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Background The MAP Kinase cascade system is a conserved signaling mechanism essential for plant development, growth, and stress tolerance. Thus far, genes from the MAPK cascade have been identified in several plant species but remain uncharacterized in the polyploid Saccharum spp. Hybrid R570 genome. Results This study identified 89 ScMAPK , 24 ScMAPKK , and 107 ScMAPKKK genes through genome-wide analysis. Phylogenetic classification revealed that four subgroups were present in each ScMAPK and ScMAPKK family, and three sub-families (ZIK-like, RAF-like, and MEKK-like) presented in the ScMAPKKK family. Conserved motif and gene structure analysis supported the evolutionary relationships of the three families inferred from the phylogenetic analysis. All of the ScMAPK , ScMAPKK and ScMAPKKK genes were mapped on four scaffolds (Scaffold_88/89/91/92) and nine chromosomes (1–8, 10). Collinearity and gene duplication analysis identified 169 pairs of allelic and non-allelic segmentally duplicated MAPK cascade genes, contributing to their expansion. Additionally, 13 putative ‘ss-miRNAs’ were predicted to target 87 MAPK cascade genes, with ‘ssp-miR168a’ alone regulating 45 genes. qRT-PCR analysis revealed differential gene expression under abiotic stressors. ScMAPK07 , ScMAPK66 , and ScRAF43 were down-regulated and acted as negative regulators. Conversely, ScMAPKK13 , ScRAF10 , and ScZIK18 were up-regulated at specific time points under drought, with ScZIK18 exhibiting strong defense. Under NaCl stress, most genes were down-regulated, except for slight increases in ScZIK18 and ScMAPKK13 , suggesting a positive role in salt stress response. Under CaCl 2 stress, five genes were significantly down-regulated, while ScRAF43 remained unchanged, reflecting their negative roles in stress adaptation and resource conservation. Conclusion This study provides insights into MAPK cascade gene evolution and function in sugarcane, highlighting distinct regulatory roles in abiotic stress responses. Interestingly, some genes acted as negative regulators, serving as a mechanism to balance stress responses and prevent overactivation. In contrast, others contributed to defense mechanisms, offering potential targets for stress resilience improvement. Clinical Trail Number This study contains no clinical trials. Not applicable.

Background Left atrial (LA) strain, a powerful parameter for assessing LA function, is underused in routine clinical practice because it requires expertise and time. The novel semi-automated method for the measurement of LA strain may circumvent these limitations. Hence, we investigated the feasibility, reproducibility, and clinical implications of the semi-automated method. Methods We prospectively enrolled 190 patients referred for coronary artery bypass grafting (CABG). LA strain was measured using the fully semi-automated and manual methods from the same apical four-chamber view 3 days before CABG. Patients were followed up every 6 months for major adverse cardiovascular and cerebrovascular events (MACCE). Results Manual border corrections were required in 26% of patients because of poor tracking quality. Measurement time was significantly shorter with the semi-automated method. Excellent intra- and inter-observer measurement agreement with minimal bias were observed for LA strain measured using the semi-automated method, which were better than those for LA strain measured using the manual method. Moreover, measured LA strain using the semi-automated method had a greater correlation coefficient with the LA ejection fraction and prediction power for left ventricular diastolic dysfunction. Over a median follow-up of 22.4 months, MACCE occurred in 36 (19.0%) patients. LA strain measured using both methods showed comparable usefulness for predicting MACCE. Conclusions The novel semi-automated method rapidly measures LA strain with excellent reproducibility and has clinical application comparable to the manual method. This method may have the potential to be integrated into routine clinical practice and facilitate the implementation of LA strain. Clinical trial number Not applicable.

