Safety and efficacy of a novel dexmedetomidine nasal spray for pre-anesthetic sedation in children: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Off-label intranasal administration of injectable dexmedetomidine has been widely applied in the pediatric sedation setting. However, the development of an improved drug delivery system that is easy to use is needed. We developed a novel dexmedetomidine nasal spray that can be administered directly without dilution or configuration for pediatric pre-anesthetic sedation. This nasal spray has a fixed dose and is stable during storage. To the best of our knowledge, this is the first licensed nasal spray preparation of dexmedetomidine worldwide. OBJECTIVE: To evaluate the pre-anesthetic sedation efficacy and safety of the novel dexmedetomidine nasal spray in children. METHODS: The study was conducted at 11 sites in China between 24 November 2021 and 20 May 2022 and was registered in ClinicalTrials.gov (NCT05111431, first registration date: 20/10/2021). Subjects (n = 159) between 2 and 6 years old who were to undergo elective surgery were randomized to the dexmedetomidine group (n = 107) or the placebo group (n = 52) in a 2:1 ratio. The dosage was 30 µg or 50 µg based on the stratified body weight. The primary outcome measure was the proportion of subjects who achieved the desired child-parent separation and Ramsay scale ≥ 3 within 45 min of administration. Safety was monitored via the assessments of adverse events, blood pressure, heart rate, respiratory rate and blood oxygen saturation. RESULTS: The proportion of subjects achieving desired parental separation and Ramsay scale ≥ 3 within 45 min was significantly higher in the dexmedetomidine group (94.4%) vs the placebo group (32.0%) (P < 0.0001). As compared with placebo, dexmedetomidine treatment led to more subjects achieving Ramsay scale ≥ 3 or UMSS ≥ 2, and shorter time to reach desired parental separation, Ramsay scale ≥ 3 and UMSS ≥ 2 (all P < 0.0001). Adverse events were reported in 90.7% and 84.0% of subjects in the dexmedetomidine and placebo groups, respectively, and all the events were mild or moderate in severity. CONCLUSIONS: This novel dexmedetomidine nasal spray presented effective pre-anesthetic sedation in children with a tolerable safety profile.

Roles of transforming growth factor-ß signaling in liver disease.

In this editorial we expand the discussion on the article by Zhang et al published in the recent issue of the World Journal of Hepatology. We focus on the diagnostic and therapeutic targets identified on the basis of the current understanding of the molecular mechanisms of liver disease. Transforming growth factor-ß (TGF-ß) belongs to a structurally related cytokine super family. The family members display different time- and tissue-specific expression patterns associated with autoimmunity, inflammation, fibrosis, and tumorigenesis; and, they participate in the pathogenesis of many diseases. TGF-ß and its related signaling pathways have been shown to participate in the progression of liver diseases, such as injury, inflammation, fibrosis, cirrhosis, and cancer. The often studied TGF-ß/Smad signaling pathway has been shown to promote or inhibit liver fibrosis under different circumstances. Similarly, the early immature TGF-ß molecule functions as a tumor suppressor, inducing apoptosis; but, its interaction with the mitogenic molecule epidermal growth factor alters this effect, activating anti-apoptotic signals that promote liver cancer development. Overall, TGF-ß signaling displays contradictory effects in different liver disease stages. Therefore, the use of TGF-ß and related signaling pathway molecules for diagnosis and treatment of liver diseases remains a challenge and needs further study. In this editorial, we aim to review the evidence for the use of TGF-ß signaling pathway molecules as diagnostic or therapeutic targets for different liver disease stages.

Isolation and identification of a novel porcine-related recombinant mammalian orthoreovirus type 3 strain from cattle in Guangxi Province, China.

