Nuclear receptors for epidermal lipid barrier: Advances in mechanisms and applications.

The skin plays an essential role in preventing the entry of external environmental threats and the loss of internal substances, depending on the epidermal permeability barrier. Nuclear receptors (NRs), present in various tissues and organs including full-thickness skin, have been demonstrated to exert significant effects on the epidermal lipid barrier. Formation of the lipid lamellar membrane and the normal proliferation and differentiation of keratinocytes (KCs) are crucial for the development of the epidermal permeability barrier and is regulated by specific NRs such as PPAR, LXR, VDR, RAR/RXR, AHR, PXR and FXR. These receptors play a key role in regulating KC differentiation and the entire process of epidermal lipid synthesis, processing and secretion. Lipids derived from sebaceous glands are influenced by NRs as well and participate in regulation of the epidermal lipid barrier. Furthermore, intricate interplay exists between these receptors. Disturbance of barrier function leads to a range of diseases, including psoriasis, atopic dermatitis and acne. Targeting these NRs with agonists or antagonists modulate pathways involved in lipid synthesis and cell differentiation, suggesting potential therapeutic approaches for dermatosis associated with barrier damage. This review focuses on the regulatory role of NRs in the maintenance and processing of the epidermal lipid barrier through their effects on skin lipid synthesis and KC differentiation, providing novel insights for drug targets to facilitate precision medicine strategies.

Exploring the Role of Ubiquitin-Proteasome System in the Pathogenesis of Parkinson's Disease.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder among the elderly population. The pathogenesis of PD encompasses genetic alterations, environmental factors, and age-related neurodegenerative processes. Numerous studies have demonstrated that aberrant functioning of the ubiquitin-proteasome system (UPS) plays a crucial role in the initiation and progression of PD. Notably, E3 ubiquitin ligases serve as pivotal components determining substrate specificity within UPS and are intimately associated with the regulation of various proteins implicated in PD pathology. This review comprehensively summarizes the mechanisms by which E3 ubiquitin ligases and deubiquitinating enzymes modulate PD-associated proteins and signaling pathways, while exploring the intricate relationship between UPS dysfunctions and PD etiology. Furthermore, this article discusses recent research advancements regarding inhibitors targeting PD-related E3 ubiquitin ligases.

Efficacy and relative safety of caplacizumab in immune-mediated thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.

Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMD = -0.72; 95% CI -0.88 to -0.56; P  < 0.05). Caplacizumab reduced the incidence of mortality (OR = 0.41; 95% CI 0.18-0.92; P  < 0.05), exacerbations (OR = 0.10; 95% CI 0.05-0.18; P  < 0.05), and recurrence (OR = 0.17; 95% CI 0.06-0.50; P  < 0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022362370.

Phytoalexin sakuranetin attenuates endocytosis and enhances resistance to rice blast.

Phytoalexin sakuranetin functions in resistance against rice blast. However, the mechanisms underlying the effects of sakuranetin remains elusive. Here, we report that rice lines expressing resistance (R) genes were found to contain high levels of sakuranetin, which correlates with attenuated endocytic trafficking of plasma membrane (PM) proteins. Exogenous and endogenous sakuranetin attenuates the endocytosis of various PM proteins and the fungal effector PWL2. Moreover, accumulation of the avirulence protein AvrCO39, resulting from uptake into rice cells by Magnaporthe oryzae, was reduced following treatment with sakuranetin. Pharmacological manipulation of clathrin-mediated endocytic (CME) suggests that this pathway is targeted by sakuranetin. Indeed, attenuation of CME by sakuranetin is sufficient to convey resistance against rice blast. Our data reveals a mechanism of rice against M. oryzae by increasing sakuranetin levels and repressing the CME of pathogen effectors, which is distinct from the action of many R genes that mainly function by modulating transcription.

The association between triglyceride glucose-body mass index and all-cause mortality in critically ill patients with atrial fibrillation: a retrospective study from MIMIC-IV database.

