Molecular Classification of HNSCC Based on Inflammatory Response-Related Genes - Integrated Single-Cell and Bulk RNA-Seq Analysis.

Objective: Tumor cells, inflammatory cells, and chemical factors collaboratively orchestrate a sophisticated signaling network, culminating in the formation of the inflammatory tumor microenvironment (TME). The present study sought to explore the nature of the inflammatory response in HNSCC and to decipher its influence on immunotherapeutic. Materials and Methods: A thorough analysis was performed utilizing the TCGA cohort along with two GEO cohorts. Unsupervised clustering of 200 inflammatory response-related genes (IRGs) was applied using the k-means algorithm to explore the heterogeneity of HNSCC. Additionally, a prognostic signature based on IRGs genes was constructed using Lasso regression. Meanwhiles, the expression of IRGs were identified in tumors and paracancerous tissues at the single-cell level. The crosstalk between IRGs was explored using CellChat and the patterns of incoming and outgoing signals were identified. Finally, qPCR was used to verify the expression of hub genes. Results: There were significant differences in immune-cell function and immune-cell infiltration among three inflammatory response clusters. Additionally, we also constructed a prognostic model which could predicted the responses of common chemotherapeutic drugs and immunotherapy. Furthermore, qPCR and sc-RNA seq corroborated that the expression profiles of the prognostic genes were largely in alignment with the findings from the bioinformatics analysis. Ultimately, the molecular docking demonstrated favorable binding affinities between the pivotal gene-SCC7 and four chemotherapeutic drugs. Conclusion: This research has uniquely shed light on the intricate connection between the inflammatory response profiles and the immune infiltration patterns in HNSCC.

Effectiveness of the Stress Process Model-Based Program in Dementia Caregiving (DeCare-SPM) for Family Caregivers: A Study Protocol for a Randomized Controlled Trial.

This paper aims to describe a randomized controlled trial protocol evaluating the effectiveness, cost, and process of a stress process model-based program in dementia caregiving (DeCare-SPM) for family caregivers. Family caregivers of individuals with dementia will be recruited from memory clinics and community settings and randomly assigned to either DeCare-SPM or usual care. DeCare-SPM comprises three face-to-face sessions (ie, problem-based coping, emotion-based coping, meaning-based coping), and a fourth session (ie, social support) including weekly telephone-based consultation for four weeks and then monthly face-to-face boosters. Outcomes will be measured at baseline (T0), and at one (T1), three (T2), and six months (T3). The primary outcome is positive aspects of caregiving and secondary outcomes are caregiving (ie, sense of competence, caregiver burden, social support, anxiety, depression, and quality of life), dementia-related (ie, care dependency, neuropsychiatric symptoms, and quality of life), and stress-related biomarkers of blood and saliva. In addition, process and economic evaluations will be performed. Mixed-effects models will be used to assess intervention effects. Content analysis will be performed on the qualitative data. This paper described the protocol for comprehensive evaluation of the effectiveness, cost, and process of the theory-driven DeCare-SPM to inform how and why interventions work. It highlights the need to reduce challenges and enhance the positive aspects of dementia care. The DeCare-SPM will provide evidence-based insights into how to support and empower family caregivers in their important roles, thereby, leading to improved dementia care.

Prevalence and Risk Factors of Pulmonary Embolism Combined with Tuberculosis and the Efficacy of Anticoagulation Combined with Anti-tuberculosis.

