An aldehyde dehydrogenase gene, GhALDH7B4_A06, positively regulates fiber strength in upland cotton (Gossypium hirsutum L.).

High fiber strength (FS) premium cotton has significant market demand. Consequently, enhancing FS is a major objective in breeding quality cotton. However, there is a notable lack of known functionally applicable genes that can be targeted for breeding. To address this issue, our study used specific length-amplified fragment sequencing combined with bulk segregant analysis to study FS trait in an F2 population. Subsequently, we integrated these results with previous quantitative trait locus mapping results regarding fiber quality, which used simple sequence repeat markers in F2, F2:3, and recombinant inbred line populations. We identified a stable quantitative trait locus qFSA06 associated with FS located on chromosome A06 (90.74-90.83 Mb). Within this interval, we cloned a gene, GhALDH7B4_A06, which harbored a critical mutation site in coding sequences that is distinct in the two parents of the tested cotton line. In the paternal parent Ji228, the gene is normal and referred to as GhALDH7B4_A06O; however, there is a nonsense mutation in the maternal parent Ji567 that results in premature termination of protein translation, and this gene is designated as truncated GhALDH7B4_A06S. Validation using recombinant inbred lines and gene expression analysis revealed that this mutation site is correlated with cotton FS. Virus-induced gene silencing of GhALDH7B4 in cotton caused significant decreases in FS and fiber micronaire. Conversely, GhALDH7B4_A06O overexpression in Arabidopsis boosted cell wall component contents in the stem. The findings of our study provide a candidate gene for improving cotton fiber quality through molecular breeding.

Aspartyl proteases identified as candidate genes of a fiber length QTL, qFLD05, that regulates fiber length in cotton (Gossypium hirsutum L.).

KEY MESSAGE: GhAP genes were identified as the candidates involved in cotton fiber length under the scope of fine mapping a stable fiber length QTL, qFLD05. Moreover, the transcription factor GhWRKY40 positively regulated GhAP3 to decrease fiber length. Fiber length (FL) is an economically important fiber quality trait. Although several genes controlling cotton fiber development have been identified, our understanding of this process remains limited. In this study, an FL QTL (qFLD05) was fine-mapped to a 216.9-kb interval using a secondary F2:3 population derived from the upland hybrid cultivar Ji1518. This mapped genomic segment included 15 coding genes, four of which were annotated as aspartyl proteases (GhAP1-GhAP4). GhAPs were identified as candidates for qFLD05 as the sequence variations in GhAPs were associated with FL deviations in the mapping population, and functional validation of GhAP3 and GhAP4 indicated a longer FL following decreases in their expression levels through virus-induced gene silencing (VIGS). Subsequently, the potential involvement of GhWRKY40 in the regulatory network was revealed: GhWRKY40 positively regulated GhAP3's expression according to transcriptional profiling, VIGS, yeast one-hybrid assays and dual-luciferase experiments. Furthermore, alterations in the expression of the eight previously reported cotton FL-responsive genes from the above three VIGS lines (GhAP3, GhAP4 and GhWRKY40) implied that MYB5_A12 was involved in the GhWRKY40-GhAP network. In short, we unveiled the unprecedented FL regulation roles of GhAPs in cotton, which was possibly further regulated by GhWRKY40. These findings will reveal the genetic basis of FL development associated with qFLD05 and be beneficial for the marker-assisted selection of long-staple cotton.

Genetic mapping, transcriptomic sequencing and metabolic profiling indicated a glutathione S-transferase is responsible for the red-spot-petals in Gossypium arboreum.