BACKGROUND: The TyG-BMI index, which is a reliable indicator of insulin resistance (IR), has been found to have a significant correlation with the occurrence of cardiovascular events. However, there still lacks study on the TyG-BMI index and prognosis in patients with atrial fibrillation (AF). The objective of the present study was to evaluate the relationship between TyG-BMI index at admission to ICU and all-cause mortality in critically ill patients with AF. METHODS: The patient's data were extracted from Medical Information Mart for Intensive Care IV(MIMIC-IV) database. All patients were divided into four groups according to TyG-BMI index. Outcomes include primary and secondary endpoints, with the primary endpoint being the 30-day and 365-day all-cause mortality and the secondary endpoint being the 90-day and 180-day all-cause mortality. TyG-BMI index was quartile and Kaplan-Meier curve was used to compare the outcome of each group. Cox proportional-hazards regression model and restricted cubic splines (RCS) were conducted to assess the relationship between TyG-BMI index and outcomes. RESULTS: Out of a total of 2509 participants, the average age was 73.26 ± 11.87 years, with 1555 (62.0%) being males. Patients with lower level of TyG-BMI had higher risk of 30-day, 90-day, 180-day and 365-day all-cause mortality, according to the Kaplan-Meier curves (log-rank P < 0.001). In addition, cox proportional-hazards regression analysis revealed that the risk of 30-day, 90-day, 180-day and 365-day all-cause mortality was significantly higher in the lowest quartile of TyG-BMI. Meanwhile, the RCS analysis indicated that L-typed relationships between TyG-BMI index and all-cause mortality, with inflection points at 223.60 for 30-day and 255.02 for 365-day all-cause mortality, respectively. Compared to patients with TyG-BMI levels below the inflection points, those with higher levels had a 1.8% lower risk for 30-day all-cause mortality (hazard ratio [HR] 0.982, 95% confidence interval [CI] 0.9676-0.988) and 1.1% lower risk for 365-day all-cause mortality (HR 0.989, 95% CI 0.986-0.991). CONCLUSION: In critically ill patients with AF, a lower TyG-BMI level is significantly associated with a higher risk of 30-day, 90-day, 180-day and 365-day all-cause mortality. TyG-BMI index could be used as a valid indicator for grading and treating patients with AF in the ICU.

Association Analysis of Gut Microbiota and Prognosis of Patients with Acute Ischemic Stroke in Basal Ganglia Region.

Previous studies have implied the potential impact of gut microbiota on acute ischemic stroke (AIS), but the relationships of gut microbiota with basal ganglia region infarction (BGRI) and the predictive power of gut microbiota in BGRI prognosis is unclear. The aim of this study was to ascertain characteristic taxa of BGRI patients with different functional outcomes and identify their predictive value. Fecal samples of 65 BGRI patients were collected at admission and analyzed with 16s rRNA gene sequencing. Three-month functional outcomes of BGRI were evaluated using modified Rankin Scale (mRS), and patients with mRS score of 0-1 were assigned to good-BGRI group while others were assigned to poor-BGRI group. We further identified characteristic microbiota using linear discriminant analysis effect size, and receiver operating characteristic (ROC) curve was used to determine the predictive value of differential bacteria. According to the mRS score assessed after 3 months of stroke onset, 22 patients were assigned to poor-BGRI group, while 43 patients were assigned to good-BGRI group. Short chain fatty acids-producing bacteria, Romboutsia and Fusicatenibacter, were characteristic microbiota of the good-BGRI group, while pro-inflammatory taxa, Acetanaerobacterium, were characteristic microbiota of the poor-BGRI group. Furthermore, the differential bacteria showed extensive associations with clinical indices. ROC curves, separately plotted based on Romboutsia and Fusicatenibacter, achieved area under the curve values of 0.7193 and 0.6839, respectively. This study identified the efficient discriminative power of characteristic microbiota in BGRI patients with different outcomes and provided novel insights into the associations of gut microbiota with related risk factors.

Association analysis of the gut microbiota in predicting outcomes for patients with acute ischemic stroke and H-type hypertension.

