Phosphatidic acid interacts with an HD-ZIP transcription factor GhHOX4 to influence its function in fiber elongation of cotton (Gossypium hirsutum).

Upland cotton, the mainly cultivated cotton species in the world, provides over 90% of natural raw materials (fibers) for the textile industry. The development of cotton fibers that are unicellular and highly elongated trichomes on seeds is a delicate and complex process. However, the regulatory mechanism of fiber development is still largely unclear in detail. In this study, we report that a homeodomain-leucine zipper (HD-ZIP) IV transcription factor, GhHOX4, plays an important role in fiber elongation. Overexpression of GhHOX4 in cotton resulted in longer fibers, while GhHOX4-silenced transgenic cotton displayed a "shorter fiber" phenotype compared with wild type. GhHOX4 directly activates two target genes, GhEXLB1D and GhXTH2D, for promoting fiber elongation. On the other hand, phosphatidic acid (PA), which is associated with cell signaling and metabolism, interacts with GhHOX4 to hinder fiber elongation. The basic amino acids KR-R-R in START domain of GhHOX4 protein are essential for its binding to PA that could alter the nuclear localization of GhHOX4 protein, thereby suppressing the transcriptional regulation of GhHOX4 to downstream genes in the transition from fiber elongation to secondary cell wall (SCW) thickening during fiber development. Thus, our data revealed that GhHOX4 positively regulates fiber elongation, while PA may function in the phase transition from fiber elongation to SCW formation by negatively modulating GhHOX4 in cotton.

Association between leptin receptor polymorphisms and polycystic ovary syndrome risk: a meta-analysis based on 11 studies.

OBJECTIVE: Published evidence indicated that the leptin receptor (LEPR) gene polymorphisms are associated with polycystic ovary syndrome (PCOS) risk. However, studies on the association between the polymorphisms of LEPR gene are inconsistent or even controversial. MATERIAL AND METHODS: We conducted this meta-analysis to explore the more precise relationship between LEPR polymorphisms and PCOS risk. Relevant articles were searched with five online databases up to March 1 2023. Odds ratios (OR) with 95% confidence intervals (CI) were selected to examine the statistical strength of each genetic model. Moreover, RNA secondary structure and variant effects of these loci were examined with in silico analysis. RESULTS: Overall, 11 publications were analyzed, and the pooled results did not present any significant association between rs1137101 A/G polymorphism and PCOS risk in general population and some subgroup analysis. But the significant association were observed in Asian population (AG vs. AA: OR = 0.51, 95%CI = 0.32-0.81, p = .01, I2=0%; AG + GG vs. AA: OR = 0.41, 95%CI = 0.26-0.65, p < .01, I2=25.9%). Moreover, similar positive associations were also observed in rs1805096 polymorphism with PCOS risk. CONCLUSION: In summary, our meta-analysis suggested that the LEPR gene polymorphisms might be associated with PCOS susceptibility. Owing to the limited studies and small sample size in our meta-analysis, more well-designed studies from different races were needed to be conducted to verify the current results.

Instantaneous sap flow velocity simulation of Euonymus bungeanus based on neural network optimization model.

The sap flow of trees is complex and difficult to express with multivariate linear or empirical models. A simple and feasible method on the basis of understanding sap flow variation to simulate its variation with environmental factors is of special importance for quantitatively analyzing forest ecohydrological processes and regional water demand. In this study, with one of the shelter forest species Euonymus bungeanus in the east sandy land of Yellow River in Ningxia as the research object, we continuously measured the trunk sap flow velocity by thermal diffusion sap flow meter, and analyzed the effects of environmental factors on stem sap flow. We used the particle swarm optimization (PSO) and sparrow search algorithm (SSA) optimized neural network model to predict sap flow velocity of E. bungeanus. Results showed that the main environmental factors influencing sap flow were solar radiation, vapor pressure deficit, air temperature, and relative humidity, with the influencing importance of 32.5%, 25.3%, 22.0% and 16.1%, respectively. The response process between sap flow and environmental factors presented a hysteresis loop relationship. The optimized BP, Elman and ELM neural network models improved the comprehensive evaluation index (GPI) by 1.5%, 30.0% and 5.3%, respectively. Compared with the PSO-Elman and SSA-ELM optimization models, the SSA-BP optimization model had the best prediction results with an improvement of 1.0% and 23.2% in GPI, respectively. Therefore, the prediction results of the BP neural network model based on the sparrow search algorithm could be used as an optimal model for predicting instantaneous sap flow velocity of E. bungeanus.