Biological invasion is a critical ecological challenge, exerting profound impacts on ecosystem stability, public health, and economic sustainability. To better understand the successful invasion mechanism, many hypotheses have been proposed. However, the roles of hormones in it are not clear, especially for the differential effects of hormones on invasive and native plants, and its mechanisms. In this study, we hypothesized that there was not only a difference in hormone (auxin) concentration between invasive and native plants but also a difference in the effect of auxin on invasive and native plants. The above characteristics drove the successful invasion of invasive plants. To verify this hypothesis and investigate the mechanism, auxin concentration, and physiological index determination, transcriptomic and metabolomic analyses were performed. Our results showed that the auxin concentration was higher in invasive plants Xanthium strumarium and the growth-promoting effect of auxin on the invader was stronger than its native congener X. sibiricum . Compared with X. sibiricum , the auxin signal transduction in X. strumarium was more strongly activated, and more genes were differentially expressed in response to auxin. Auxin strongly promoted the growth of X. strumarium by enhancing photosynthesis, reducing the resources investment in defense and stress resistance, and promoting cell growth and division. However, the promoting effect of auxin on X. sibiricum was mainly achieved by enhancing photosynthesis. Our results elucidated the mechanism of auxin driving X. strumarium invasion, which contributed to the systematic proposal of the hormone-driven hypothesis.

Background The brain is a common site for metastasis in non-small-cell lung cancer (NSCLC). This study was designed to evaluate the relationship between the mutational of the epidermal growth factor receptor (EGFR) and overall survival (OS) in NSCLC patients with brain metastases. Methods Searches were performed in PubMed, EmBase, and the Cochrane Library to identify studies evaluating the association of EGFR mutation with OS in NSCLC patients through September 2017. Results 4373 NSCLC patients with brain metastases in 18 studies were involved. Mutated EGFR associated with significantly improved OS compared with wild type. Subgroup analyses suggested that this relationship persisted in studies conducted in Eastern, with retrospective design, with sample size ≥500, mean age of patients ≥65.0 years, percentage male < 50.0%, percentage of patients receiving tyrosine kinase inhibitor ≥30.0%. Finally, although significant publication bias was observed using the Egger test, the results were not changed after adjustment using the trim and fill method. Conclusions This meta-analysis suggests that EGFR mutation is an important predictive factor linked to improved OS for NSCLC patients with brain metastases. It can serve as a useful index in the prognostic assessment of NSCLC patients with brain metastases.

BackgroundPast studies have found a strong relationship between alcohol drinking and human health.MethodsIn this study, we first tested the association of rs671 with alcohol use in 2349 participants in southeast China. We then evaluated the causal impact between alcohol use and cardiovascular traits through a Mendelian randomisation (MR) analysis.ResultsWe found strong evidence for the association of rs671 in the ALDH2 gene with alcohol drinking (p=6.08×10-47; ORadj G=4.50, 95% CI 3.67 to 5.52). We found that female G carriers of rs671 had a higher proportion of non-drinkers than male G carriers (88.01% vs 38.70%). In non-drinkers, the female G allele frequency was higher than the male G allele frequency (71.1% vs 55.2%). MR analysis suggested that alcohol use had a causal effect on blood pressure (increasing 9.46 mm Hg for systolic blood pressure (p=9.67×10-4) and 7.50 mm Hg for diastolic blood pressure (p=9.62×10-5)), and on hypertension in men (p=0.011; OR =1.19, 95% CI 1.04 to 1.36) and in pooled samples (p=0.013; OR =1.20, 95% CI 1.04 to 1.39), but not in women. We did not observe a causal effect of alcohol use on body mass index and lipid levels; further studies are needed to clarify the non-causal relationship.ConclusionsCompared to never-drinkers, current and previous alcohol use had a causal effect on blood pressure and hypertension in pooled samples and in men. These results reflect Chinese culture which does not encourage women to drink.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints. Microbial infection is considered a crucial inducer of RA. Alterations in the composition of intestinal bacteria in individuals with preclinical and established RA suggest a vital role of the gut microbiota in immune dysfunction characteristic of RA. However, the mechanisms by which gut dysbiosis contributes to RA are not fully understood. Furthermore, multiple therapies commonly used to treat RA may alter gut microbiota diversity, suggesting that modulating the gut microbiota may help prevent or treat RA. Hence, a better understanding of the changes in the gut microbiota that accompany RA should aid the development of novel therapeutic approaches. This mini-review discusses the impact of gut dysbiosis in the pathogenesis of RA, the selection of gut microbiota-related biomarkers for diagnosing RA, and provides examples of cross-modulation between the gut microbiota and some drugs commonly used to treat RA. Some suggestions and outlooks are also raised, which may help guide future research efforts.

