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The spleen is an important site of hematopoietic stem/progenitor cell (HSPC) preconditioning and tumor-promoting myeloid cell generation in cancer, but the regulatory mechanism remains unclear. Here, we found that PKR-like endoplasmic reticulum kinase (PERK) mediated HSPC reprogramming into committed MDSC precursors in the spleen via PERK–ATF4–C/EBPβ signaling. Pharmacological and genetic inhibition of this pathway in murine and human HSPCs prevented their myeloid descendant cells from becoming MDSCs even with subsequent exposure to tumor microenvironment (TME) factors. In mice, the selective delivery of PERK antagonists to the spleen was not only sufficient but more effective than the tumor-targeted strategy in preventing MDSC activation in the tumor, leading to profound TME reshaping and tumor regression. Clinically, HSPCs in the spleen of cancer patients exhibit increased PERK signaling correlated with enhanced myelopoiesis. Our findings indicate that PERK-mediated HSPC preconditioning plays a crucial role in MDSC generation, suggesting novel spleen-targeting therapeutic opportunities for restraining the tumor-promoting myeloid response at its source.

Human senescence-associated β-galactosidase (SA-β-gal), the most widely used biomarker of aging, is a valuable tool for assessing the extent of cell ‘healthy aging’ and potentially predicting the health life span of an individual. Human SA-β-gal is an endogenous lysosomal enzyme expressed from GLB1, the catalytic domain of which is very different from that of E. coli β-gal, a bacterial enzyme encoded by lacZ. However, existing chemical probes for this marker still lack the ability to distinguish human SA-β-gal from β-gal of other species, such as bacterial β-gal, which can yield false positive signals. Here, we show a molecular design strategy to construct fluorescent probes with the above ability with the aid of structure-based steric hindrance adjustment catering to different enzyme pockets. The resulting probes normally work as traditional SA-β-gal probes, but they are unique in their powerful ability to distinguish human SA-β-gal from E. coli β-gal, thus achieving species-selective visualization of human SA-β-gal for the first time. NIR-emitting fluorescent probe KSL11 as their representative further displays excellent species-selective recognition performance in biological systems, which has been herein verified by testing in senescent cells, in lacZ-transfected cells and in E. coli-β-gal-contaminated tissue sections of mice. Because of our probes, it was also discovered that SA-β-gal content in mice increased gradually with age and SA-β-gal accumulated most in the kidneys among the main organs of naturally aging mice, suggesting that the kidneys are the organs with the most severe aging during natural aging., The first-generation chemical probes for species-selective fluorescence imaging of human senescence-associated β-galactosidase are developed.

We first discuss some properties of the solution set of a pseudomonotone second-order cone linear complementarity problem (SOCLCP), and then analyse the limiting behavior of a sequence of strictly feasible solutions within a new wide neighborhood of the central trajectory for the pseudomonotone SOCLCP under assumptions of strict complementarity. Based on this, we derive four different characterizations of an error bound for the pseudomonotone SOCLCP.

Planting soybeans (Glycine max (L.) Merr.) in tea gardens decreased soil pH in theory but increased it in practice. This controversy was addressed in this study by treating the tea garden soil consecutively with different parts of a soybean cover crop: aboveground soybean (ASB) parts, underground soybean (USB) root residues, and the whole soybean (WSB) plants. In comparison with the control, the soil pH increased significantly after the third ASB and WSB treatments, but there was no significant change in the soil pH in the USB treatment. Concordantly, the soil exchangeable acidity decreased significantly and the soil exchangeable bases increased significantly in the ASB and WSB treatments. The exchangeable acidity increased in the USB treatment, but the amount of the increased acidity was less than that of the increased bases in the ASB treatment, resulting in a net increase in the exchangeable bases in the WSB treatment. Soybean planting and covering also increased the microbial richness and abundance significantly, which led to significantly more soil organic matters. Exchangeable K+ and Mg2+, and soil organic matters played significantly positive roles and exchangeable Al3+ played negative roles in improving soil pH. Our data suggest that consecutive plantings of soybean cover crop increase the pH of the acidified tea garden soil.