Introduction: H-type hypertension (HHTN) is a subtype of hypertension that tends to worsen the prognosis of acute ischemic stroke (AIS). Recent studies have highlighted the vital role of gut microbiota in both hypertension and AIS, but there is little available data on the relationship between gut microbiota and the progression of AIS patients with HHTN. In this study, we investigated the microbial signature of AIS patients with HHTN and identified characteristic bacteria as biomarkers for predicting prognosis. Methods: AIS patients with HHTN (n = 150) and without HHTN (n = 50) were enrolled. All patients received a modified Rankin Scale (mRS) assessment at 3 months after discharge. Fecal samples were collected from the participants upon admission, including 150 AIS patients with HHTN, 50 AIS patients with non-HHTN, and 90 healthy subjects with HHTN. These samples were analyzed using 16S rRNA sequencing to characterize the bacterial taxa, predict functions, and conduct correlation analysis between specific taxa and clinical features. Results: Our results showed that the composition of the gut microbiota in HHTN patients differed significantly from that in non-HHTN patients. The abundance of the genera Bacteroides, Escherichia-Shigella, Lactobacillus, Bifidobacterium, and Prevotella in AIS patients with HHTN was significantly increased compared to AIS patients without HHTN, while the genus Streptococcus, Faecalibacterium, and Klebsiella were significantly decreased. Moreover, Bacteroides, Lactobacillus, Bifidobacterium, and Klebsiella in AIS patients with HHTN were more abundant than healthy subjects with HHTN, while Escherichia-Shigella, Blautia, and Faecalibacterium were less abundant. Moreover, the genera Butyricicoccus, Rothia, and Family_XIII_UCG-001 were negatively connected with the NIHSS score, and the genera Butyricicoccus and Rothia were observed to be negatively associated with the mRS score. The genera Butyricicoccus, Romboutsia, and Terrisporobacter were associated with a poor prognosis, whereas the increase in Butyricimonas and Odoribacter was correlated with good outcomes. Generated by eight genera and clinical indexes, the area under the curve (AUC) value of the receiver operating characteristic (ROC) curve achieved 0.739 to effectively predict the prognosis of AIS patients with HHTN. Conclusion: These findings revealed the microbial signature of AIS patients with HHTN and further provided potential microbial biomarkers for the clinical diagnosis of AIS patients with HHTN.

The Diagnostic Value of Gut Microbiota Analysis for Post-Stroke Sleep Disorders.

BACKGROUND: Gut microbiota have been associated with many psychiatric disorders. However, the changes in the composition of gut microbiota in patients with post-stroke sleep disorders (PSSDs) remain unclear. Here, we determined the gut microbial signature of PSSD patients. METHODS: Fecal samples of 205 patients with ischemic stroke were collected within 24 h of admission and were further analyzed using 16 s RNA gene sequencing followed by bioinformatic analysis. The diversity, community composition, and differential microbes of gut microbiota were assessed. The outcome of sleep disorders was determined by the Pittsburgh Sleep Quality Index (PSQI) at 3 months after admission. The diagnostic performance of microbial characteristics in predicting PSSDs was assessed by receiver operating characteristic (ROC) curves. RESULTS: Our results showed that the composition and structure of microbiota in patients with PSSDs were different from those without sleep disorders (PSNSDs). Moreover, the linear discriminant analysis effect size (LEfSe) showed significant differences in gut-associated bacteria, such as species of Streptococcus, Granulicatella, Dielma, Blautia, Paeniclostridium, and Sutterella. We further managed to identify the optimal microbiota signature and revealed that the predictive model with eight operational-taxonomic-unit-based biomarkers achieved a high accuracy in PSSD prediction (AUC = 0.768). Blautia and Streptococcus were considered to be the key microbiome signatures for patients with PSSD. CONCLUSIONS: These findings indicated that a specific gut microbial signature was an important predictor of PSSDs, which highlighted the potential of microbiota as a promising biomarker for detecting PSSD patients.

Mono- and Co-Doped Mn-Doped CsPbCl3 Perovskites with Enhanced Doping Efficiency and Photoluminescent Performance.

To investigate the effect of Mn and other metal dopants on the photoelectronic performance of CsPbCl3 perovskites, we conducted a series of theoretical analyses. Our findings showed that after Mn mono-doping, the CsPbCl3 lattice contracted and the bonding strength increased, resulting in a more compact structure of the metal octahedral cage. The relaxation of the metal octahedral cage, along with the Jahn-Teller effect, results in a decrease in lattice strain between the octahedra and a reduction in the energy of the entire lattice due to the deformation of the metal octahedron. These three factors work together to reduce intrinsic defects and enhance the stability and electronic properties of CsPbCl3 perovskites. The solubility of the Mn dopant is significantly increased when co-doped with Ni, Fe, and Co dopants, as it compensates for the lattice strain induced by Mn. Doping CsPbCl3 perovskites reduces the band gap due to the decreased contributions of 3d orbitals from the dopants. Our analyses have revealed that strengthening the CsPbCl3 lattice and reducing intrinsic defects can result in improved stability and PL properties. Moreover, increasing Mn solubility and decreasing the bandgap can enhance the PLQY of orange luminescence in CsPbCl3 perovskites. These findings offer valuable insights for the development of effective strategies to enhance the photoelectronic properties of these materials.

