Miao sour soup alleviates DSS-induced colitis in mice: modulation of gut microbiota and intestinal barrier function.

Miao sour soup (MSS), a daily fermented food in Guizhou, China, is rich in microorganisms with various beneficial activities, including anti-inflammatory and antioxidant activities. However, the therapeutic effects of MSS on IBD remain unexplored. This study aimed to investigate the protective effect of MSS against colitis in mice. In this study, we examined the microbial community structure of MSS by metagenomic sequencing and also explored the protective effect of MSS on DSS-induced colitis in mice. We investigated the effects of MSS on intestinal inflammatory response and intestinal barrier function in mice. Finally, the changes in intestinal flora were analyzed based on the 16S rRNA gene sequencing results. Significantly, the experiment result shows that MSS ameliorated the severity of DSS-induced disease in mice by mitigating colitis-associated weight loss, reducing the disease activity index of IBD, alleviating colonic hemorrhagic lesions, increasing colon length, and improving colonic tissue damage. Moreover, MSS preserved intestinal barrier integrity and restored intestinal epithelial function in mice. Additionally, MSS modulated the structure and composition of the intestinal flora. Furthermore, MSS downregulated pro-inflammatory factors and attenuated the NF-κB p65 expression, thereby mitigating the inflammatory response. These findings highlight the protective effect of MSS against DSS-induced colitis, providing substantial scientific support for potential applications of MSS as a functional food.

Gut microbiota dysbiosis in hyperuricaemia promotes renal injury through the activation of NLRP3 inflammasome.

BACKGROUND: The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown. RESULTS: A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3-/-) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated. CONCLUSION: Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract.

Gut microbiome and metabolome alterations in traditional Chinese medicine damp-heat constitution following treatment with a Chinese patent medicine and lifestyle intervention.

BACKGROUND: The gut microbiota is crucial in human health and diseases. Traditional Chinese Medicine Constitution (TCMC) divides people into those with a balanced constitution (Ping-he [PH]) and those with an unbalanced constitution. Dampness-heat constitution (Shi-re [SR]) is a common unbalanced constitution in the Chinese population and is susceptible to diseases. However, unbalanced constitutions can be regulated by Chinese medicine and lifestyle interventions in clinical practice. Ermiao Pill (EMP) is a Chinese medicine known for clearing heat and draining dampness and improving SR. However, the efficacy and mechanism of EMP are unclear. HYPOTHESIS/PURPOSE: To determine alterations in the gut microbiota and metabolome in SR and any changes after EMP treatment combined with lifestyle intervention. STUDY DESIGN: Randomized clinical trial. METHODS: We enrolled 112 healthy SR individuals and evaluated the efficacy of EMP along with lifestyle interventions. We further assessed serum cytokine levels, serum and urinary metabolomes, and the gut microbiota by 16S rRNA gene sequencing analysis before and after the EMP and lifestyle interventions. RESULTS: 107 SR individuals (55 in the intervention group and 52 in the control group) completed the 1-month-intervention and 1-year-follow-up. The intervention group significantly improved their health status within 1 month, with a reduced SR symptom score, and the efficacy lasted to the 1-year follow-up. The control group needed a further 6 months to reduce the SR symptom score. The gut microbiota of PH individuals was more diverse and had significantly higher proportions of many bacterial species than the SR. Microbiota co-occurrence network analysis showed that SR enriches metabolites correlating with microbial community structure, consistent with traits of healthy SR-enriched microbiota. CONCLUSION: EMP combined with lifestyle intervention produced health benefits in SR individuals. Our study indicates a pivotal role of gut microbiota and metabolome alterations in distinguishing between healthy SR and PH. Furthermore, the study reveals structural changes of gut microbiota and metabolites induced by EMP and lifestyle intervention. The treatment enriched the number of beneficial bacteria, such as Akkermansia muciniphila and Lactobacillus in the gut. Our findings provide a strong indication that several metabolite factors are associated with the gut microbiota. Moreover, the gut microbiome and metabolome might be powerful tools for TCMC diagnosis and personalized therapy.

Two-Photon Nanoparticle Probe for Formaldehyde Detection via the AILE Luminescence Mechanism.

A two-photon nanoparticle probe was designed and developed based on the principle of intermolecular interaction of the aggregation-induced locally excited emission luminescence mechanism. The probe has the advantages of simple synthesis, convenient use, strong atomic economy, good biocompatibility, and photobleaching resistance. It can produce a specific and sensitive response to formaldehyde, help detect FA in normal cells and cancer cells, and is expected to become a specific detection probe for FA in vitro and in vivo.