It is crucial to prevent the secondary pollution when recycling wastes. During the recycling of waste printed circuit boards by the pyrometallurgical process, bromine in the raw materials is normally released in the form of HBr/Br2 into the flue gas. In the present work, for the first time the conversion of HBr to Br2 during the cooling of flue gas in the post combustion area (PCA) was studied to provide evidences for the control of PBDD/Fs and the recycling of Br. The 1200 °C flue gas was cooled down at various cooling rates in a lab-scale system. The influence of PCA operating conditions, i.e., cooling temperature (Tc), residence time in the cooling zone (RTcz) and Oxygen partial pressure (PO2), on the conversion ratio was studied systematically. And the study was based on the newly developed method to determine HBr and Br2 contents in the flue gas at various temperatures. For each RTcz, i.e., 0.3, 0.5 and 0.7s, the ratio first increases with decreasing Tc to a maximum value at Tcmax and then decreases as Tc further drops. Tcmax depends on RTcz. For Tc = 200 °C and RTcz = 0.3s, approximately 31.1% HBr is converted to Br2. This is 51% lower than the highest. Moreover, at lower Tc and longer RTcz, the ratio can be less than that at higher Tc and shorter RTcz, vice versa. Accordingly, when cooling the system to a certain temperature, the shorter the RTcz is, the lower the conversion ratio will be. PO2 slightly influences the ratio. These are vital to the determination of Br sources for PBDD/Fs formation in PCA, which is valuable for the future pollution control. Besides, extension of the cooling time in the lower temperature range (from 200 °C at RTcz = 0.3s to 50 °C) within 300s greatly improves the ratio up to 91%. This provides the basis for the Br recovery rather than removal by chemical agents.

Purpose The aim was to evaluate the repeatability of dynamic measurement of the accommodative stimulus–response curve (ASRC) at three different dioptric speeds using a modified instrument and its agreement with two other methods. Methods Twenty‐nine adults (23.5 ± 2.0 years) were enrolled in the study. ASRC was measured monocularly using three methods: dynamic and static measurement using a motorised Badal system mounted on an open‐field auto‐refractor (WAM‐5500, Grand Seiko Co., Ltd, Japan) and the minus lens technique. Dynamic measurements were conducted at three dioptric stimulus speeds to simulate continuous stimuli for ASRC (0.25, 0.40 and 0.55 D/s), with three repetitions for each speed. All three types of ASRCs were fitted with third‐degree polynomial equations. The slope and objective accommodative amplitude of the ASRC were analysed. Results The repeatability of objective accommodative amplitude worsened as the speed of the stimuli increased. The repeatability of the slope was best at a speed of 0.40 D/s and worst at 0.55 D/s. The measurement method significantly influenced the objective accommodative amplitude values and slope (both, p 0.05) and the slope was lowest at 0.55 D/s. Conclusion The accommodative stimulus–response curve values are method‐dependent and the significant differences between three methods used to determine the ASRC based on slope and accommodative amplitude indicate that these methods are non‐interchangeable. Using dynamic measurements, accommodative behaviour varies with the speed of dioptric‐change of the stimulus. A speed of 0.40 D/s appears to be the best compromise in terms of time, results and repeatability for dynamic ASRC measurement.

Previous evidence has revealed that increase in intracellular levels of calcium promotes cellular senescence. However, whether calcium channel blockers (CCBs) can slow aging and extend lifespan is still unknown. In this study, we showed that verapamil, an L-type calcium channel blocker, extended the Caenorhabditis elegans (C. elegans) lifespan and delayed senescence in human lung fibroblasts. Verapamil treatment also improved healthspan in C. elegans as reflected by several age-related physiological parameters, including locomotion, thrashing, age-associated vulval integrity, and osmotic stress resistance. We also found that verapamil acted on the α1 subunit of an L-type calcium channel in C. elegans. Moreover, verapamil extended worm lifespan by inhibiting calcineurin activity. Furthermore, verapamil significantly promoted autophagy as reflected by the expression levels of LGG-1/LC3 and the mRNA levels of autophagy-related genes. In addition, verapamil could not further induce autophagy when tax-6, calcineurin gene, was knocked down, indicating that verapamil-induced lifespan extension is mediated via promoting autophagy processes downstream of calcineurin. In summary, our study provided mechanistic insights into the anti-aging effect of verapamil in C. elegans.