Objective: This retrospective study aimed to determine the prevalence and risk factors of combined pulmonary embolism (PE) among patients with pulmonary tuberculosis (TB), as well as evaluate the clinical efficacy of anticoagulation in combination with anti-tuberculosis therapy. Methods: A total of 96 TB patients were included in the study. Among them, 31 patients had combined PE (PE group) and 65 patients did not have PE (no-PE group). Various indicators including lung images, clinical symptoms, blood tests, coagulation function, and others were analyzed to identify risk factors for combined PE in TB patients. Within the PE group, patients were divided into a combined treatment group (received anticoagulation therapy alongside anti-tuberculosis treatment) and a control group (received only anti-tuberculosis treatment). The effectiveness of anticoagulation, serological indexes, and incidence of adverse reactions were compared between the two groups. Results: The prevalence of combined PE in TB patients was 32.29%. Encapsulated effusion or upper lobe predominance, dyspnea, and high creatinine levels were identified as risk factors for combined PE in TB patients. The combined treatment group showed a significantly higher anticoagulation efficiency rate (95.00%) compared to the control group (72.73%). After treatment, serum D-dimer levels were significantly lower in the rivaroxaban group compared to the warfarin group. The incidence of adverse reactions did not differ significantly between the two groups. Conclusion: Combined PE was found in 32.29% of TB patients. Encapsulated effusion or upper lobe predominance, dyspnea, and high creatinine levels were identified as risk factors for combined PE in TB patients. Anticoagulation combined with anti-tuberculosis therapy was effective and safe for managing TB patients with combined PE.

Differences in Toxoplasma gondii distribution in different muscle and viscera of naturally infected sheep.

Toxoplasma gondii (T. gondii) is a zoonotic parasite that can cause serious pathology in intermediate hosts such as humans and animals. Eating undercooked or raw meat is the most important route of infection by T. gondii. Sheep are an important source of meat worldwide, and they are also susceptible to T. gondii. Mutton infected with T. gondii poses a serious threat to the food safety of consumers. At present, studies have mainly focused on the infection ratio of T. gondii in livestock; however, systematic studies have not been performed on differences in the distribution of this parasite in different muscle and viscera tissues of animals. In this study, the differences in the distribution of T. gondii in naturally infected Small-tailed Han sheep was studied. By amplifying the B1 gene of the parasite via real-time fluorescence quantification PCR (RT‒qPCR), we found that the parasite burden of T. gondii differed among different parts of the sheep, with the highest burden observed in the heart among the viscera and the external ridge among the muscle. The relative expression was ranked from high to low in our study as follows: heart, spleen, external ridge, tenderloin, lung, liver, kidney, neck meat, forelegs, cucumber strips, hind leg, lamb belly, and lamb chops. This study provided important guidance for monitoring the food safety of mutton products.

Study on the effect of koumiss on reactivation of Toxoplasma gondii infection.

Toxoplasma gondii is an obligate intracellular parasite that infects nucleated cells of all warm-blooded animals, and most patients have latent infections. The latent infection will be reactivated in the immunocompromised or immunocompromised individuals, which will lead to severe toxoplasmosis. At present, less research has been focused on the reactivation of T. gondii infection. Koumiss is a kind of fermented milk made from fresh mare's milk through natural fermentation that can be applied to clinical and rehabilitation medicine to mitigate the development of various diseases due to its unique functional characteristics. In this study, we explored the antagonistic effect of koumiss on reactivation of T. gondii infection. Mice were treated with dexamethasone to establish a reactivation model after infection with T. gondii and then treated with koumiss. The survival rate, SHIRPA test, serum cytokine levels, organ parasite burden and intestinal microbiota were measured, respectively. Our results showed that koumiss treatment improved the clinical symptoms of mice, significantly reduced the organ parasite burden of mice, and improved the composition and structure of intestinal flora. This study provides new evidence for the alleviation and treatment of toxoplasmosis and provides a novel idea for the development and utilization of koumiss.

Study on the antagonistic effects of koumiss on Toxoplasma gondii infection in mice.

