RiboDiffusion: tertiary structure-based RNA inverse folding with generative diffusion models.

MOTIVATION: RNA design shows growing applications in synthetic biology and therapeutics, driven by the crucial role of RNA in various biological processes. A fundamental challenge is to find functional RNA sequences that satisfy given structural constraints, known as the inverse folding problem. Computational approaches have emerged to address this problem based on secondary structures. However, designing RNA sequences directly from 3D structures is still challenging, due to the scarcity of data, the nonunique structure-sequence mapping, and the flexibility of RNA conformation. RESULTS: In this study, we propose RiboDiffusion, a generative diffusion model for RNA inverse folding that can learn the conditional distribution of RNA sequences given 3D backbone structures. Our model consists of a graph neural network-based structure module and a Transformer-based sequence module, which iteratively transforms random sequences into desired sequences. By tuning the sampling weight, our model allows for a trade-off between sequence recovery and diversity to explore more candidates. We split test sets based on RNA clustering with different cut-offs for sequence or structure similarity. Our model outperforms baselines in sequence recovery, with an average relative improvement of 11% for sequence similarity splits and 16% for structure similarity splits. Moreover, RiboDiffusion performs consistently well across various RNA length categories and RNA types. We also apply in silico folding to validate whether the generated sequences can fold into the given 3D RNA backbones. Our method could be a powerful tool for RNA design that explores the vast sequence space and finds novel solutions to 3D structural constraints. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/ml4bio/RiboDiffusion.

Mobile iodides capture for highly photolysis- and reverse-bias-stable perovskite solar cells.

For halide perovskites that are susceptible to photolysis and ion migration, iodide-related defects, such as iodine (I2) and iodine vacancies, are inevitable. Even a small number of these defects can trigger self-accelerating chemical reactions, posing serious challenges to the durability of perovskite solar cells. Fortunately, before I2 can damage the perovskites under illumination, they generally diffuse over a long distance. Therefore, detrimental I2 can be captured by interfacial materials with strong iodide/polyiodide (Ix-) affinities, such as fullerenes and perfluorodecyl iodide. However, fullerenes in direct contact with perovskites fail to confine Ix- ions within the perovskite layer but cause detrimental iodine vacancies. Perfluorodecyl iodide, with its directional Ix- affinity through halogen bonding, can both capture and confine Ix-. Therefore, inverted perovskite solar cells with over 10 times improved ultraviolet irradiation and thermal-light stabilities (under 85 °C and 1 sun illumination), and 1,000 times improved reverse-bias stability (under ISOS-V ageing tests) have been developed.

A Streptomyces species from the ginseng rhizosphere exhibits biocontrol potential.

Plants and their associated microbes live in complicated, changeable, and unpredictable environments. They usually interact with each other in many ways through multidimensional, multiscale, and multilevel coupling manners, leading to challenges in the coexistence of randomness and determinism or continuity and discreteness. Gaining a deeper understanding of these diverse interaction mechanisms can facilitate the development of data-mining theories and methods for complex systems, coupled modeling for systems with different spatiotemporal scales and functional properties, or even a universal theory of information and information interactions. In this study, we use a "closed-loop" model to present a plant-microbe interaction system and describe the probable functions of microbial natural products. Specifically, we report a rhizosphere species, Streptomyces ginsengnesis G7, which produces polyketide lydicamycins and other active metabolites. Interestingly, these distinct molecules have the potential to function both as antibiotics and as herbicides for crop protection. Detailed laboratory experiments conducted in Arabidopsis (Arabidopsis thaliana), combined with a comprehensive bioinformatics analysis, allow us to rationalize a model for this specific plant-microbe interaction process. Our work reveals the benefits of exploring otherwise neglected resources for the identification of potential functional molecules and provides a reference to better understand the system biology of complex ecosystems.

Zearalenone modulates the function of goat endometrial cells via the mitochondrial quality control system.

