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In highly uncertain times, firms are increasingly exhibiting risk aversion to uncertain demand and altruism to supply chain partners to reduce risk and maintain stability. To deal with high demand fluctuations, numerous firms are adopting information‐sharing strategies. We study how a retailer's risk aversion and altruism affect her demand information‐sharing decision by constructing game‐theoretic models. We first show that information sharing makes double marginalization (DM) stronger and hurts the retailer and generates an information‐sharing DM effect. The retailer's risk aversion strengthens this effect, while her altruism weakens the effect. Meanwhile, information sharing generates an uncertainty reduction effect on the risk‐averse retailer by reducing volatility and an altruism improvement effect on the altruistic retailer by increasing the manufacturer's profit. Whether information sharing benefits the retailer depends on her level of risk aversion and altruism. The retailer prefers voluntary sharing when both her risk aversion and altruism are high. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic retinopathy (DR) is a common complication of diabetes. Retinal neuronal degeneration is an early event in DR, indicated by the declined electroretinogram (ERG). Dipeptide alanine-glutamine (Ala-Gln) is widely used as a nutritional supplement in the clinic and has anti-inflammatory effects on the gastrointestinal system. Studies also reported that glutamine has beneficial effects on diabetes. This study aimed to investigate the possible therapeutic effects of Ala-Gln in diabetic retinal neurodegeneration and to delineate its mechanism of action. Methods: The Streptozotocin (STZ)-induced rat model was used as a DR model. ERG was used to measure the neuronal function of the retina. Western blot analysis was performed to test the expression of proteins. Immunofluorescence staining was used for the detection and localization of proteins. Results: In diabetic rats, the amplitudes of ERG were declined, while Ala-Gln restored the declined ERG. Retinal levels of inflammatory factors were significantly decreased in Ala-Gln-treated diabetic rats. Ala-Gln mitigated the declined levels of glutamine synthetase and ameliorated the upregulated levels of glial fibrillary acidic protein (GFAP) in diabetic retinas. Moreover, Ala-Gln upregulated the glycolytic enzymes pyruvate kinase isozymes 2 (PKM2), lactate dehydrogenase A (LDHA) and LDHB and stimulated the mTOR signaling pathway in diabetic retinas. The mitochondrial function was improved after the treatment of Ala-Gln in diabetic retinas. Discussion: Ala-Gln ameliorates retinal neurodegeneration by reducing inflammation and enhancing glucose metabolism and mitochondrial function in DR. Therefore, manipulation of metabolism by Ala-Gln may be a novel therapeutic avenue for retinal neurodegeneration in DR. [ABSTRACT FROM AUTHOR]

The life‐threatening colorectal cancer exhibits multilevel immunosuppressive characteristics, including low immunogenicity, abnormal cellular metabolism, and acidic immunosuppressive microenvironment. In this work, multi‐synergistic chemotherapeutic drug assemblies are fabricated to activate colorectal cancer immunotherapy by modulating the multilevel immunosuppressive characteristics. Without any drug excipients, the glycolysis inhibitor of lonidamine (LON), indoleamine 2,3‐dioxygenase 1 (IDO‐1) inhibitor of NLG919 (NLG), and the photosensitizer of chlorine e6 could self‐assemble into drug assemblies (LNC) with uniform nano‐size distribution and increased drug stability. Moreover, LNC could also promote cellular uptake and enhance drug penetration to enable efficient drug co‐delivery. Especially, the photodynamic therapy (PDT) of LNC could disrupt tumor cells to release tumor‐associated antigens, thus efficiently suppressing primary tumor growth and improving tumor immunogenicity. Meanwhile, LNC could also reduce the activity of IDO‐1 and attenuate the glycolysis metabolism, thereby reversing the multilevel immunosuppressive characteristics to promote T cell activation. Benefiting from the multi‐synergistic effects, LNC efficiently eradicates the primary tumor growth and also activates systemic antitumor immunity for metastatic tumor inhibition. Such a simple formulation but a multi‐synergistic strategy may accelerate the development of translational nanomedicine for colorectal cancer immunotherapy by using small molecular drug combinations. [ABSTRACT FROM AUTHOR]

