Development of high barrier-coated white cardboard for fruit preservation.

Environment-friendly and biodegradable packaging materials have attracted widespread attention. Development of green solutions to extend the fruit shelf life and address fruit preservation thus has a far-reaching impact. In this study, high-barrier white cardboard (WC) was prepared by a facile coating method. Compared with the WC substrate, the WVP value of the polyvinylidene chloride (PVDC) emulsion-coated WC (3.46 × 10-11 g m m-2 s-1 kPa-1) decreased 73.8% and the OP value (14.8 cm3 m-2 day-1·Pa-1) decreased 61.9%. In addition, the mechanical properties of the PVDC emulsion-coated WC increased significantly. The weight loss rate and decay rate of the stored fruits packaged with PVDC emulsion-coated WC decreased by about 5%. The high barrier PVDC emulsion-coated WC with excellent mechanical properties, good barrier effect, and preservation function was successfully prepared. Benefitting from these investigated characteristics, the obtained coated WC can be used to package fruits to reduce water loss and delay ripening, and thus extend their shelf life, exhibiting a favorable effect on blueberry and grape storage. Overall, the fabricated eco-friendly coated white cardboard has shown great potential for biodegradable packaging applications. We believe the current work presents an approach to address perishable fruit preservation and provide a supplement alternative.

Risk factors and a predictive model for the occurrence of adverse outcomes in patients with new-onset refractory status epilepsy.

Objectives: To determine risk factors for the occurrence of adverse outcomes in patients with new-onset refractory status epilepsy (NORSE) and to construct a concomitant nomogram. Methods: Seventy-six adult patients with NORSE who were admitted to the Department of Neurology, First Affiliated Hospital of Sun Yat-sen University between January 2016 and December 2022 were enrolled for the study. Participants were divided into two-those with good and poor functional outcomes-and their pertinent data was obtained from the hospital medical recording system. Univariate analysis was used to identify potential causes of poor outcomes in both groups and a multivariate logistic regression model was used to identify risk factors for the occurrence of poor outcomes. Using the R programming language RMS package, a nomogram was created to predict the occurrence of poor outcomes. Results: The NORSE risk of adverse outcome nomogram model included four predictors, namely duration of mechanical ventilation (OR = 4.370, 95% CI 1.221-15.640, p = 0.023), antiviral therapy (OR = 0.045, 95% CI 0.005-0.399, p = 0.005), number of anesthetics (OR = 13.428, 95% CI 2.16-83.48, p = 0.005) and neutrophil count/lymphocyte count ratio (NLR) (OR = 5.248, 95% CI 1.509-18.252, p = 0.009). The nomogram had good consistency and discrimination in predicting risk and can thus assist clinical care providers to assess outcomes for NORSE patients. Through ordinary bootstrap analyses, the results of the original set prediction were confirmed as consistent with those of the test set. Conclusion: The nomogram model of risk of adverse outcomes in NORSE adult patients developed in this study can facilitate clinicians to predict the risk of adverse outcomes in NORSE patients and make timely and reasonable interventions for patients at high risk of adverse outcomes.

Determination of Azole Fungicide Residues in Fresh Juice by Magnetic Solid Phase Extraction Based on Fe3O4@ZnAl-LDH@MIL-53(Al) Sorbent in Combination with High-Performance Liquid Chromatograph.

In this work, a magnetic adsorption material based on metal-organic framework (Fe3O4@ZnAl-LDH@MIL-53(Al)) was synthesized and used as an adsorbent in the process of magnetic solid phase extraction. Then, a high-performance liquid chromatograph was used to quantitatively detect triazole fungicides in samples. In order to verify the successful preparation of the material, a series of characterization analyses were carried out. Besides, the key parameters that may affect the extraction efficiency have been optimized, and under optimal conditions the three triazole fungicides showed good linearity in the range of 10-1000 µg/L (R2 ≥ 0.9796); Limit of detections were ranged from 0.013 to 0.030 µg/mL. Finally, the established method was applied to the detection of triazole fungicides in four fresh juice samples. The results showed that the target analyte was not detected in all the test samples. By detecting the recoveries (73.3-104.3%) and coefficient variation (RSD ≤ 6.8%) of triazole fungicides in fortified samples, it proved that this established method meets the requirements of pesticide residue analysis and showed excellent application potential.