Zearalenone (ZEN) is a mycotoxin known for its estrogen-like effects, which can disrupt the normal physiological function of endometrial cells and potentially lead to abortion in female animals. However, the precise mechanism by which ZEN regulates endometrial function remains unclear. In this study, we found that the binding receptor estrogen receptors for ZEN is extensively expressed across various segments of the uterus and within endometrial cells, and a certain concentration of ZEN treatment reduced the proliferation capacity of goat endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs). Meanwhile, cell cycle analysis revealed that ZEN treatment leaded to cell cycle arrest in goat EECs and ESCs. To explore the underlying mechanism, we investigated the mitochondrial quality control systems and observed that ZEN triggered excessive mitochondrial fission and disturbed the balance of mitochondrial fusion-fission dynamics, impaired mitochondrial biogenesis, increased mitochondrial unfolded protein response and mitophagy in goat EECs and ESCs. Additionally, ZEN treatment reduced the activities of mitochondrial respiratory chain complexes, heightened the production of hydrogen peroxide and reactive oxygen species, and caused cellular oxidative stress and mitochondrial dysfunction. These results suggest that ZEN has adverse effects on goat endometrium cells by disrupting the mitochondrial quality control system and affecting cell cycle and proliferation. Understanding the underlying molecular pathways involved in ZEN-induced mitochondrial dysfunction and its consequences on cell function will provide critical insights into the reproductive toxicity of ZEN and contribute to safeguarding the health and wellbeing of animals and humans exposed to this mycotoxin.

Compact bone mesenchymal stem cells-derived paracrine mediators for cell-free therapy in sepsis.

Sepsis, a life-threatening condition resulting in multiple organ dysfunction, is characterized by a dysregulated immune response to infection. Current treatment options are limited, leading to unsatisfactory outcomes for septic patients. Here, we present a series of studies utilizing compact bone mesenchymal stem cells (CB-MSCs) and their derived paracrine mediators, especially exosome (CB-MSCs-Exo), to treat mice with cecal ligation and puncture-induced sepsis. Our results demonstrate that CB-MSCs treatment significantly improves the survival rate of septic mice by mitigating excessive inflammatory response and attenuating sepsis-induced organ injuries. Furthermore, CB-MSCs-conditioned medium, CB-MSCs secretome (CB-MSCs-Sec), and CB-MSCs-Exo exhibit potent anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated murine macrophage (RAW264.7). Intriguingly, intravenous administration of CB-MSCs-Exo confers superior protection against inflammation and organ damage in septic mice compared to CB-MSCs in certain aspects. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) shotgun proteomic analysis, we identify a range of characterized proteins derived from the paracrine activity of CB-MSCs, involved in critical biological processes such as immunomodulation and apoptosis. Our findings highlight that the paracrine products of CB-MSCs could serve as a promising cell-free therapeutic agent for sepsis.

Room-Temperature Liquid Crystalline Tetraphenylethylene-Surfactant Complex with Chiral Supramolecular Structure and Tunable Circularly Polarized Luminescence.

A novel room-temperature liquid crystal of tetraphenylethylene derivative (TPE-DHAB) was synthesized using an ionic self-assembly strategy. The TPE-DHAB complex exhibits typical aggregation-induced emission properties and a unique helical supramolecular structure. Moreover, the generation and handedness inversion of circularly polarized luminescence (CPL) can be achieved through further chiral solvation, providing a facile approach to fabricate room-temperature liquid crystalline materials with controllable supramolecular structures and tunable CPL properties through a synergistic strategy of ionic self-assembly and chiral solvation process.

Changes in liver and kidney function, red blood cell count and hemoglobin levels 1 day after ultrasound-guided percutaneous microwave ablation for uterine fibroids.