Toxoplasma gondii is an important food-borne zoonotic parasite, and approximately one-third of people worldwide are positive for T. gondii antibodies. To date, there are no specific drugs or vaccines against T. gondii. Therefore, developing a new safe and effective method has become a new trend in treating toxoplasmosis. Koumiss is rich in probiotics and many components that can alleviate the clinical symptoms of many diseases via the functional characteristics of koumiss and its regulation of intestinal flora. To investigate the antagonistic effect of koumiss on T. gondii infection, the model of acute and chronic T. gondii infection was established in this study. The survival rate, SHIRPA score, serum cytokine levels, brain cyst counts, ß-amyloid deposition and intestinal flora changes were measured after koumiss feeding. The results showed that the clinical symptoms of mice were improved at 6 dpi and that the SHIRPA score decreased after koumiss feeding (P < 0.05). At the same time, the levels of IL-4, IFN-γ and TNF-α decreased (P < 0.001, P < 0.001, P < 0.01). There was no significant difference of survival rate between koumiss treatment and the other groups. Surprisingly, the results of chronic infection models showed that koumiss could significantly reduce the number of brain cysts in mice (P < 0.05), improve ß-amyloid deposition in the hippocampus (P < 0.01) and decrease the levels of IFN-γ and TNF-α (P < 0.01, P < 0.05). Moreover, koumiss could influence the gut microbiota function in resisting T. gondii infection. In conclusion, koumiss had a significant effect on chronic T. gondii infection in mice and could improve the relevant indicators of acute T. gondii infection in mice. The research provides new evidence for the development of safe and effective anti-T. gondii methods, as well as a theoretical basis and data support for the use of probiotics against T. gondii infection and broadened thoughts for the development and utilization of koumiss.

Sp1 transcription factor represses transcription of phosphatase and tensin homolog to aggravate lung injury in mice with type 2 diabetes mellitus-pulmonary tuberculosis.

Type 2 diabetes mellitus (T2DM) can enhance the risk of mycobacterium tuberculosis (Mtb) infection and aggravate pulmonary tuberculosis (PTB). This study intended to explore the function of phosphatase and tensin homolog (PTEN) in T2DM-PTB and the molecules involved. Mice were treated with streptozotocin to induce T2DM and then infected with Mtb. The mice with T2DM had increased weight, blood glucose level, glucose intolerance and insulin resistance, and increased susceptibility to PTB after Mtb infection. PTEN was significantly downregulated in mice with T2DM-PTB and it had specific predictive value in patients. Overexpression of PTEN improved mouse survival and reduced bacterial load, inflammatory infiltration, cell apoptosis, and fibrosis in lung tissues. Sp1 transcription factor (SP1) was predicted and identified as an upstream regulator of PTEN. SP1 suppressed PTEN transcription. Silencing of SP1 enhanced mouse survival and alleviated the lung injury, and it promoted the M1 polarization of macrophages in murine lung tissues. However, further downregulation of PTEN increased protein kinase B (Akt) phosphorylation and blocked the alleviating roles of SP1 silencing in T2DM-PTB. This study demonstrates that SP1 represses PTEN transcription to promote lung injury in mice with T2DM-PTB through Akt activation.

Study on the effect of koumiss on the intestinal microbiota of mice infected with Toxoplasma gondii.

Toxoplasma gondii is a worldwide food-borne parasite that can infect almost all warm-blooded animals, including humans. To date, there are no effective drugs to prevent or eradicate T. gondii infection. Recent studies have shown that probiotics could influence the relationship between the microbiota and parasites in the host. Koumiss has been used to treat many diseases based on its probiotic diversity. Therefore, we explored the effect of koumiss on T. gondii infection via its effect on the host intestinal microbiota. BALB/c mice were infected with T. gondii and treated with PBS, koumiss and mares' milk. Brain cysts were counted, and long-term changes in the microbiota and the effect of koumiss on gut microbiota were investigated with high-throughput sequencing technology. The results suggested that koumiss treatment significantly decreased the cyst counts in the brain (P < 0.05). Moreover, T. gondii infection changed the microbiota composition, and koumiss treatment increased the relative abundance of Lachnospiraceae and Akkermansia muciniphila, which were associated with preventing T. gondii infection. Moreover, koumiss could inhibit or ameliorate T. gondii infection by increasing the abundance of certain bacteria that control unique metabolic pathways. The study not only established a close interaction among the host, intracellular pathogens and intestinal microbiota but also provided a novel focus for drug development to prevent and eradicate T. gondii infection.

The mid-domain effect of mountainous plants is determined by community life form and family flora on the Loess Plateau of China.