MRI brain structural and functional networks changes in Parkinson disease with REM sleep behavior disorders.

Background: Rapid eye movement sleep behavior disorder (RBD) is common in individuals with Parkinson's disease (PD). In spite of that, the precise mechanism underlying the pathophysiology of RBD among PD remains unclear. Objective: The aim of the present study was to analyze gray matter volumes (GMVs) as well as the changes of functional connectivity (FC) among PD patients with RBD (PD-RBD) by employing a combination of voxel-based morphometry (VBM) and FC methods. Methods: A total of 65 PD patients and 21 healthy control (HC) subjects were included in this study. VBM analyses were performed on all subjects. Subsequently, regions with significant different GMVs between PD patients with and without RBD (PD-nRBD) were selected for further analysis of FC. Correlations between altered GMVs and FC values with RBD scores were also investigated. Additionally, receiver operating characteristic (ROC) curves were employed for the evaluation of the predictive value of GMVs and FC in identifying RBD in PD. Results: PD-RBD patients exhibited lower GMVs in the left middle temporal gyrus (MTG) and bilateral cuneus. Furthermore, we observed higher FC between the left MTG and the right postcentral gyrus (PoCG), as well as lower FC between the bilateral cuneus (CUN) and the right middle frontal gyrus (MFG) among PD-RBD patients in contrast with PD-nRBD patients. Moreover, the GMVs of MTG (extending to the right PoCG) was positively correlated with RBD severity [as measured by REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) score]. Conversely, the FC value between the bilateral CUN and the right MTG in PD-RBD patients was negatively correlated with RBDSQ score. Conclusion: This study revealed the presence replace with GMV and FC changes among PD-RBD patients, which were closely linked to the severity of RBD symptoms. Furthermore, the combination of basic clinical characteristics, GMVs and FC values effectively predicted RBD for individuals with PD.

Clinicopathologic and Molecular Characterization of Xanthomatous Giant Cell Renal Cell Carcinomas: Further Support for a Close Morphologic Spectrum to Eosinophilic Solid and Cystic Renal Cell Carcinomas.

A recent study described a rare subtype of tuberous sclerosis complex ( TSC )-mutated renal cell carcinoma primarily characterized by Xanthomatous giant cell morphology. Only 2 cases in young individuals have been reported so far, making the correct diagnosis challenging from a pathological perspective. It remains unknown whether this tumor represents an independent subtype or belongs to other TSC -mutated tumors. We conducted a clinicopathologic evaluation and immunohistochemical profiling of 5 cases of Xanthomatous Giant Cell Renal Cell Carcinoma (XGC RCC) with confirmed TSC2 mutations through targeted DNA sequencing. In addition, we analyzed transcriptomic profiles using RNA-seq for the following samples: XGC RCC, Low-grade Oncocytic tumors (LOT), High-grade Oncocytic tumors/Eosinophilic Vacuolar Tumors (HOT/EVT), Eosinophilic Solid and Cystic Renal Cell Carcinomas (ESC RCC), Chromophobe cell Renal Cell Carcinomas (ChRCC), Renal Oncocytomas (RO), clear cell Renal Cell Carcinomas (ccRCC), and normal renal tissues. There were 2 female and 3 male patients, aged 22 to 58 years, who underwent radical nephrectomy for tumor removal. The tumor sizes ranged from 4.7 to 9.5 cm in diameter. These tumors exhibited ill-defined boundaries, showed an expansive growth pattern, and featured distinctive tumor giant cells with abundant eosinophilic to Xanthomatous cytoplasm and prominent nucleoli. All tumors had low Ki-67 proliferation indices (<1%) and demonstrated immune reactivity for CD10, PAX8, CK20, CathepsinK, and GPNMB. Next-generation sequencing confirmed TSC2 mutations in all cases. RNA sequencing-based clustering indicated a close similarity between the tumor and ESC RCC. One patient (1/5) died of an accident 63 months later, while the remaining patients (4/5) were alive without tumor recurrences or metastases at the time of analysis, with a mean follow-up duration of 43.4 months. Our research supports the concept that Xanthomatous giant cell renal cell carcinoma (XGC RCC) shares clinicopathological and molecular characteristics with ESC RCC and shows a relatively positive prognosis, providing further support for a close morphologic spectrum between the two. We propose considering XGC RCC as a distinct subtype of ESC RCC.