OBJECTIVE: To investigate the changes in liver and kidney function, red blood cell (RBC) count and hemoglobin (HGB) levels in patients undergoing ultrasound-guided percutaneous microwave ablation (UPMWA) for uterine fibroids on postoperative day 1. METHODS: The changes in liver and kidney function, RBC count and HGB levels in 181 patients who underwent selective UPMWA in the Second Affiliated Hospital of Shantou University Medical College, China, between August 2017 and January 2023 were retrospectively analyzed. RESULTS: All patients underwent UPMWA for uterine fibroids; 179 patients had multiple uterine fibroids and 2 patients had single uterine fibroids. The maximum fibroid diameter ranged from 18 to 140 mm, with an average of 68.3 mm. Ultrasound imaging was used to confirm that the blood flow signal within the mass had disappeared in all patients, indicating that the ablation was effective. Within 24 h, compared with before UPMWA, levels of total bilirubin, direct bilirubin, indirect bilirubin and aspartate aminotransferase had significantly increased (p < 0.01), whereas levels of total protein, albumin, globulin, alanine aminotransferase, creatinine and urea had significantly decreased (p < 0.01). Acute kidney injury (AKI) occurred in 1 of the 181 patients. The RBC count and HGB levels decreased significantly after UPMWA (p < 0.01). CONCLUSION: Ultrasound-guided percutaneous microwave ablation for uterine fibroids can impose a higher detoxification load on the liver and cause thermal damage to and the destruction of RBCs within local circulation, potentially leading to AKI. Protein levels significantly decreased after UPMWA. Therefore, perioperative organ function protection measures and treatment should be actively integrated into clinical practice to improve prognosis and enhance recovery.

γ-Aminobutyric Acid-Ergic Development Contributes to the Enhancement of Electroencephalogram Slow-Delta Oscillations Under Volatile Anesthesia in Neonatal Rats.

BACKGROUND: General anesthetics (eg, propofol and volatile anesthetics) enhance the slow-delta oscillations of the cortical electroencephalogram (EEG), which partly results from the enhancement of (γ-aminobutyric acid [GABA]) γ-aminobutyric acid-ergic (GABAergic) transmission. There is a GABAergic excitatory-inhibitory shift during postnatal development. Whether general anesthetics can enhance slow-delta oscillations in the immature brain has not yet been unequivocally determined. METHODS: Perforated patch-clamp recording was used to confirm the reversal potential of GABAergic currents throughout GABAergic development in acute brain slices of neonatal rats. The power density of the electrocorticogram and the minimum alveolar concentrations (MAC) of isoflurane and/or sevoflurane were measured in P4-P21 rats. Then, the effects of bumetanide, an inhibitor of the Na + -K + -2Cl - cotransporter (NKCC1) and K + -Cl - cotransporter (KCC2) knockdown on the potency of volatile anesthetics and the power density of the EEG were determined in vivo. RESULTS: Reversal potential of GABAergic currents were gradually hyperpolarized from P4 to P21 in cortical pyramidal neurons. Bumetanide enhanced the hypnotic effects of volatile anesthetics at P5 (for MAC LORR , isoflurane: 0.63% ± 0.07% vs 0.81% ± 0.05%, 95% confidence interval [CI], -0.257 to -0.103, P < .001; sevoflurane: 1.46% ± 0.12% vs 1.66% ± 0.09%, 95% CI, -0.319 to -0.081, P < .001); while knockdown of KCC2 weakened their hypnotic effects at P21 in rats (for MAC LORR , isoflurane: 0.58% ± 0.05% to 0.77% ± 0.20%, 95% CI, 0.013-0.357, P = .003; sevoflurane: 1.17% ± 0.04% to 1.33% ± 0.04%, 95% CI, 0.078-0.244, P < .001). For cortical EEG, slow-delta oscillations were the predominant components of the EEG spectrum in neonatal rats. Isoflurane and/or sevoflurane suppressed the power density of slow-delta oscillations rather than enhancement of it until GABAergic maturity. Enhancement of slow-delta oscillations under volatile anesthetics was simulated by preinjection of bumetanide at P5 (isoflurane: slow-delta changed ratio from -0.31 ± 0.22 to 1.57 ± 1.15, 95% CI, 0.67-3.08, P = .007; sevoflurane: slow-delta changed ratio from -0.46 ± 0.25 to 0.95 ± 0.97, 95% CI, 0.38-2.45, P = .014); and suppressed by KCC2-siRNA at P21 (isoflurane: slow-delta changed ratio from 16.13 ± 5.69 to 3.98 ± 2.35, 95% CI, -18.50 to -5.80, P = .002; sevoflurane: slow-delta changed ratio from 0.13 ± 2.82 to 3.23 ± 2.49, 95% CI, 3.02-10.79, P = .003). CONCLUSIONS: Enhancement of cortical EEG slow-delta oscillations by volatile anesthetics may require mature GABAergic inhibitory transmission during neonatal development.

