The microRNA319 (miR319) family is conserved among diverse plant species. In rice (Oryza sativa L.), the miR319 gene family is comprised of two members, Osa-miR319a and Osa-miR319b. We found that overexpressing Osa-miR319b in rice resulted in wider leaf blades and delayed development. Here, we focused on the biological function and potential molecular mechanism of the Osa-miR319b gene in response to cold stress in rice. The expression of Osa-miR319b was down-regulated by cold stress, and the overexpression of Osa-miR319b led to an enhanced tolerance to cold stress, as evidenced by higher survival rates and proline content. Also, the expression of a handful of cold stress responsive genes, such as DREB1A/B/C, DREB2A, TPP1/2, was increased in Osa-miR319b transgenic lines. Furthermore, we demonstrated the nuclear localization of the transcription factors, OsPCF6 and OsTCP21, which may be Osa-miR319b-targeted genes. We also showed that OsPCF6 and OsTCP21 expression was largely induced by cold stress, and the degree of induction was obviously repressed in plants overexpressing Osa-miR319b. As expected, the down-regulation of OsPCF6 and OsTCP21 resulted in enhanced tolerance to cold stress, partially by modifying active oxygen scavenging. Taken together, our findings suggest that Osa-miR319b plays an important role in plant response to cold stress, maybe by targeting OsPCF6 and OsTCP21.

The aim of the present study was to determine the effects of low-level laser therapy (LLLT) on the homeostasis of reactive oxygen species (ROS) and expression of IGF-1 and TGF-β1 in the gastrocnemius muscles of rats following contusion. Muscle regeneration involves cell proliferation, migration, and differentiation and is regulated by growth factors. A growing body of evidence suggests that LLLT promotes skeletal muscle regeneration and accelerates tissue repair. Adult male Sprague-Dawley rats (n=96) were randomly divided into three groups: control group (no lesion, untreated, n=6), contusion group (n=48), and contusion-plus-LLLT group (n=42). Gallium aluminum arsenide (GaAlAs) laser irradiation (635 nm; beam spot, 0.4 cm(2); output power, 7 mW; power density, 17.5 mW/cm(2); 20 min) was administered to the gastrocnemius contusion for 20 min daily for 10 days. Muscle remodeling was evaluated at 0 h and 1, 2, 3, 7, 14, 21, and 28 days after injury. Hematoxylin and eosin and Van Gieson staining were used to evaluate regeneration and fibrosis; muscle superoxide dismutase (SOD) and malondialdehyde (MDA) were detected via biochemical methods; expression of transforming growth factor beta-1 (TGF-β1) and insulin-like growth factor-1 (IGF-1) were investigated via immunohistochemistry. The results showed that LLLT markedly promoted the regeneration of muscle and reduced scar formation. LLLT also significantly enhanced muscle SOD activity and significantly decreased muscle MDA levels 1, 2, and 3 days after injury. LLLT increased the expression of IGF-1 2, 3, and 7 days after injury and decreased the expression of IGF-1 21 and 28 days after injury. LLLT decreased the expression of TGF-β1 3 and 28 days after injury but increased expression at 7 and 14 days after injury. Our study showed that LLLT could modulate the homeostasis of ROS and of the growth factors IGF-1 and TGF-β1, which are known to play important roles in the repair process. This may constitute a new preventive approach to muscular fibrosis.

Stress has been reported to activate the locus coeruleus (LC)–noradrenergic system. However, the molecular link between chronic stress and noradrenergic neurons remains to be elucidated. In the present study adult Fischer 344 rats were subjected to a regimen of chronic social defeat (CSD) for 4 weeks. Measurements by in situ hybridization and Western blotting showed that CSD significantly increased mRNA and protein levels of the norepinephrine transporter (NET) in the LC region and NET protein levels in the hippocampus, frontal cortex and amygdala. CSD-induced increases in NET expression were abolished by adrenalectomy or treatment with corticosteroid receptor antagonists, suggesting the involvement of corticosterone and corticosteroid receptors in this upregulation. Furthermore, protein levels of protein kinase A (PKA), protein kinase C (PKC), and phosphorylated cAMP-response element binding (pCREB) protein were significantly reduced in the LC and its terminal regions by the CSD paradigm. Similarly, these reduced protein levels caused by CSD were prevented by adrenalectomy. However, effects of corticosteroid receptor antagonists on CSD-induced down-regulation of PKA, PKC, and pCREB proteins were not consistent. While mifeprestone and spironolactone, either alone or in combination, totally abrogate CSD effects on these protein levels of PKA, PKC and pCREB in the LC and those in the hippocampus, frontal cortex and amygdala, their effects on PKA and PKC in the hippocampus, frontal cortex and amygdala were region-dependent. The present findings indicate a correlation between chronic stress and activation of the noradrenergic system. This correlation and CSD-induced alteration in signal transduction molecules may account for their critical effects on the development of symptoms of major depression.

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Immunotherapy against cancer, through immune checkpoint inhibitors targeting the programmed cell death‐1/programmed cell death‐ligand 1 axis, is particularly successful in tumors by relieving the immune escape. However, interindividual responses to immunotherapy are often heterogeneous. Therefore, it is essential to screen out predictive tumor biomarkers. In this study, we analyzed the commensal microbiota in stool samples and paired sputum samples from 75 metastatic non‐small‐cell lung cancer (NSCLC) patients at baseline and during treatment with immune checkpoint inhibitors. Results showed distinct microbes’ signatures between the gut microbiota and paired respiratory microbiota. The alpha diversity between the gut and respiratory microbiota was uncorrelated, and only the gut microbiota alpha diversity was associated with anti‐programmed cell death‐1 response. Higher gut microbiota alpha diversity indicated better response and more prolonged progression‐free survival. Comparison of bacterial communities between responders and nonresponders showed some favorable/unfavorable microbes enriched in responders/nonresponders, indicating that commensal microbiota had potential predictive value for the response to immune checkpoint inhibitors. Generally, some rare low abundance gut microbes and high abundance respiratory microbes lead to discrepancies in microbial composition between responders and nonresponders. A significant positive correlation was observed between the abundance of Streptococcus and CD8+ T cells. These results highlighted the intimate relationship between commensal microbiota and the response to immunotherapy in NSCLC patients. Gut microbiota and respiratory microbiota are promising biomarkers to screen suitable candidates who are likely to benefit from immune checkpoint inhibitor‐based immunotherapy.