Clinical and CT Quantitative Features for Predicting Liver Metastases in Patients with Pancreatic Neuroendocrine Tumors: A Study with Prospective/External Validation.

RATIONALE AND OBJECTIVES: We aimed to evaluate clinical characteristics and quantitative CT imaging features for the prediction of liver metastases (LMs) in patients with pancreatic neuroendocrine tumors (PNETs). METHODS: Patients diagnosed with pathologically confirmed PNETs were included, 133 patients were in the training group, 22 patients in the prospective internal validation group, and 28 patients in the external validation group. Clinical information and quantitative features were collected. The independent variables for predicting LMs were confirmed through the implementation of univariate and multivariate logistic analyses. The diagnostic performance was evaluated by conducting receiver operating characteristic curves for predicting LMs in the training and validation groups. RESULTS: PNETs with LMs demonstrated significantly larger diameter and lower arterial/portal tumor-parenchymal enhancement ratio, arterial/portal absolute enhancement value (AAE/PAE value) (p < 0.05). After multivariate analyses, A high level of tumor marker (odds ratio (OR): 5.32; 95% CI, 1.54-18.35), maximum diameter larger than 24.6 mm (OR: 7.46; 95% CI, 1.70-32.72), and AAE value ≤ 51 HU (OR: 4.99; 95% CI, 0.93-26.95) were independent positive predictors of LMs in patients with PNETs, with area under curve (AUC) of 0.852 (95%CI, 0.781-0.907). The AUCs for prospective internal and external validation groups were 0.883 (95% CI, 0.686-0.977) and 0.789 (95% CI, 0.602-0.916), respectively. CONCLUSION: Tumor marker, maximum diameter and absolute enhancement value in arterial phase were independent predictors with good predictive performance for the prediction of LMs in patients with PNETs. Combining clinical and quantitative features may facilitate the attainment of good predictive precision in predicting LMs.

Qi-dan-dihuang decoction ameliorates renal fibrosis in diabetic rats via p38MAPK/AKT/mTOR signaling pathway.

CONTEXT: Qi-dan-dihuang decoction (QDD) has been used to treat diabetic kidney disease (DKD), but the underlying mechanisms are poorly understood. OBJECTIVE: This study reveals the mechanism by which QDD ameliorates DKD. MATERIALS AND METHODS: The compounds in QDD were identified by high-performance liquid chromatography and quadrupole-time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS). Key targets and signaling pathways were screened through bioinformatics. Nondiabetic Lepr db/m mice were used as control group, while Lepr db/db mice were divided into model group, dapagliflozin group, 1% QDD-low (QDD-L), and 2% QDD-high (QDD-H) group. After 12 weeks of administration, 24 h urinary protein, serum creatinine, and blood urea nitrogen levels were detected. Kidney tissues damage and fibrosis were evaluated by pathological staining. In addition, 30 mmol/L glucose-treated HK-2 and NRK-52E cells to induce DKD model. Cell activity and migration capacity as well as protein expression levels were evaluated. RESULTS: A total of 46 key target genes were identified. Functional enrichment analyses showed that key target genes were significantly enriched in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, in vivo and in vitro experiments confirmed that QDD ameliorated renal fibrosis in diabetic mice by resolving inflammation and inhibiting the epithelial-mesenchymal transition (EMT) via the p38MAPK and AKT-mammalian target of rapamycin (mTOR) pathways. DISCUSSION AND CONCLUSION: QDD inhibits EMT and the inflammatory response through the p38MAPK and AKT/mTOR signaling pathways, thereby playing a protective role in renal fibrosis in DKD.

Peripheral T cell lymphoma initially presenting in lung biopsies: A diagnostic challenge.