To determine the relationships among retinal/choroidal thickness, retinal microvascular network and visual field in high myopia.This cross-sectional study included a total of 62 subjects, comprising 31 eyes with high myopia and 31 eyes with emmetropia or low myopia. Optical coherence tomography was used to quantify the thickness of ganglion cell complex (GCC), inner nuclear layer and outer plexiform layer (INOPL), outer retinal layer (ORL) and choroid layer (ChL). Optical coherence tomography angiography was used to quantify the superficial vessel density (SVD) and deep vessel density (DVD). Retinal light sensitivity (RLS) was measured by microperimetry-1 (MP1). The inner ring (1-1.75 mm), the outer ring (1.75-2.5 mm) and the whole ring (1-2.5 mm) around the macula were analysed and compared between the two groups. Pearson correlation analysis was performed to analyse the relationship among them.In the highly myopic group, the thinning of retinal/choroidal thickness and the decrease in retinal vessel density and RLS were found when compared to the emmetropia or low myopia (p 0.05). Decreased RLS was correlated with decreased ORL thickness (r = -0.469, p = 0.008) and choroid thickness (r = 0.398, p = 0.030). There was no correlation between retinal microvascular network parameters and RLS (p 0.05), but DVD showed a negative correlation with ORL (r = -0.474, p = 0.007).Early visual field defects in highly myopic eyes may be influenced by the ORL loss and defect of choroidal circulation. The deep retinal microvascular network may have a compensatory action in the hypoxic setting of high myopia.

Under a Slater-type condition, we reformulate a convex quadratic symmetric cone programming problem as an unconstrained eigenvalue minimization problem, and obtain a sufficient condition ensuring the existence of a Lipschitzian error bound for the eigenvalue minimization problem. This error bound, in turn, provides an estimation of the distance from a feasible solution of the convex quadratic symmetric cone program to its optimal solution set.

We first discuss some properties of the solution set of a monotone symmetric cone linear complementarity problem (SCLCP), and then consider the limiting behaviour of a sequence of strictly feasible solutions within a wide neighbourhood of central trajectory for the monotone SCLCP. Under assumptions of strict complementarity and Slater’s condition, we provide four different characterizations of a Lipschitzian error bound for the monotone SCLCP in general Euclidean Jordan algebras. Thanks to the observation that a pair of primal-dual convex quadratic symmetric cone programming (CQSCP) problems can be exactly formulated as the monotone SCLCP, thus we obtain the same error bound results for CQSCP as a by-product.

The structural characteristics of the outer retinal layers in primary open angle glaucoma (POAG) are still controversial, and these changes, along with those in the inner retinal layers, could have clinical and/or pathophysiological significance. A custom-built ultra-high resolution optical coherence tomography (UHR-OCT) combined with an automated segmentation algorithm can image and measure the eight intra-retinal layers. The purpose of this study is to determine the thickness characteristics of the macular intra-retinal layers, especially the outer layers, in POAG patients. Thirty-four POAG patients (56 eyes) and 33 normal subjects (63 eyes) were enrolled. Thickness profiles of the eight intra-retinal layers along a 6-mm length centred on the fovea at the horizontal and vertical meridians were obtained and the regional thicknesses were compared between two groups. The associations between the thicknesses of each intra-retinal layer and the macular visual field (VF) sensitivity were then analysed. POAG affected not only the inner retinal layers but also the photoreceptor layers and retinal pigment epithelium of the outer retina. However, the VF loss was correlated mainly with the damage of the inner retinal layers. UHR-OCT with automated algorithm is a useful tool in detecting microstructural changes of macula with respect to the progression of glaucoma.

The method and the sequence of accommodative stimuli are two factors affecting the steady-state accommodative response. This study investigated the possible effects of these two factors on the accommodative stimulus response curves (ASRCs) and compared three indexes to evaluate ASRC in the different stimulus conditions.In this study, we investigated the difference in the accommodative stimulus response curves under six stimulus conditions. The ASRCs of 10 emmetropes were measured when the accommodative stimulus (AS) was induced using three methods: negative lenses, positive lenses, and a Badal stimulator; and the stimulus was presented using two sequences: ascending and descending sequences. Three indexes, accommodative error area (AEA), accommodative error index (AEI), and the slope of ASRC, were used for comparison.The accommodative error was larger when accommodative stimulus was presented in the ascending sequence than in the descending sequence (p0.05) in the Badal stimulator method whenever AEI, AEA, or the slope of ASRC was used. The ASRCs elicited with positive lenses were more accurate than that elicited with negative lenses or the Badal stimulator when AEA and AEI were used. However, when the slope of the ASRC was used, the result was not significant.The results suggest that the accommodative response in the steady state may be affected by the method used for inducing AS and the sequence of AS presented. The AEA is suggested to be used in the evaluation of the accuracy of the ASRC in future studies.