The Mammalian orthoreovirus (MRV) infects various mammals, including humans, and is linked to gastrointestinal, respiratory, and neurological diseases. A recent outbreak in Liuzhou, Guangxi, China, led to the isolation of a new MRV strain, GXLZ2301, from fecal samples. This strain replicates in multiple cell lines and forms lattice-like structures. Infected cells exhibit single-cell death and syncytia formation. The virus's titers peaked at 107.2 TCID50/0.1 mL in PK-15 and BHK cells, with the lowest at 103.88 TCID50/0.1 mL in A549 cells. Electron microscopy showed no envelope with a diameter of about 70 nm. Genetic analysis revealed GXLZ2301 as a recombinant strain with gene segments from humans, cows, and pigs, similar to type 3 MRV strains from Italy (2015-2016). Pathogenicity tests indicated that while the bovine MRV strain did not cause clinical symptoms in mice, it caused significant damage to the gut, lungs, liver, kidneys, and brain. The emergence of this MRV strain may pose a threat to the health of animals and humans, and it is recommended that its epidemiology and recombination be closely monitored.

ADH4-a potential prognostic marker for hepatocellular carcinoma with possible immune-related implications.

OBJECTIVE: This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment. METHODS: HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues. RESULTS: ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy. CONCLUSION: This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.

Paraneoplastic dermatomyositis and Hodgkin's lymphoma in a 14-year-old girl: a case report and literature review.

Background: Juvenile dermatomyositis (JDM) is a rare autoimmune myopathy whose main clinical manifestations include a characteristic rash, symmetrical proximal muscle weakness, and elevated muscle enzymes. While approximately one-third of adult patients with dermatomyositis (DM) develop malignancies, typically within a year of diagnosis, this phenomenon is not commonly observed in patients with JDM. In this study, we present a rare case of both JDM and Hodgkin's lymphoma (HL) diagnosed in an adolescent female patient. Case description: A 14-year-old girl with proximal muscle weakness and myalgia for 8 weeks was admitted to the hospital and ultimately received a diagnosis of DM. A thorough physical examination revealed enlarged lymph nodes on both sides of the cervical, and a lymph node biopsy was performed to diagnose HL. After she underwent radiotherapy and chemotherapy, her symptoms of both HL and DM were alleviated. Conclusion: The phenomenon of JDM as a paraneoplastic syndrome associated with HL is very rare. Thus, routine cancer screening for DM in adolescents is currently not recommended. The diagnosis of JDM requires a detailed physical examination, and further tumor screening is necessary for patients with unusual physical findings, such as atypical rashes, enlarged lymph nodes, and enlargement of the spleen and/or liver. Even if no malignancy is detected when JDM is diagnosed, long-term follow-up is necessary.

Recent Progress in Synthesis of Alkyl Fluorinated Compounds with Multiple Contiguous Stereogenic Centers.

Organic fluorides are widely used in pharmaceuticals, agrochemicals, material sciences, and other fields due to the special physical and chemical properties of fluorine atoms. The synthesis of alkyl fluorinated compounds bearing multiple contiguous stereogenic centers is the most challenging research area in synthetic chemistry and has received extensive attention from chemists. This review summarized the important research progress in the field over the past decade, including asymmetric electrophilic fluorination and the asymmetric elaboration of fluorinated substrates (such as allylic alkylation reactions, hydrofunctionalization reactions, Mannich addition reactions, Michael addition reactions, aldol addition reactions, and miscellaneous reactions), with an emphasis on synthetic methodologies, substrate scopes, and reaction mechanisms.

Adverse social determinants of health elevate uncontrolled hypertension risk: a cardio-oncology prospective cohort study.

The role of social determinants of health (SDOH) in controlling hypertension (HTN) in cancer patients is unknown. We hypothesize that high SDOH scores correlate with uncontrolled HTN in hypertensive cancer patients. In our prospective study, patients completed the Protocol for Responding to & Assessing Patients' Assets, Risks & Experiences questionnaire. After integrating home and clinic blood pressure readings, uncontrolled HTN was defined as systolic blood pressure greater than or equal to 140 mm Hg and/or diastolic blood pressure greater than or equal to 90 mm Hg. Using Cox regression, we analyzed the impact of SDOH on HTN control, adjusting for relevant factors. The study involved 318 participants (median age 66.4, median follow-up 166 days, SDOH score 6.5 ± 3.2), with stress, educational insecurity, and social isolation as prevalent adverse SDOH. High SDOH scores led to 77% increased risk of uncontrolled HTN (adjusted hazards ratio = 1.77; 95% confidence interval = 1.10 to 2.83, P = .018). Urban residents with high SDOH scores were at an even greater risk. Identifying SDOH and mitigating underlying factors may help control HTN, the most typical disease process treated in all cardio-oncology clinics.