BACKGROUND: Primary or secondary pulmonary involvement by peripheral T cell lymphoma (PTCL) is rare and difficult to diagnose particularly via lung biopsies. METHODS: 22 cases of PTCL diagnosed initially in lung biopsies between January 2006 and November 2020 were retrospectively reviewed followed at Nanjing Drum Tower Hospital and the First Affiliated Hospital of Zhengzhou University, respectively, including clinical manifestations, baseline biochemical indexes, images, histological findings and other available ancillary studies such as immunostaining, Epstein-Barr virus encoded RNA (EBER) in situ hybridization and T-cell receptor rearrangement analysis upon diagnosis. RESULTS: The median age of these patients was 59 years old (range: 29-82 years) at diagnosis. The majority of them complained of fever, cough and fatigue. Computed tomography scans mainly revealed multiple ill-defined nodules/masses of various sizes and densities with or without air bronchogram. Microscopically, most lesions showed lymphoid cells with clear cytoplasm and irregular nuclear contours diffusely infiltrating alveolar septa or alveolar spaces in an inflammatory background. Several cases had a predominance of small neoplastic cells (n = 4) with atypical, irregular nuclei. One case showed a diffuse monotonous pattern of growth. Angioinvasion and necrosis were not uncommon findings. The neoplastic cells in all cases were positive for one or more T-cell markers, and negative for B-cell-lineage antigens and EBER. 19 out of 22 patients had complete follow-up information, and 17 patients were dead at the last follow-up. CONCLUSIONS: Pulmonary involvement by PTCL is rare with dismal outcome. Aggressive clinical course and several clinicopathologic clues, albeit unspecific, may alert the pathologists of the possibilities of pulmonary PTCLs.

Functional analyses of TRAF6 gene in Argopecten scallops.

The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family has been reported to be involved in many immune pathways. In a previous study, we identified 5 TRAF genes, including TRAF2, 3, 4, 6, and 7, in the bay scallop (Argopecten irradians, Air) and the Peruvian scallop (Argopecten purpuratus, Apu). Since TRAF6 is a key molecular link in the TNF superfamily, we conducted a series of studies targeting the TRAF6 gene in the Air and Apu scallops as well as their hybrid progeny, Aip (Air ♀ × Apu ♂) and Api (Apu ♀ × Air ♂). Subcellular localization assay showed that the Air-, Aip-, and Api-TRAF6 were widely distributed in the cytoplasm of the human embryonic kidney cell line (HEK293T). Additionally, dual-luciferase reporter assay revealed that among TRAF3, TRAF4, and TRAF6, only the overexpression of TRAF6 significantly activated NF-κB activity in the HEK293T cells in a dose-dependent manner. These results suggest a crucial role of TRAF6 in the immune response in Argopecten scallops. To investigate the specific immune mechanism of TRAF6 in Argopecten scallops, we conducted TRAF6 knockdown using RNA interference. Transcriptomic analyses of the TRAF6 RNAi and control groups identified 1194, 2403, and 1099 differentially expressed genes (DEGs) in the Air, Aip, and Api scallops, respectively. KEGG enrichment analyses revealed that these DEGs were primarily enriched in transport and catabolism, amino acid metabolism, peroxisome, lysosome, and phagosome pathways. Expression profiles of 28 key DEGs were confirmed by qRT-PCR assays. The results of this study may provide insights into the immune mechanisms of TRAF in Argopecten scallops and ultimately benefit scallop breeding.

Creating saponin-free yellow pea seeds by CRISPR/Cas9-enabled mutagenesis on ß-amyrin synthase.

Dry pea (Pisum sativum) seeds are valuable sources of plant protein, dietary fiber, and starch, but their uses in food products are restricted to some extent due to several off-flavor compounds. Saponins are glycosylated triterpenoids and are a major source of bitter, astringent, and metallic off-flavors in pea products. ß-amyrin synthase (BAS) is the entry point enzyme for saponin biosynthesis in pea and therefore is an ideal target for knock-out using CRISPR/Cas9 genome editing to produce saponin deficient pea varieties. Here, in an elite yellow pea cultivar (CDC Inca), LC/MS analysis identified embryo tissue, not seed coat, as the main location of saponin storage in pea seeds. Differential expression analysis determined that PsBAS1 was preferentially expressed in embryo tissue relative to seed coat and was selected for CRISPR/Cas9 genome editing. The efficiency of CRISPR/Cas9 genome editing of PsBAS1 was systematically optimized in pea hairy roots. From these optimization procedures, the AtU6-26 promoter was found to be superior to the CaMV35S promoter for gRNA expression, and the use of 37°C was determined to increase the efficiency of CRISPR/Cas9 genome editing. These promoter and culture conditions were then applied to stable transformations. As a result, a bi-allelic mutation (deletion and inversion mutations) was generated in the PsBAS1 coding sequence in a T1 plant, and the segregated psbas1 plants from the T2 population showed a 99.8% reduction of saponins in their seeds. Interestingly, a small but statistically significant increase (~12%) in protein content with a slight decrease (~5%) in starch content was observed in the psbas1 mutants under phytotron growth conditions. This work demonstrated that flavor-improved traits can be readily introduced in any pea cultivar of interest using CRISPR/Cas9. Further field trials and sensory tests for improved flavor are necessary to assess the practical implications of the saponin-free pea seeds in food applications.

