Duloxetine, a Balanced Serotonin-Norepinephrine Reuptake Inhibitor, Improves Painful Chemotherapy-Induced Peripheral Neuropathy by Inhibiting Activation of p38 MAPK and NF-κB

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe, toxic side effect that frequently occurs in anticancer treatment and may result in discontinuation of treatment as well as a serious reduction in life quality. The CIPN incidence rate is as high as 85–90%. Unfortunately, there is currently no standard evidence-based CIPN treatment. In several clinical trials, it has been reported that duloxetine can improve CIPN pain induced by oxaliplatin (OXA) and paclitaxel (PTX); thus, The American Society of Clinical Oncology (ASCO) recommends duloxetine as the only potential treatment for CIPN. However, this guidance lacks the support of sufficient evidence. Our study shows that duloxetine markedly reduces neuropathic pain evoked by OXA or PTX. Duloxetine acts by inhibiting the activation of p38 phosphorylation, thus preventing the activation and nuclear translocation of the NF-κB transcription factor, reducing the inflammatory response and inhibiting nerve injury by regulating nerve growth factor (NGF). Furthermore, in this study, it is shown that duloxetine does not affect the antitumor activity of OXA or PTX. This study not only provides biological evidence to support the use of duloxetine as the first standard CIPN drug but will also lead to potential new targets for CIPN drug development

A microencapsulation approach to design microbial seed coatings to boost wheat seed germination and seedling growth under salt stress

IntroductionSalt stress in seed germination and early seedling growth is the greatest cause of crop loss in saline-alkali soils. Microbial seed coating is an effective way to promote plant growth and salt resistance, but these coatings suffer from poor seed adhesion and low survival rates under typical storage conditions.MethodsIn this study, the marine bacterium Pontibacter actiniarum DSM 19842 from kelp was isolated and microencapsulated with calcium alginate using the emulsion and internal gelation method.ResultsCompared to unencapsulated seeds, the spherical microcapsules demonstrated a bacterial encapsulation rate of 65.4% and survival rate increased by 22.4% at 25°C for 60 days. Under salt stress conditions, the seed germination percentage of microcapsule-embedded bacteria (M-Embed) was 90%, which was significantly increased by 17% compared to the germination percentage (73%) of no coating treatment (CK). Root growth was also significantly increased by coating with M-Embed. Chlorophyll, peroxidase, superoxide dismutase, catalase, proline, hydrogen peroxide and malondialdehyde levels indicated that the M-Embed had the best positive effects under salt stress conditions.DiscussionTherefore, embedding microorganisms in suitable capsule materials provides effective protection for the survival of the microorganism and this seed coating can alleviate salt stress in wheat. This process will benefit the development of sustainable agriculture in coastal regions with saline soils

How does strategic flexibility affect bricolage: The moderating role of environmental turbulence.

While most studies have viewed strategic flexibility as a capability to cope with the environmental turbulence and promote the product innovation, few of them investigate the mediating mechanism in the relationship between the strategic flexibility and product innovation. According to the resource-based view, we regard the bricolage as a concrete activity of recombining the different resources in the product development process and explore the underlying mechanism. Our results reveal that strategic flexibility has a positive and significant effect on bricolage. The effect of strategic flexibility on product innovation is partially mediated by bricolage. Furthermore, environmental turbulence moderates the relationship between strategic flexibility and bricolage positively. We contribute to the strategic flexibility research by exploring the effect of strategic flexibility on the bricolage and product innovation form a mediating perspective and offering a more nuanced and in-depth understanding of the impact of strategic flexibility. This research also provides new evidence on the effect of strategic flexibility on product innovation in transition economies such as China, where strategic flexibility is essential for firms to adapt to an uncertain environment

Exploring the Functions of 9-Lipoxygenase (DkLOX3) in Ultrastructural Changes and Hormonal Stress Response during Persimmon Fruit Storage

Lipoxygenase (LOX) initiates the hydroperoxidation of polyunsaturated fatty acids and is involved in multiple physiological processes. In this study, investigation of various microscopic techniques showed that the fruit peel cellular microstructure of the two persimmon cultivars differed after 12 days of storage, resulting in fruit weight loss and an increased number and depth of microcracks. Analysis of subcellular localization revealed that greater amounts of DkLOX3-immunolabelled gold particles accumulated in “Fupingjianshi” than in “Ganmaokui” during storage. In addition, the expression of DkLOX3 was positively up-regulated by abscisic acid (ABA), concomitant with the promotion of ethylene synthesis and loss of firmness, and was suppressed by salicylic acid (SA), concomitant with the maintenance of fruit firmness, inhibition of ethylene production and weight loss. In particular, the expression of DkLOX3 differed from the ethylene trajectory after methyl jasmonate (MeJA) treatment. Furthermore, we isolated a 1105 bp 5′ flanking region of DkLOX3 and the activity of promoter deletion derivatives was induced through various hormonal treatments. Promoter sequence cis-regulatory elements were analysed, and two conserved hormone-responsive elements were found to be essential for responsiveness to hormonal stress. Overall, these results will provide us with new clues for exploring the functions of DkLOX3 in fruit ripening and hormonal stress response

