Diversity and functional traits of seed endophytes of Dysphania ambrosioides from heavy metal contaminated and non-contaminated areas.

Seed endophytes played a crucial role on host plants stress tolerance and heavy metal (HM) accumulation. Dysphania ambrosioides is a hyperaccumulator and showed strong tolerance and extraordinary accumulation capacities of multiple HMs. However, little is known about its seed endophytes response to field HM-contamination, and its role on host plants HM tolerance and accumulation. In this study, the seed endophytic community of D. ambrosioides from HM-contaminated area (H) and non-contaminated area (N) were investigated by both culture-dependent and independent methods. Moreover, Cd tolerance and the plant growth promoting (PGP) traits of dominant endophytes from site H and N were evaluated. The results showed that in both studies, HM-contamination reduced the diversity and richness of endophytic community and changed the most dominant endophyte, but increased resistant species abundance. By functional trait assessments, a great number of dominant endophytes displayed multiple PGP traits and Cd tolerance. Interestingly, soil HM-contamination significantly increased the percentage of Cd tolerance isolates of Agrobacterium and Epicoccum, but significantly decreased the ration of Agrobacterium with the siderophore production ability. However, the other PGP traits of isolates from site H and N showed no significant difference. Therefore, it was suggested that D. ambrosioides might improve its HM tolerance and accumulation through harboring more HM-resistant endophytes rather than PGP endophytes, but to prove this, more work need to be conducted in the future.

Identification of a novel phenotype of external ear deformity related to Coffin-Siris syndrome-9 and literature review.

De novo germline variants of the SRY-related HMG-box 11 gene (SOX11) have been reported to cause Coffin-Siris syndrome-9 (CSS-9), a rare congenital disorder associated with multiple organ malformations, including ear anomalies. Previous clinical and animal studies have found that intragenic pathogenic variant or haploinsufficiency in the SOX11 gene could cause inner ear malformation, but no studies to date have documented the external ear malformation caused by SOX11 deficiency. Here, we reported a Chinese male with unilateral microtia and bilateral sensorineural deafness who showed CSS-like manifestations, including dysmorphic facial features, impaired neurodevelopment, and fingers/toes malformations. Using trio-based whole-exome sequencing, a de novo missense variant in SOX11 (NM_003108.4: c.347A>G, p.Y116C) was identified and classified as pathogenic variant as per American College of Medical Genetics guidelines. Moreover, a systematic search of the literature yielded 12 publications that provided data of 55 SOX11 intragenic variants affecting various protein-coding regions of SOX11 protein. By quantitatively analyzing phenotypic spectrum information related to these 56 SOX11 variants (including our case), we found variants affecting different regions of SOX11 protein (high-mobility group [HMG] domain and non-HMG regions) appear to influence the phenotypic spectrum of organ malformations in CSS-9; variants altering the HMG domain were more likely to cause the widest range of organ anomalies. In summary, this is the first report of CSS with external ear malformation caused by pathogenic variant in SOX11, indicating that the SOX11 gene may be not only essential for the development of the inner ear but also critical for the morphogenesis of the external ear. In addition, thorough clinical examination is recommended for patients who carry pathogenic SOX11 variants that affect the HMG domain, as these variants may cause the widest range of organ anomalies underlying this condition.

Machine learning-based nomogram to predict poor response to overnight orthokeratology in Chinese myopic children: A multicentre, retrospective study.