Exploring organic matter conversion pathway and its effect on nitrogen removal in tidal flow constructed wetlands.

Achieving effective nitrogen removal remains a significant challenge faced by constructed wetlands. Although organic matter is a crucial factor influencing nitrogen removal, little attention has been paid to the impact of organic matter conversion pathways on nitrogen removal in constructed wetlands. Here, we showed that endogenous microorganisms performing carbon internalization could be easily enriched in tidal flow constructed wetlands (TFCWs) under its special rhythmic cycle of anaerobic/aerobic operational mode. Endogenous microorganisms could translate influent carbon sources into intracellular carbons during the anaerobic stage and supply the carbon source for endogenous denitrification after the aerobic stage (rest period). Based on these findings, an innovative combined TFCW and Nitrifying-CW system was developed, and robust total nitrogen (TN) removal (82% on average) was achieved even under carbon source limiting conditions. This performance was a substantial improvement compared to the conventional single bed TFCW with multiple "tides" (corresponding to the multiple contact/rest periods) with TN removal of only 54% on average. Simultaneous nitrification-endogenous denitrification (SNED) was found to be the major nitrogen removal pathway in the proposed system. Compared with classical nitrification-denitrification, simultaneous nitrification-endogenous denitrification brings high nitrogen conversion rates and significantly reduces the demand for oxygen and organic carbon. Furthermore, microbial community analysis indicated that endogenous microorganisms such as Candidatus_Competibacter and Defluviicoccus were successfully enriched, accounting for 50.73% and 3.46% in CW1, and 25.25% and 1.76% in CW2, respectively. Together, these mechanisms allow the proposed system to achieve efficient TN removal.

A cucumber protein, Phloem Phosphate Stress-Repressed 1, rapidly degrades in response to a phosphate stress condition.

Under depleted external phosphate (Pi), many plant species adapt to this stress by initiating downstream signaling cascades. In plants, the vascular system delivers nutrients and signaling agents to control physiological and developmental processes. Currently, limited information is available regarding the direct role of phloem-borne long-distance signals in plant growth and development under Pi stress conditions. Here, we report on the identification and characterization of a cucumber protein, Cucumis sativus Phloem Phosphate Stress-Repressed 1 (CsPPSR1), whose level in the phloem translocation stream rapidly responds to imposed Pi-limiting conditions. CsPPSR1 degradation is mediated by the 26S proteasome; under Pi-sufficient conditions, CsPPSR1 is stabilized by its phosphorylation within the sieve tube system through the action of CsPPSR1 kinase. Further, we discovered that CsPPSR1 kinase was susceptible to Pi starvation-induced degradation in the sieve tube system. Our findings offer insight into a molecular mechanism underlying the response of phloem-borne proteins to Pi-limited stress conditions.

Acacetin protects against sepsis-induced acute lung injury by facilitating M2 macrophage polarization via TRAF6/NF-κB/COX2 axis.

Acute lung injury (ALI) is the leading cause of death in patients with sepsis syndrome and without effective protective or therapeutic treatments. Acacetin, a natural dietary flavonoid, reportedly exerts several biological effects, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, acacetin's effect and underlying mechanism on sepsis-induced ALI remain unclear. Here, the mouse model was established to explore the impact of acacetin on sepsis-induced ALI. Acacetin significantly increased ALI murine survival and attenuated lung injury in histological examinations. Additionally, acacetin down-regulated myeloperoxidase activity, protein concentration, and number of neutrophils and macrophages in bronchoalveolar lavage fluid. Subsequently, inflammatory cytokines, including TNF-α, IL-1ß, and IL-6, were examined. Results showed that acacetin dramatically suppressed the production of TNF-α, IL-1ß, and IL-6. These above results indicated that acacetin attenuated sepsis-induced ALI by inhibiting the inflammatory response. Moreover, acacetin inhibited the expression of markers for M1-type (iNOS, CD86) macrophages and promoted the expression of markers for M2-type (CD206, Arg1) macrophages by western blot. In addition, acacetin down-regulated the expression TRAF6, NF-κB, and Cyclooxygenase-2 (COX2) by western blot. The high concentration of acacetin had a better effect than the low concentration. Besides, over-expression of TRAF6 up-regulated the expression of COX2, CD86, and iNOS, and the ratio of p-NF-κB to NF-κB increased the mRNA levels of TNF-α, IL-1ß, and IL-6, down-regulated the expression of CD206 and Arg1. The effects of TRAF6 were the opposite of acacetin. And TRAF6 could offset the impact of acacetin. This study demonstrated that acacetin could prevent sepsis-induced ALI by facilitating M2 macrophage polarization via TRAF6/NF-κB/COX2 axis.