Identification and Full-Length Sequence Analysis of a Novel Recombinant Goat Astrovirus Genotype in Guangxi, China.

Astroviruses are single-stranded, positive-sense RNA viruses capable of infecting humans as well as a wide range of mammalian and avian species, with a length of approximately 6.6-7.7 kb. In this study, 139 goat fecal samples collected from the Guangxi province were used for the RT-PCR detection, and two of these were positive for goat astrovirus, with a positivity rate of 1.44% (2/139). The complete genome sequence of an astrovirus strain and the partial genome sequence of a strain astrovirus, named GX WZ 2023 and GX HC 2023, were amplified and sequenced, and their sequence lengths were 6284 nt and 6213 nt, respectively. Among them, the capsid protein of goat astrovirus GX HC 2023 showed the highest amino acid identity of 95.9% with ovine astrovirus GX, which belonged to the MAstV-2 genotype. However, the closest relative of the GX WZ 2023 strain was found to be the caprine astrovirus Sichuan, with a nucleotide sequence identity of 76.8%. The ORF1ab nonstructural protein of this strain showed the highest amino acid identities of 89.2 and 95.8% with the ovine astrovirus S5.1 and caprine astrovirus G5.1 strains, respectively. However, its ORF2 capsid protein has 68.4% amino acid identity with the bovine astrovirus (BAstV) 16 2021 CHN strain and only 21.9-64% amino acid identity with all available strains of goat astrovirus. The GX WZ 2023 strain was recombined with the Chinese (BAstV 16 2021 CHN) and Japanese bovine strains (BAstV JPN 2015) in the ORF2 region. Therefore, the goat astrovirus GX WZ 2023 is proposed as a new member of the family goat astroviridae based on the species classification criteria of the International Committee on Taxonomy of Viruses. These findings enhance our understanding of the prevalence and genetic evolution of goat astrovirus and provide a scientific basis for future studies of these viruses in other animals.

Association Between Obesity and Risk of Total and Obesity-Related Cancer in People With Incident Cardiovascular Disease.

BACKGROUND: Cardiovascular disease (CVD) and cancer frequently co-occur due to shared risk factors such as obesity, which is linked to CVD and 14 cancer types. This study explores whether CVD pathophysiologies, combined with obesity, increase cancer risk, impacting clinical management. METHODS AND RESULTS: Data from the ARIC (Atherosclerosis Risk in Communities) study, spanning 28 years, were analyzed. The cohort included 5127 participants with incident CVD (myocardial infarction, stroke, heart failure, coronary heart disease), of whom 1511 developed a first primary cancer. Follow-up began at CVD diagnosis after Visit 1. Obesity was assessed using body mass index, waist circumference, and waist-to-hip ratio. Incidence rate differences between obesity groups were adjusted for age, sex, and center, whereas the obesity-cancer association was estimated using Fine-Gray regression adjusted for shared risk factors including smoking. Cancer incidence in obese individuals with CVD (body mass index: rate differences=226.6/100 000 person-years) was higher than in those with normal weight. Although obesity was not linked to overall cancer after adjusting for shared risk factors, it was nominally associated with obesity-related cancers. Specifically, women with CVD and obesity had increased obesity-related cancer risk (body mass index: hazard ratio, 1.67 [95% CI, 1.17-2.31]). No significant associations were found in men, even after excluding prostate cancer. CONCLUSIONS: This study suggests that obesity is linked to higher obesity-related cancer risk in women with incident CVD, independent of shared risk factors. Further research is needed to eliminate residual confounding, understand sex differences, and explore how CVD pathophysiologies and obesity together influence cancer risk.