Trust (in)congruence, open innovation, and circular economy performance: Polynomial regression and response surface analyses.

Engaging partner firms in open innovation is critical to overcoming internal resource/capability constraints to achieve firm and supply chain circular economy (CE) performance, yet scholars have not examined this link empirically. Further, while researchers have repeatedly emphasized trust as a key driver of open innovation performance, little is known from a dyadic trust perspective (e.g., congruence vs. incongruence, high-high congruence vs. low-low congruence). To fill these gaps, we propose a theoretical model based on the social exchange theory (SET) and test it using a dyadic dataset of listed Chinese manufacturing firms. The results suggest that 1) rather than unilateral trust from the focal firm or its partners, trust congruence is more predictive of successful open process and product innovations, 2) regarding congruence types (low-low vs. high-high), congruence at higher levels of trust facilitates open product innovation more than low-low trust congruence; interestingly, such an effect is not significant for open process innovation, 3) open process innovation has a positive influence on the focal firm's CE performance, but its impact on supply chain CE performance is not statistically significant, and 4) open product innovation has a significantly positive impact on the focal firm and supply chain CE performance. Our findings still hold after analyzing time-lagged models and alternative measurements as robustness checks. Our study provides meaningful theoretical contributions to the literature and useful, practical insights for managing inter-organizational relationships, open innovation, and CE performance.

Serum ITIH5 as a novel diagnostic biomarker in cholangiocarcinoma.

Cholangiocarcinoma often remains undetected until advanced stages due to the lack of reliable diagnostic markers. Our goal was to identify a unique secretory protein for cholangiocarcinoma diagnosis and differentiation from other malignancies, benign hepatobiliary diseases, and chronic liver conditions. We conducted bulk RNA-seq analysis to identify genes specifically upregulated in cholangiocarcinoma but not in most other cancers, benign hepatobiliary diseases, and chronic liver diseases focusing on exocrine protein-encoding genes. Single-cell RNA sequencing examined subcellular distribution. Immunohistochemistry and enzyme-linked immunosorbent assays assessed tissue and serum expression. Diagnostic performance was evaluated via receiver-operating characteristic (ROC) analysis. Inter-alpha-trypsin inhibitor heavy chain family member five (ITIH5), a gene encoding an extracellular protein, is notably upregulated in cholangiocarcinoma. This elevation is not observed in most other cancer types, benign hepatobiliary diseases, or chronic liver disorders. It is specifically expressed by malignant cholangiocytes. ITIH5 expression in cholangiocarcinoma tissues exceeded that in nontumorous bile duct, hepatocellular carcinoma, and nontumorous hepatic tissues. Serum ITIH5 levels were elevated in cholangiocarcinoma compared with controls (hepatocellular carcinoma, benign diseases, chronic hepatitis B, and healthy individuals). ITIH5 yielded areas under the ROC curve (AUCs) from 0.839 to 0.851 distinguishing cholangiocarcinoma from controls. Combining ITIH5 with carbohydrate antigen 19-9 (CA19-9) enhanced CA19-9's diagnostic effectiveness. In conclusion, serum ITIH5 may serve as a novel noninvasive cholangiocarcinoma diagnostic marker.

Assessing the determinants of corporate environmental investment: a machine learning approach.