Potential optimized route for mesenchymal stem cell transplantation in a rat model of cerebral palsy.

Cerebral palsy (CP) is a movement and posture disorder that affects over 50 million people worldwide. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation has emerged as an attractive therapeutic strategy for CP. The administration route appears to be crucial for hUC-MSC to provide adequate neuroprotection. Wistar rats were given hypoxia-ischemia to make the CP model on postnatal day 5. On postnatal day 21, DiR-labeled hUC-MSC were transplanted into the CP rats by intravenous, intrathecal, and lateral ventricle for cell tracking. Uninfused CP rats served as the negative control. The motor behavioral and pathological alteration was analyzed 11, 25, and 39 days after transplantation to assess motor function, immune inflammation, neurotrophy, and endogenous repair. In vivo imaging tracking techniques revealed that intravenous infusion resulted in fewer transplanted cells in the target brain than intrathecal and lateral ventricle infusion (p＜0.05). Three different routes of hUC-MSC infusion improved the motor function of CP rats (p＜0.05). At 11 days post-infusion, intrathecal infusion outperformed intravenous with a significant neurotrophic and oligodendrocyte maturation effect (p＜0.05). Intrathecal infusion equaled lateral ventricle infusion after 25 days. At 39 days post-infusion, lateral ventricle infusion exceeded intravenous and intrathecal infusion with a significant immunosuppressive effect (p＜0.05). Considering the improved effect and less trauma shown early in the intrathecal infusion, repeated intrathecal administration may ultimately lead to the greatest benefit.

In Vivo Evaluation of Self-assembled nano-Saikosaponin-a for Epilepsy Treatment.

Saikosaponin-a (SSa) exhibits antiepileptic effects. However, its poor water solubility and inability to pass through the blood-brain barrier greatly limit its clinical development and application. In this study, SSa-loaded Methoxy poly (ethylene glycol)-poly(ε-caprolactone) (MePEG-SSa-PCL) NPs were successfully prepared and characterized. Our objective was to further investigate the effect of this composite on acute seizure in mice. First, we confirmed the particle size and surface potential of the composite (51.00 ± 0.25 nm and - 33.77 ± 2.04 mV, respectively). Further, we compared the effects of various MePEG-SSa-PCL doses (low, medium, and high) with those of free SSa, valproic acid (VPA - positive control), and saline only (model group) on acute seizure using three different acute epilepsy mouse models. We observed that compared with the model group, the three MePEG-SSa-PCL treatments showed significantly lowered seizure frequency in mice belonging to the maximum electroconvulsive model group. In the pentylenetetrazol and kainic acid (KA) acute epilepsy models, MePEG-SSa-PCL increased both clonic and convulsion latency periods and shortened convulsion duration more effectively than equivalent SSa-only doses. Furthermore, hematoxylin-eosin and Nissl staining revealed considerably less neuronal damage in the hippocampal CA3 area of KA mice in the SSa, VPA, and three MePEG-SSa-PCL groups relative to mice in the model group. Hippocampal gamma-aminobutyric acid-A (GABA-A) receptor and cleaved caspase-3 expression levels in KA mice were significantly higher and lower, respectively, in the three MePEG-SSa-PCL treatment groups than in the model group. Thus, MePEG-SSa-PCL exhibited a more potent antiepileptic effect than SSa in acute mouse epilepsy models and could alleviate neuronal damage in the hippocampus following epileptic seizures, possibly via GABA-A receptor expression upregulation.

Constraint therapy promotes motor cortex remodeling and functional improvement by regulating c-Jun/miR-182-5p/Nogo - A signals in hemiplegic cerebral palsy mice.