The Persimmon 9-lipoxygenase Gene DkLOX3 Plays Positive Roles in Both Promoting Senescence and Enhancing Tolerance to Abiotic Stress

The lipoxygenase (LOX) pathway is a key regulator for lipid peroxidation, which is crucial for plant senescence and defence pathways. In this study, the transcriptional expression patterns of three persimmon (Diospyros kaki L. ‘Fupingjianshi’) 9-lipoxygenase genes (DkLOX1, DkLOX3 and DkLOX4) were investigated. DkLOX1 was specifically expressed in fruit, particularly in young fruit, and showed little response to the postharvest environments. DkLOX4 was expressed in all tissues and slightly stimulated by mechanical damage and low temperature. DkLOX3 was expressed mainly in mature fruit, and the expression was extremely high throughout the storage period, apparently up-regulated by mechanical damage and high carbon dioxide treatments. Further functional analysis showed that overexpression of DkLOX3 in tomato (Solanum lycopersicum cv. Micro-Tom) accelerated fruit ripening and softening. This was accompanied by higher MDA content and lycopene accumulation, advanced ethylene release peak and elevated expression of ethylene synthesis genes, including ACS2, ACO1 and ACO3. In addition, DkLOX3 overexpression promoted dark induced transgenic Arabidopsis leaf senescence with more chlorophyll loss, increased electrolyte leakage and MDA content. Furthermore, the functions of DkLOX3 in response to abiotic stresses, including osmotic stress, high salinity and drought were investigated. Arabidopsis DkLOX3-OX transgenic lines were found to be more tolerant to osmotic stress with higher germination rate and root growth than wild-type. Moreover, DkLOX3-OX Arabidopsis plants also exhibited enhanced resistance to high salinity and drought, with similar decreased O2- and H2O2 accumulation and upregulation of stress-responsive genes expression, including RD22, RD29A, RD29B and NCED3, except for FRY1, which plays a negative role in stress response. Overall, these results suggested that DkLOX3 plays positive roles both in promoting ripening and senescence through lipid peroxidation and accelerated ethylene production and in stress response via regulating ROS accumulation and stress responsive genes expression

A Virtual Supermarket Program for the Screening of Mild Cognitive Impairment in Older Adults: Diagnostic Accuracy Study

BackgroundMild cognitive impairment (MCI) is often a precursor of dementia, and patients with MCI develop dementia at a higher rate than healthy older adults. Early detection of cognitive decline at the MCI stage supports better planning of care and interventions. At present, the use of virtual reality (VR) in screening for MCI in older adults is promising, but there is little evidence regarding the use of virtual supermarkets to screen for MCI. ObjectiveThe objectives of this study are to validate a VR game–based test, namely, the Virtual Supermarket Program (VSP), for differentiating patients with MCI and healthy controls and to identify cutoff scores for different age levels. MethodsSubjects were recruited from several nursing homes and communities in Changchun, China. They were divided into a healthy control group (n=64) and an MCI group (n=62). All subjects were administered the VSP and a series of neuropsychological examinations. The study determined the optimal cutoff, discriminating validity, concurrent validity, and retest reliability of the VSP. We used the area under the receiver operating characteristic curve (AUC) to evaluate the discriminating validity and obtain the optimal cutoff values. Pearson correlation analysis and the intraclass correlation coefficient were used to evaluate the concurrent validity and retest reliability, respectively. ResultsA cutoff score of 46.4 was optimal for the entire sample, yielding a sensitivity of 85.9% and specificity of 79.0% for differentiating individuals with MCI and healthy controls, and the AUC was 0.870 (95% CI 0.799-0.924). The median index of VSP score was 51.1 (range 42.6-60.0). There was a moderate positive correlation between the VSP total score and Mini-Mental State Examination score (r=0.429, P<.001). There was a strong positive correlation between VSP total score and Montreal Cognitive Assessment score (r=0.645, P<.001). The retest reliability of the VSP was feasible (r=0.588, P=.048). ConclusionsThe VSP is interesting and feasible for subjects. It shows high sensitivity and specificity for the identification of MCI in older adults, which makes it a promising screening method. The VSP may be generalized to older adults in other countries, although some cultural adaptation may be necessary. Trial RegistrationChinese Clinical Trial Registry ChiCTR2000040074; https://www.chictr.org.cn/showprojen.aspx?proj=6463

Differential Analysis of Gene Expression of Toll-like Receptors and Antimicrobial Peptides in Immune Organs and Tissues of Tibetan and Duroc-Landrace-Yorkshire pigs

