Association of DOK3 and infiltrated tumor-associated macrophages with risk for the prognosis of Porphyromonas gingivalis-infected oral cancer: a 12-year data analysis of 200 patients from a tertiary teaching hospital, Urumqi, China.

BACKGROUND: While there is an understanding of the association between the expression of Porphyromonas gingivalis (P. gingivalis) and prognosis of oral squamous cell carcinoma (OSCC), significance specially to address the relevance between different immunohistochemical intensities of P. gingivalis and tumor-associated macrophages (TAMs) in OSCC tissue and related clinicopathologic characteristics has not been well investigated. The present study aimed to investigate the pathological features related to M2-TAM in P. gingivalis-infected OSCC and ascertain its clinical relevance with patients' prognosis. METHODS: A prospective cohort study was designed to comparatively analyze 200 patients from June 2008 to June 2020. Bioinformatics analyses were implemented to identify DOK3 as a key molecule and to appraise immunocyte infiltration using Gene Expression Omnibus and The Cancer Genome Atlas databases. Immunohistochemical evaluation was performed to analyze the association between the expression levels of P. gingivalis, DOK3, and M2-TAM and clinicopathological variables using Fisher's exact test or Pearson's chi-square test. Cox analysis was used to calculate hazard ratios (HR) with corresponding 95% confidence interval (CI) for various clinicopathological features. The Kaplan-Meier approach and log-rank test were used to plot the survival curves. RESULTS: The expression level of P. gingivalis was positively associated with DOK3 and M2-TAMs expression level (P < 0.001). Parameters, including body mass index, clinical stage, recurrence, tumor differentiation, and P. gingivalis, DOK3, and M2-TAM immunoexpression levels, affected the prognosis of patients with OSCC (all P < 0.05). In addition, P. gingivalis (HR = 1.674, 95%CI 1.216-4.142, P = 0.012), DOK3 (HR = 1.881, 95%CI 1.433-3.457, P = 0.042), and M2-TAM (HR = 1.649, 95%CI 0.824-3.082, P = 0.034) were significantly associated with the 10-year cumulative survival rate. CONCLUSIONS: Elevated expression of P. gingivalis and DOK3 indicates M2-TAM infiltration and unfavorable prognosis of OSCC, and could be considered as three novel independent risk factors for predicting the prognosis of OSCC.

Contribution of body mass index, waist circumference, and 25-OH-D3 on the risk of pre-diabetes mellitus in the Chinese population.

This study aimed to investigate the associations between body mass index (BMI), waist circumference (WC), 25-hydroxy-vitamin D3 (25-OH-D3), and the risk of pre-diabetes mellitus (PDM), as well as their predictive values in identifying PDM. A total of 1688 participants were included in this cross-sectional investigation. Spearman's correlation analysis was used to assess the relationships between candidate indicators and PDM. The impact of indicators on PDM risk was determined by multivariate logistic regression. The receiver operating characteristic (ROC) analysis was performed to evaluate the prognostic value of indicators. Our study indicated a positive correlation between WC, BMI, and 25-OH-D3 and PDM. WC (OR = 1.05, 95% CI = 1.04-1.06, p < 0.001), BMI (OR = 1.11, 95% CI = 1.08-1.15, p < 0.001), and 25-OH-D3 (OR = 1.01, 95% CI = 1.00-1.02, p = 0.037) and an increased risk of PDM. Additionally, the ROC analysis demonstrated that WC (AUC = 0.651, Specificity = 55.00%, Sensitivity = 67.900%) had a higher diagnostic value for predicting PDM compared to the other variables (BMI, 25-OH-D3, TG, TC, LDL-C, HDL-C, and UA). A cut-off value of WC > 80.5 cm predicted PDM with both good sensitivity and specificity. Additionally, the cut-off value of waist circumference (WC) for men with prediabetes was 86.500, while for women with prediabetes, it was 76.500.