Implementation of Engagement Detection for Human-Robot Interaction in Complex Environments.

This study develops a comprehensive robotic system, termed the robot cognitive system, for complex environments, integrating three models: the engagement model, the intention model, and the human-robot interaction (HRI) model. The system aims to enhance the naturalness and comfort of HRI by enabling robots to detect human behaviors, intentions, and emotions accurately. A novel dual-arm-hand mobile robot, Mobi, was designed to demonstrate the system's efficacy. The engagement model utilizes eye gaze, head pose, and action recognition to determine the suitable moment for interaction initiation, addressing potential eye contact anxiety. The intention model employs sentiment analysis and emotion classification to infer the interactor's intentions. The HRI model, integrated with Google Dialogflow, facilitates appropriate robot responses based on user feedback. The system's performance was validated in a retail environment scenario, demonstrating its potential to improve the user experience in HRIs.

Sentiment analysis of online reviews of energy-saving products based on transfer learning and LBBA model.

With the exacerbation of global climate change and the growing environmental awareness among the general public, the concept of green consumption has gained significant attention across various sectors of society. As a representative example of green consumer products, energy-saving products play a crucial role in the timely realization of dual carbon goals. However, an analysis of online comments regarding energy-saving products reveals that the majority of these products still exhibit shortcomings in terms of efficacy, noise level, cost-effectiveness, and particularly, energy-saving appliances. This study focuses on the user-generated online comments data from the Taobao e-commerce platform for Grade 1 energy-saving refrigerators. By employing text mining techniques, the study aims to extract the essential information and sentiments expressed in the comments, in order to explore the consumption characteristics of Grade 1 energy-saving refrigerators. Moreover, the LBBA (LDA-Bert-BiLSTM-Attention) model is utilized to investigate the consumer topics of interest and emotional features. Initially, the LDA model is adopted to identify the attributes and weights of consumer concerns. Subsequently, the Bert model is pre-trained with the online comment data, and combined with the BiLSTM algorithm and Attention mechanism to predict sentiment categories. Finally, a transfer learning approach is utilized to determine the sentiment inclination of user-generated online comments and to identify the primary driving factors behind each sentiment category. This research employs sentiment analysis on online comments data regarding energy-saving products to uncover consumer sentiment attributes and emotional characteristics. It provides decision-makers with a comprehensive and systematic understanding of public consumption intentions, offering decision support for the efficient operation and management of the energy-saving product market.

Alternation of social behaviors for zebrafish (Danio rerio) in response to acute cold stress.

Low temperature is one of the most common abiotic stresses for aquatic ectotherms. Ambient low temperatures reduce the metabolic rate of teleosts, therefore, teleosts have developed strategies to modulate their physiological status for energy saving in response to cold stress, including behaviors, circulatory system, respiratory function, and metabolic adjustments. Many teleosts are social animals and they can live in large schools to serve a variety of functions, including predator avoidance, foraging efficiency, and reproduction. However, the impacts of acute cold stress on social behaviors of fish remain unclear. In the present study, we test the hypothesis that zebrafish alter their social behaviors for energy saving as a strategy in response to acute cold stress. We found that acute cold stress increased shoaling behavior that reflected a save-energy strategy for fish to forage and escape from the predators under cold stress. The aggressive levels measured by fighting behavior tests and mirror fighting tests were reduced by cold treatment. In addition, we also found that acute cold stress impaired the learning ability but did not affect memory. Our findings provided evidence that acute cold stress alters the social behaviors of aquatic ectotherms for energy saving; knowledge of their responses to cold is essential for their conservation and management.