Application value of tumor necrosis factor inhibitors in in vitro fertilization-embryo transfer in infertile women with polycystic ovary syndrome.

BACKGROUND: Clinical value of tumor necrosis factor (TNF) inhibitors in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with polycystic ovary syndrome (PCOS) was investigated in this study. METHODS: A retrospective analysis was performed on the clinical data of 100 PCOS patients who received IVF-ET for the first time at Hebei Institute of reproductive health science and technology from January 2010 to June 2020. The patients were divided into Inhibitor group and Control group according to whether they were treated with or without TNF inhibitors. Next, the two groups were subject to comparison in terms of the days of gonadotropin (Gn) use, total dosage of Gn, trigger time, hormone level and endometrial condition on the day of human chorionic gonadotropin (HCG) injection, the effects of two different regimens on controlled ovarian hyperstimulation (COH) and pregnancy outcomes. RESULTS: There were no significant differences in baseline characteristics between the two groups, including age, duration of infertility, body mass index (BMI), ovarian volume, antral follicle count, and basal hormone levels. Compared with the Control group, the days of Gn use and trigger time of patients in the Inhibitor group were significantly shortened, and the total Gn dosage was notably reduced. In terms of sex hormone levels on the HCG injection, the Inhibitor group displayed much lower serum estradiol levels while higher serum luteinizing hormone and progesterone (P) levels than the Control group. Notably, the high-quality embryo rate was also significantly increased with the use of TNF inhibitors. However, significant differences were not observed in endometrial thickness (on the day of HCG injection), proportion of endometrial A, B and C morphology (on the day of HCG injection), cycle cancellation rate, number of oocytes retrieved, fertilization rate, and cleavage rate between the two groups. Importantly, the clinical pregnancy rate in the Inhibitor group was significantly higher than that in the Control group, but there was no significant difference in the biochemical pregnancy rate, early abortion rate, multiple birth rate, ectopic pregnancy rate and number of live births between the two groups. CONCLUSION: Collectively, after application of TNF-α inhibitor regimen, superior overall treatment effect can be observed in infertile PCOS patients receiving IVF-ET. Therefore, TNF inhibitors have certain application value in IVF-ET in infertile women with PCOS.

C(sp3)-H Alkenylation of Tetrahydroisoquinolines via Merging Electrochemistry and Organocatalysis.

C(sp3)-H alkenylation of tetrahydroisoquinoline by merging Shono oxidation and the Morita-Baylis-Hillman reaction is developed, employing 4-dimethylaminopyridine as an organocatalyst and TEMPO/NaBr as an electrocatalyst. The reaction proceeds via the interception of an iminium cation intermediate, which is generated in situ from anodic oxidation, leading to aza-Morita-Baylis-Hillman reaction products. Additionally, the use of TEMPO and NaBr as mediators is crucial to avoid the decomposition of products by lowering the oxidation potential of the reaction.

Clinical characteristics of a patient with de novo acute promyelocytic leukemia with JAK2 v617f mutation.

BACKGROUND: The V617F mutation of Janus-associated kinase 2 (JAK2) is common in myeloproliferative neoplasms (MPN). JAK2 V617F mutation can be detected in patients with de novo acute myeloid leukemia (AML), but de novo acute promyelocytic leukemia (APL) with JAK2 V617F mutation is rare. CASE PRESENTATION: We report a case of APL with both the t(15;17) translocation as well as the JAK2 V617F mutation that transformed into MPN (PV/ET). CONCLUSIONS: A de novo APL patient presented initially with JAK2 V617F. After ATRA and ATO dual induction and chemotherapy consolidation, the patient achieved complete remission (CR) with undetectable PML/RARα. However, the JAK2 V617F remained positive, and the patient developed MPN (PV/ET) 22 months later, which responded well to interferon therapy.AML, acute myeloid leukemia; APL, acute promyelocytic leukemia; ATRA, all-trans retinoic acid; ATO, arsenic trioxide; BM, bone marrow; CR, complete remission; ET, essential thrombocythemia; Hb, hemoglobin; JAK2, Janus-associated kinase 2; MPN, myeloproliferative neoplasms; PLT, platelets; PMF, primary myelofibrosis; PML/RARα; PV, polycythemia vera; WBC, white blood cells.