Undergoing Lung Surgery (PSA-Lung) was appropriate for symptom assessment after discharge.

PURPOSE: To examine whether a 7-day or 24-h recall period of Perioperative Symptom Assessment for Patients Undergoing Lung Surgery (PSA-Lung) was appropriate for symptom assessment after discharge. METHODS: A total of 377 patients were recruited in a cohort study of patients who underwent lung surgery. We measured patient symptoms daily and weekly using the two recall period versions of the PSA-Lung scale, respectively. The psychometric properties of both versions were calculated. Spearman rank correlation coefficients and kappa (k) coefficients were used to measure the association between items score measured by the two version scales each week. Cohen's d effect size and mixed linear model were used to measure responsiveness to change over time. RESULTS: Spearman rank correlation coefficients between the symptom scores generated by the 7-day and 24-h versions (range 0.48-0.77; all P < 0.05). The correlations increased in patients in stable condition (weekly symptom change < 2). Cronbach's α coefficients for both ratings were > 0.87 and both had good test-retest reliability. The longitudinal analysis and Cohen's d effect sizes showed that both ratings had good ability to detect changes in all items. CONCLUSION: The 7-day retrospective scale was as effective as the 24-h retrospective scale in terms of psychometric performance. In the stage where the patient's symptoms change rapidly, it is recommended to use the 24-h retrospective scale for symptom monitoring. On the contrary, in a stable state, it can be considered to use the 7-day retrospective scale for monitoring to reduce the patient's burden.

Achieving NPVR ≥ 80% as technical success of high-intensity focused ultrasound ablation for uterine fibroids: a cohort study.

OBJECTIVE: To report the long-term re-intervention of patients with uterine fibroids after ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation and to analyse the influencing factors of re-intervention in patients in the NPVR ≥ 80% group. MATERIALS AND METHODS: Patients with a single uterine fibroid who underwent USgHIFU at our hospital from January 2012 to December 2019 were enrolled. The patients were divided into four groups according to different nonperfusion volume ratio (NPVR). Kaplan-Meier survival curve was used to analyse long-term re-intervention in different NPVR groups, and Cox regression was used to analyse the influencing factors of re-intervention in the NPVR ≥ 80% group. MAIN RESULTS: A total of 1,257 patients were enrolled, of whom 920 were successfully followed up. The median follow-up time was 88 months, and the median NPVR was 85.0%. The cumulative re-intervention rates at 1, 3, 5, 8 and 10 years after USgHIFU were 3.4%, 11.8%, 16.8%, 22.6% and 24.1%, respectively. The 10-year cumulative re-intervention rate was 37.3% in the NPVR < 70% group, 31.0% in the NPVR 70-79% group, 18.2% in the NPVR 80-89% group and 17.8% in the NPVR ≥ 90% group (P < 0.05). However, no difference was found between the group of NPVR 80-89% and the group of NPVR ≥ 90% (P = 0.499). Age of patients and signal intensity on T2-weighted imaging (T2WI) of tumours were found to be independent risk factors for long-term re-intervention in the NPVR ≥ 80% group. A younger age and greater signal intensity on T2W images corresponded to a greater risk of re-intervention. CONCLUSION: USgHIFU, an alternative treatment for uterine fibroids, has reliable long-term efficacy. NPVR ≥ 80% can be used as a sign of technical success, which can reduce re-intervention rates. However, an important step is to communicate with patients in combination with the age of patients and the signal intensity on T2WI of fibroids. TRIAL REGISTRATION: This retrospective study was approved by the ethics committee at our institution (Registration No. HF2023001; Date: 06/04/2023). The Chinese Clinical Trial Registry provided full approval for the study protocol (Registration No. CHiCTR2300074797; Date: 16/08/2023).

Circulating microRNA-33b levels are associated with the presence and severity of coronary heart disease.