KEY MESSAGE: A GST for red-spot-petals in Gossypium arboreum was identified as the candidate under the scope of multi-omics approaches. Colored petal spots are correlated with insect pollination efficiency in Gossypium species. However, molecular mechanisms concerning the formation of red spots on Gossypium arboreum flowers remain elusive. In the current study, the Shixiya1-R (SxyR, with red spots) × Shixiya1-W (SxyW, without red spots) segregating population was utilized to determine that the red-spot-petal phenotype was levered by a single dominant locus. This phenotype was expectedly related to the anthocyanin metabolites, wherein the cyanidin and delphinidin derivatives constituted the major partition. Subsequently, this dominant locus was narrowed to a 3.27 Mb range on chromosome 7 by genomic resequencing from the two parents and the two segregated progeny bulks that have spotted petals or not. Furthermore, differential expressed genes generated from the two bulks at either of three sequential flower developmental stages that spanning the spot formation were intersected with the annotated ones that allocated to the 3.27 Mb interval, which returned eight genes. A glutathione S-transferase-coding gene (Gar07G08900) out of the eight was the only one that exhibited simultaneously differential expression among all three developmental stages, and it was therefore considered to be the probable candidate. Finally, functional validation upon this candidate was achieved by the appearance of scattered petal spots with inhibited expression of Gar07G08900. In conclusion, the current report identified a key gene for the red spotted petal in G. arboreum under the scope of multi-omics approaches, such efforts and embedded molecular resources would benefit future applications underlying the flower color trait in cotton.

Genome-wide characterization of carotenoid oxygenase gene family in three cotton species and functional identification of GaNCED3 in drought and salt stress.

Cotton that serves natural fiber for the textile industry is an important industrial crop. However, abiotic stress imposed a significant negative impact on yield and quality of cotton fiber. Carotenoid cleavage oxygenases (CCOs) that specifically catalyze the cleavage of carotenoid are essential for plant growth and development and abiotic stress response. While information of cotton CCOs and their potential functions in abiotic stress is still far from satisfactory, which imposes restrictions on application in genetic breeding for stress resistance. In this study, 15, 15, and 30 CCOs were identified from Gossypium arboreum, Gossypium raimondii, and Gossypium hirsutum, respectively. Phylogenetic relationship indicated that CCO genes could be classified into two groups (NCEDs and CCDs). Cis-elements prediction showed that there were 18 types of stress-related cis-elements in promoter regions. Analysis with transcriptome data revealed tissue-specific expression pattern of cotton CCOs. qRT-PCR analysis revealed only that GhNCED3a_A/D and GhNCED3c_A/D had strong response to drought, salt, and cold stress, while GhCCD1_A/D and GhCCD4_A showed relatively slight expression changes. Virus-induced gene silencing of GaNCED3a, the ortholog gene of GhNCED3a_A/D, suggested that silenced plants exhibited decreased resistance not only to drought but also to salt, with significantly reduced proline content, and high malondialdehyde content and water loss rate. In addition, stress response genes RD29A, DREB1A, and SOS1 significantly downregulated under drought and salt stress in silenced plants compared to control plants, indicating that GaNCED3a played an important role in drought and salt response. The results provided valuable insights into function analysis of cotton CCOs in abiotic stress response, and suggested potential benefit genes for stress-resistant breeding.

Tristetraprolin, a Potential Safeguard Against Carcinoma: Role in the Tumor Microenvironment.

Tristetraprolin (TTP), a well-known RNA-binding protein, primarily affects the expression of inflammation-related proteins by binding to the targeted AU-rich element in the 3' untranslated region after transcription and subsequently mediates messenger RNA decay. Recent studies have focused on the role of TTP in tumors and their related microenvironments, most of which have referred to TTP as a potential tumor suppressor involved in regulating cell proliferation, apoptosis, and metastasis of various cancers, as well as tumor immunity, inflammation, and metabolism of the microenvironment. Elevated TTP expression levels could aid the diagnosis and treatment of different cancers, improving the prognosis of patients. The aim of this review is to describe the role of TTP as a potential safeguard against carcinoma.

The cellulose synthase (CesA) gene family in four Gossypium species: phylogenetics, sequence variation and gene expression in relation to fiber quality in Upland cotton.