[Proteomics of serum exosomes in children in the acute stage of Kawasaki disease: a prospective study]. / æ€¥æ€§æœŸå·å´Žç— æ‚£å„¿è¡€æ¸ å¤–æ³Œä½“è›‹ç™½è´¨ç»„å­¦çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the biological processes and functions of serum exosomes in children in the acute stage of Kawasaki disease (KD), so as to provide new biomarkers for the early diagnosis of KD. METHODS: In this prospective study, 13 children with KD who were treated in Children's Hospital of Soochow University from June 2019 to August 2020 were enrolled as the KD group, and 13 children who were hospitalized due to bacterial infection during the same period were enrolled as the control group. Whole blood was collected on the next morning after admission, serum samples were obtained by centrifugation, and exosomes were extracted through ultracentrifugation. Serum exosomes were analyzed by label-free quantitative proteomics, and differentially expressed proteins (DEPs) were screened out for functional enrichment analysis. A protein-protein interaction (PPI) network was plotted, and unique proteins were validated by targeted proteomics. RESULTS: A total of 131 DEPs were screened out for the two groups, among which 27 proteins were detected in both groups. There were 48 unique DEPs in the KD group, among which 23 were upregulated and 25 were downregulated, and these proteins acted on "complement and coagulation cascades" and "the MAPK signaling pathway". Validation by targeted proteomics showed that FGG, SERPING1, C1R, C1QA, IGHG4, and C1QC proteins were quantifiable in the KD group. A total of 29 proteins were only expressed in the control group, among which 12 were upregulated and 17 were downregulated. Four proteins were quantifiable based on targeted proteomics, i.e., VWF, ECM1, F13A1, and TTR. A PPI network was plotted for each group. In the KD group, FGG and C1QC had close interaction with other proteins, while in the control group, VWF had close interaction with other proteins. CONCLUSIONS: The serum exosomes FGG and C1QC in children in the acute stage of KD are expected to become the biomarkers for the early diagnosis of KD. For children with unexplained fever, detection of FGG, C1QC1, and VWF may help with etiological screening.

[Anti-inflammation mechanism of electro-scalp acupuncture in treatment of ischemic stroke based on IL-12 mediated JAK/STAT signaling pathway].

OBJECTIVE: To observe the impact of electro-scalp acupuncture (ESA) on the neural function and inflammatory response of ischemic cortex in the model rats with ischemic stroke and explore the anti-inflammation mechanism of ESA in treatment of ischemic stroke from the perspective of modulating the interleukin 12 (IL-12) mediated JAK (Janus kinase)/STAT (signal transduction and transcription activator) signal pathway. METHODS: Ninety male SD rats were randomized into a normal group (n =16) and a model preparation group (n=74). In the model preparation group, the model of middle cerebral artery occlusion (MCAO) was duplicated with suture-occlusion method. After modeled successfully, 48 rats with neurological deficit score of 1-3 were divided into a model group, an inhibitor group and an ESA group, 16 rats in each one. In the inhibitor group, IL-12 inhibitor (apilimod, 5 mg/kg) was used via intragastric administration. In the ESA group, the anterior oblique line of vertex-temporal (MS6) was stimulated bilaterally with electric acupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 1 mA in current intensity. The needles were retained for 30 min. The treatment was given once daily and for 7 days in above two intervention groups. Before and after intervention, the neurological deficit score (NDS) and neurobehavioral score (NBS) were assessed in each group. HE staining method was adopted to observe the morphological manifestations of ischemic cortical lesion; the concentrations of IL-12 and IL-12R of the brain tissue in the ischemic cortical lesion were measured by enzyme-linked immunosorbent assay (ELISA); the mRNA expression levels of STAT4 and Tbx21 were detected by real-time PCR technique; and the protein expression of IL-2, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-4 were detected using immunohistochemistry. RESULTS: NDS and NBS in the model group, the inhibitor group and the ESA group were all higher than those in the normal group before intervention (P<0.01). After intervention, NDS and NBS in the model group were higher than the normal group (P<0.01); the two scores were all reduced when compared with those before intervention in the inhibitor group and the ESA group (P<0.01), and lower than those of the model group (P<0.01). NDS in the ESA group was lower than the inhibitor group (P<0.05). In the model group, the cells were shrunk and vacuolated in the ischemic cortical lesion. Many normal cells were visible in the ESA group and the inhibitor group. Compared with the normal group, the concentrations of IL-12 and IL-12R , the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ in brain tissue of ischemic cortical lesion were all increased in the model group (P<0.01), while the protein expression level of IL-4 decreased (P<0.01). The concentrations of IL-12 and IL-12R, the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ were all reduced (P<0.01), while the protein expression level of IL-4 increased (P<0.01) in the ESA group and the inhibitor group when compared with the model group. The concentration of IL-12, the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ in the ESA group were all higher than those of the inhibitor group (P<0.05); while the concentration of IL-12R and the protein expression level of IL-4 were lower than the inhibitor group (P<0.05). CONCLUSION: Electro-scalp acupuncture may improve the neurological function of the rats with ischemic stroke. The modulation to IL-12 mediated JAK/STAT signaling pathway is the potential molecular mechanism of this therapy for the inflammatory response in ischemic cortical lesion.