MicroRNA-33b (miR-33b) affected various biological pathways in regulating cholesterol homeostasis which may link to the pathogenesis of atherosclerotic lesions. However, whether this marker is associated with the presence and severity of coronary heart disease (CHD) is undetermined. We aim to explore the diagnostic value of circulating miR-33b level in the presence and severity of CHD. Altogether 320 patients were enrolled, including 240 patients diagnosed with CHD while 80 were classified as controls after CAG examination. Circulating miR-33b level was analyzed in all subjects, the Gensini score was calculated to assess the severity of stenotic lesions. The association between miR-33b and the presence and severity of CHD was analyzed, and the diagnostic potential of miR-33b of CHD was performed by the receiver operating characteristic (ROC) analysis. The CHD group had higher miR-33b levels (p < 0.001), and the miR-33b content significantly elevated following an increasing Gensini score (p for trend < 0.001). After adjustments for potential risk factors, such as several blood lipid markers, miR-33b remained a significant determinant for CHD (p < 0.001). ROC analysis disclosed that the AUC was 0.931. The optimal cutoff value of miR-33b was with a sensitivity of 81.3% and a specificity of 98.7% in differentiating CHD. It can prognosticate that the higher level of miR-33b was linked to increased severity of disease in CHD patients. Thus, the application of this marker might assist in the diagnosis and classification of CHD patients. Nevertheless, additional studies with larger sample sizes will be required to verify these results.

Factors influencing USgHIFU ablation for adenomyosis with NPVR ≥ 50.

OBJECTIVE: To investigate the influencing factors of ultrasound-guided HIFU (USgHIFU) ablation for adenomyosis with a non-perfused volume ratio (NPVR)≥50%. METHODS: A total of 299 patients with adenomyosis who underwent USgHIFU ablation were enrolled. Quantitative signal intensity (SI) analysis was performed on T2WI and dynamic enhancement type. The energy efficiency factor (EEF) was defined as the ultrasound energy delivered for ablating 1 mm3 of tissue. NPVR ≥ 50% was used as the criterion for technical success. Adverse effects and complications were recorded. Logistic regression analyses of variables were conducted to identify the factors affecting NPVR ≥ 50%. RESULTS: The median NPVR was 53.5% (34.7%). There were 159 cases in the NPVR ≥ 50% group and 140 cases in the NPVR < 50% group. The EEF in NPVR < 50.0% group was significantly higher than that in NPVR ≥ 50% group (p < 0.05). The incidence of intraoperative adverse effects and postoperative adverse events in the NPVR < 50% group were higher than those in the NPVR ≥ 50% group (p < 0.05 for both). Logistic regression analysis showed that abdominal wall thickness, SI difference on T2WI between adenomyosis and rectus abdominis, and enhancement type on T1WI were protective factors for NPVR ≥ 50% (p < 0.05), while the history of childbirth was an independent risk factor (p < 0.001). CONCLUSIONS: Compared with NPVR < 50%, NPVR ≥ 50% did not increase the intraprocedural and postprocedural adverse reactions. The possibility of NPVR ≥ 50% was higher in patients with thinner abdominal walls, showed slight enhancement of adenomyosis on T1WI, with a history of childbirth, or in whom the SI difference on T2WI between adenomyosis and rectus abdominis was more minor.

Duplicated adrenal veins in primary aldosteronism misdiagnosed with ectopic aldosteronoma due to apparent bilateral aldosterone suppression.