Cellulose synthases (CesAs) are multi-subunit enzymes found on the plasma membrane of plant cells and play a pivotal role in cellulose production. The cotton fiber is mainly composed of cellulose, and the genetic relationships between CesA genes and cotton fiber yield and quality are not fully understood. Through a phylogenetic analysis, the CesA gene family in diploid Gossypium arboreum and Gossypium raimondii, as well as tetraploid Gossypium hirsutum ('TM-1') and Gossypium barbadense ('Hai-7124' and '3-79'), was divided into 6 groups and 15 sub-groups, with each group containing two to five homologous genes. Most CesA genes in the four species are highly collinear. Among the five cotton genomes, 440 and 1929 single nucleotide polymorphisms (SNPs) in the CesA gene family were identified in exons and introns, respectively, including 174 SNPs resulting in amino acid changes. In total, 484 homeologous SNPs between the A and D genomes were identified in diploids, while 142 SNPs were detected between the two tetraploids, with 32 and 82 SNPs existing within G. hirsutum and G. barbadense, respectively. Additionally, 74 quantitative trait loci near 18 GhCesA genes were associated with fiber quality. One to four GhCesA genes were differentially expressed (DE) in ovules at 0 and 3 days post anthesis (DPA) between two backcross inbred lines having different fiber lengths, but no DE genes were identified between these lines in developing fibers at 10 DPA. Twenty-seven SNPs in above DE CesA genes were detected among seven cotton lines, including one SNP in Ghi_A08G03061 that was detected in four G. hirsutum genotypes. This study provides the first comprehensive characterization of the cotton CesA gene family, which may play important roles in determining cotton fiber quality.

Can Prohibitin 1 be a Safeguard against liver disease?

Prohibitin (PHB) 1 is involved in multiple regulatory pathways in liver disease to protect hepatocytes, and its function is associated with subcellular localization. PHB1 located in the nucleus, cytoplasm and the mitochondrial inner membrane has anti-oxidative stress and anti-inflammatory effects in hepatitis and cirrhosis, which can protect liver cells from damage caused by inflammatory factors and reactive oxygen species (ROS) stimulation. The low expression of PHB1 located in the nucleus of liver cancer cells inhibits the proliferation and metastasis of liver cancer; thus, PHB1 exhibits the function of a tumor suppressor gene. Understanding the mechanisms of PHB1 in liver diseases may be useful for further research on the disease and may provide new ideas for the development of targeted therapeutic drugs in the future. Therefore, this review puts forward an overview of the role of PHB1 and its protective mechanism in liver diseases.

Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer.

Diallyl disulfide (DADS), a volatile component of garlic oil, has various biological properties, including antioxidant, antiangiogenic and anticancer effects. The present study aimed to explore novel targets of DADS that may slow or stop the progression of breast cancer. First, xenograft tumor models were created by subcutaneously injecting MCF-7 and MDA-MB-231 breast cancer cells into nude mice. Subsequently, western blot analysis was performed to investigate the expression of tristetraprolin (TTP), urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in the xenograft tumors, and cell cultures. Tablet cloning, Transwell and wound healing assays revealed that DADS treatment significantly inhibited the proliferation, invasion and migration of breast cancer cells. In addition, DADS treatment led to significant downregulation of uPA and MMP-9 protein expression, but significantly upregulated TTP expression in vivo and in vitro. Knocking down TTP expression using small interfering RNA reversed the aforementioned effects of DADS, which suggests TTP is a key target of DADS in inhibiting the progression of breast cancer.

Ibrolipim attenuates high glucose-induced endothelial dysfunction in cultured human umbilical vein endothelial cells via PI3K/Akt pathway.