PURPOSE: To develop and validate an effective nomogram for predicting poor response to orthokeratology. METHODS: Myopic children (aged 8-15 years) treated with orthokeratology between February 2018 and January 2022 were screened in four hospitals of different tiers (i.e. municipal and provincial) in China. Potential predictors included 32 baseline clinical variables. Nomogram for the outcome (1-year axial elongation ≥0.20 mm: poor response; <0.20 mm: good response) was computed from a logistic regression model with the least absolute shrinkage and selection operator. The data from the First Affiliated Hospital of Chengdu Medical College were randomly assigned (7:3) to the training and validation cohorts. An external cohort from three independent multicentre was used for the model test. Model performance was assessed by discrimination (the area under curve, AUC), calibration (calibration plots) and utility (decision curve analysis). RESULTS: Between January 2022 and March 2023, 1183 eligible subjects were screened from the First Affiliated Hospital of Chengdu Medical College, then randomly divided into training (n = 831) and validation (n = 352) cohorts. A total of 405 eligible subjects were screened in the external cohort. Predictors included in the nomogram were baseline age, spherical equivalent, axial length, pupil diameter, surface asymmetry index and parental myopia (p < 0.05). This nomogram demonstrated excellent calibration, clinical net benefit and discrimination, with the AUC of 0.871 (95% CI 0.847-0.894), 0.863 (0.826-0.901) and 0.817 (0.777-0.857) in the training, validation and external cohorts, respectively. An online calculator was generated for free access (http://39.96.75.172:8182/#/nomogram). CONCLUSION: The nomogram provides accurate individual prediction of poor response to overnight orthokeratology in Chinese myopic children.

An insular cortical circuit required for itch sensation and aversion.

Itch encompasses both sensory and emotional dimensions, with the two dimensions reciprocally exacerbating each other. However, whether a shared neural circuit mechanism governs both dimensions remains elusive. Here, we report that the anterior insular cortex (AIC) is activated by both histamine-dependent and -independent itch stimuli. The activation of AIC elicits aversive emotion and exacerbates pruritogen-induced itch sensation and aversion. Mechanistically, AIC excitatory neurons project to the GABAergic neurons in the dorsal bed nucleus of the stria terminalis (dBNST). Manipulating the activity of the AIC → dBNST pathway affects both itch sensation and itch-induced aversion. Our study discovers the shared neural circuit (AIC â†’ dBNST pathway) underlying the itch sensation and aversion, highlights the critical role of the AIC as a central hub for the itch processing, and provides a framework to understand the neural mechanisms underlying the sensation and emotion interaction.

Water in water emulsion stabilized by liposomes developed from whey protein isolate and xanthan gum: Environmental stability and photoprotection effect for riboflavin.

The purpose of this work is to explore the feasibility of water in water (W/W) emulsion stabilized with liposomes as a water-soluble nutraceutical carrier. A W/W emulsion system composed of xanthan gum (XG) and whey protein isolate (WPI) with different amount (0.2 %, 0.4 %, and 0.6 %) of liposomes as stabilizer was constructed. Fast green staining observation showed that XG was the internal phase and WPI was the continuous phase respectively. Confocal laser scanning microscopy revealed that with the increase of liposomes concentration from 0.4 % to 0.6 %, the interface thickness of the W/W emulsions was approximately twice that of the 0.2 % liposome-stabilized emulsion.The emulsions remained stable under neutral and weakly alkaline conditions. The droplet sizes of the emulsions were little affected by ionic strength. The binding constant (Ka) for XG to riboflavin (12.22) was approximately 5 times that for WPI to riboflavin (2.46), suggesting that riboflavin had a stronger binding affinity for the XG molecule compared to WPI. The fluorescence spectra of riboflavin showed that 0.4 % and 0.6 % liposome stabilized emulsions could effectively retard the photodegradation of riboflavin under ultraviolet irradiation. The successful construction of liposomes stabilized W/W emulsion provides a novel strategy for delivering water-soluble bioactive substances.

One-year results for myopia control of orthokeratology with different back optic zone diameters: a randomized trial using a novel multispectral-based topographer.