BACKGROUND: Primary aldosteronism (PA) is considered the number one aetiology for secondary hypertension. Apart from confirmatory tests and localisation of PA determined by computed tomography (CT), adrenal venous sampling (AVS) is used to define whether aldosterone hypersecretion occurs inside one or both adrenal glands. However, even correctly-performed AVS may lead to undiagnostic results such as apparent bilateral adrenal suppression (apparent bilateral aldosterone suppression), in which the adrenal aldosterone-to-cortisol ratios (AC ratios) are decreased bilaterally compared to the peripheral blood sample, with several causes contributing to it. CASE DESCRIPTION: Here, we describe the case of a 48-year-old man who was referred to our department for further investigation with a history of refractory hypertension, hypokalaemia, and aortic dissection. His hypertension and hypokalaemia were initially attributed to ectopic aldosteronoma due to his adrenal CT scan and AVS results. However, the correct diagnosis of an adenoma with duplicated right adrenal veins (duplicated adrenal veins) due to apparent bilateral aldosterone suppression was confirmed during surgery. CONCLUSION: AVS is the gold standard accepted for PA subtyping, but sometimes when apparent bilateral aldosterone suppression is present, it can give ambiguous results. Duplicated right adrenal veins, may impact results, thus, AVS may not accurately provide evidence of unilateral hypersecretion for all PA patients. Repeat AVS or adrenal surgery can provide worthwhile diagnostic conclusions.

The recognition and diagnosis of primary aldosteronism (PA) have increased in recent years and clinicians usually require adrenal venous sampling (AVS) to identify the affected side, and it's crucial for further treatments of PA patients (surgery or medicine).We presented an example of unilateral aldosteronoma with duplicated adrenal veins whose AVS results suggested apparent bilateral aldosterone suppression (the adrenal venous aldosterone/cortisol ratios are bilaterally lower than the peripheral ratios). He was misdiagnosed with ectopic aldosteronoma due to computed tomography (CT) features, but surgery findings revealed duplicated adrenal veins.Unclear AVS results such as apparent bilateral aldosterone suppression can lead to a missed diagnosis of unilateral PA, preventing patients from receiving potentially curative adrenal resection.Our case can serve as an example for clinicians that encounter the same condition to provide further investigational clues to ensure the correct aetiological diagnosis for patients with PA.

Comparison efficacy of ultrasound-guided HIFU for adenomyosis-associated dysmenorrhea with different signal intensity on T2-weighted MR imaging.

AIM: To compare the therapeutic efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) in the treatment of adenomyosis with different signal intensity (SI) on T2-weighted images (T2WI). METHODS: A total of 299 adenomyosis patients who underwent HIFU and completed a one-year follow-up were retrospectively reviewed. Based on the SI values of adenomyosis relative to myometrium and endometrium on T2WI MRI, the patients were classified into three groups: the hypointense adenomyosis (Hypo-AM) group, the isointense adenomyosis (Iso-AM) group, and the hyperintense adenomyosis (Hyper-AM) group. The non-perfused volume ratio (NPVr) and relief of dysmenorrhea were used to assess the therapeutic efficacy. Optimal cutpoints (CPs) of NPVr were determined using the postoperative dysmenorrhea score as an anchor. Logistic regression analysis was used to test the relationship between the NPVr and SI. RESULTS: The clinical effectiveness rate was significantly lower in the Hyper-AM group than in the Hypo-AM and Iso-AM groups (P < 0.05 for both). The NPVr in the Hypo-AM and Iso-AM groups were significantly higher than that in the Hyper-AM group (P < 0.05 for both). The optimal CP was 54.0% for NPVr. Logistic regression analysis showed that the SI on T2WI was an effect factor for NPVr (P < 0.05), and the probability of NPVr ≥54.0% decreased continuously as the SI of adenomyosis increased. CONCLUSIONS: The NPVr of 54.0% has a clinically significant impact on dysmenorrhea scores in patients. The efficiency of the Hypo-AM and Iso-AM was better than that of the Hyper-AM.

Meloidogyne graminicola Population Structure in China Suggests a South-to-North Expansion.

