proper surfaces are introduced and studied to balance the local aberrations. Accordingly, an MCIS with uniform illumination and good image quality is presented. The MCIS achieves a wide-FOV of 116.4° and an instantaneous FOV of 0.0021°. It keeps a relative illumination exceeding 97% during the full FOV. The modulation transfer function (MTF) is over 0.285 at the Nyquist frequency of 270 lp/mm. This paper provides a profound theorical reference for further applications and developments of MCIS.

High spectral resolution compact Offner spectrometer based on the aberration-reduced convex holographic gratings recorded by spherical waves under Rowland circle mounting.

High spectral resolution, excellent imaging quality, and compact configuration have become a recent trend in push-broom imaging spectrometers. The concentric Offner imaging spectrometer has become popular due to its high optical performance and compactness. However, astigmatism is the dominant residual aberration in the Offner imaging spectrometer, which makes the meridional and sagittal images unable to be focused well and causes a deterioration in image quality and spectral resolution. In this paper, we present a compact Offner imaging spectrometer with a high resolution based on an aberration-reduced convex holographic grating (ACHG), which is recorded by spherical waves under Rowland circle mounting. The holographic aberration coefficients of ACHG and geometric aberration coefficients of the Offner imaging spectrometer are derived based on the analysis of the light-path function. Furthermore, we analyzed the relationship between holographic aberration coefficients and holographic recording parameters of ACHG under Rowland circle mounting. To balance the geometric aberration of the Offner imaging spectrometer, proper holographic aberration coefficients of the ACHG are achieved through adjusting the holographic recording parameters. The design result indicated that the Offner imaging spectrometer with ACHG provides better images than those with mechanically ruled convex grating (MRCG). Moreover, the spectral resolution is significantly improved. This lays down a theoretical basis for subsequent construction work in the Offner imaging spectrometer with holographic aberration-reduced gratings.

Cost-utility of afatinib and gefitinib as first-line treatment for EGFR-mutated advanced non-small-cell lung cancer.

AIM: To evaluate the cost-utility of gefitinib and afatinib as first-line EGFR-mutated non-small-cell lung cancer treatments from the Chinese healthcare system perspective. MATERIALS & METHODS: A Markov model was established, state transition probabilities were extracted from the LUX-Lung7 trial and utility values were from previous studies. The cost was extracted from local charge or relevant literature. Incremental cost-effectiveness ratio was calculated for intention-to-treat, EGFR exon 19 deletion (del19) and exon Leu858Arg (21L858R, L858R) muation subgroups.  Results: For the entire population, the afatinib regimen afforded additional 0.29 quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios were US$9820.41/QALY, US$18,529.65/QALY and US$1585.51/QALY for intention-to-treat, L858R and del19, respectively. CONCLUSION: First-line afatinib was more cost-effective than gefitinib for EFGR-mutated advanced non-small-cell lung cancer in China.