Histone deacetylase (HDAC) inhibitors are promising anti-fibrosis drugs; however, nonselective inhibition of class I and class II HDACs does not allow a detailed elucidation of the individual HDAC functions in renal fibrosis. In this study, we investigated the effect of MS-275, a selective class I HDAC inhibitor, on the development of renal fibrosis in a murine model of unilateral ureteral obstruction (UUO) and activation of cultured renal interstitial fibroblasts. The UUO model was established by ligation of the left ureter and the contralateral kidney was used as a control. At seven days after UUO injury, kidney developed fibrosis as indicated by deposition of collagen fibrils and increased expression of collagen I, fibronectin and alpha-smooth muscle actin (alpha-SMA). Administration of MS-275 inhibited all these fibrotic responses and suppressed UUO-induced production of transforming growth factor-beta1 (TGF-beta), increased expression of TGF-beta receptor I, and phosphorylation of Smad-3. MS-275 was also effective in suppressing phosphorylation and expression of epidermal growth factor receptor (EGFR) and its downstream signaling molecule, signal transducer and activator of transcription-3. Moreover, class I HDAC inhibition reduced the number of renal tubular cells arrested in the G2/M phase of the cell cycle, a cellular event associated with TGF-beta1overproduction. In cultured renal interstitial fibroblasts, MS-275 treatment inhibited TGF-beta induced phosphorylation of Smad-3, differentiation of renal fibroblasts to myofibroblasts and proliferation of myofibroblasts. These results demonstrate that class I HDACs are critically involved in renal fibrogenesis and renal fibroblast activation through modulating TGF-beta and EGFR signaling and suggest that blockade of class I HDAC may be a useful treatment for renal fibrosis.

Background The adaption of brain region is fundamental to the development and maintenance of nervous system disorders. The prelimbic cortex (PrL) participates in the affective components of the pain sensation. However, whether and how the adaptation of PrL contributes to the comorbidity of neuropathic pain and depression are unknown. Methods Using resting-state functional magnetic resonance imaging (rs-fMRI), genetic knockdown or overexpression, we systematically investigated the activity of PrL region in the pathogenesis of neuropathic pain/depression comorbid using the combined approaches of immunohistochemistry, electrophysiology, and behavior. Results The activity of PrL and the excitability of pyramidal neurons were decreased, and the osteoclastic tartrate-resistant acid phosphatase 5 (Acp5) expression in PrL neurons was upregulated following the acquisition of spared nerve injury (SNI)-induced comorbidity. Genetic knockdown of Acp5 in pyramidal neurons, but not parvalbumin (PV) neurons or somatostatin (SST) neurons, attenuated the decrease of spike number, depression-like behavior and mechanical allodynia in comorbidity rats. Overexpression of Acp5 in PrL pyramidal neurons decreased the spike number and induced the comorbid-like behavior in naïve rats. Moreover, the expression of interleukin-6 (IL-6), phosphorylated STAT3 (p-STAT3) and acetylated histone H3 (Ac-H3) were significantly increased following the acquisition of comorbidity in rats. Increased binding of STAT3 to the Acp5 gene promoter and the interaction between STAT3 and p300 enhanced acetylation of histone H3 and facilitated the transcription of Acp5 in PrL in the modeled rodents. Inhibition of IL-6/STAT3 pathway prevented the Acp5 upregulation and attenuated the comorbid-like behaviors in rats. Conclusions These data suggest that the adaptation of PrL mediated by IL-6/STAT3/Acp5 pathway contributed to the comorbidity of neuropathic pain/depression induced by SNI.