The distribution range of root-knot nematode Meloidogyne graminicola is rapidly expanding, posing a severe threat to rice production. In this study, the sequences of cytochrome oxidase subunit I (COI) genes of rice M. graminicola populations from all reported provinces in China were amplified and sequenced by PCR. The distribution pattern and phylogenetic tree showed that all 54 M. graminicola populations in China have distinct geographical distribution characteristics; specifically, cluster 1 (southern China), cluster 2 (central south and southwest China), and cluster 3 (central and eastern China). The high haplotype diversity (Hd = 0.646) and low nucleotide diversity (π = 0.00682), combined with the negative value of Tajima's D (-1.252) and Fu's Fs (-3.06764), suggested that all nematode populations were expanding. The existence of high genetic differentiation (Fst = 0.5933) and low gene flow (Nm = 0.3333) indicated that there was a block of gene exchange between most populations. Mutation accumulation with population expansion might be directly responsible for the high genetic differentiation; therefore, the tested nematode population showed high within-group genetic variation (96.30%). The haplotype Hap8 was located at the bottom of the network topology, with the widest distribution and the highest frequency (59.26%), indicating that it was the ancestral haplotype. The populations in cluster 3 were newly invasive according to the lowest frequency of occurrence of Hap8, the highest number of endemic haplotypes, and the highest total haplotype frequency (60%). In contrast, cluster 1 having the highest genetic diversity (Hd = 0.772, π = 0.01127) indicated that it was the most primitive. Interestingly, the highest gene flow (Nm > 1), lowest genetic differentiation (Fst ≤ 0.33), and closest genetic distance (0.000) only occurred between the Guangdong/Hainan population and others, which suggested that there might be channels for gene exchange between them and that long-distance dispersal occurred. This suggestion is further confirmed by the weak correlation between genetic distance and geographical distance. Based on these data, a hypothesis can be drawn that M. graminicola populations in China were spreading from south to north, specifically from Guangdong and Hainan Provinces to other regions. Natural selection (including anthropogenic) and genetic drift were the main drivers of their evolution. Coincidentally, this hypothesis was consistent with the gradual warming trend and the chronological order of reporting these populations. The main factors influencing current M. graminicola population expansion and distribution patterns might be geography, climate, long-distance seedling transport, interregional operations of agricultural machinery, and rotation mode. It reminds human beings of the necessity to be vigilant about preventing nematode disease according to local conditions all year round.

Bacterial and Fungal Biocontrol Agents for Plant Disease Protection: Journey from Lab to Field, Current Status, Challenges, and Global Perspectives.

Plants are constantly exposed to various phytopathogens such as fungi, Oomycetes, nematodes, bacteria, and viruses. These pathogens can significantly reduce the productivity of important crops worldwide, with annual crop yield losses ranging from 20% to 40% caused by various pathogenic diseases. While the use of chemical pesticides has been effective at controlling multiple diseases in major crops, excessive use of synthetic chemicals has detrimental effects on the environment and human health, which discourages pesticide application in the agriculture sector. As a result, researchers worldwide have shifted their focus towards alternative eco-friendly strategies to prevent plant diseases. Biocontrol of phytopathogens is a less toxic and safer method that reduces the severity of various crop diseases. A variety of biological control agents (BCAs) are available for use, but further research is needed to identify potential microbes and their natural products with a broad-spectrum antagonistic activity to control crop diseases. This review aims to highlight the importance of biocontrol strategies for managing crop diseases. Furthermore, the role of beneficial microbes in controlling plant diseases and the current status of their biocontrol mechanisms will be summarized. The review will also cover the challenges and the need for the future development of biocontrol methods to ensure efficient crop disease management for sustainable agriculture.

COVID-19 Pandemic and Corporate Liquidity: The Role of SOEs' Trade Credit Response.