OBJECTIVE: Endothelial dysfunction is a key event in the onset and progression of atherosclerosis associated with diabetes. Increasing cell apoptosis may lead to endothelial dysfunction and contribute to vascular complications. Therefore, we aimed to elucidate the possible role and mechanism of ibrolipim in preventing endothelial dysfunction induced by high glucose. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured respectively under normal glucose level (5.5mM), high glucose level (33mM), and high glucose level with ibrolipim treatment. Endothelial dysfunction was identified by the expression of ET-1 and vWF through reverse transcription PCR (RT-PCR). HUVECs apoptosis was assessed by fluorescent staining with Hoechst 33258. Akt activity was analyzed by western blot. RESULTS: High glucose condition significantly increased the rate of apoptotic cells, weakened cell viability, and decreased the expression of ET-1 and vWF. Ibrolipim treatment significantly attenuated these alterations of endothelial dysfunction. The lower concentrations (2, 4, 8 microM) of ibrolipim inhibited apoptosis of cultured HUVECs, improved cell viability, down-regulated the mRNA levels of ET-1, vWF, and attenuated the cytotoxicity; however, higher concentration (16, 32 microM) of ibrolipim aggravated the damage of HUVECs cultured under high glucose level. Meanwhile, high glucose induced a decrease of Akt activity which led to apoptosis, and ibrolipim prevented the decrease and attenuated apoptotic effect induced by high glucose. Furthermore, the PI3K inhibitor LY294002 significantly abolished the anti-apoptotic effect of ibrolipim, and decreased Akt phosphorylation. Although, the expression of Akt mRNA and total protein were not altered in cultured HUVECs. CONCLUSION: Ibrolipim at lower concentrations can inhibit high glucose-induced apoptosis in cultured HUVECs, which might be related to the alternation of Akt activity. Ibrolipim has the potential to attenuate endothelial dysfunction and lower the risk of diabetes-associated vascular diseases. And it might be a therapeutic agent for diabetic vascular complications.

[Study on antioxidant activity of pigment of Lycium ruthenicum].

OBJECTIVE: To elvaulate the antioxidant activity of the pigment of Lycium ruthenicum. METHOD: The antioxidant activities were measured by the effects of the reducing ability, scavenging DPPH. H2O2-induced hemolysis of mice erythrocyte, serum resistance of reactive oxygen species, content of MDA in liver tissue, and swelling effect of mitochondria in liver tissue. RESULT: The pigment of L. ruthenicum could scaveng DPPH* remarkably with IC50 0.164 mg x mL(-1), inhibitte hemolysis of mice erythrocyte evidently with IC50 0.112 mg x mL(-1). The resistant of reactive oxygen species was enhanced by the tested substances, simultanously. The concentration of MDA of peroxidation of lipid in mice liver could be reduced, and the swelling of mice liver mitochondria alse be restrained. CONCLUSION: The pigment of L. ruthenicum has antioxidant activity in tested concentration.

[Inhibitory effects of saponins from Tribulus terrestris on alpha-glucosidase in small intestines of rats].

OBJECTIVE: To determine the effects of saponins from Tribulus terrestris (STT) on small intestinal a-glucosidase and postprandial blood glucose levels in rats. METHOD: The inhibitory effects of STT on a-glucosidase extracted from small intestines in rats were carried out in vitro. The blood glucose levels were measured after 60 min when sucrose (2 g x kg(-1)) or glucose (2 g x kg(-1)) was administered orally with STT (100 mg x kg(-1)). After treated with STT (100 mg x kg(-1)) for 14 d, the activities of a-glucosidase were determined daily, as well as the postprandial blood glucose levels after oraly administered sucrose (2 g x kg(-1)). RESULT: STT at concentrations of 0.1, 1 and 10 mg x mL(-1) reduced significantly the activities of alpha-glucosidase with inhibitory rates of (20.83 +/- 1.66)%, (43.73 +/- 2.39)% and (52.62 +/- 2.69)%, respectively. In facts STT (100 mg x kg(-1)) considerably decreased the blood glucose levels which was 52.61% of that of the control in rats co-administered orally with sucrose (2 g x kg(-1)). However, it showed no such effect on the rats co-administered orally with glucose (2 g x kg(-1)). After orally administered of STT for 14 d, the activity of alpha-glucosidase was significantly reduced (P < 0.05) to (58.17 +/- 3.24)% of that those in control. Meanwhile, The rats were oral administered with sucrose, the increase of postprandial blood glucose levels were (69.50 +/- 4.28)% of that in control 60 min later ( P < 0.05). CONCLUSION: It was through inhibiting the activity of a-glucosidase in small intestines that STT significantly retarded the increase in postprandial blood glucose levels in rats.

The catecholamine-beta-adrenoreceptor-cAMP system and prediction of cardiovascular events in hypertension.