Delirium is a postoperative complication that occurs frequently in patients older than 65 years, and presages adverse outcomes. We investigated whether prophylactic low-dose dexmedetomidine, a highly selective α2 adrenoceptor agonist, could safely decrease the incidence of delirium in elderly patients after non-cardiac surgery. We did this randomised, double-blind, placebo-controlled trial in two tertiary-care hospitals in Beijing, China. We enrolled patients aged 65 years or older, who were admitted to intensive care units after non-cardiac surgery, with informed consent. We used a computer-generated randomisation sequence (in a 1:1 ratio) to randomly assign patients to receive either intravenous dexmedetomidine (0·1 μg/kg per h, from intensive care unit admission on the day of surgery until 0800 h on postoperative day 1), or placebo (intravenous normal saline). Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method for intensive care units during the first 7 postoperative days. Analyses were done by intention-to-treat and safety populations. This study is registered with Chinese Clinical Trial Registry, www.chictr.org.cn, number ChiCTR-TRC-10000802. Between Aug 17, 2011, and Nov 20, 2013, of 2016 patients assessed, 700 were randomly assigned to receive either placebo (n=350) or dexmedetomidine (n=350). The incidence of postoperative delirium was significantly lower in the dexmedetomidine group (32 [9%] of 350 patients) than in the placebo group (79 [23%] of 350 patients; odds ratio [OR] 0·35, 95% CI 0·22–0·54; p<0·0001). Regarding safety, the incidence of hypertension was higher with placebo (62 [18%] of 350 patients) than with dexmedetomidine (34 [10%] of 350 patients; 0·50, 0·32–0·78; p=0·002). Tachycardia was also higher in patients given placebo (48 [14%] of 350 patients) than in patients given dexmedetomidine (23 [7%] of 350 patients; 0·44, 0·26–0·75; p=0·002). Occurrence of hypotension and bradycardia did not differ between groups. For patients aged over 65 years who are admitted to the intensive care unit after non-cardiac surgery, prophylactic low-dose dexmedetomidine significantly decreases the occurrence of delirium during the first 7 days after surgery. The therapy is safe. Braun Anaesthesia Scientific Research Fund and Wu Jieping Medical Foundation, Beijing, China. Study drugs were manufactured and supplied by Jiangsu Hengrui Medicine Co, Ltd, Jiangsu, China.

Irisin is a recently identified myokine which brings increases in energy expenditure and contributes to the beneficial effects of exercise through the browning of white adipose tissues. However, its effects in the heart remains unknown. This study sought to determine the effects of irisin on hypoxia/reoxygenation injury and its relationship with HDAC4. Wild type and stable HDAC4-overexpression cells were generated from H9c2 cardiomyoblasts. HDAC4 overexpression cells and wild type H9c2 cells were exposed to 24 hours of hypoxia followed by one hour of reoxygenation in vitro in the presence or absence of irisin (5 ng/ml). Cell cytotoxicity, apoptosis, mitochondrial respiration, and mitochondrial permeability transition pore (mPTP) were determined. Western blotting was employed to determine active-caspase 3, annexin V, and HDAC4 expression. As compared to wild type H9c2 group, HDAC4 overexpression remarkably led to a great increase in cell death as evident by the increased lactate dehydrogenase (LDH) leakage, ratio of caspase-3-positive cells as well as the upregulated levels of active-caspase 3 and annexin V shown by western blot analysis. In addition, HDAC4 overexpression also induced much severe mitochondrial dysfunction, as indicated by apoptotic mitochondria and increased mPTP. However, irisin treatment significantly attenuated all of these effects. Though irisin treatment did not influence the expression of HDAC4 at the transcriptional level, western blot analysis showed that HDAC4 protein levels decreased in a time-dependent way after administration of irisin, which is associated with the degradation of HDAC4 mediated by small ubiquitin-like modification (SUMO). Our results are the first to demonstrate that the protective effects of irisin in cardiomyoblasts exposed to hypoxia/reoxygenation might be associated with HDAC4 degradation.