Although state-owned enterprises are associated with less efficiency and lead to resource misallocation, they may have stabilizing effect in face of a crisis. Exploiting the COVID-19 pandemic as a natural experiment, we study the role of firm ownership in trade credit provision and find robust evidence that SOEs increase their trade credit to downstream firms more than non-SOEs after the outbreak of the pandemic. Moreover, we explore the underlying mechanism and find that better financing ability and multitask of the SOEs contribute to greater trade credit during the pandemic, and the latter plays a more active role. Further analyses show that SOEs' advantage in trade credit extension is more pronounced in industries with higher external financial dependence and provinces with a higher level of government involvement, suggesting that SOEs might have greater comparative advantage in screening due to its involvements in local economy during crisis periods. Our paper provides new insights into the real effects of SOEs on the economy.

Host genetic determinants drive compartment-specific assembly of tea plant microbiomes.

Diverse host factors drive microbial variation in plant-associated environments, whereas their genetic mechanisms remain largely unexplored. To address this, we coupled the analyses of plant genetics and microbiomes in this study. Using 100 tea plant (Camellia sinensis) cultivars, the microbiomes of rhizosphere, root endosphere and phyllosphere showed clear compartment-specific assembly, whereas the subpopulation differentiation of tea cultivars exhibited small effects on microbial variation in each compartment. Through microbiome genome-wide association studies, we examined the interactions between tea genetic loci and microbial variation. Notably, genes related to the cell wall and carbon catabolism were heavily linked to root endosphere microbial composition, whereas genes related to the metabolism of metal ions and small organic molecules were overrepresented in association with rhizosphere microbial composition. Moreover, a set of tea genetic variants, including the cytoskeleton-related formin homology interacting protein 1 gene, were strongly associated with the ß-diversity of phyllosphere microbiomes, implying their interactions with the overall structure of microbial communities. Our results create a catalogue of tea genetic determinants interacting with microbiomes and reveal the compartment-specific microbiome assembly driven by host genetics.

Silicon Mediated Plant Immunity against Nematodes: Summarizing the Underline Defence Mechanisms in Plant Nematodes Interaction.

Silicon (Si) is known to stimulate plant resistance against different phytopathogens, i.e., bacteria, fungi, and nematodes. It is an efficient plant growth regulator under various biotic and abiotic stresses. Silicon-containing compounds, including silicon dioxide, SiO2 nanoparticles (NPs), nano-chelated silicon fertilizer (NCSF), sodium siliconate, and sodium metasilicate, are effective in damaging various nematodes that reduce their reproduction, galling, and disease severity. The defence mechanisms in plant-nematodes interaction may involve a physical barrier, plant defence-associated enzyme activity, synthesis of antimicrobial compounds, and transcriptional regulation of defence-related genes. In the current review, we focused on silicon and its compounds in controlling plant nematodes and regulating different defence mechanisms involved in plant-nematodes interaction. Furthermore, the review aims to evaluate the potential role of Si application in improving plant resistance against nematodes and highlight its need for efficient plant-nematodes disease management.

Salt-tolerance diversity in diploid and polyploid cotton (Gossypium) species.

The development of salt-tolerant genotypes is pivotal for the effective utilization of salinized land and to increase global crop productivity. Several cotton species comprise the most important source of textile fibers globally, and these are increasingly grown on marginal or increasingly saline agroecosystems. The allopolyploid cotton species also provide a model system for polyploid research, of relevance here because polyploidy was suggested to be associated with increased adaptation to stress. To evaluate the genetic variation of salt tolerance among cotton species, 17 diverse accessions of allopolyploid (AD-genome) and diploid (A- and D-genome) Gossypium were evaluated for a total of 29 morphological and physiological traits associated with salt tolerance. For most morphological and physiological traits, cotton accessions showed highly variable responses to 2 weeks of exposure to moderate (50 mm NaCl) and high (100 mm NaCl) hydroponic salinity treatments. Our results showed that the most salt-tolerant species were the allopolyploid Gossypium mustelinum from north-east Brazil, the D-genome diploid Gossypium klotzschianum from the Galapagos Islands, followed by the A-genome diploids of Africa and Asia. Generally, A-genome accessions outperformed D-genome cottons under salinity conditions. Allopolyploid accessions from either diploid genomic group did not show significant differences in salt tolerance, but they were more similar to one of the two progenitor lineages. Our findings demonstrate that allopolyploidy in itself need not be associated with increased salinity stress tolerance and provide information for using the secondary Gossypium gene pool to breed for improved salt tolerance.