9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice.

Atherosclerotic cardiovascular disease is a common and severe complication of diabetes. There is a large need to identify the effective and safety strategies on diabetic cardiovascular disease (DCVD). 9-PAHSA is a novel endogenous fatty acid, and has been reported to reduce blood glucose levels and attenuate inflammation. We aim to evaluate the effects of 9-PAHSA on DCVD and investigate the possible mechanisms underlying it. Firstly, serum 9-PAHSA levels in human were detected by HPLC-MS/MS analysis. Then 9-PAHSA was synthesized and purified. The synthesized 9-PAHSA was gavaged to db/db mice with 50 mg/kg for 4 weeks. The carotid arterial plaque and cardiac structure was assessed by ultrasound. Cardiac autophagy was tested by western blot analysis, electron microscope and iTRAQ. The results showed that 9-PAHSA, in patients with type 2 diabetes mellitus (T2DM), was significantly lower than that in non-diabetic subjects. Administration of 9-PAHSA for 2 weeks reduced blood glucose levels. Ultrasound observed that continue administration of 9-PAHSA for 4 weeks ameliorated carotid vascular calcification, and attenuated myocardial hypertrophy and dysfunction in db/db mice. Electron microscopy showed continue 9-PAHSA treatment significantly increased autolysosomes, while dramatically decreased greases in the myocardial cells of the db/db mice. Moreover, iTRAQ analysis exhibited that continue 9-PAHSA treatment upregulated BAG3 and HSPB8. Furthermore, western blot analysis confirmed that 9-PAHSA down-regulated Akt/mTOR and activated PI3KIII/BECN1 complex in diabetic myocardium. Thus, 9-PAHSA benefits DCVD in diabetic mice by ameliorating carotid vascular calcification, promoting autophagic flux and reducing myocardial hypertrophy.

Durable Cord Blood Cell Engraftment in a Patient with Severe Aplastic Anemia after a Matched Sibling Bone Marrow Transplantation and an Unrelated Cord Blood Transplantation.

OBJECTIVE: Severe aplastic anemia (SAA) is a fatal bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a matched sibling donor is the first-line treatment for older SAA patients. However, the number of CD34+ cells collected from a matched donor is often lower than expected. To overcome the problem, this study was conducted to combine a matched sibling donor with an unrelated cord blood transplantation for the treatment of a patient with SAA. CASE REPORT: A 45-year-old male patient with SAA was treated with a sibling-matched allo-HSCT. Due to the low amount of donor CD34+ cells, an unrelated umbilical cord blood stem cell transplantation (UCBT) with 9/10 HLA matching was subsequently carried out. Successful hematopoietic reconstitution was achieved by the dual transplantation. Unexpectedly, beginning in the fourth month after transplantation, the sibling donor chimerism was transformed to a stable and complete UCB source. CONCLUSION: This study provides evidence that UCB-derived HSCs have a higher capacity for hematopoietic reconstitution, suggesting that UCB plus an HLA-matched sibling donor is a good alternative for older patients with SAA.

Phosphorylation of WRKY16 by MPK3-1 is essential for its transcriptional activity during fiber initiation and elongation in cotton (Gossypium hirsutum).