AbstractVariable selection is a fundamental tool to identify important factors from a large number of candidate covariates and has been successfully adopted in various fields. In survival analysis, developing variable selection techniques is often intractable since the failure times of interest are accompanied by censoring and other complex features, such as left truncation. Despite enormous variable selection methods for right-censored data, they seldom accommodate left truncation. In this work, for the left-truncated and right-censored data, we present a penalized composite likelihood approach to achieve variable selection and parameter estimation simultaneously in the proportional hazards model. To be specific, the composite likelihood is essentially a combination of the conditional likelihood and the pairwise likelihood that can properly take into account the marginal distribution of the observed truncation times. An explicit solution of the baseline hazard function is obtained through solving a series of self-consistent estimating equations. The sparse estimators of regression parameters under various classical penalty functions are calculated with a unified shooting algorithm. Simulation results indicate that the proposed method performs reasonably well and has some desirable advantages over the penalized conditional likelihood approach and the approach that ignores the presence of left truncation. An application to a set of left-truncated breast cancer data is also provided. [ABSTRACT FROM AUTHOR]

Tau is a microtubule-associated protein that plays a vital role in the mammalian nervous system. Alternative splicing of the MAPT gene leads to the formation of tau isoforms with varying N-terminal inserts and microtubule-binding repeats. Dysregulation of tau alternative splicing has been linked to diseases in the central nervous system, but the roles of tau isoforms in the peripheral nervous system remain unclear. Here, we investigated the alternative splicing of tau exons 4A and 10 in the sciatic nerve and Schwann cells during development and following injury. We discovered that low-molecular-weight (LMW) tau, resulting from the exclusion of exon 4A, and 3R tau, generated by the exclusion of exon 10, diminishes with aging in rat sciatic nerve and Schwann cells. High-molecular-weight (HMW) tau and 3R tau increase in the adult sciatic nerve post-injury. We constructed viruses that expressed HMW−4R, LMW−4R, HMW−3R, and LMW−3R and introduced them into cultured cells or the distal part of the injured sciatic nerve to assess their effects on Schwann cell migration and proliferation. We also examined the effects of the four isoforms on axon growth and debris clearance after sciatic nerve injury. Our results demonstrated that tau isoforms inhibit Schwann cell proliferation while promoting Schwann cell migration and sciatic nerve regeneration. Specifically, the 3R−tau isoforms were more effective than the 4R−tau isoforms in promoting nerve regeneration. In conclusion, our study reveals the roles of tau isoforms in the peripheral nervous system and provides insights into the development of new therapeutic strategies for peripheral nerve injuries. [ABSTRACT FROM AUTHOR]

Farmers' livelihoods are critical for global sustainable development and the conservation and transmission of rural heritage. However, neglecting farmers' livelihoods increases the risks to living heritage conservation. Therefore, it is essential to explore the impact of livelihood capital on farmers' landscape services cognition and their behavioral intentions. Based on the Sustainable Livelihoods Approach, this study examines the rural areas of Mulanbei irrigation district, which was recognized as a World Heritage Irrigation Structure in 2014, and uses a structural equation model to investigate the relationships between farmers' livelihood capital, landscape services cognition and behavioral intentions. The study's key findings include the following: (1) The levels of human capital (0.541), social capital (0.671), and cultural capital (0.645) are relatively high, while the levels of natural, physical, and financial capital are comparatively low. (2) There are significant differences in landscape service cognition and behavioral intentions among farmers of different livelihood strategies, with diversified livelihood farmers demonstrating the highest levels of both cognition and intentions, while subsidy-dependent farmers show the lowest levels. (3) Natural, cultural and financial capital play a crucial role in influencing farmers' landscape services cognition and their behavioral intentions. Landscape service cognition mediates the relationship between livelihood capital and behavioral intentions. (4) To increase farmers' willingness to protect and promote rural heritage, efforts should focus on enhancing natural, physical, and financial capital while fostering cultural capital to promote advocacy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is typically characterized by rich vascularity, with angiogenesis playing a crucial role in its growth and invasion. Molecular imaging of specific receptors in blood vessels is crucial in HCC diagnosis. In particular, in vivo imaging utilizing the second near‐infrared (NIR‐II) window offers improved tissue penetration, reduced light scattering, and lower autofluorescence. Despite the great potential of the NIR‐II window, developing safe and effective probes to provide better imaging performance for HCC is urgently needed. In this study, NIR‐II imaging integrated with a vascular endothelial growth factor receptor (VEGFR)‐targeted probe generated by combining a VEGFR‐targeted peptide with indocyanine green (ICG) is used to characterize HCC‐related angiogenesis at a resolution of 56.0 µm. For the first time, liver metabolic curves and parameters of liver function reserve (LFR) are obtained by fitting NIR‐II fluorescence signals with high spatiotemporal resolution, showing significant differences between HCC mice and controls. Moreover, unlike ICG, the targeting probe has a targeted effect on blood vessels in vivo. The tumor‐to‐normal (T/N) ratio in NIR‐II imaging reaches up to 3.30 after post‐injection of the targeting probe. The results indicate that the VEGFR‐targeted probe is a powerful tool for NIR‐II fluorescence imaging to enhance early diagnosis of HCC. [ABSTRACT FROM AUTHOR]