Hyperlipidemia Affects Tight Junctions and Pump Function in the Corneal Endothelium.

Hyperlipidemia impacts on various diseases, such as atherosclerosis, hypertension, and diabetes mellitus. However, its influence, if any, on ocular tissues is largely unknown. Herein, we developed hyperlipidemic murine models by feeding 4-week-old male wild-type mice with a high-fat diet and apolipoprotein E knockout (ApoE-/-) mice with a high-fat diet or standard diet to investigate the corneal endothelial change under hyperlipidemic conditions. Oil Red O staining showed an accumulation of lipid droplets in corneal endothelial cells (CECs) of hyperlipidemic mice. Other manifestations included a reduced cell density and distorted cell morphology, a disruption of the endothelial cell tight junctions and adhesion junctions, a reduced number of surface microvilli, down-regulation of Na+-K+-ATPase expression and function, activation of oxidative stress, changes in mitochondrial ultrastructure, and increased apoptosis. CEC recovery after injury, moreover, was diminished in hyperlipidemic mice; and high palmitate levels were found in the aqueous humor. In vitro hyperlipemia model, moreover, was found to be associated with dose-dependent CEC cytotoxicity, altered cell morphology, reduced pump function, and an induction of oxidative stress, leading to functional and pathologic changes in the corneal endothelium.

Whole-genome resequencing of 240 Gossypium barbadense accessions reveals genetic variation and genes associated with fiber strength and lint percentage.

KEY MESSAGE: Genetic variation in a G. barbadense population was revealed using resquencing. GWAS on G.barbadense population identified several candidate genes associated with fiber strength and lint percentage. Gossypium barbadense is the second-largest cultivated cotton species planted in the world, which is characterized by high fiber quality. Here, we described the global pattern of genetic polymorphisms for 240 G. barbadense accessions based on the whole-genome resequencing. A total of 3,632,231 qualified single-nucleotide polymorphisms (SNPs) and 221,354 insertion-deletions (indels) were obtained. We conducted a genome-wide association study (GWAS) on 12 traits under four environments. Two traits with more stable associated variants, fiber strength and lint percentage, were chosen for further analysis. Three putative candidate genes, HD16 orthology (GB_D11G3437), WDL2 orthology (GB_D11G3460) and TUBA1 orthology (GB_D11G3471), on chromosome D11 were found to be associated with fiber strength, and one gene orthologous to Arabidopsis Receptor-like protein kinase HERK 1 (GB_A07G1034) was predicated to be the candidate gene for the lint percentage improvement. The identified genes may serve as promising targets for genetic engineering to accelerate the breeding process for G. barbadense and the high-density genome variation map constructed in this work may facilitate our understanding of the genetic architecture of cotton traits.

MEKK3 coordinates with FBW7 to regulate WDR62 stability and neurogenesis.

Mutations of WD repeat domain 62 (WDR62) lead to autosomal recessive primary microcephaly (MCPH), and down-regulation of WDR62 expression causes the loss of neural progenitor cells (NPCs). However, how WDR62 is regulated and hence controls neurogenesis and brain size remains elusive. Here, we demonstrate that mitogen-activated protein kinase kinase kinase 3 (MEKK3) forms a complex with WDR62 to promote c-Jun N-terminal kinase (JNK) signaling synergistically in the control of neurogenesis. The deletion of Mekk3, Wdr62, or Jnk1 resulted in phenocopied defects, including premature NPC differentiation. We further showed that WDR62 protein is positively regulated by MEKK3 and JNK1 in the developing brain and that the defects of wdr62 deficiency can be rescued by the transgenic expression of JNK1. Meanwhile, WDR62 is also negatively regulated by T1053 phosphorylation, leading to the recruitment of F-box and WD repeat domain-containing protein 7 (FBW7) and proteasomal degradation. Our findings demonstrate that the coordinated reciprocal and bidirectional regulation among MEKK3, FBW7, WDR62, and JNK1, is required for fine-tuned JNK signaling for the control of balanced NPC self-renewal and differentiation during cortical development.