Cotton, one of the most important crops in the world, produces natural fiber materials for the textile industry. WRKY transcription factors play important roles in plant development and stress responses. However, little is known about whether and how WRKY transcription factors regulate fiber development of cotton so far. In this study, we show that a fiber-preferential WRKY transcription factor, GhWRKY16, positively regulates fiber initiation and elongation. GhWRKY16-silenced transgenic cotton displayed a remarkably reduced number of fiber protrusions on the ovule and shorter fibers compared to the wild-type. During early fiber development, GhWRKY16 directly binds to the promoters of GhHOX3, GhMYB109, GhCesA6D-D11, and GhMYB25 to induce their expression, thereby promoting fiber initiation and elongation. Moreover, GhWRKY16 is phosphorylated by the mitogen-activated protein kinase GhMPK3-1 at residues T-130 and S-260. Phosphorylated GhWRKY16 directly activates the transcription of GhMYB25, GhHOX3, GhMYB109, and GhCesA6D-D11 for early fiber development. Thus, our data demonstrate that GhWRKY16 plays a crucial role in fiber initiation and elongation, and that GhWRKY16 phosphorylation by GhMPK3-1 is essential for the transcriptional activation on downstream genes during the fiber development of cotton.

An Insight of the First Community Infected COVID-19 Patient in Beijing by Imported Case: Role of Deep Learning-Assisted CT Diagnosis.

In the era of coronavirus disease 2019 (COVID-19) pandemic, imported COVID-19 cases pose great challenges to many countries. Chest CT examination is considered to be complementary to nucleic acid test for COVID-19 detection and diagnosis. We report the first community infected COVID-19 patient by an imported case in Beijing, which manifested as nodular lesions on chest CT imaging at the early stage. Deep Learning (DL)-based diagnostic systems quantitatively monitored the progress of pulmonary lesions in 6 days and timely made alert for suspected pneumonia, so that prompt medical isolation was taken. The patient was confirmed as COVID-19 case after nucleic acid test, for which the community transmission was prevented timely. The roles of DL-assisted diagnosis in helping radiologists screening suspected COVID cases were discussed.

Corrigendum: 9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice.

[This corrects the article DOI: 10.3389/fphar.2021.754387.].

Porphyromonas gingivalis-Induced NLRP3 Inflammasome Activation and Its Downstream Interleukin-1ß Release Depend on Caspase-4.

Background: Oral commensals contribute to microbe-host symbiosis in periodontal homeostasis, and Porphyromonas gingivalis (P. gingivalis) as the keystone pathogen critically accounts for the shift of symbiosis to dysbiosis and periodontal destruction. Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome-mediated interleukin-1ß (IL-1ß) is significantly involved in periodontal diseases, and notably P. gingivalis enables to modulate the induction and expression of NLRP3. Whereas, the exact mechanism by which NLRP3 inflammasome is regulated in response to commensal and pathogenic bacteria remains unclear. Methods: To examine the expression of IL-1ß and NLRPs inflammasome in tissues with severe chronic periodontitis, and further investigate how Caspase-4-dependent non-canonical NLRP3 inflammasome pathways functioned during the interactions of Streptococcus mitis (S. mitis) and P. gingivalis with human THP-1 cells. Results: IL-1ß and NLRP3, NLRP6, NLRP12, and absent in melanoma 2 (AIM2) inflammasomes are highly expressed in gingival tissues with severe chronic periodontitis. In human THP-1 cells, P. gingivalis activates the synthesis and secretion of IL-1ß to higher levels than S. mitis. Importantly, NLRP3-, Caspase-1-, and Caspase-4-siRNA knockdown THP-1 cells treated with P. gingivalis exhibited a lower expression level of IL-1ß as compared to the control cells. In addition, silencing of either CASP4 or CASP1 can lead to a concurrent or reciprocal decrease in the expression of the other. Of note, the IL-1ß induction is not affected in the S. mitis-treated THP-1 cells with the silence of NLRP3, Caspase-1, and Caspase-4 genes. Conclusion: NLRP3/Caspase-4 and NLRP3/Caspase-1 dependent IL-1ß production may crucially contribute to the dysregulated immuno-inflammatory response in periodontal pathogenesis.

Development of a 67.8 W, 2.5 ps ultrafast chirped-pulse amplification system based on single-crystal fiber amplifiers.