AIM: To present the 1-year results of a prospective cohort study investigating the efficacy, potential mechanism, and safety of orthokeratology (ortho-k) with different back optic zone diameters (BOZD) for myopia control in children. METHODS: This randomized clinical study was performed between Dec. 2020 and Dec. 2021. Participants were randomly assigned to three groups wearing ortho-k: 5 mm BOZD (5-MM group), 5.5 mm BOZD (5.5-MM group), and 6 mm BOZD (6-MM group). The 1-year data were recorded, including axial length, relative peripheral refraction (RPR, measured by multispectral refractive topography, MRT), and visual quality. The contrast sensitivity (CS) was evaluated by CSV-1000 instrument with spatial frequencies of 3, 6, 12, and 18 cycles/degree (c/d); the corneal higher-order aberrations (HOAs) were measured by iTrace aberration analyzer. The one-way ANOVA was performed to assess the differences between the three groups. The correlation between the change in AL and RPR was calculated by Pearson's correlation coefficient. RESULTS: The 1-year results of 20, 21, and 21 subjects in the 5-MM, 5.5-MM, and 6-MM groups, respectively, were presented. There were no statistical differences in baseline age, sex, or ocular parameters between the three groups (all P>0.05). At the 1-year visit, the 5-MM group had lower axial elongation than the 6-MM group (0.07±0.09 vs 0.18±0.11 mm, P=0.001). The 5-MM group had more myopic total RPR (TRPR, P=0.014), with RPR in the 15°-30° (RPR 15-30, P=0.015), 30°-45° (RPR 30-45, P=0.011), temporal (RPR-T, P=0.008), and nasal area (RPR-N, P<0.001) than the 6-MM group. RPR 15-30 in the 5.5-MM group was more myopic than that in the 6-MM group (P=0.002), and RPR-N in the 5-MM group was more myopic than that in the 5.5-MM group (P<0.001). There were positive correlations between the axial elongation and the change in TRPR (r=0.756, P<0.001), RPR 15-30 (r=0.364, P=0.004), RPR 30-45 (r=0.306, P=0.016), and RPR-N (r=0.253, P=0.047). The CS decreased at 3 c/d (P<0.001), and the corneal HOAs increased in the 5-MM group (P=0.030). CONCLUSION: Ortho-k with 5 mm BOZD can control myopia progression more effectively. The mechanism may be associated with greater myopic shifts in RPR.

Corrigendum: A comprehensive analysis of HAVCR1 as a prognostic and diagnostic marker for pan-cancer.

[This corrects the article DOI: 10.3389/fgene.2022.904114.].

Liposome-exosome hybrids for in situ detection of exosomal miR-1246 in breast cancer.

Several lines of evidence suggest that exosomal miRNAs are potential biomarkers for cancer monitoring. An urgent need remains for the in situ detection of exosomal miRNAs at low concentrations without destroying the exosome structure. In the present study, a novel sensitive exosomal miR-1246 in situ detection strategy has been developed by integrating the CRISPR/Cas13a system with the formation of hybrids between exosomes and cationic liposomes. The liposomes were loaded with CRISPR/Cas13a, CRISPR RNA (crRNA), and RNA reporter probes. In the presence of exosomes, the liposome-exosome hybrids were formed through electrostatic interactions, and CRISPR/Cas13a was activated to cleave the reporter probes by exosomal miR-1246. The acquired fluorescence signal showed a linear response to the logarithm of MCF-7 exosome concentrations, indicating a quantitative response to exosomal miR-1246. The regression equation is y = 5021 log C - 9976 (R2 = 0.9985) with a limit of detection of 3 × 102 particles per mL. This strategy could not only be used to detect serum exosomal miR-1246 in breast cancer patients but also to distinguish early form advanced disease. This strategy can be exploited in future exosomal miRNA analyses.

The Influences of Rainfall Intensity and Timing on the Assemblage of Dung Beetles and the Rate of Dung Removal in an Alpine Meadow.

Changes in precipitation patterns, including rainfall intensity and rainfall timing, have been extensively demonstrated to impact biological processes and associated ecosystem functions. However, less attention has been paid to the effects of rainfall intensity and rainfall timing on the assembly of detritivore communities and the decomposition rate of detritus such as animal dung. In a grazed alpine meadow on the eastern Qinghai-Tibet Plateau, we conducted a manipulative experiment involving two levels of rainfall intensity (heavy rainfall, 1000 mL/5 min; light rainfall, 100 mL/5 min) and five levels of rainfall timing (0, 2, 4, 24, and 48 h after yak dung deposition). The aim was to determine the effects of rainfall intensity, timing, and their interaction on the assemblage of dung beetles and dung removal rate during the early stage (i.e., 96 h after yak dung deposition) of dung decomposition. Light rainfall significantly increased species richness in the treatment of 48 h after dung pats were deposited. Heavy rainfall significantly decreased beetle abundance in both the 0 h and 48 h treatments while light rainfall had no effect on beetle abundance. Dung mass loss was significant lower in the 2 h treatment compared to other treatments regardless of rainfall intensity. The structural equation model further revealed that the species richness of dung beetles and dung mass loss were significantly affected by rainfall timing but not by rainfall intensity. However, no significant relationships were observed between any variables examined. These findings suggest that changes in precipitation patterns can influence both the structure of dung beetles and the rate of dung decomposition but may also decouple their relationship under a certain circumstance. Therefore, it is crucial to pay greater attention to fully understand local variability between the biological processes and ecosystem functions within a global climate change scenario.