In recent years, experts and academics in the environmental management field have developed an interest in the factors and evaluation techniques that influence corporate environmental investment decisions. However, there are substantial differences between studies employing the most recent evaluation methodologies and those that use indicator systems. To explore the mechanisms that influence corporate environmental investment, this study investigated the determinants of environmental investment through the perspectives of firm, board, chair, and chief executive officer (CEO) characteristics using a machine learning approach. Based on a large-scale data sample from Chinese-listed companies, the results indicated that the extreme gradient boosting (XGBoost) model had an accuracy of up to 97.63%, thus performing the best. Additionally, the model that used SHapley Additive exPlanations (SHAP) to interpret XGBoost showed that a company's sales performance was the most important factor that influenced environmental investment, followed by CEO tenure, board independence, board gender diversity, chair academic experience, and the company's level of internationalization. Furthermore, when examining the sample of heavily polluting enterprises, sales, board gender diversity, CEO tenure, chair academic experience, board independence, and chair-CEO duality, all were found to play crucial roles in predicting environmental investment. Overall, this study aids in evaluating the factors that influence corporate environmental investment decisions and provides policymakers and practitioners with a machine learning approach for use when assessing these factors.

Thymoma-associated autoimmune encephalitis with myasthenia gravis: Case series and literature review.

OBJECTIVES: This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their clinical characteristics. METHODS: Clinical records of 3 AE patients in the first affiliated hospital of Sun Yat-sen University were reviewed. All of them were diagnosed with AE between 1 November 2021 and 1 March 2022, and clinical evidence about thymoma and MG was found. All published case reports were searched for comprehensive literature from January 1990 to June 2022. RESULTS: A total of 18 cases diagnosed with thymoma-associated autoimmune encephalitis (TAAE) and thymoma-associated myasthenia gravis (TAMG) were included in this complication, wherein 3 cases were in the first affiliated hospital of Sun Yat-sen University and the other 15 were published case reports. 5/18 patients had alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibody (AMPAR-Ab) in their serum and cerebrospinal fluid (CSF). All of them had positive anti-acetylcholine receptor antibody (AChR-Ab). And 12/18 patients showed a positive response to thymectomy and immunotherapy. Besides, thymoma recurrences were detected because of AE onset. And the shortest interval between operation and AE onset was 2 years in patients with thymoma recurrence. CONCLUSIONS: There was no significant difference in the clinical manifestations between these patients and others with only TAMG or TAAE. TAAE was commonly associated with AMPAR2-Ab. Significantly, AE more commonly heralded thymoma recurrences than MG onset. And the intervals of thymectomy and MG or AE onset had different meanings for thymoma recurrence and prognoses of patients.

Hydrophobization of Ribonucleic Acids for Facile Systemic Delivery and Multifaceted Cancer Immunotherapy.

Ribonucleic acids (RNAs) enable disease-related gene inhibition, expression, and editing and represent promising therapeutics in various diseases. The efficacy of RNA relies heavily on the presence of a secure and effective delivery system. Herein, we found that RNA could be hydrophobized by cationic lipid and ionizable lipid and conveniently coassemble with amphiphilic polymer to achieve micelle-like nanoparticles (MNP). The results of the study indicate that MNP exhibits a high level of efficiency in delivering RNA. Besides, the MNP encapsulating siRNA that targets CD47 and PD-L1 remarkably blocked these immune checkpoints in a melanoma tumor model and elicited a robust immune response. Moreover, the MNP encapsulating the mRNA of OVA achieved antigen translation and presentation, leading to an effective antitumor immunoprophylaxis outcome against OVA-expressing melanoma model. Our findings suggest that RNA hydrophobization could serve as a viable approach for delivering RNA, thereby facilitating the exploration of RNA therapy in disease treatment.

Smoking cessation policy and treatments derived from the protective motivation of smokers: a study on graphic health warning labels.