Cropland acidification seriously restricts sustainable agricultural development. The main purpose of this study was to determine whether deeper tilling could alleviate topsoil acidification to improve the quality of arable land. A soil column incubation experiment simulating tillage depths (10 cm, 30 cm and 50 cm) and lime addition was conducted to determine their effects on soil acidification improvement. The changes in soil pH, exchangeable acidity, ammonium nitrogen (NH4+-N), nitrate nitrogen (NO3−-N), available phosphorus (AP), and microbial phospholipid fatty acids (PLFA) were analyzed. Tillage depth, lime application, and their interaction all had significant impacts on soil pH. T50 (simulated tillage depth of 50 cm) and T50+Lime (simulated tillage depth of 50 cm plus lime) treatments significantly increased the topsoil pH from 5.41 to 6.35 and 7.12, respectively. T50 treatment significantly reduced the soil exchangeable acid content compared to the T10 treatment. The nutrient accumulation along soil column indicated that the T50 and T50+Lime treatments significantly increased NO3−-N and AP content in the >30–50 cm soil layer. Compared with T30, NO3−-N accumulation in the >30–50 cm soil layers of T50 and T50+Lime treatments was 6.62 and 7.93 times higher, respectively. The accumulation of AP in the >30–50 cm soil layers of the T50 and T50+Lime treatments was 1.33 and 1.54 times higher than in the T30 treatment, respectively. These findings imply tillage up to 50 cm without exogenous materials could be a potential measure to reduce topsoil acidification and increase nutrition availability of >30–50 cm soil layers. Tillage of up to 30 cm combined with lime application confers greater benefits, which would particularly impact crops with shallow root systems. Subsequent field experiments will be conducted to further investigate the efficacy of these strategies in enhancing crop yield. [ABSTRACT FROM AUTHOR]

Fundus photography (FP) is a crucial technique for diagnosing the progression of ocular and systemic diseases in clinical studies, with wide applications in early clinical screening and diagnosis. However, due to the nonuniform illumination and imbalanced intensity caused by various reasons, the quality of fundus images is often severely weakened, brings challenges for automated screening, analysis, and diagnosis of diseases. To resolve this problem, we developed strongly constrained generative adversarial networks (SCGAN). The results demonstrate that the quality of various datasets were more significantly enhanced based on SCGAN, simultaneously more effectively retaining tissue and vascular information under various experimental conditions. Furthermore, the clinical effectiveness and robustness of this model were validated by showing its improved ability in vascular segmentation as well as disease diagnosis. Our study provides a new comprehensive approach for FP and also possesses the potential capacity to advance artificial intelligence‐assisted ophthalmic examination. [ABSTRACT FROM AUTHOR]

Philosophical work on self‐respect has distinguished between various kinds of self‐respect. In this paper, Shiying Li begins by introducing important kinds of self‐respect and exploring the conceptual and empirical relations among them. She then discusses the value and political significance of social bases of self‐respect for both individuals and society. While political theory on this topic, especially from the Rawlsian tradition, has focused on the social bases of self‐respect in a well‐ordered society, Li takes on the task of uncovering the social bases of self‐respect in an unjust society marked by structural injustices such as racism, sexism, social stigmas, and economic and other social inequalities. She provides arguments, including public reason arguments, for the political priority and urgency of securing robust self‐respect for all in an unjust society, and thus paves the way for a discussion of the role that education, especially schooling, can and should play in securing robust self‐respect. Li concludes by offering reasons to direct special attention to specific aspects of schooling and by making suggestions regarding a curriculum and pedagogy aimed at securing robust self‐respect for all. [ABSTRACT FROM AUTHOR]

Bereavement of one or both parents is known to cause many kinds of internalizing and externalizing problems in adolescents. However, less is known about factors that are protective of the mental health of orphaned adolescents and differences by their gender and orphanhood type. To fill these gaps, the current study used a sample from southwestern China to test the association between types of orphans, life satisfaction, adolescents' psychological distress and problem behaviours. The results showed that orphan girls were prone to have lower levels of problem behaviours but higher levels of psychological distress than orphan boys. Female paternal orphans tended to have the highest psychological distress, while male paternal orphans tended to have the lowest psychological distress. In addition, school satisfaction had a stronger association with problem behaviour, and self‐satisfaction had a stronger association with psychological distress. Interventions and preventive measures aimed at reducing the psychological distress of orphans could benefit from the findings regarding the correlates of psychological distress and the most vulnerable group among orphans. [ABSTRACT FROM AUTHOR]