Insight into the role of non-coding RNA in the diagnosis and treatment of retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common type of inherited retinal dystrophy. The course of RP is irreversible and leads to progressive loss of vision. It is characterized by hypotrophic degeneration of photoreceptor cells and retinal pigment epithelium. Multiple factors are involved in the development of the disease, including apoptosis, oxidative stress, and inflammatory/immune responses. In the past decades, gene therapy, stem cell therapy and other therapeutic approaches have been extensively investigated. However, due to the heritability and high heterogeneity of the disease and the difficulty in diagnosis and treatment, there is still a lack of standardized and effective therapies. Therefore, there is a need to develop new diagnostic and therapeutic approaches suitable for diseases with pathogenic mutations. With the understanding of the interaction between gene expression regulation and retinal pathology, the value of clinical applications of non-coding RNAs (ncRNAs) in retinal degeneration has gained attention. There is growing evidence that ncRNAs are widely distributed and involved in the regulation of multiple biological processes in the retina as well as processes associated with the development of RP, making them promising biomarkers for the diagnosis, treatment, and prognosis of RP. This paper reviews the crosstalk between ncRNA and RP, systematically discusses the role of ncRNAs in normal retinal cell physiology and RP pathogenesis and explores the potential of ncRNAs as therapeutic agents for clinical applications in RP.

Machine Learning Methods Based on CT Features Differentiate G1/G2 From G3 Pancreatic Neuroendocrine Tumors.

RATIONALE AND OBJECTIVES: To identify CT features for distinguishing grade 1 (G1)/grade 2 (G2) from grade 3 (G3) pancreatic neuroendocrine tumors (PNETs) using different machine learning (ML) methods. MATERIALS AND METHODS: A total of 147 patients with 155 lesions confirmed by pathology were retrospectively included. Clinical-demographic and radiological CT features was collected. The entire cohort was separated into training and validation groups at a 7:3 ratio. Least absolute shrinkage and selection operator (LASSO) algorithm and principal component analysis (PCA) were used to select features. Three ML methods, namely logistic regression (LR), support vector machine (SVM), and K-nearest neighbor (KNN) were used to build a differential model. Receiver operating characteristic (ROC) curves and precision-recall curves for each ML method were generated. The area under the curve (AUC), accuracy rate, sensitivity, and specificity were calculated. RESULTS: G3 PNETs were more likely to present with invasive behaviors and lower enhancement than G1/G2 PNETs. The LR classifier yielded the highest AUC of 0.964 (95% confidence interval [CI]: 0.930, 0.972), with 95.4% accuracy rate, 95.7% sensitivity, and 92.9% specificity, followed by SVM (AUC: 0.957) and KNN (AUC: 0.893) in the training group. In the validation group, the SVM classier reached the highest AUC of 0.952 (95% CI: 0.860, 0.981), with 91.5% accuracy rate, 97.3% sensitivity, and 70% specificity, followed by LR (AUC: 0.949) and KNN (AUC: 0.923). CONCLUSIONS: The LR and SVM classifiers had the best performance in the training group and validation group, respectively. ML method could be helpful in differentiating between G1/G2 and G3 PNETs.

Phloem-Mobile MYB44 Negatively Regulates Expression of PHOSPHATE TRANSPORTER 1 in Arabidopsis Roots.