Neural signatures of default mode network subsystems in first-episode, drug-naive patients with major depressive disorder after 6-week thought induction psychotherapy treatment.

Evidence indicates that the default mode network (DMN) plays a crucial role in the neuropathology of major depressive disorder (MDD). However, the neural signatures of DMN subsystems in MDD after low resistance Thought Induction Psychotherapy (TIP) remain incompletely understood. We collected functional magnetic resonance imaging data from 20 first-episode, drug-naive MDD and 20 healthy controls (HCs). The DMN was segmented into three subsystems and seed-based functional connectivity (FC) was computed. After 6-week treatment, the significantly reduced FCs with the medial temporal lobe memory subsystem in MDD at baseline were enhanced and were comparable to that in HCs. Changed Hamilton Depression Rating Scale scores were significantly related with changed FC between the posterior cingulate cortex (PCC) and the right precuneus (PCUN). Further, changed serotonin 5-hydroxytryptamine levels were significantly correlated with changed FCs between the PCC and the left PCUN, between the posterior inferior parietal lobule and the left inferior temporal gyrus, and between the retrosplenial cortex and the right inferior frontal gyrus, opercular part. Finally, the support vector machine obtained an accuracy of 67.5% to distinguish between MDD at baseline and HCs. These findings may deepen our understanding of the neural basis of the effects of TIP on DMN subsystems in MDD.

Integrated transcriptome and targeted metabolome analyses provide insights into flavonoid biosynthesis in kiwifruit (Actinidia chinensis).

So far, a variety of metabolite components of kiwifruit have been elucidated. However, the identification and analysis of flavonoids in different tissues of kiwifruit are rarely carried out. In this study, we performed transcriptome and metabolome analyses of roots (Gkf_R), stems (Gkf_T), leaves (Gkf_L), and fruits (Gkf_F) to provide insights into the differential accumulation and regulation mechanisms of flavonoids in kiwifruit. Results showed that a total of 301 flavonoids were identified, in four tissues with different accumulation trends, and a large proportion of flavonoids had high accumulation in Gkf_L and Gkf_R. A total of 84 genes have been identified involved in the flavonoid biosynthesis pathway, and the expression levels of five LAR, two DFR, and one HCT were significantly correlated with the accumulation of 16 flavonoids and co-localized in the flavonoid biosynthesis pathway. In addition, a total of 2362 transcription factor genes were identified, mainly MYBs, bHLHs, ERFs, bZIPs and WRKYs, among which the expression level of bHLH74, RAP2.3L/4L/10L, MYB1R1, and WRKY33 were significantly correlated with 25, 56, 43, and 24 kinds of flavonoids. Our research will enrich the metabolomic data and provide useful information for the directed genetic improvement and application in the pharmaceutical industry of kiwifruit.

Daily Physical Activity Does Not Contribute to Differences in Muscle Oxidative Capacity Between Overweight and Obesity.

BACKGROUND: The interaction between physical activity, skeletal muscle health, and adiposity has been explored in normal weight and overweight/obesity grouped together; however, the overall risks associated with being overweight are less than those observed with obesity and can be confounded by disparities in both sex and race. Thus, the present study sought to investigate the intricate interplay of daily physical activity and skeletal muscle oxidative capacity (SMOC) in overweight and obesity, while exploring how sex and race impact this dynamic relationship. METHODS: One hundred and forty participants were grouped by body mass index (BMI) as overweight (n = 73; BMI >25-<30 kg/m2) or obese (n = 67; BMI ≥30 kg/m2). SMOC was assessed using near-infrared spectroscopy and daily physical activity was assessed for 7 days using accelerometry. RESULTS: Overweight individuals exhibited a higher (p = 0.004) SMOC and engaged in more (p = 0.007) vigorous physical activity compared to obese individuals. In addition, SMOC was lower (p = 0.005) in obese non-Hispanic Black (NHB) men compared to overweight NHB men. No relationships between physical activity and SMOC were observed. CONCLUSION: Physical activity is not associated with differences in SMOC in overweight and obesity. Obese individuals engage in less vigorous physical activity and exhibit lower SMOC compared to overweight individuals and these differences are emphasised in NHB men.