The mid-domain effect (MDE) explains altitudinal patterns of species diversity of mountainous plants at different elevations. However, its application is limited by the species life form and family flora in different layers of plant communities. To verify the MDE hypothesis at the plant community level, we chose a mountain with representative characteristics of the study area in the east of the Loess Plateau, China, such as obvious elevation (from 1324 to 2745 m) and latitude (from 36° 23' to 39° 03') gradients and considerable vegetation types (mainly coniferous and broad-leaved forests). We measured the life forms, families, and species diversity indices of tree, shrub, and herb communities along different elevations. We determined that the family numbers of the herb and shrub communities presented unimodal patterns across an altitudinal gradient, and the highest values occurred at intermediate elevations. The importance values of dominant families in the shrub and tree communities presented unimodal patterns, but the lowest values occurred at intermediate elevations. The species diversity indices of the herb, shrub, and tree communities conformed to unimodal change patterns following an altitudinal gradient, but the greatest diversity occurred at high, low, and intermediate elevations, respectively. At higher elevations, forbs and grasses grew well, whereas sedges grew well at lower elevations. Responses of different tree life forms to the altitudinal gradient were greater for evergreen coniferous tree species than for deciduous coniferous and deciduous broad-leaved tree species. We concluded that the MDE hypothesis of species diversity for mountainous plants is influenced greatly by the community life form and family at the plant community level in a temperate semi-arid region of the Loess Plateau, China. This conclusion tested and modified the MDE hypothesis and may be valuable for fueling prediction of biodiversity models and for the comparison with similar studies in arid and semi-arid mountainous regions.

Hand Hygiene Compliance and Influencing Factors Among Nursing Assistants in Nursing Homes.

The current study explored compliance with hand hygiene and related influencing factors among nursing assistants (NAs) in nursing homes. A descriptive observational research design was used. Seven nursing homes in Chongqing, China, including hospital-affiliated, public, and private, were selected. A hand hygiene observation tool was used to assess NAs' (N = 237) hand hygiene practice (N = 2,370 opportunities). NAs' overall compliance rate was 3.6%: 6.8%, 3.1%, and 1.9% at hospital-affiliated, public, and private nursing homes, respectively. Compliance rate between two opportunities, after contact with residents and after contact with residents' surroundings, differed significantly (p = 0.002 and 0.038, respectively). The highest and lowest compliance rates occurred after bodily fluid exposure (8.3%; odds ratio [OR] = 0.37, 95% confidence interval [CI] [0.218, 0.627], p < 0.001) and before resident contact (1.2%; OR = 3.142, 95% CI [1.265, 7.805], p = 0.014), respectively. Working experience and educational background were the two major influencing factors for hand hygiene. It is urgent to improve NAs' hand hygiene accordingly. [Journal of Gerontological Nursing, 47(4), 45-52.].

Genetic elucidation of hydrogen signaling in plant osmotic tolerance and stomatal closure via hydrogen sulfide.

Although ample evidence showed that exogenous hydrogen gas (H2) controls a diverse range of physiological functions in both animals and plants, the selective antioxidant mechanism, in some cases, is questioned. Importantly, most of the experiments on the function of H2 in plants were based on pharmacological approaches due to the synthesis pathway(s) in plants are still unclear. Here, we observed that the seedling growth inhibition of Arabidopsis caused by low doses of mannitol could progressively recover by recuperation, accompanied with the increased hydrogenase activity and H2 synthesis. To investigate the functions of endogenous H2, a hydrogenase gene (CrHYD1) for H2 biosynthesis from Chlamydomonas reinhardtii was expressed in Arabidopsis. Transgenic plants could intensify higher H2 synthesis compared with wild type and Arabidopsis transformed with the empty vector, and exhibited enhanced osmotic tolerance in both germination and post-germination stages. In response to mannitol, transgenic plants enhanced L-Cys desulfhydrase (DES)-dependent hydrogen sulfide (H2S) synthesis in guard cells and thereafter stomatal closure. The application of des mutant further highlights H2S acting as a downstream molecule of endogenous H2 control of stomatal closure. These results thus open a new window for increasing plant tolerance to osmotic stress.

Molecular selectivity design of mitogen-inducible gene-derived phosphopeptides between oncogenic HER kinases.