Oxfendazole Induces Apoptosis in Ovarian Cancer Cells by Activating JNK/MAPK Pathway and Inducing Reactive Oxygen Species Generation.

Ovarian cancer (OC) is one of the most common and high mortality type of cancer among women worldwide. The majority of patients with OC respond to chemotherapy initially; however, most of them become resistant to chemotherapy and results in a high level of treatment failure in OC. Therefore, novel agents for the treatment of OC are urgently required. Benzimidazole anthelmintics might have the promising efficacy for cancer therapy as their selectively binding activity to ß-tubulin. Recent study has shown that one of the benzimidazole anthelmintics oxfendazole inhibited cell growth of non-small cell lung cancer cells, revealing its anti-cancer activity; however, the pharmacological action and detailed mechanism underlying the effects of oxfendazole on OC cells remain unclear. Therefore, the present study investigated the cytotoxic effects of oxfendazole on OC cells. Our results demonstrated that oxfendazole significantly decreased the viability of OC cells. Oxfendazole inhibited the proliferation, induced G2/M phase arrest and apoptotic cell death in A2780 cells. The c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) pathway was activated and reactive oxygen species (ROS) generation was increased in OC cells treated with oxfendazole; oxfendazole-induced apoptosis was notably abrogated when co-treated with JNK inhibitor SP600125 and ROS scavenger N-acetyl-L-cysteine (NAC), indicating that JNK/MAPK pathway activation and ROS accumulation was associated with the oxfendazole-induced apoptosis of OC cells. Moreover, oxfendazole could also induce the proliferation inhibition and apoptosis of cisplatin resistant cells. Collectively, these results revealed that oxfendazole may serve as a potential therapeutic agent for the treatment of OC.

[Return to sports WeChat applet for evaluating the rehabilitation effects after anterior cruciate ligament reconstruction].