BACKGROUND: Our previous study has confirmed that constraint-induced movement therapy (CIMT) could promote neural remodeling in hemiplegic cerebral palsy (HCP) mice through Nogo-A/NgR/RhoA/ROCK signaling, however, the upstream mechanism was still unclear. Therefore, the present study aimed to further explore the mechanism of CIMT regulating the expression of Nogo-A in HCP mice. METHOD: HCP mice were well established through ligating the left common carotid artery of 7-day-old pups and being placed in a hypoxic box which was filled with a mixture of 8% oxygen and 92% nitrogen. CIMT intervention was conducted by taping to fix the entire arm of the contralateral side (left) to force the mice to use the affected limb (right). Bioinformatics prediction and luciferase experiment were performed to confirm that miR-182-5p was targeted with Nogo-A. The beam test and grip test were applied to examine the behavioral performance under the intervention of c-Jun and CIMT. Also, immunofluorescence, Golgi staining, and transmission electron microscopy were conducted to show that the lenti-expression of c-Jun could increases the expression of myelin, and downregulates the expression of Nogo-A under the CIMT on HCP mice. RESULT: (1) The beam walking test and grip test experiment results showed that compared with the control group, the HCP + nCIMT group's forelimb grasping ability and balance coordination ability were decreased (P < 0.05). (2) The results of Golgi staining, and transmission electron microscopy showed that the thickness of myelin sheath and the density of dendritic spines in the HCP + nCIMT group were lower than those in the control group (P < 0.05). Compared with the HCP + nCIMT group, the cerebral cortex myelin sheath thickness, dendrite spine density and nerve filament expression were increased in HCP + CIMT group (P < 0.05). (3) Immunofluorescence staining showed that the expression of Nogo-A in the cerebral cortex of the HCP + nCIMT group was higher than that of the HCP + CIMT group (P < 0.05). Compared with the HCP + CIMT group, the expression of Nogo-A in the HCP + LC + CIMT group was decreased and, in the HCP, + SC + CIMT group was significantly increased (P < 0.05). Compared with the HCP + nCIMT group, the expression of c-Jun in the control, HCP + CIMT, HCP + LC + nCIMT and HCP + LC + CIMT groups was significantly increased, and in the HCP + SC + CIMT was decreased (P < 0.05). (4) Real-time quantitative polymerase chain reaction (RT-qPCR) results showed that the expression level of miR-182-5p in the HCP + LC + CIMT group was more increased than that in the HCP + nCIMT group (P < 0.05). The expression level of miR-182-5p in the HCP + LC + CIMT group was higher than that in the HCP + LC + nCIMT group and the HCP + SC + CIMT group (P < 0.05). CONCLUSION: These data identified that CIMT might stimulate the remodeling of neurons and myelin in the motor cortex by partially inhibiting the c-Jun/miR-182-5p/Nogo-A pathway, thereby facilitating the grasping performance and balance function of HCP mice.

FBXO7, a tumor suppressor in endometrial carcinoma, suppresses INF2-associated mitochondrial division.

Endometrial carcinoma (ECa) is the most common malignant gynecological cancer, with an increased incidence and fatality rate worldwide, while the pathogenesis is still largely unknown. In this study, we confirmed that FBXO7, a gene coding FBXO7 E3 ubiquitin ligase, is significantly downregulated and mutated (5.87%; 31/528) in ECa specimens, and the abnormal low expression and mutations of FBXO7 are associated with the occurrence of ECa. We also identify the excessive expression of INF2 protein, a key factor that triggers mitochondrial division by recruiting the DRP1 protein, and the elevated INF2 protein is significantly negatively correlated with the low FBXO7 protein in ECa specimens. Mechanistically, FBXO7 restrains ECa through inhibiting INF2-associated mitochondrial division via FBXO7-mediated ubiquitination and degradation of INF2. Moreover, we found that ECa-associated FBXO7 mutants are defective in the ubiquitination and degradation of INF2, promoting ECa cells proliferation, migration and apoptosis inhibition via inducing mitochondrial hyper-division. In addition, we found that it could reverse FBXO7 deletion or ECa-associated FBXO7 mutants-induced proliferation, migration, apoptosis inhibition and mitochondrial hyper-division of ECa cells by INF2 or DNM1L knockdown, or DRP1 inhibitor Mdivi-1. In summary, our study shows that FBXO7 acts as a novel tumor suppressor in ECa by inhibiting INF2-DRP1 axis-associated mitochondrial division through the ubiquitination and degradation of INF2 while the effect is destroyed by ECa-associated FBXO7 and INF2 mutants, highlights the key role of FBXO7-INF2-DRP1 axis in ECa tumorigenesis and provides a new viewpoint to treat ECa patients with FBXO7 deletion or mutations by targeting INF2-DRP1 axis-associated mitochondrial division.

Predictive microbial feature analysis in patients with depression after acute ischemic stroke.