Mitogen-inducible gene (MIG) is a natural negative regulator of the oncogenic HER kinase signaling by binding at the activation interface of kinase domain to disrupt the kinase dimerization. In this study, we systematically examine the binding structures, dynamics and energetics of MIG region 2 to four HER kinases based on their crystal or modeled complex structures, and identify an 8-mer phosphopeptide segment pYpY from the core strand sequence of MIG region 2 as the binding hotspot of MIG protein to HER kinases. We demonstrate that the small pYpY phosphopeptide can partially restore the binding affinity of full-length MIG protein, but exhibit a moderate selectivity over different HER kinases (S = 2.3-fold). In addition, the two phosphotyrosine residues pTyr394 and pTyr395 play an essential role in MIG-HER binding; dephosphorylation of them would fully eliminate the binding capability. A machine evolution algorithm is used to optimize the wild-type pYpY phosphopeptide, aiming to simultaneously improve affinity for these kinases and to maximize the affinity gap between different kinases. Consequently, a population is computationally evolved as selective phosphopeptide candidates; the dissociation constants of four representatives with HER kinases are systematically determined using binding affinity analysis, from which their selectivity is derived. The designed pYpYp3 phosphopeptide possesses a high selectivity over different HER kinases (S = 4.8-fold) and satisfactory affinity profile to these kinase (KD = 140-1000 µM). Structural analysis observes that the global binding modes of pYpYp3 to different kinases are roughly consistent, but its local conformation may vary considerably, thus conferring specificity to the phosphopeptide.

Reverse of microtubule-directed chemotherapeutic drugs resistance induced by cancer-associated fibroblasts in breast cancer.

PURPOSE: This study was designed to expound the underlying mechanism of microtubule-directed chemotherapeutic drugs resistance induced by cancer-associated fibroblasts (CAFs) in breast cancer. MATERIALS AND METHODS: We collected 10 microtubule-directed chemotherapeutic drugs resistant breast tumor samples and 10 normal breast tumor samples to analyze the CAFs distribution by immunohistochemistry and flow cytometry. We also detected the collagen expression in CAFs by real-time PCR. We detected the activation of PI3K/AKT signaling pathway in tumor cells by Western blotting and immunofluorescence. The subcutaneous 4T1/MCF-7 bearing mice were used to investigate the anticancer effects of integrin ß1 inhibitor combined with microtubule-directed chemotherapeutic drugs. RESULTS: In our studies, accumulation of CAFs was observed in tumor samples from microtubule-directed chemotherapeutic drugs resistant patients. Those isolated CAFs could efficiently induce the acquisition of microtubule-directed chemotherapeutic drugs resistance in breast cancer cells. More importantly, we found that CAFs could regulate the microtubule-directed chemotherapeutic drugs resistance through the secretion of collagen to activate the integrin ß1/PI3K/AKT signaling pathway. Combination of integrin α2ß1 inhibitor and paclitaxel/vincristine sulfate could efficiently overcome the microtubule-directed chemotherapeutic drugs resistance induced by CAFs and enhanced the anticancer effects of chemotherapy in subcutaneous 4T1/MCF-7 bearing mice. CONCLUSION: Our results demonstrated that CAFs constitute a supporting niche for cancer drug resistance acquisition. Thus, traditional microtubule-directed chemotherapeutic drugs combined with integrin ß1 inhibitor may present an innovative therapeutic strategy for breast cancer therapy.

Identification of cotton MOTHER OF FT AND TFL1 homologs, GhMFT1 and GhMFT2, involved in seed germination.