Introduction: Smoking is a leading public health risk. Many countries are reducing the demand for tobacco through graphic health warning labels (GHWLs). This study aims to explore smokers' perceptions of GHWLs and analyze the effect of GHWLs on their behavioral intentions to quit smoking. Methods: A theoretical model is designed by synthesizing protection motivation theory, an extension of the extended parallel process model, and the theory of planned behavior. We collected a cross-sectional sample of 547 anonymous smokers through a stratified random sampling strategy. GHWLs published in 2011 by the US Food and Drug Administration were used in the survey to assess smokers' responses to them, and then the hypotheses are validated through structural equation models. Results: The results suggest that perceived severity, perceived vulnerability, response efficacy, and health anxiety have a significant impact on smokers' protection motivation. Furthermore, smokers' protection motivation directly impacts the behavioral intention to quit smoking and indirectly influences intention to quit through attitudes. Discussion: These findings have practical implications for the implementation and improvement of GHWLs policies. Meanwhile, this study enriches the literature on public health protection measures (i.e., GHWLs) and smokers' behavioral intention to quit smoking.

The psoas muscle density as a predictor of postoperative complications in elderly patients undergoing rectal cancer resection.

Background: Muscle depletion that impairs normal physiological function in elderly patients leads to poor prognosis. This study aimed to evaluate the association between total abdominal muscle area (TAMA), total psoas area (TPA), psoas muscle density (PMD), and short-term postoperative complications in elderly patients with rectal cancer. Methods: All elderly patients underwent rectal cancer resection with perioperative abdominal computed tomography (CT). Complications were assessed according to the Clavien-Dindo classification. Severe complications were defined as grade III-V following the Clavien-Dindo classification. Univariate and multivariate analyses were performed to evaluate risk factors of short-term severe postoperative complications. Results: The cohort consisted of 191 patients with a mean age of 73.60 ± 8.81 years. Among them, 138 (72.25%) patients had Clavien-Dindo 0- II, 53 (27.75%) patients had severe postoperative complications (Clavien-Dindo III-V), and 1(0.52%) patient died within 30 days of surgery. PMD was significantly higher in the Clavien-Dindo 0-II cohort compared to the Clavien-Dindo III-V cohort (p=0.004). Nevertheless, TAMA and TPA failed to exhibit significant differences. Moreover, the multivariate regression analysis implied that advanced age [OR 1.07 95%CI (1.02-1.13) p=0.013], male [OR 5.03 95%CI (1.76-14.41) p=0.003], high charlson comorbidity index (CCI) score [OR 3.60 95%CI (1.44-9.00) p=0.006], and low PMD [OR 0.94 95%CI (0.88-0.99) p=0.04] were independent risk factors of Clavien-Dindo III-V. Conclusion: Preoperative assessment of the PMD on CT can be a simple and practical method for identifying elderly patients with rectal cancer at risk for severe postoperative complications.

Promoting the Recruitment, Engagement, and Reinvigoration of Effector T Cells via an Injectable Hydrogel with a Supramolecular Binding Capability for Cancer Immunotherapy.

T cells play a basic and key role in immunotherapy against solid tumors, and efficiently recruiting them into neoplastic foci and sustaining long-term effector function are consistent goals that remain a critical challenge. Here, an injectable alginate-based hydrogel with abundant ß-cyclodextrin (ALG-ßCD) sites is developed and intratumorally injected to recruit CCR9+ CD8+ T cells (a subset of T cells with robust antitumor activity) via the trapped chemokine CCL25. In the meantime, an intravenously injected adamantane-decorated anti-PD1 antibody (Ad-aPD1) would hitchhike on recruited CCR9+ CD8+ T cells to achieve the improved intratumoral accumulation of Ad-aPD1. Moreover, the Ad-PD1 and Ad-PDL1 antibodies are immobilized in the ALG-ßCD hydrogel through supramolecular host-guest interactions of Ad and ßCD, which facilitate engagement between CD8+ T cells and tumor cells and reinvigorate CD8+ T cells to avoid exhaustion. Based on this treatment strategy, T cell-mediated anticancer activity is promoted at multiple levels, eventually achieving superior antitumor efficacy in both orthotopic and postsurgical B16-F10 tumor models.