Cardiovascular Diseases Increase Cancer Mortality in Adults: NHANES-Continuous Study.

BACKGROUND: Both cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. Although our previous study detected a relationship between CVD and cancer incidence, limited evidence is available regarding the relationship between CVD, cardiovascular risk factors, and cancer mortality. METHODS AND RESULTS: A prospective cohort study using data from the continuous NHANES (National Health and Nutrition Examination Survey, 1999-2016) merged with Medicare and National Death Index mortality data, through December 31, 2018. We included individuals with no history of cancer at baseline. The primary exposure was CVD at baseline. We also conducted a comprehensive risk factor analysis as secondary exposure. The main outcome was cancer mortality data collected from Medicare and National Death Index. We included 44 591 adult individuals representing 1 738 423 317 individuals (52% female, 67% non-Hispanic White, and 9% Hispanic). Competing risk modeling showed a significantly higher risk of cancer mortality in individuals with CVD (adjusted hazard ratio [aHR], 1.37 [95% CI 1.07-1.76], P=0.01) after adjusting for age, sex, and race and ethnicity. Notably, cancer mortality increased with aging (aHR, 1.08 [95% CI 1.05-1.11], P<0.0001), current smoking status (aHR, 6.78 [95% CI, 3.43-13.42], P<0.0001), and obesity (aHR, 2.32 [95% CI, 1.13-4.79], P=0.02). Finally, a significant interaction (P=0.034) was found where those with CVD and obesity showed higher cancer mortality than those with normal body mass index (aHR, 1.73 [95% CI, 1.03-2.91], P=0.04). CONCLUSIONS: Our study highlights the close relationship between cardiovascular health and cancer mortality. Our findings suggest that obesity may play a significant role in cancer mortality among individuals with CVD. These findings emphasize the need for a more proactive approach in managing the shared risk factors for CVD and cancer.

Targeting thioredoxin reductase by eupalinilide B promotes apoptosis of colorectal cancer cells in vitro and in vivo.

Aberrant activation of thioredoxin reductase (TrxR) is correlated with tumor occurrence and progression, suggesting that TrxR inhibitors can be used as antitumor agents. In this study, we evaluated the anticancer efficacy of eupalinilides B on colorectal cancer cells. Eupalinilides B primarily targeted the conserved selenocysteine 498 residues in TrxR. Besides, it inhibited the enzyme activity in an irreversible manner. After eupalinilides B was used to pharmacologically inhibit TrxR, reactive oxygen species accumulated, and the intracellular redox balance was broken, finally causing oxidative stress-induced tumor cell apoptosis. Significantly, eupalinilides B treatment inhibited in vivo tumor growth. Targeting TrxR by eupalinilides B reveals the new mechanism underlying eupalinilides B and provides insight in developing eupalinilides B as the candidate antitumor chemotherapeutic agent for the treatment of cancer.

Model-Informed individualized dosage regimen of sirolimus in pediatric patients with intractable lymphatic malformations.

Intractable lymphatic malformations (iLM) pose a significant threat to affected children, demonstrating limited responses to conventional treatments. Sirolimus, effectively inhibiting endothelial cell proliferation in lymphatic vessels, plays a crucial role in iLM treatment. However, the drug's narrow therapeutic window and substantial interindividual variability necessitate customized dosing strategies. This study aims to establish a Population Pharmacokinetic Model (PopPK model) for sirolimus in pediatric iLM patients, identifying quantitative relationships between covariates and sirolimus clearance and volume of distribution. Initial dosages are recommended based on a target concentration range of 5-15 ng/mL. Retrospective data from our institution, encompassing 53 pediatric patients with 275 blood concentration results over the past five years (average age: 4.64 ± 4.19 years), constituted the foundation of this analysis. The final model, adopting a first-order absorption and elimination single-compartment model, retained age as the sole covariate. Results indicated a robust correlation between apparent clearance (CL/F) at 5.56 L/h, apparent volume of distribution (V/F) at 292.57 L, and age. Monte Carlo simulation guided initial dosages for patients aged 0-18 years within the target concentration range. This study presents the first PopPK model using a large Therapeutic Drug Monitoring (TDM) database to describe personalized sirolimus dosing for pediatric iLM patients, contributing to pharmacokinetic guidance and potentially improving long-term clinical outcomes.