Objective: To clarify the intervention guidance of return to sports WeChat applet and evaluate the rehabilitation effectiveness after anterior cruciate ligament (ACL) reconstruction. Methods: Between September 2020 and September 2022, 80 patients who met the selection criteria and underwent ACL anatomical single bundle reconstruction were selected as the research objects. According to the double-blind random method, they were divided into the applet group and the regular group, with 40 cases in each group. Patients in the applet group were rehabilitated under the guidance of the return to sports WeChat applet, and the patients were asked to perform the test once a month after operation, including patients' subjective scores [Tegner score, knee injury and osteoarthritis outcome score (KOOS), International Knee Documentation Committee (IKDC) score, American Hospital for Special Surgery (HSS) score], psychological assessment [ACL recovery sports injury scale (ACL-RSI) score], jumping test, balance test, bending angle test. Patients in the regular group were followed up by doctors and nurses regularly by telephone every month. All the patients were reexamined at 3, 6, 9, and 12 months after operation, and the range of motion of the knee joint with 6 degrees of freedom (flexion and extension angle, varus and valgus angle, internal and external rotation angle, anteroposterior displacement, superior and inferior displacement, and internal and external displacement) recorded by Opti_Knee three-dimensional knee joint motion measurement gait analysis system was observed. The anterior tibial translation difference (ATTD) was measured by Ligs knee measuring instrument when a forward thrust of 120 N was applied to the posterior part of the proximal tibia. Tegner score, IKDC score, KOOS score (including KOOS-Pain score, KOOS-Symptoms score, KOOS-Activities of daily living score, KOOS-Sport score, and KOOS-Quality of life score), HSS score, ACL-RSI score, jumping ability, balance ability, patients' satisfaction with the rehabilitation process, and ACL healing grading according to ACL continuity and signal intensity shown by MRI. Results: There were significant differences in various indicators between different time points after operation in the two groups ( P<0.05). At 3 months after operation, except that the ACL-RSI score of the applet group was significantly higher than that of the regular group ( P<0.05), there was no significant difference in the other indicators between the two groups ( P>0.05). At 6 months after operation, the ACL-RSI score, IKDC score, Tegner score, KOOS scores of different items, HSS score, balance and jumping ability of the applet group were significantly higher than those of the regular group ( P<0.05), and there was no significant difference in the other indicators between the two groups ( P>0.05). At 9 months after operation, there was no significant difference in all indicators between the two groups ( P>0.05). At 12 months after operation, 27 cases (67.5%) in the applet group and 21 cases (52.5%) in the regular group returned to sport, with a significant difference of the return to sports incidence between the two groups [ RR(95% CI)=1.50 (1.00, 2.25), P=0.049]. In the applet group, 27 cases were very satisfied with the rehabilitation process, 10 cases were satisfied, 2 cases were basically satisfied, and 1 case was not satisfied, while 19, 13, 5, and 3 cases in the regular group, respectively. The satisfaction degree of the applet group was significantly better than that of the regular group ( P=0.049). MRI examination of the two groups showed that the ACL was continuous without secondary rupture or necrosis. The ACL healing grade of the applet group was 31 cases of grade 1 and 9 cases of grade 2, and that of the regular group was 28 cases of grade 1 and 12 cases of grade 2, there was no significant difference in ACL healing grade between the two groups ( P=0.449). Conclusion: The application of return to sports WeChat applet in the rehabilitation of patients after ACL reconstruction can significantly reduce the fear of return to sports and improve the rate of return to sports. The return to sports WeChat applet is convenient to operate, with high utilization rate and high patient compliance, which significantly improves the satisfaction.

Development and validation of a nomogram based on common biochemical indicators for survival prediction of children with high-risk neuroblastoma: A valuable tool for resource-limited hospitals.

BACKGROUND: Despite multiple attempts have been made to develop risk stratification within high-risk neuroblastoma (NB) patients (age of diagnosis ≥ 18 month-old with metastatic NB), the definition of "ultra high-risk NB" is still lack of consensus, and indicators for identifying this subgroup are still unclear. This study aimed to develop a nomogram based on easy-to-obtain blood-derived biofactors for identifying ultra high-risk NB patients with highest risk of death within 3 or 5 years. METHODS: One hundred sixty-seven NB patients who treated at Sun Yat-sen University Cancer Center between 2015 and 2023 were recruited and clustered randomly into training and validation cohorts (116 and 51 cases, respectively). Univariate and multivariate Cox analysis were performed in training set to screen independent prognostic indicators for constructing nomogram model of predicting 1-, 3- and 5-year overall survival (OS). The discrimination power of the nomogram in training and validation sets were assessed by concordance index (C-index) and calibration plot. Based on the risk score obtained from nomogram model, the prognostic accuracy of 1-, 3- and 5-year OS rates in training and validation cohorts were further evaluated using the area under receiver operating characteristic (ROC) curves (AUC). RESULTS: Through univariate and multivariate Cox analysis, independent prognostic indicators, including serum lactate dehydrogenase (LDH) and albumin (ALB), were identified in training set, and used to establish a nomogram model. The model showed good discrimination power with C-index in training cohort being 0.706 (95%CI: 0.633-0.788). According to the cut-point calculated based on the established nomogram, patients with a nomogram score > 34 points could be stratified to ultra high-risk NB subgroup, and this subgroup had poorer OS than those in non-ultra one (p < 0.001). AUC values of ROC curves for 3- and 5-year OS rates in the training set were 0.758 and 0.756, respectively. Moreover, based on the cut-point score (34 points) developed in training set, The model also showed good discrimination power with C-index of 0.773 (95%CI: 0.664-0.897) and powerful prognostic accuracy of AUC for 3- and 5-year OS rates being 0.825 and 0.826, respectively, in validation cohort. CONCLUSIONS: We developed a simple-to-use nomogram based on common laboratory indicators to identify the subgroup of ultra high-risk NB before treatment, providing these children even from developing countries or regions access to intensified multimodal treatments earlier and thus improving their long-term outcome.