Hybrid DAER Based Cross-Modal Retrieval Exploiting Deep Representation Learning.

Information retrieval across multiple modes has attracted much attention from academics and practitioners. One key challenge of cross-modal retrieval is to eliminate the heterogeneous gap between different patterns. Most of the existing methods tend to jointly construct a common subspace. However, very little attention has been given to the study of the importance of different fine-grained regions of various modalities. This lack of consideration significantly influences the utilization of the extracted information of multiple modalities. Therefore, this study proposes a novel text-image cross-modal retrieval approach that constructs a dual attention network and an enhanced relation network (DAER). More specifically, the dual attention network tends to precisely extract fine-grained weight information from text and images, while the enhanced relation network is used to expand the differences between different categories of data in order to improve the computational accuracy of similarity. The comprehensive experimental results on three widely-used major datasets (i.e., Wikipedia, Pascal Sentence, and XMediaNet) show that our proposed approach is effective and superior to existing cross-modal retrieval methods.

Protective effect of quercetin on lung epithelial cell bystander-effect in the conditioned medium model of lung cancer metastasis induced by radiation.

To investigate the protective effect of Quercetin (Que) on lung epithelial cells (BEAS-2B) induced bystander effect (RIBE) after heavy ion irradiation of A549 cells. A549 cells were irradiated with 2 Gy X heavy ion rays to obtain a conditioned medium. BEAS-2B was incubated with a conditioned medium or Que. CCK-8 assay was used to screen the optimal effective concentration of Que and detect cell proliferation. Cell number was measured by cell counter and apoptosis rate was measured by flow cytometry. HMGB1 and ROS levels were measured by ELISA. Western blot was used to detect the protein expression of HMGB1, TLR4, p65, Bcl-2, Bax, Caspase3 and Cleaved Caspase3. The growth and proliferation rate of BEAS-2B decreased while the apoptosis rate increased after conditioned medium stimulation, and Que intervention inhibited this effect. The expression of HMGB1 and ROS increased after conditioned medium stimulation, and this effect was inhibited by Que intervention. In addition, the conditioned medium increased the levels of proteins of HMGB1, TLR4, p65, Bax, Caspase3 and Cleaved Caspase 3, and decreased levels of Bcl-2 protein, but Que intervention decreased the levels of HMGB1, TLR4, p65, Bax, Caspase3 and Cleaved Caspase 3proteins, and increased levels of Bcl-2 protein. The RIBE of BEAS-2B induced by irradiation of A549 is associated with HMGB1TLR4/NF-κB signaling pathway in conditioned medium inducing apoptosis by activating ROS, and Que may block RIBE-induced apoptosis by regulating HMGB1/TLR4/NF-κB pathway.

A manganese-phenolic network platform amplifying STING activation to potentiate MRI guided cancer chemo-/chemodynamic/immune therapy.

Low immune infiltration severely hinders the efficacy of cancer immunotherapy. Here, we developed a manganese-phenolic network platform (TMPD) to boost antitumor immunity via a stimulator of interferon gene (STING)-amplified activation cascade. TMPD is based on doxorubicin (DOX)-loaded PEG-PLGA nanoparticles and further coated with manganese (Mn2+)-tannic acid (TA) networks. Mechanistically, DOX-based chemotherapy and Mn2+-mediated chemodynamic therapy effectively promoted immunogenic cell death (ICD), characterized by abundant damage-associated molecular pattern (DAMP) exposure, which subsequently enhanced dendritic cells' (DCs) presentation of antigens. DOX-elicited DNA damage simultaneously caused cytoplasmic leakage of intracellular double-stranded DNA (dsDNA) as the STING signal initiator, while Mn2+ mediated significant upregulation in the expression of a STING pathway-related protein thereby amplifying the STING signal. Systemic intravenous administration of TMPD remarkably promoted DC maturation and CD8+ T cell infiltration, thus eliciting strong antitumor effects. Meanwhile, the released Mn2+ could serve as a contrast agent for tumor-specific T1-weighted magnetic resonance imaging (MRI). Moreover, TMPD combined with immune checkpoint blockade (ICB) immunotherapy significantly inhibited tumor growth and lung metastasis. Collectively, these findings indicate that TMPD has great potential in activating robust innate and adaptive immunity for MRI guided cancer chemo-/chemodynamic/immune therapy.

mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study.