Plant phosphatidylethanolamine-binding protein (PEBP) is comprised of three clades: FLOWERING LOCUS T (FT), TERMINAL FLOWER1 (TFL1) and MOTHER OF FT AND TFL1 (MFT). FT/TFL1-like clades regulate identities of the determinate and indeterminate meristems, and ultimately affect flowering time and plant architecture. MFT is generally considered to be the ancestor of FT/TFL1, but its function is not well understood. Here, two MFT homoeologous gene pairs in Gossypium hirsutum, GhMFT1-A/D and GhMFT2-A/D, were identified by genome-wide identification of MFT-like genes. Detailed expression analysis revealed that GhMFT1 and GhMFT2 homoeologous genes were predominately expressed in ovules, and their expression increased remarkably during ovule development but decreased quickly during seed germination. Expressions of GhMFT1 and GhMFT2 homoeologous genes in germinating seeds were upregulated in response to abscisic acid (ABA), and their expressions also responded to gibberellin (GA). In addition, ectopic overexpression of GhMFT1 and GhMFT2 in Arabidopsis inhibited seed germination at the early stage. Gene transcription analysis showed that ABA metabolism genes ABA-INSENSITIVE3 (ABI3) and ABI5, GA signal transduction pathway genes REPRESSOR OF ga1-3 (RGA) and RGA-LIKE2 (RGL2) were all upregulated in the 35S:GhMFT1 and 35S:GhMFT2 transgenic Arabidopsis seeds. GhMFT1 and GhMFT2 localize in the cytoplasm and nucleus, and both interact with a cotton bZIP transcription factor GhFD, suggesting that both of GhMFT1, 2 have similar intracellular regulation mechanisms. Taken together, the results suggest that GhMFT1 and GhMFT2 may act redundantly and differentially in the regulation of seed germination.

Highly Efficient Targeted Gene Editing in Upland Cotton Using the CRISPR/Cas9 System.

The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) gene editing system has been shown to be able to induce highly efficient mutagenesis in the targeted DNA of many plants, including cotton, and has become an important tool for investigation of gene function and crop improvement. Here, we developed a simple and easy to operate CRISPR/Cas9 system and demonstrated its high editing efficiency in cotton by targeting-ALARP, a gene encoding alanine-rich protein that is preferentially expressed in cotton fibers. Based on sequence analysis of the target site in the 10 transgenic cottons containing CRISPR/Cas9, we found that the mutation frequencies of GhALARP-A and GhALARP-D target sites were 71.4⁻100% and 92.9⁻100%, respectively. The most common editing event was deletion, but deletion together with large insertion was also observed. Mosaic mutation editing events were detected in most transgenic plants. No off-target mutation event was detected in any the 15 predicted sites analyzed. This study provided mutants for further study of the function of GhALARP in cotton fiber development. Our results further demonstrated the feasibility of use of CRISPR/Cas9 as a targeted mutagenesis tool in cotton, and provided an efficient tool for targeted mutagenesis and functional genomics in cotton.

Nitric Oxide Is Required for Melatonin-Enhanced Tolerance against Salinity Stress in Rapeseed (Brassica napus L.) Seedlings.

Although melatonin (N-acetyl-5-methoxytryptamine) could alleviate salinity stress in plants, the downstream signaling pathway is still not fully characterized. Here, we report that endogenous melatonin and thereafter nitric oxide (NO) accumulation was successively increased in NaCl-stressed rapeseed (Brassica napus L.) seedling roots. Application of melatonin and NO-releasing compound not only counteracted NaCl-induced seedling growth inhibition, but also reestablished redox and ion homeostasis, the latter of which are confirmed by the alleviation of reactive oxygen species overproduction, the decreases in thiobarbituric acid reactive substances production, and Na⁺/K⁺ ratio. Consistently, the related antioxidant defense genes, sodium hydrogen exchanger (NHX1), and salt overly sensitive 2 (SOS2) transcripts are modulated. The involvement S-nitrosylation, a redox-based posttranslational modification triggered by NO, is suggested. Further results show that in response to NaCl stress, the increased NO levels are strengthened by the addition of melatonin in seedling roots. Above responses are abolished by the removal of NO by NO scavenger. We further discover that the removal of NO does not alter endogenous melatonin content in roots supplemented with NaCl alone or together with melatonin, thus excluding the possibility of NO-triggered melatonin production. Genetic evidence reveals that, compared with wild-type Arabidopsis, the hypersensitivity to NaCl in nia1/2 and noa1 mutants (exhibiting null nitrate reductase activity and indirectly reduced endogenous NO level, respectively) cannot be rescued by melatonin supplementation. The reestablishment of redox homeostasis and induction of SOS signaling are not observed. In summary, above pharmacological, molecular, and genetic data conclude that NO operates downstream of melatonin promoting salinity tolerance.

Hydrogen peroxide acts downstream of melatonin to induce lateral root formation.