Although the importance of elevated circulating plasma catecholamines on cardiac structural and functional remodelling of hypertension is well documented, it is unclear whether the catecholamine-beta-adrenoreceptor (beta AR)-cAMP system can predict different cardiovascular events. 2. A total of 601 identified hypertensive patients with baseline and follow-up plasma levels of noradrenaline (NA) and adrenaline (Adr), lymphocyte beta AR density (B(max)) and intra-lymphocyte cAMP levels in peripheral blood (last examination 60+/-26 months apart) were followed up for an additional 24+/-12 months. 3. After the last follow up, a composite end-point of cardiovascular death, non-fatal myocardial infarction (MI) and stroke occurred in 139 patients (23.1%). In Cox analyses, adjusting for other standard factors as well as treatment effect, NA (hazard ratio 1.22; 95% confidence interval (CI) 1.17-1.28; P=0.0008), Adr (hazard ratio 1.53; 95% CI 1.18-2.00; P=0.002), beta AR (hazard ratio 1.12; 95% CI 1.06-1.17; P=0.007) and cAMP (hazard ratio 1.15; 95% CI 1.09-1.21; P=0.005) separately predicted cardiovascular mortality. Noradrenaline, Adr, beta AR and intra-lymphocyte cAMP separately predicted fatal/non-fatal MI; NA and Adr predicted fatal/non-fatal stroke, whereas B(max) and intra-lymphocyte cAMP levels were not a significant predictor of fatal/non-fatal stroke. When stratifying the study population by NA or Adr (median 4 nmol/L), B(max) (median 600 fmol/10(7) cells) and cAMP (median 5.0 pmol/mg protein) above and below the median values in both parameters categories, patients above the median had composite cardiovascular end-point (all P<0.001) and high cardiovascular death (all P<0.01, log-rank test). 4. These results suggest that plasma NA and Adr are significant predictors of cardiovascular mortality, MI and stroke. The B(max) and intra-lymphocyte cAMP levels are significant predictors of cardiovascular mortality and MI, but not stroke.

Cardiac risk stratification in patients with congestive heart failure: a catecholamines-beta-adrenoceptor-cAMP pathway.

OBJECTIVE: To investigate the stratification risk of catecholamines-beta-adrenoceptor (beta-AR)-cAMP pathway for cardiogenic death events in patients with congestive heart failure (CHF). METHODS: A total of 83 identified CHF patients with a baseline and follow-up plasma levels of norepinephrine (NE) and epinephrine (E), lymphocytes beta-AR density (Bmax), and intralymphocyte cAMP content in peripheral blood were followed up. Major cardiogenic death events were registered. RESULTS: The period between the initial entry and the last follow-up measurement were 51 +/- 16 months, the total duration of clinical follow-up after the last measurement were 14 +/- 8 months. During follow-up, 39 patients died of cardiogenic (sudden death 17 patients, worsening heart failure 22 patients). Persistence of high NE, E, and cAMP from baseline to follow-up were confirmed as risk predicting factors of cardiovascular events. Persistence NE above 4.0 nmol/L, E above 3.5 nmol/L, and the intralymphocyte cAMP content above 3.5 pmd x mg(-1) x pro(-1) from baseline to follow-up were significant adverse prognostic predictors. The major cardiogenic death events rates per 100 patients-years were 1.33 and 4.82 in patients with NE below and above 4.0 nmol/L (HR: 2.91; 95% CI: 1.08-7.33; P = 0.015); were 1.42 and 4.36 in the patients with E levels below and above 3.5 nmol/L (HR: 2.64; 95% CI: 1.02-6.41; P = 0.019); were 1.81 and 4.67 in the patients with the intralymphocyte cAMP content below and above 3.5 pmd x mg(-1) x pro(-1) (HR: 2.79; 95% CI: 1.04-6.83; P = 0.017), but difference was not significant between the beta-AR density below and above median. CONCLUSIONS: Persistent increase in circulating catecholamines and intralymphocyte cAMP content may increase the long-term mortality in CHF patients.