Introduction: Post-stroke depression (PSD) is the most common emotional problem following a stroke, which requires early diagnosis to improve the prognosis. Gut microbiota plays important role in the pathological mechanisms of acute ischemic stroke and influences the outcome of patients. However, the relationship between PSD and gut microbiota remains unknown. Here, we explored whether the microbial signatures of gut microbiota in the patients with stroke could be an appropriate predictor of PSD. Methods: Fecal samples were collected from 232 acute ischemic stroke patients and determined by 16s rRNA sequencing. All patients then received 17-Hamilton Depression Rating Scale (HAMD-17) assessment 3 months after discharge, and were further divided into PSD group and non-PSD group. We analyzed the differences of gut microbiota between these groups. To identify gut microbial biomarkers, we then established microbial biomarker model. Results: Our results showed that the composition of gut microbiota in the PSD patients differed significantly from that in non-PSD patients. The genus Streptococcus, Akkermansia, and Barnesiella were significantly increased in PSD patients compared to non-PSD, while the genus Escherichia-Shigella, Butyricicoccus, and Holdemanella were significantly decreased. Correlation analyses displayed that Akkermansia, Barnesiella, and Pyramidobacter were positively correlated with HAMD score, while Holdemanella was negatively correlated with HAMD score. The optimal microbial markers were determined, and the combination achieved an area under the curve (AUC) value of 0.705 to distinguish PSD from non-PSD. Conclusions: Our findings suggest that PSD patients had distinct gut microbiota compared to non-PSD patients, and explore the potential of microbial markers, which might provide clinical decision-making in PSD.

Salicylic acid inhibits rice endocytic protein trafficking mediated by OsPIN3t and clathrin to affect root growth.

Salicylic acid (SA) plays important roles in different aspects of plant development, including root growth, where auxin is also a major player by means of its asymmetric distribution. However, the mechanism underlying the effect of SA on the development of rice roots remains poorly understood. Here, we show that SA inhibits rice root growth by interfering with auxin transport associated with the OsPIN3t- and clathrin-mediated gene regulatory network (GRN). SA inhibits root growth as well as Brefeldin A-sensitive trafficking through a non-canonical SA signaling mechanism. Transcriptome analysis of rice seedlings treated with SA revealed that the OsPIN3t auxin transporter is at the center of a GRN involving the coat protein clathrin. The root growth and endocytic trafficking in both the pin3t and clathrin heavy chain mutants were SA insensitivity. SA inhibitory effect on the endocytosis of OsPIN3t was dependent on clathrin; however, the root growth and endocytic trafficking mediated by tyrphostin A23 (TyrA23) were independent of the pin3t mutant under SA treatment. These data reveal that SA affects rice root growth through the convergence of transcriptional and non-SA signaling mechanisms involving OsPIN3t-mediated auxin transport and clathrin-mediated trafficking as key components.

The Humeral Metastasis as the Initial Presentation of Lung Adenocarcinoma Revealed by 18F-FDG PET/CT.

ABSTRACT: Lung adenocarcinoma with humeral metastasis as the initial presentation is rare. We reported FDG PET/CT findings of solitary humeral metastasis from adenocarcinoma of the lung in a 57-year-old man with the right upper arm pain as the initial presentation. MRI showed bone destruction of the right humerus with a soft tissue mass, suggesting the possibility of malignancy. FDG PET/CT showed that the right humeral mass had strong activity, and there were additional FDG lesions in the right armpit, left apical lung, and left adrenal gland, which was later confirmed as humeral metastasis from lung adenocarcinoma by pathological examination.

Relationship Between Nutritional Status and Severity of Cerebral Palsy: A Multicentre Cross-Sectional Study.

BACKGROUND: Nutritional problems are common in children with cerebral palsy (CP), yet the relationship between nutritional status and the severity of CP is unclear. OBJECTIVE: To describe the nutritional status and characteristics of children with CP, and to explore the relationship between severity of CP and nutritional status in children. METHODS: This multicentre cross-sectional study included children with CP in China. Weight and height were measured and converted to z-scores. Gross Motor Function Classification System (GMFCS), Eating and Drinking Ability Classification System (EDACS), Subjective Global Nutritional Assessment (SGNA), social life ability, and blood indicators were tested. RESULTS: All 1,151 participants were given oral-feeding and 50.8% of them demonstrated undernutrition. Compared with those in GMFCS or EDACS levels I-III, the odds of moderate and severe undernutrition were 2.6 and 8.9 times higher in GMFCS levels IV and V, and 4.3 and 12.6 times higher in EDACS levels IV and V, respectively. Except for serum 25-hydroxyvitamin D, no significant differences were found in blood indicators among normal, undernourished and overnourished groups. CONCLUSION: Degrees of undernutrition in children with CP are correlated with the severity of eating and drinking dysfunction and with gross motor impairment. Blood indicators may not reflect nutritional status in children with CP.