【Objective】In mammals, Toll-like receptors and antimicrobial peptide genes are important components of the innate immune system, which play a crucial role in fighting against pathogen attacks. The study was conducted to explore the expression differences of Toll-like receptor and antimicrobial peptide genes between different immune organs or tissues in Tibetan pigs and Duroc-Landrace-Yorkshire pigs, with an aim to reveal the potential contribution of these genes to disease resistance and immune response and provide theoretical support for the screening of molecular markers for disease resistance.【Method】The mRNA abundance of Toll-like receptors genes (TLR1-TLR9) and two types of antimicrobial peptide genes (PBD-1 and PR-39) in lungs, mesenteric lymph nodes, inguinal lymph nodes, submandibular lymph nodes and spleens of 6-month-old Tibetan and Duroc-Landrace-Yorkshire pigs were detected by qPCR.【Result】The mRNA expression of Tolllike receptors and antimicrobial peptide genes in most of the immune organs or tissues of Tibetan pigs was significantly higher than that of Duroc-Landrace-Yorkshire pigs. Among them, the mRNA expression of TLR1 and TLR2 in lungs was increased by about 50%, and PR-39 was increased by 2.6 times; the expression of TLR4 in mesenteric lymph nodes was increased by 40%, and the expression of TLR1 and PR-39 was increased by 88% and 3 times, respectively. In the inguinal lymph nodes, the expression of TLR1 and TLR2 was increased by about 2 times, and the expression of TLR9 and PR-39 was increased by 70%, especially, the expression of PR-39 increasing by 7 times; The expression of TLR1, TLR2, TLR4 and TLR7 in submandibular lymph nodes was increased by more than 2 times, and the expression of PR-39 was increased by nearly 7 times, which was similar to that in inguinal lymph nodes; the expression of TLR1 in the spleen rose by 3.5 times, which was similar to that in submandibular lymph nodes. The expression of TLR4 and TLR9 increased by about 50%, and the expression of PR-39 increased by 2.5 times.【Conclusion】Tibetan pigs show higher expression levels of Toll-like receptors and antimicrobial peptide genes in multiple immune organs or tissues compared to Duroc-Landrace-Yorkshire pigs. It is implied that Tibetan pigs may possess stronger innate immunity and be able to generate more effective local or systemic immune responses against pathogenic microbial infections. The results of this study provide important theoretical support for the identification of disease resistance molecular markers and are expected to provide a scientific basis for further improvement of disease resistance in Tibetan pigs and other pig breeds

Application of Gene Editing Technology in Resistance Breeding of Livestock

As a new genetic engineering technology, gene editing can precisely modify the specific gene sequence of the organism&rsquo;s genome. In the last 10 years, with the rapid development of gene editing technology, zinc-finger nucleases (ZFNs), transcription activator-like endonucleases (TALENs), and CRISPR/Cas9 systems have been applied to modify endogenous genes in organisms accurately. Now, gene editing technology has been used in mice, zebrafish, pigs, cattle, goats, sheep, rabbits, monkeys, and other species. Breeding for disease-resistance in agricultural animals tends to be a difficult task for traditional breeding, but gene editing technology has made this easier. In this work, we overview the development and application of gene editing technology in the resistance breeding of livestock. Also, we further discuss the prospects and outlooks of gene editing technology in disease-resistance breeding

Xylooligosaccharides Enhance Lettuce Root Morphogenesis and Growth Dynamics

Enhancing root development is pivotal for boosting crop yield and augmenting stress resilience. In this study, we explored the regulatory effects of xylooligosaccharides (XOSs) on lettuce root growth, comparing their impact with that of indole-3-butyric acid potassium salt (IBAP). Treatment with XOS led to a substantial increase in root dry weight (30.77%), total root length (29.40%), volume (21.58%), and surface area (25.44%) compared to the water-treated control. These enhancements were on par with those induced by IBAP. Comprehensive phytohormone profiling disclosed marked increases in indole-3-acetic acid (IAA), zeatin riboside (ZR), methyl jasmonate (JA-ME), and brassinosteroids (BRs) following XOS application. Through RNA sequencing, we identified 3807 differentially expressed genes (DEGs) in the roots of XOS-treated plants, which were significantly enriched in pathways associated with manganese ion homeostasis, microtubule motor activity, and carbohydrate metabolism. Intriguingly, approximately 62.7% of the DEGs responsive to XOS also responded to IBAP, underscoring common regulatory mechanisms. However, XOS uniquely influenced genes related to cutin, suberine, and wax biosynthesis, as well as plant hormone signal transduction, hinting at novel mechanisms of stress tolerance. Prominent up-regulation of genes encoding beta-glucosidase and beta-fructofuranosidase highlights enhanced carbohydrate metabolism as a key driver of XOS-induced root enhancement. Collectively, these results position XOS as a promising, sustainable option for agricultural biostimulation