Whether metagenomic next-generation sequencing (mNGS) could benefit patients with suspected severe central nervous system (CNS) infection in terms of diagnosis and antibiotic treatment remains unknown. We retrospectively analyzed 79 patients with suspected CNS infection and undertook mNGS. The value of mNGS was investigated in terms of identification of pathogen and guidance for the adjustment of antibiotic treatment. The relationship between the time of initiating mNGS since onset and the Glasgow Outcome Scale (GOS) score after 90-day follow-up were analyzed. Fifty out of 79 cases with suspicious severe CNS infection were finally diagnosed. Despite previous routine laboratory tests, mNGS further promoted the accurate identification of pathogens in 23 cases (47.9%). The sensitivity, specificity, and accuracy of mNGS test in this study were 84.0, 79.3, and 82.3%, respectively. Furthermore, mNGS facilitated the adjustment of empirical antibiotic treatments in 38 cases (48.1%). The time of taking mNGS since onset had an insignificant weak positive correlation with GOS after 90-day follow-up (r = -0.73, P = 0.08). mNGS facilitated the accurate identification of pathogens in suspicious severe CNS infections and promoted the accurate antibiotic therapy even empirical antibiotics were administrated. It should be taken as early as possible to improve the clinical outcome of patients with suspicious severe CNS infection.

Effects of Al/Na and Si/Na Molar Ratios on the Alkalinity of Metakaolin-Based Geopolymer Pore Solutions.

The pH values of pore solutions are of great significance for the durability of concrete, but the influencing factors and mechanisms of geopolymer pore solutions are still unclear and the composition of raw material elements has a great influence on the geological polymerization behavior of geopolymers. Therefore, we prepared geopolymers with different Al/Na and Si/Na molar ratios using metakaolin, and the pH and compressive strength values of the pore solutions were determined using solid-liquid extraction. Finally, the influencing mechanisms of sodium silica on the alkalinity and geological polymerization behavior of geopolymer pore solutions were also analyzed. The results showed that the pH values of the pore solutions decreased with an increase in the Al/Na ratio and increased with an increase in the Si/Na ratio. The compressive strength of the geopolymers first increased and then decreased with an increase in the Al/Na ratio and decreased with an increase in the Si/Na ratio. The exothermic rates of the geopolymers first increased and then slowed down with an increase in the Al/Na ratio, indicating that the reaction levels first increased and then decreased with an increase in the Al/Na ratio. The exothermic rates of the geopolymers gradually slowed down with an increase in the Si/Na ratio, indicating that an increase in the Si/Na ratio reduced the reaction levels. In addition, the results obtained from SEM, MIP, XRD and other test methods were consistent with the pH change laws of geopolymer pore solutions, i.e., the higher the reaction level, the denser the microstructure and the smaller the porosity, whereas the larger the pore size, the smaller the pH value of the pore solution.

Fas/FasL and Complement Activation are Associated with Chronic Active Epstein-Barr Virus Hepatitis.