Association between oxidative balance score and 10-year atherosclerotic cardiovascular disease risk: results from the NHANES database.

Introduction: The oxidative balance score (OBS) is a holistic measure that represents the overall equilibrium between prooxidants and antioxidants in one's diet and lifestyle. Little research has been conducted on the correlation between OBS and 10-year atherosclerotic cardiovascular disease risk (ASCVD). Therefore, the objective of this investigation was to examine the potential correlation between OBS and 10-year risk. Methods: A total of 11,936 participants from the NHANES conducted between 2001 and 2016 were chosen for the study and their dietary and lifestyle factors were used to assess the OBS score. Logistic regression and restricted cubic splines (RCS) were employed in the cross-sectional study to evaluate the correlation between OBS and the 10-year ASCVD risk. The cohort study utilized Cox proportional hazards models and RCS to assess the correlation between OBS and all-causes and cardiovascular disease (CVD) mortality in individuals with high ASCVD risk. Results: The cross-sectional study found that the OBS (OR = 0.94, 95% CI = 0.93-0.98), as well as the dietary OBS (OR = 0.96, 95% CI = 0.92-0.96) and lifestyle OBS (OR = 0.74, 95% CI = 0.69-0.79), were inversely associated with the 10-year ASCVD risk. A significant linear relationship was observed between OBS, dietary OBS, lifestyle OBS, and the 10-year ASCVD risk. The cohort study found that the OBS was inversely associated with all-cause (aHRs = 0.97, 95% CI = 0.96-0.99) and CVD (aHRs = 0.95, 95% CI = 0.93-0.98) mortality in individuals with high ASCVD risk. A significant linear correlation was observed between OBS, dietary OBS, lifestyle OBS, and all-cause and CVD mortality in participants with high ASCVD risk. Conclusion: The findings indicate that OBS, OBS related to diet, and OBS related to lifestyle were significantly inversely correlated with the 10-year ASCVD risk. Adopting a healthy eating plan and making positive lifestyle choices that result in increased OBS levels can help lower the likelihood of all-cause and CVD mortality in individuals with high ASCVD risk.

Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease.

Amyloid plaques, a major pathological hallmark of Alzheimer's disease (AD), are caused by an imbalance between the amyloidogenic and non-amyloidogenic pathways of amyloid precursor protein (APP). BACE1 cleavage of APP is the rate-limiting step for amyloid-ß production and plaque formation in AD. Although the alteration of BACE1 expression in AD has been investigated, the underlying mechanisms remain unknown. In this study, we determined MEIS2 was notably elevated in AD models and AD patients. Alterations in the expression of MEIS2 can modulate the levels of BACE1. MEIS2 downregulation improved the learning and memory retention of AD mice and decreased the number of amyloid plaques. MEIS2 binds to the BACE1 promoter, positively regulates BACE1 expression, and accelerates APP amyloid degradation in vitro. Therefore, our findings suggest that MEIS2 might be a critical transcription factor in AD, since it regulates BACE1 expression and accelerates BACE1-mediated APP amyloidogenic cleavage. MEIS2 is a promising early intervention target for AD treatment.

Integrated analysis of miRNAs, transcriptome and phytohormones in the flowering time regulatory network of tea oil camellia.