Physicochemical properties and in vitro digestion behavior of emulsion gels stabilized by rice bran protein aggregates: Effects of heating time and induction methods.

To investigate the effects of heating time and induction methods on the physicochemical properties and in vitro digestion behavior of emulsion gels, rice bran protein aggregates (RBPAs) were formed by acid-heat induction (90 °C, pH 2.0) and the emulsion gels were further prepared by adding GDL or/and laccase for single/double cross-linked induction. Heating time affected the aggregation and oil/water interfacial adsorption behavior of RBPAs. Suitable heating (1-6 h) was conducive to faster and more adsorption of aggregates at the oil/water interface. While excessive heating (7-10 h) resulted in protein precipitation, which inhibited the adsorption at the oil/water interface. The heating time at 2, 4, 5 and 6 h was thus chosen to prepare the subsequent emulsion gels. Compared with the single cross-linked emulsion gels, the double-cross-linked emulsion gels showed higher water holding capacity (WHC). After simulated gastrointestinal digestion, the single/double cross-linked emulsion gels all exhibited slow-release effect on free fatty acid (FFA). Moreover, the WHC and final FFA release rate of emulsion gels were closely related to the surface hydrophobicity, molecular flexibility, sulfhydryl, disulfide bond and interface behavior of RBPAs. Generally, these findings proved the potential of emulsion gels in designing fat alternatives, which could provide a novel technique for the fabrication of low-fat food.

Wild Rosa Endophyte M7SB41-Mediated Host Plant's Powdery Mildew Resistance.

Our previous studies indicated that endophyte M7SB41 (Seimatosporium sp.) can significantly enhance host plants powdery mildew (PM) resistance. To recover the mechanisms, differentially expressed genes (DEGs) were compared between E+ (endophte-inoculated) and E- (endophyte-free) plants by transcriptomics. A total of 4094, 1200 and 2319 DEGs between E+ and E- were identified at 0, 24, and 72 h after plants had been infected with PM pathogen Golovinomyces cichoracearum, respectively. Gene expression pattern analysis displayed a considerable difference and temporality in response to PM stress between the two groups. Transcriptional profiling analysis revealed that M7SB41 induced plant resistance to PM through Ca2+ signaling, salicylic acid (SA) signaling, and the phenylpropanoid biosynthesis pathway. In particular, we investigated the role and the timing of the SA and jasmonic acid (JA)-regulated defensive pathways. Both transcriptomes and pot experiments showed that SA-signaling may play a prominent role in PM resistance conferred by M7SB41. Additionally, the colonization of M7SB41 could effectively increase the activities and the expression of defense-related enzymes under PM pathogen stress. Meanwhile, our study revealed reliable candidate genes from TGA (TGACG motif-binding factor), WRKY, and pathogenesis-related genes related to M7SB41-mediate resistance. These findings offer a novel insight into the mechanisms of endophytes in activating plant defense responses.

Orthokeratology with increased compression factor in adolescent myopia control: a 2-year prospective randomized clinical trial.