Background and Aims: Chronic active Epstein-Barr virus hepatitis (CAEBVH) is a rare and highly lethal disease characterized by hepatitis and hepatomegaly. This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH. Methods: Ten patients with confirmed Epstein-Barr virus hepatitis infection were enrolled. The clinicopathological characteristics of these patients were summarized and analyzed. Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms. Lastly, immunohistochemical staining was employed to verify pathogenic mechanisms. Results: Clinical features observed in all Epstein-Barr virus hepatitis patients included fever (7/10), splenomegaly (10/10), hepatomegaly (9/10), abnormal liver function (8/10), and CD8+ T cell lymphopenia (6/7). Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver. Positive Epstein-Barr virus-encoded small RNA in-situ hybridization (EBER-ISH) of lymphocytes of liver tissues was noted. Whole exome sequencing indicated that cytotoxic T lymphocytes and the complement system were involved. The expression of CD8, Fas, FasL, and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls (p<0.05). Lastly, Complement 1q and complement 3d expression, were higher in CAEBVH patients relative to controls (p<0.05). Conclusions: CAEBVH patients developed fever, hepatosplenomegaly, and lymphadenopathy. Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity. Fas/FasL and complement activation were involved in CAEBVH patients.

Peripheral Nerve Denervation in Streptozotocin-Induced Diabetic Rats Is Reduced by Cilostazol.

Background and Objective: Our previous study demonstrated that consistent treatment of oral cilostazol was effective in reducing levels of painful peripheral neuropathy in streptozotocin-induced type I diabetic rats. As diabetic neuropathy is characterized by hyperglycemia-induced nerve damage in the periphery, this study aims to examine the neuropathology as well as the effects of cilostazol treatments on the integrity of peripheral small nerve fibers in type I diabetic rats. Materials and Methods: A total of ninety adult male Sprague-Dawley rats were divided into the following groups: (1) naïve (control) group; (2) diabetic rats (DM) group for 8 weeks; DM rats receiving either (3) 10 mg/kg oral cilostazol (Cilo10), (4) 30 mg/kg oral cilostazol (Cilo30), or (5) 100 mg/kg oral cilostazol (Cilo100) for 6 weeks. Pain tolerance thresholds of hind paws toward thermal and mechanical stimuli were assessed. Expressions of PGP9.5, P2X3, CGRP, and TRPV-1 targeting afferent nerve fibers in hind paw skin and glial cells in the spinal dorsal horn were examined via immunohistochemistry and immunofluorescence. Results: Oral cilostazol ameliorated the symptoms of mechanical allodynia but not thermal analgesia in DM rats. Significant reductions in PGP9.5-, P2X3-, CGRP, and TRPV-1-labeled penetrating nerve fibers in the epidermal layer indicated denervation of sensory nerves in the hind paw epidermis of DM rats. Denervation significantly improved in groups that received Cilo30 and Cilo100 in a dose-dependent manner. Cilostazol administration also suppressed microglial hyperactivation and increased astrocyte expressions in spinal dorsal horns. Conclusions: Oral cilostazol ameliorated hyperglycemia-induced peripheral small nerve fiber damage in the periphery of diabetic rats and effectively mitigated diabetic neuropathic pain via a central sensitization mechanism. Our findings present cilostazol not only as an effective option for managing symptoms of neuropathy but also for deterring the development of diabetic neuropathy in the early phase of type I diabetes.

Increasing Couriers' Job Satisfaction through Social-Sustainability Practices: Perceived Fairness and Psychological-Safety Perspectives.

Due to the spike in online-retail demand during the pandemic, couriers confront increased workload and safety concerns, posing significant social-sustainability challenges for courier companies. This study explores the impact of social-sustainability practices on couriers' job satisfaction in the context of the COVID-19 pandemic. We designed the research model from the theoretical lens of Maslow's hierarchy of needs, equity, and psychological-safety theories. We collected the views of 428 couriers from the Chinese market, where there is a developed e-commerce industry. The structural-equation-model analysis results found that social-sustainability practices such as working environment, working conditions, health and safety, education, and training positively affected the job satisfaction of couriers during the pandemic through the mediators (psychological safety and perceived fairness). These findings provide empirical recommendations for improving employees' job satisfaction in courier companies during COVID-19 and addressing the social-sustainability issues of courier companies.