We demonstrate a high-power, high-energy chirped-pulse amplification (CPA) system based on three Yb:YAG amplifiers and a chirped-volume Bragg grating (CVBG). With an all-fiber laser as the seed light, a Yb:YAG rod amplifier and two Yb:YAG single-crystal fiber (SCF) amplifiers as the amplification stages, a laser power of 96 W at 200 kHz repetition rate corresponding to a pulse energy of 0.48 mJ has been generated. The stability of different output power has been measured and compared. To the best of our knowledge, this is the first report on a stable 100 W-level laser with sub-mJ pulse energy based on SCF. The beam quality M2 of different output lasers has also been measured, which is below 1.55 when the output power is 92 W. The amplified laser is seeded into the CVBG to be compressed, and a compression efficiency of 0.724 has been obtained with an output power of 67.8 W and pulse duration of 2.5 ps. The ultrafast CPA system delivering high pulse energy (sub-mJ) with hundreds of kHz repetition rate is expected to be used as the driving source of high-flux high-harmonic generation after further compression.

Pollen-Specific Protein PSP231 Activates Callose Synthesis to Govern Male Gametogenesis and Pollen Germination.

Spatiotemporally regulated callose deposition is an essential, genetically programmed phenomenon that promotes pollen development and functionality. Severe male infertility is associated with deficient callose biosynthesis, highlighting the significance of intact callose deposition in male gametogenesis. The molecular mechanism that regulates the crucial role of callose in production of functional male gametophytes remains completely unexplored. Here, we provide evidence that the gradual upregulation of a previously uncharacterized cotton (Gossypium hirsutum) pollen-specific SKS-like protein (PSP231), specifically at the post pollen-mitosis stage, activates callose biosynthesis to promote pollen maturation. Aberrant PSP231 expression levels caused by either silencing or overexpression resulted in late pollen developmental abnormalities and male infertility phenotypes in a dose-dependent manner, highlighting the importance of fine-tuned PSP231 expression. Mechanistic analyses revealed that PSP231 plays a central role in triggering and fine-tuning the callose synthesis and deposition required for pollen development. Specifically, PSP231 protein sequesters the cellular pool of RNA-binding protein GhRBPL1 to destabilize GhWRKY15 mRNAs, turning off GhWRKY15-mediated transcriptional repression of GhCalS4/GhCalS8 and thus activating callose biosynthesis in pollen. This study showed that PSP231 is a key molecular switch that activates the molecular circuit controlling callose deposition toward pollen maturation and functionality and thereby safeguards agricultural crops against male infertility.

Genome-wide identification of the mitogen-activated protein kinase (MAPK) family in cotton (Gossypium hirsutum) reveals GhMPK6 involved in fiber elongation.

Mitogen-activated protein kinases (MAPKs) are important in regulating plant development as well as stress response. In this study, we genome-widely identified 56 MAPK genes in upland cotton. These MAPK genes unequally distribute on 22 chromosomes of cotton genome, but no MAPK gene is located on At_Chr6, Dt_Chr6, At_Chr13 and Dt_Chr13. The exons and introns in GhMAPK gene family vary widely at the position, number and length. Furthermore, GhMAPK family can be divided into 4 groups (A, B, C and D), and the TEY type of T-loop exists in three groups (A, B and C), but the TDY type of T-loop is only in group D. Further study revealed that some GhMAPK genes (including GhMPK6) are preferentially expressed in elongating fibers. GhMPK6 maintains a high phosphorylation level in elongating fibers, and its phosphorylation was enhanced in fibers by phytohormones brassinosteroid (BR), ethylene and indole-3-acetic acid (IAA). Additionally, GhMPK6 could interact with GhMKK2-2 and GhMKK4, suggesting that GhMKK2-2/4-GhMPK6 module may be involved in phosphorylation of its downstream proteins for regulating fiber elongation of cotton.

Somatic and germline mutations in the tumor suppressor gene PARK2 impair PINK1/Parkin-mediated mitophagy in lung cancer cells.