AIM: To explore the long-term efficacy, safety, and optical mechanism of orthokeratology with increased compression factor in adolescent myopia control. METHODS: A prospective, double-masked, and randomized clinical trial was performed from May 2016 to June 2020. Subjects aged between 8 and 16y, with myopia (-5.00 to -1.00 D), low astigmatism (≥-1.50 D) and anisometropia (≤1.00 D), were stratified into low (-2.75 to -1.00 D) and moderate (-5.00 to -3.00 D) myopia groups. Then they were randomly assigned to wear either increased compression factor (ICF; 1.75 D) orthokeratology or conventional compression factor (CCF; 0.75 D) orthokeratology. The data were recorded including axial length (AL), spherical equivalent (SE), best corrected visual acuity (BCVA), near visual acuity (NVA), corneal staining (using Efron grading scales), corneal hysteresis (CH), corneal resistance factor (CRF), higher-order aberrations (HOAs, expressed as root mean square, RMSh), and subfoveal choroidal thickness (SFChT) in the 2-year follow-up period. Pearson's correlation coefficient was conducted to analyze the association between the changes in AL and RMSh, SFChT. RESULTS: At the 2-year visit, there were no statistical differences in all the parameters between the ICF group and the CCF group in low myopia subjects (P>0.05). For the moderate myopia subjects, the ICF group had shorter AL elongation (0.23±0.08 vs 0.30±0.11 mm, P=0.015), higher RMSh (1.94±0.50 vs 1.65±0.51 µm, P=0.041), and higher SFChT (279.04±35.72 vs 254.08±29.60 µm, P=0.008) than those in CCF group. The change in AL was negatively correlated with RMSh (r=-0.687, P<0.001) and SFChT (r=-0.464, P=0.013). CONCLUSION: ICF orthokeratology can control the progression of moderate myopia more effectively, which might be related to greater RMSh and SFChT.

KCNQ1OT1 promotes retinoblastoma progression by targeting miR-339-3p that suppresses KIF23.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in tumor formation and development. KCNQ1OT1 regulates the malignant proliferation of retinoblastoma (RB), but the specific mechanism remains to be further investigated. METHODS: The KCNQ1OT1, miR-339-3p and KIF23 expression levels in RB were detected by qRT-PCR and western blotting. The cell viability, proliferation, migration ability and caspase-3 activity of RB cells were evaluated by CCK-8, BrdU, transwell and caspase-3 activity analysis. Western blot was used to detect the Bax and Bcl-2 protein expression in RB cells. The binding relationship between KCNQ1OT1, miR-339-3p and KIF23 was detected by luciferase, RIP and RNA pull-down assay. RESULTS: KCNQ1OT1 and KIF23 were up-regulated frequently in RB, and miR-339-3p was down-regulated. Functional studies showed that downregulation of KCNQ1OT1 or KIF23 inhibited the survival and migration of RB cells, and facilitated apoptosis. Interference with miR-339-3p showed the opposite effect. Mechanisms suggested that KCNQ1OT1 exited its oncogenic activity by positively regulating the expression of KIF23 and sponging miR-339-3p. CONCLUSION: KCNQ1OT1/miR-339-3p/KIF23 may be a new biomarker for the diagnosis and treatment of RB.

Endophytic Fungal Community of Stellera chamaejasme L. and Its Possible Role in Improving Host Plants' Ecological Flexibility in Degraded Grasslands.

Stellera chamaejasme L. is a widely distributed poisonous plant in Chinese degraded grasslands. To investigate the role of endophytic fungi (EF) in S. chamaejasme's quick spread in grasslands, the endophytic fungal community of S. chamaejasme was studied through culture-dependent and culture-independent methods, and the plant-growth-promoting (PGP) traits of some culturable isolates were tested. Further, the growth-promoting effects of 8 isolates which showed better PGP traits were evaluated by pot experiments. The results showed that a total of 546 culturable EF were isolated from 1114 plant tissue segments, and the colonization rate (CR) of EF in roots (33.27%) was significantly higher than that in shoots (22.39%). Consistent with this, the number of specific types of EF was greater in roots (8 genera) than in shoots (1 genus). The same phenomenon was found in culture-independent study. There were 95 specific genera found in roots, while only 18 specific genera were found in shoots. In addition, the dominant EF were different between the two study methods. Cladosporium (18.13%) and Penicillium (15.93%) were the dominant EF in culture-dependent study, while Apiotrichum (13.21%) and Athelopsis (5.62%) were the dominant EF in culture-independent study. PGP trait tests indicated that 91.30% of the tested isolates (69) showed phosphorus solubilization, IAA production, or siderophores production activity. The benefit of 8 isolates on host plants' growth was further studied by pot experiments, and the results indicated that all of the isolates can improve host plants' growth. Among them, STL3G74 (Aspergillus niger) showed the best growth-promotion effect; it can increase the plant's shoot and root dry biomass by 68.44% and 74.50%, respectively, when compared with the controls. Our findings revealed that S. chamaejasme has a wide range of fungal endophytic assemblages, and most of them possess PGP activities, which may play a key role in its quick spread in degraded grasslands.