Camellia oleifera is a crucial cash crop in the southern region of China. Timely flowering is a crucial characteristic for maximizing crop productivity. Nevertheless, the cold temperature and wet weather throughout the fall and winter seasons in South China impact the timing of flowering and the yield produced by C. oleifera. This study examined the miRNAs, transcriptomes, and phytohormones that are part of the flowering time regulatory networks in distinct varieties of C. oleifera (Sep, Oct, and Nov). This study provides evidence that phytohormones significantly impact the timing of flowering in C. oleifera leaves. There is a positive correlation between the accumulation variations of zeatin (cZ), brassinolide (BL), salicylic acid (SA), 1-amino cyclopropane carboxylic acid (ACC), and jasmonic acid (JA) and flowering time. This means that blooming occurs earlier when the quantity of these substances in leaves increases. Abscisic acid (ABA), trans-zeatin-riboside (tZR), dihydrozeatin (dh-Z), and IP (N6-Isopentenyladenine) exhibit contrasting effects. Furthermore, both miR156 and miR172 play a crucial function in regulating flowering time in C. oleifera leaves by modulating the expression of SOC1, primarily through the miR156-SPL and miR172-AP2 pathways. These findings establish a strong basis for future research endeavors focused on examining the molecular network associated with the flowering period of C. oleifera and controlling flowering time management through external treatments. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01473-2.

Moxibustion improves motor function by down-regulating SNX5 and inhibiting ferroptosis in neurons of corpus striatum in mice with Parkinson's disease. / 艾灸调控SNX5å¯¹å¸•é‡‘æ£®ç— æ¨¡åž‹å°é¼ ç¥žç»å ƒé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To explore the effect of moxibustion on the expression of sorting nexin 5 (SNX5), glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1) in the corpus striatum in mice with Parkinson's disease (PD), so as to explore its mechanisms underlying improvement of PD by ameliorating ferroptosis in the substantia nigra striatum. METHODS: C57BL/6J mice were randomly divided into normal, sham operation, model, and moxibustion groups, with 10 mice in each group. The PD model was established by unilateral injection of 6-hydroxydopamine (3.5 µL) into the right medial forebrain bundle (AP=-1.2 mm, ML=-1.3 mm, DV=-4.75 mm). The mice in the moxibustion group received moxibustion at "Baihui"(GV20) and "Sishencong"(EX-HN1) for 20 min each time, once a day, 6 times a week for 4 weeks. After the intervention, mice received apomorphine rotation behavior detection and pole climbing test. The expression of tyrosine hydroxylase (TH) in the substantia nigra was detected by immunofluorescence, the contents of Fe2+, malondialdehyde (MDA), the ratio of glutathione/oxidized glutathione (GSH/GSSG) in the corpus striatum were detected by using photocolorimetric method, and the expression levels of SNX5 (endocytosomal protein), GPX4 (one of the key targets for inhibiting ferroptosis) and FTH1 proteins and mRNAs in the corpus striatum were detected by Western blot and qPCR, respectively. RESULTS: Behavior tests showed that the pole climbing time and number of body rotation were significantly increased in the model group relevant to the sham operation group (P<0.01), and strikingly decreased in the moxibustion group relevant to the model group (P<0.01). The immunofluorescence intensity of TH in the substantia nigra, the ratio of GSH/GSSG, and the expression levels of GPX4 and FTH1 mRNAs and proteins in the corpus striatum were markedly decreased (P<0.01, P<0.05), while the contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein in the corpus striatum significantly increased in the model group relevant to the sham operation group (P<0.01, P<0.05). Compared with the model group, the decreased immunofluorescence intensity of TH, GSH/GSSH, and the expression levels of GPX4 and FTH1 mRNAs and proteins, and the increased contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein were reversed in the moxibustion group relevant to the model group (P<0.01, P<0.05). CONCLUSIONS: Moxibustion may improve motor dysfunction in PD mice, which may be related to its effects in down-regulating the expression of SNX5, promoting the synthesis of GSH, decreasing the contents of Fe2+ and MDA, up-regulating the ratio of GSH/GSSG and the expression of GPX4 and FTH1 mRNAs and proteins in the corpus striatum, and inhibiting the occurrence of ferroptosis.