The role of BMI1 in endometrial cancer and other cancers.

Endometrial cancer (EC) is the third leading gynecological malignancy, and its treatment remains challenging. B cell-specific Moloney murine leukemia virus integration site-1 (BMI1) is one of the core members of the polycomb group (PcG) family, which plays a promoting role in the occurrence and development of various tumors. Notably, BMI1 has been found to be frequently upregulated in endometrial cancer (EC) and promote the occurrence of EC through promoting epithelial-mesenchymal transition (EMT) and AKT/PI3K pathways. This review summarizes the structure and upstream regulatory mechanisms of BMI1 and its role in EC. In addition, we focused on the role of BMI1 in chemoradiotherapy resistance and summarized the current drugs that target BMI1.

Association of Nogo-A Gene Polymorphisms with Cerebral Palsy in Southern China: A Case-Control Study.

Cerebral palsy (CP) is a motor and postural disorder syndrome caused by the nonprogressive dysfunction of the developing brain. Previous studies strongly indicated that the Nogo-A gene might be related to the pathogenesis of CP. The objective of this research was to explore the relationship between Nogo-A polymorphisms (rs1012603, rs12464595, and rs2864052) and CP in Southern China. The Hardy-Weinberg equilibrium (HWE) testing, allele and genotype frequencies analysis, and haplotype association analysis were applied to the genotyping of 592 CP children and 600 controls. The results showed that the allele and genotype frequencies of rs1012603 of CP group were significantly different from the control group. The haplotype "TTGGG" was significantly associated with an increased risk of CP. The allele frequencies of rs1012603 were significant differences between CP with spastic diplegia, female CP cases, and controls. Furthermore, significant differences in allele and genotype frequencies were also noticed between GMFCS I of CP and controls for rs1012603, and significant differences in allele and genotype frequencies were observed between the ADL (>9) of CP and controls for rs1012603 and rs12464595. This study showed that the SNPs rs1012603 of Nogo-A were significantly correlated with CP, and the correlations were also found in spastic diplegia, GMFCS I of CP, ADL (>9) of CP, and female subgroups, indicating that Nogo-A might mainly affect mild types of CP and there might be sex-related differences.

Gut microbiota alterations are associated with functional outcomes in patients of acute ischemic stroke with non-alcoholic fatty liver disease.

Introduction: Patients with acute ischemic stroke (AIS) with non-alcoholic fatty liver disease (NAFLD) frequently have poor prognosis. Many evidences suggested that the changes in gut microbiota may play an important role in the occurrence and development of AIS patients with NAFLD. The purpose of this study was to explore microbial characteristics in patients of AIS with NAFLD, and the correlation between gut microbiota and functional outcomes. Methods: The patients of AIS were recruited and divided into NAFLD group and non-NAFLD group. The stool samples and clinical information were collected. 16 s rRNA sequencing was used to analyze the characteristics of gut microbiota. The patients of AIS with NAFLD were followed-up to evaluate the functional outcomes of disease. The adverse outcomes were determined by modified Rankin scale (mRS) scores at 3 months after stroke. The diagnostic performance of microbial marker in predicting adverse outcomes was assessed by recipient operating characteristic (ROC) curves. Results: Our results showed that the composition of gut microbiota between non-NAFLD group and NAFLD group were different. The characteristic bacteria in the patients of AIS with NAFLD was that the relative abundance of Dorea, Dialister, Intestinibacter and Flavonifractor were decreased, while the relative abundance of Enorma was increased. Moreover, the characteristic microbiota was correlated with many clinical parameters, such as mRS scores, mean arterial pressure and fasting blood glucose level. In addition, ROC models based on the characteristic microbiota or the combination of characteristic microbiota with independent risk factors could distinguish functional dependence patients and functional independence patients in AIS with NAFLD (area under curve is 0.765 and 0.882 respectively). Conclusion: These findings revealed the microbial characteristics in patients of AIS with NAFLD, and further demonstrated the predictive capability of characteristic microbiota for adverse outcomes in patients of AIS with NAFLD.