Background and Aims: Although several studies have confirmed the beneficial roles of exogenous melatonin in lateral root (LR) formation, the molecular mechanism is still elusive. Here, the role of hydrogen peroxide (H2O2) in the induction of LR formation triggered by melatonin was investigated. Methods: Alfalfa (Medicago sativa 'Biaogan') and transgenic Arabidopsis seedlings were treated with or without melatonin, diphenyleneiodonium (DPI, NADPH oxidase inhibitor), N,N'-dimethylthiourea (DMTU, H2O2 scavenger), alone or combined. Then, H2O2 content was determined with 2',7'-dichlorofluorescein diacetate (H2DCFDA)-dependent fluorescence and spectrophotography. Transcript levels of cell cycle regulatory genes were analysed by real-time reverse transcription-PCR. Key Results: Application of exogenous melatonin not only increased endogenous H2O2 content but also induced LR formation in alfalfa seedlings. Consistently, melatonin-induced LR primordia exhibited an accelerated response. These inducible responses were significantly blocked when DPI or DMTU was applied. Compared with the wild-type, transgenic Arabidopsis plants overexpressing alfalfa MsSNAT (a melatonin synthesis gene) increased H2O2 accumulation and thereafter LR formation, both of which were blocked by DPI or DMTU. Similarly, melatonin-modulated expression of marker genes responsible for LR formation, including MsCDKB1;1, MsCDKB2;1, AtCDKB1;1 and AtCDKB2;1, was obviously impaired by the removal of H2O2 in both alfalfa and transgenic Arabidopsis plants. Conclusions: Pharmacological and genetic evidence revealed that endogenous melatonin-triggered LR formation was H2O2-dependent.

Effects of nurse-led home-based exercise & cognitive behavioral therapy on reducing cancer-related fatigue in patients with ovarian cancer during and after chemotherapy: A randomized controlled trial.

BACKGROUND: High levels of fatigue have been documented in ovarian cancer patients. However, increased levels of fatigue are positively associated with a high risk of sleep disturbance and depression. OBJECTIVE: To investigate the feasibility of a nurse-led home-based exercise and cognitive behavioral therapy (E&CBT) for ovarian cancer adults with cancer-related fatigue on outcomes of fatigue, plus other secondary outcomes (sleep disturbance and depression), either during or after completion of primary cancer treatment. DESIGN: Randomized, single-blind control trial. SETTINGS: Gynaecologic oncology department of the First Hospital of Jilin University in China. PARTICIPANTS: 72 eligible women who recently had surgery and completed their first cycle of adjuvant chemotherapy were randomly assigned to two groups. INTERVENTION: The experimental group received exercise and cognitive behavioral therapy. Five nurses with nursing master degree were trained to deliver this intervention. Patients received online interventions each week in the patient's place of residence or in the nurse-led clinic, as requested. Home visits, coupled with telephone-based motivational interviews twice a week were available with the permission of the participants. comparison group participants received services as usual. MEASUREMENTS: The primary outcome was measured by the Chinese version of the Piper Fatigue Scale that has 4 subscales (Behavior, Affect, Sensory, and Cognition). Secondary outcomes were measured using the Self-Rating Depression Scale and the Pittsburgh Sleep Quality Index questionnaire. Repeated-measure ANOVA was used to examine the effectiveness of this intervention in reducing fatigue, depression, and improving sleep quality. RESULTS: For baseline comparisons, no significant differences were found between the two groups. After the interventions, total fatigue scores were significantly reduced from T1 to T2, to T3 in the experimental group (4.37, 4.24, 3.90), respectively. The comparison group showed almost no change in total fatigue score over time. In the repeated measures ANOVA, the differences of behavioral fatigue score (F=11.647, p=0.001) and cognitive fatigue score (F=5.741, p=0.019) were statistically significant for the group by time interaction. After the interventions, the experimental group participants demonstrated significantly lower symptoms of depression compared with the comparison group (T2: p=0.001 and T3: p<0.001). Sleep duration, sleep dysfunction, daytime dysfunction as well as total sleep quality significantly improved. CONCLUSION: Nurse-delivered home-based E&CBT have measurable benefits in helping women with ovarian cancer to decrease cancer-related fatigue, depressive symptoms, and improving their quality of sleep.