Faecalibacterium prausnitzii Improves Lipid Metabolism Disorder and Insulin Resistance in Type 2 Diabetic Mice.

Purpose: Additional effective therapeutic strategies for Type 2 diabetes (T2D) patients are urgently needed. Gut microbiota plays an important role in T2D development and is a promising treatment strategy for T2D patients. Faecalibacterium prausnitzii (F. prausnitzii) is regarded as one of the most important bacterial indicators for a healthy gut, but the mechanisms of its anti-diabetic properties are still unclear. Methods and Results: The abundance of F. prausnitzii in feces of patients with T2D was detected by using qPCR. The effects of F. prausnitzii on glucose homeostasis, insulin resistance (IR), dyslipidemia, hepatic steatosis and inflammation were investigated in type 2 diabetic (T2D) db/db mice. We also investigated F. prausnitzii in people. Our results showed that the abundance of F. prausnitzii was significantly lower in T2D patients compared to healthy subjects. In T2D mice, we found that F. prausnitzii treatment significantly decreased fasting blood glucose and IR index, indicating improved glucose intolerance as well as IR. Furthermore, based on evaluation of lipid-regulating enzyme activities and proinflammatory cytokine levels, F. prausnitzii was not only able to improve inflammation in both adipose tissue and liver, but also ameliorate hepatic steatosis through inhibiting the activity of hepatic lipogenic enzymes. Conclusion: These results suggested that F. prausnitzii might serve as a therapeutic option for T2D by improved IR, lipid metabolism and inflammation.

Clinical significance of nonerythrocytic spectrin Beta 1 (SPTBN1) in human kidney renal clear cell carcinoma and uveal melanoma: a study based on Pan-Cancer Analysis.

BACKGROUND: Nonerythrocytic spectrin beta 1 (SPTBN1) is an important cytoskeletal protein that involves in normal cell growth and development via regulating TGFß/Smad signaling pathway, and is aberrantly expressed in various cancer types. But, the exact role of SPTBN1 in pan-cancer is still unclear. This report aimed to display expression patterns and prognostic landscapes of SPTBN1 in human cancers, and further assess its prognostic/therapeutic value and immunological role in kidney renal carcinoma (KIRC) and uveal melanoma (UVM). METHODS: We firstly analyzed expression patterns and prognostic landscapes of SPTBN1 in human cancers using various databases and web-based tools. The relationships between SPTBN1 expression and survival/tumor immunity in KIRC and UVM were further investigated via R packages and TIMER 2.0 platform. The therapeutic roles of SPTBN1 in KIRC and UVM were also explored via R software. Following this, the prognostic value and cancer immunological role of SPTBN1 in KIRC and UVM were validated in our cancer patients and GEO database. RESULTS: Overall, cancer tissue had a lower expression level of SPTBN1 frequently in pan-cancer, compared with those in adjacent nontumor one. SPTBN1 expression often showed a different effect on survival in pan-cancer; upregulation of SPTBN1 was protective to the survival of KIRC individuals, which was contrary from what was found in UVM patients. In KIRC, there were significant negative associations between SPTBN1 expression and pro-tumor immune cell infiltration, including Treg cell, Th2 cell, monocyte and M2-macrophage, and expression of immune modulator genes, such as tumor necrosis factor superfamily member 9 (TNFSF9); while, in UVM, these correlations exhibited opposite patterns. The following survival and expression correlation analysis in our cancer cohorts and GEO database confirmed these previous findings. Moreover, we also found that SPTBN1 was potentially involved in the resistance of immunotherapy in KIRC, and the enhance of anti-cancer targeted treatment in UVM. CONCLUSIONS: The current study presented compelling evidence that SPTBN1 might be a novel prognostic and therapy-related biomarker in KIRC and UVM, shedding new light on anti-cancer strategy.