Doyle-Kirmse reaction using 3,3-difluoroallyl sulfide and N-sulfonyl-1,2,3-triazole: an efficient access to gem-difluoroallylated multifunctional quaternary carbon.

A Doyle-Kirmse reaction of N-sulfonyl-1,2,3-triazole with 3,3-difluoroallyl sulfide through a Rh(ii)-catalyzed [2,3]-sigmatropic rearrangement has been developed, which provides an efficient access to multifunctional quaternary centers containing aryl, imino, thio, and brominated gem-difluoroallyl groups. The reaction features broad substrate scope with moderate to excellent yields. The applicability of the method is confirmed by gram-scale synthesis and further transformations.

Fluoride exposure, dopamine relative gene polymorphism and intelligence: A cross-sectional study in China.

BACKGROUND: Excessive fluoride exposure is related to adverse health outcomes, but whether dopamine (DA) relative genes are involved in the health effect of low-moderate fluoride exposure on children's intelligence remain unclear. OBJECTIVES: We conducted a cross-sectional study to explore the role of DA relative genes in the health effect of low-moderate fluoride exposure in drinking water. METHODS: We recruited 567 resident children, aged 6-11 years old, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. Spot urine samples were tested for urinary fluoride concentration, combined Raven`s test was used for intelligence quotient test. Fasting venous blood were collected to analyze ANKK1 Taq1A (rs1800497), COMT Val158Met (rs4680), DAT1 40 bp VNTR and MAOA uVNTR. Multivariable linear regression models were used to assess associations between fluoride exposure and IQ scores. We applied multiplicative and additive models to appraise single gene-environment interaction. Generalized multifactor dimensionality reduction (GMDR) was used to evaluate high-dimensional interactions of gene-gene and gene-environment. RESULTS: In adjusted model, fluoride exposure was inversely associated with IQ scores (ß = -5.957, 95% CI: -9.712, -2.202). The mean IQ scores of children with high-activity MAOA genotype was significantly lower than IQ scores of those with low-activity (P = 0.006) or female heterozygote (P = 0.016) genotype. We detected effect modification by four DA relative genes (ANKK1, COMT, DAT1 and MAOA) on the association between UF and IQ scores. We also found a high-dimensional gene-environment interaction among UF, ANKK1, COMT and MAOA on the effect of IQ (testing balanced accuracy = 0.5302, CV consistency: 10/10, P = 0.0107). CONCLUSIONS: Our study suggests DA relative genes may modify the association between fluoride and intelligence, and a potential interaction among fluoride exposure and DA relative genes on IQ.

[Study on difference of effect of Huoxue drugs and Yiqi Huoxue drugs on tumor metastasis based on immune remodeling].

Tumor metastasis is an important cause of tumor treatment failure. Its molecular mechanism is closely related to tumor cells remodeling immune cells and immunosuppressive microenvironment, so as to create a suitable soil for tumor cell invasion and growth. "Huoxue Huayu" is one of the important therapeutic principles in cancer treatment, but the influence of Huoxue drugs on tumor metastasis has been controversial in clinical application. In this paper, we systematically summarized the comparative study of Huoxue drugs and Yiqi Huoxue drugs in tumor metastasis in recent years, and discussed the differences of molecular mechanisms of Huoxue drugs and Yiqi Huoxue drugs in anti-tumor metastasis from the perspective of immune remodeling, so as to provide scientific basis for clinical rational application of Huoxue drugs and Yiqi Huoxue drugs.