PARK2, which encodes Parkin, is a disease-causing gene for both neurodegenerative disorders and cancer. Parkin can function as a neuroprotector that plays a crucial role in the regulation of mitophagy, and germline mutations in PARK2 are associated with Parkinson's disease (PD). Intriguingly, recent studies suggest that Parkin can also function as a tumor suppressor and that somatic and germline mutations in PARK2 are associated with various human cancers, including lung cancer. However, it is presently unknown how the tumor suppressor activity of Parkin is affected by these mutations and whether it is associated with mitophagy. Herein, we show that wild-type (WT) Parkin can rapidly translocate onto mitochondria following mitochondrial damage and that Parkin promotes mitophagic clearance of mitochondria in lung cancer cells. However, lung cancer-linked mutations inhibit the mitochondrial translocation and ubiquitin-associated activity of Parkin. Among all lung cancer-linked mutants that we tested, A46T Parkin failed to translocate onto mitochondria and could not recruit downstream mitophagic regulators, including optineurin (OPTN) and TFEB, whereas N254S and R275W Parkin displayed slower mitochondrial translocation than WT Parkin. Moreover, we found that deferiprone (DFP), an iron chelator that can induce mitophagy, greatly increased the death of A46T Parkin-expressing lung cancer cells. Taken together, our results reveal a novel mitophagic mechanism in lung cancer, suggesting that lung cancer-linked mutations in PARK2 are associated with impaired mitophagy and identifying DFP as a novel therapeutic agent for PARK2-linked lung cancer and possibly other types of cancers driven by mitophagic dysregulation.

A basic helix-loop-helix protein (GhFP1) promotes fibre elongation of cotton (Gossypium hirsutum) by modulating brassinosteroid biosynthesis and signalling.

Basic helix-loop-helix (bHLH) proteins are involved in transcriptional networks controlling a number of biological processes in plants. However, little information is known on the roles of bHLH proteins in cotton fibre development so far. Here, we show that a cotton bHLH protein (GhFP1) positively regulates fibre elongation. GhFP1 transgenic cotton and Arabidopsis plants were generated to study how GhFP1 regulates fibre cell elongation. Fibre length of the transgenic cotton overexpressing GhFP1 was significantly longer than that of wild-type, whereas suppression of GhFP1 expression hindered fibre elongation. Furthermore, overexpression of GhFP1 in Arabidopsis promoted trichome development. Expression of the brassinosteroid (BR)-related genes was markedly upregulated in fibres of GhFP1 overexpression cotton, but downregulated in GhFP1-silenced fibres. BR content in the transgenic fibres was significantly altered, relative to that in wild-type. Moreover, GhFP1 protein could directly bind to the promoters of GhDWF4 and GhCPD to activate expression of these BR-related genes. Therefore, our data suggest that GhFP1 as a positive regulator participates in controlling fibre elongation by activating BR biosynthesis and signalling. Additionally, homodimerisation of GhFP1 may be essential for its function, and interaction between GhFP1 and other cotton bHLH proteins may interfere with its DNA-binding activity.

A cotton (Gossypium hirsutum) WRKY transcription factor (GhWRKY22) participates in regulating anther/pollen development.

Anther/pollen development is a highly programmed process in flowering plants. However, the molecular mechanism of regulating anther/pollen development is still largely unclear so far. Here, we report a cotton WRKY transcription factor (GhWRKY22) that functions in anther/pollen development. Quantitative RT-PCR and GUS activity analyses revealed that GhWRKY22 is predominantly expressed in the late developing anther/pollen of cotton. The transgenic Arabidopsis plants expressing GhWRKY22 displayed the male fertility defect with the fewer viable pollen grains. Expression of the genes involved in jasmonate (JA) biosynthesis was up-regulated, whereas expression of the JA-repressors (JAZ1 and JAZ8) was down-regulated in the transgenic Arabidopsis plants expressing GhWRKY22, compared with those in wild type. Yeast one-hybrid and ChIP-qPCR assays demonstrated that GhWRKY22 modulated the expression of JAZ genes by directly binding to their promoters for regulating anther/pollen development. Yeast two-hybrid assay indicated that GhMYB24 could interact with GhJAZ8-A and GhJAZ13-A. Furthermore, expression of AtMYB24, AtPAL2 and AtANS2 was enhanced in the transgenic Arabidopsis plants, owing to GhWRKY22 overexpression. Taking the data together, our results suggest that GhWRKY22 acts as a transcriptional repressor to regulate anther/pollen development possibly by modulating the expression of the JAZ genes.