Phosphorus (P) is an essential plant macronutrient; however, its availability is often limited in soils. Plants have evolved complex mechanisms for efficient phosphate (Pi) absorption, which are responsive to changes in external and internal Pi concentration, and orchestrated through local and systemic responses. To explore these systemic Pi responses, here we identified AtMYB44 as a phloem-mobile mRNA, an Arabidopsis homolog of Cucumis sativus MYB44, that is responsive to the Pi-starvation stress. qRT-PCR assays revealed that AtMYB44 was up-regulated and expressed in both shoot and root in response to Pi-starvation stress. The atmyb44 mutant displayed higher shoot and root biomass compared to wild-type plants, under Pi-starvation conditions. Interestingly, the expression of PHOSPHATE TRANSPORTER1;2 (PHT1;2) and PHT1;4 was enhanced in atmyb44 in response to a Pi-starvation treatment. A split-root assay showed that AtMYB44 expression was systemically regulated under Pi-starvation conditions, and in atmyb44, systemic controls on PHT1;2 and PHT1;4 expression were moderately disrupted. Heterografting assays confirmed graft transmission of AtMYB44 transcripts, and PHT1;2 and PHT1;4 expression was decreased in heterografted atmyb44 rootstocks. Taken together, our findings support the hypothesis that mobile AtMYB44 mRNA serves as a long-distance Pi response signal, which negatively regulates Pi transport and utilization in Arabidopsis.

Brain morphology and functional connectivity alterations in patients with severe obstructive sleep apnea.

BACKGROUND: It has been demonstrated that widespread structural and functional brain alterations influence the development of cognitive impairment in patients with obstructive sleep apnea (OSA). However, the literature has limited evidence regarding the neuropathophysiological mechanisms behind these impairments. This research aimed to investigate brain morphologic and functional connectivity (FC) abnormalities related to neurocognitive function in OSA. METHODS: Fifty treatment-naïve males, newly diagnosed patients with severe OSA, and 50 well-matched healthy controls (HCs) were enrolled prospectively. All subjects underwent an MRI scan, cognitive psychological and sleep scale assessment. The differences of brain morphological and seed-based FC between the two groups were compared. The correlation analysis and receiver operating characteristic curve were performed for further analysis. RESULTS: Compared with HCs, the right brainstem, left dorsal-lateral superior frontal gyrus (SFGdor), and superior temporal gyrus (STG) exhibited atrophy in the OSA group. In addition, FC between the left SFGdor and the right postcentral gyrus (PoCG) was increased, which was positively correlated with disease duration (r = 0.312, FDR-corrected P = 0.027). The Jacobian values of the brainstem were negatively correlated with MoCA and recall scores (r = -0.449, FDR-corrected P = 0.0025; r = -0.416, FDR-corrected P = 0.005). Furthermore, the Jacobian values of the left SFGdor demonstrated a relatively high diagnostic performance (sensitivity: 86%, specificity: 56%, AUC: 0.740, 95% CI: 0.643-0.836, P < 0.0001). CONCLUSIONS: Structural atrophy in brainstem and frontotemporal lobe and altered FC may be the neurobiological hallmark of brain impairment in OSA. Notably, brainstem atrophy has been associated with cognitive impairment, which may provide new insights into understanding the neuropathophysiological mechanisms of cognitive impairment in OSA patients.

Value of Combined Bone Morphogenetic Protein-2/7 Testing in the Assessment of Infected Preterm Labor.

Objective: To analyze the clinical significance of bone morphogenetic protein-2 (BMP-2) and bone morphogenetic protein-7 (BMP-7), members of the bone morphogenetic protein family, in infectious preterm birth, to provide references for future prevention and management of IPB. Methods: The study participants were 20 pregnant women with IPB admitted to between January 2022 and January 2023 (research group) and 20 concurrent normal pregnancies (control group). Serum BMP2, BMP-7 inflammatory factors were quantified. Differences in BMP2 and BMP-7 were identified. The Receiver Operating Characteristic curve analyzed the evaluation value of BMP2 and BMP-7 on infectious preterm birth and adverse pregnancy outcomes in pregnant women, and Pearson correlation coefficient determined the correlation of the two with inflammatory factors levels. Results: The research group was higher in serum BMP2 and BMP-7 levels than control group (P < .05). The joint detection by BMP2 and BMP-7 had a sensitivity of 80.00% and a specificity of 90.00% in diagnosing infectious preterm birth (P < .05), and its sensitivity and specificity in predicting adverse pregnancy outcomes in infectious preterm birth pregnant women were 100.0% and 66.67%, respectively (P < .05). According to Pearson correlation coefficient analysis, there was an obvious positive relationship between BMP-2 and BMP-7 and inflammatory factors in research group (P < .05). Conclusions: BMP-2 and BMP-7 are elevated in IPB and are linked to inflammatory factor levels. Joint detection of BMP2 and BMP-7 shows promising potential for evaluating infectious preterm birth.