PURPOSE To investigate the effects of different near addition lenses and prisms on accommodative microfluctuations (AMFs) in Chinese early-onset myopic (EOM) and emmetropic (EMM) children. METHODS Twenty-one EMM and 27 EOM children aged between 9 and 14years participated in the study. At near, 23 children were exophoric (exo

We present an inexact spectral bundle method for solving convex quadratic semidefinite optimization problems. This method is a first-order method, hence requires much less computational cost in each iteration than second-order approaches such as interior-point methods. In each iteration of our method, we solve an eigenvalue minimization problem inexactly, and solve a small convex quadratic semidefinite program as a subproblem. We give a proof of the global convergence of this method using techniques from the analysis of the standard bundle method, and provide a global error bound under a Slater type condition for the problem in question. Numerical experiments with matrices of order up to 3000 are performed, and the computational results establish the effectiveness of this method.

Summary Berberine, one of the main constituents of a Chinese traditional herb used to treat bacterial diarrhea, has an effect of lowering glucose, which has been recently confirmed by many studies. However, the mechanism of berberine’s antidiabetic effect has not yet been well explained. Recent evidence suggests that the gut microbiota composition is associated with obesity and type 2 diabetes, which are closely associated with a low-grade inflammatory state. The protective effect against diabetes of gut microbiota modulation with probiotics or antibiotics has been confirmed in recent observations. Berberine has significant antimicrobial activity against several microbes through inhibiting the assembly function of FtsZ and halting the bacteria cell division. Because berberine acts topically in the gastrointestinal tract and it is poorly absorbed, berberine might modulate gut microbiota without systemic anti-infective activity. Our hypothesis is that gut microbiota modulation may be one mechanism of the antidiabetic effect of berberine. Our hypothesis may provide a novel explanation for berberine’s therapeutic effect in patients with diabetes mellitus.

In this study, we investigated whether the objective depth-of-focus (DOF) is different from the subjective DOF and whether it correlates to accommodative microfluctuations (AMF). The objective DOF and subjective DOF at 1.5 D accommodative stimulus (AS) level were compared in the same group of subjects. The objective DOF and magnitude of AMF were measured at 5 AS levels from 0 D to 4 D. Results showed that there was a significant difference and no correlation between the objective DOF and the subjective DOF. The objective DOF was correlated to the magnitude of AMF. The results suggest that objective DOF and subjective DOF represent the blur sensitivity of two different systems. AMF are correlated with the blur sensitivity of the accommodative system.

An algorithm is developed to solve a special case of reverse problems of linear systems, and as its application, a method is presented to solve optimal problem over the special orthogonal group. An algorithm is designed to find out an orthogonal matrix A such that A transforms a set of orthogonal vectors to another, and as its application, a method is given to generate subgroups of the orthogonal group preserving several orthogonal vectors fixed. It is prove that the symmetric (or rotational) group of the simplex S n preserving its center fixed is isomorphic to the group consisting of all n × n permutational matrices. All algorithms in this paper can be realized by algebraic system CoCoA 4.3.

Digital technology (DT) has a significant role to play in modern education. This study examined motivational goals of student teachers in initial teacher education in Singapore and the influences of goals on their use of DT personally and in the classroom. The participants (N=312) responded to a survey about their motivational goals (learning vs. performance) and DT application (personal vs. classroom application). Results showed that personal use of DT, especially for younger teachers, was clearly more than classroom application. Females were found to have higher performance goal. Structural equation modelling found that learning goals were positively related to both personal use and classroom application, but performance goals were not positively related to either outcome. As performance goals were found to be unrelated to classroom application of DT, teacher education should focus more on the development of learning goals so as to encourage teachers, especially females, to use DT for teaching.