Immunological relationship between Helicobacter pylori and anti-tumor necrosis factor α agents in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a group of diseases characterized by refractory and chronic inflammation of the bowel, which can be treated with biologics in clinical practice. Anti-tumor necrosis factor α (TNF-α) agents, which are among the most widely used biologics, alleviate the inflammatory activity in a variety of ways. Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric mucosa, which could cause chronic inflammation and even induce gastric cancer. However, it has been suggested that H. pylori has a potential protective role in IBD patients. Yet there has been limited research on the mechanisms of the effect of H. pylori infection in IBD patients, and whether there is an interaction between H. pylori and anti-TNF-α agents. This review aims to summarize the possible mechanisms of H. pylori and anti-TNF-α agents in the development and treatment of IBD, and to explore the possible interaction between H. pylori infection and anti-TNF-α agents.

[Activated phosphoinositide 3-kinase delta syndrome: report of seven cases]. / PI3Kδ过度活化综合征7例报道.

OBJECTIVES: To summarize the clinical data of 7 children with activated phosphoinositide 3-kinase delta syndrome (APDS) and enhance understanding of the disease. METHODS: A retrospective analysis was conducted on clinical data of 7 APDS children admitted to Hunan Provincial People's Hospital from January 2019 to August 2023. RESULTS: Among the 7 children (4 males, 3 females), the median age of onset was 30 months, and the median age at diagnosis was 101 months. Recurrent respiratory tract infections, hepatosplenomegaly, and multiple lymphadenopathy were observed in all 7 cases. Sepsis was observed in 5 cases, otitis media and multiple caries were observed in 3 cases, and diarrhea and joint pain were observed in 2 cases. Lymphoma and systemic lupus erythematosus were observed in 1 case each. Fiberoptic bronchoscopy was performed in 4 cases, revealing scattered nodular protrusions in the bronchial lumen. The most common respiratory pathogen was Streptococcus pneumoniae (4 cases). Six patients had a p.E1021K missense mutation, and one had a p.434-475del splice site mutation. CONCLUSIONS: p.E1021K is the most common mutation site in APDS children. Children who present with one or more of the following symptoms: recurrent respiratory tract infections, hepatosplenomegaly, multiple lymphadenopathy, otitis media, and caries, and exhibit scattered nodular protrusions on fiberoptic bronchoscopy, should be vigilant for APDS. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(5): 499-505.

[Value of calprotectin S100 A8/A9 in predicting the severity of Mycoplasma pneumoniae pneumonia in children]. / 钙卫蛋白S100 A8/A9å¯¹è‚ºç‚Žæ”¯åŽŸä½“è‚ºç‚Žæ‚£å„¿ç— æƒ ä¸¥é‡ç¨‹åº¦çš„é¢„æµ‹ä»·å€¼.

OBJECTIVES: To investigate the role of calprotectin S100 A8/A9 complex in evaluating the condition of children with severe Mycoplasma pneumoniae pneumonia (SMPP). METHODS: A prospective study was conducted among 136 children with Mycoplasma pneumoniae pneumonia (MPP) and 30 healthy controls. According to the severity of the condition, the children with MPP were divided into mild subgroup (40 children) and SMPP subgroup (96 children). The levels of S100 A8/A9 complex and related inflammatory factors were compared between the MPP group and the healthy control group, as well as between the two subgroups of MPP. The role of S100 A8/A9 in assessing the severity of MPP was explored. RESULTS: The MPP group had a significantly higher level of S100 A8/A9 than the healthy control group, with a significantly greater increase in the SMPP subgroup (P<0.05). The multivariate logistic regression analysis showed that the increases in serum C reactive protein (CRP) and S100A8/A9 were closely associated with SMPP (P<0.05). The receiver operating characteristic (ROC) curve analysis showed that the combined measurement of serum S100 A8/A9 and CRP had an area under the ROC curve of 0.904 in predicting SMPP, which was significantly higher than the AUC of S100 A8/A9 or CRP alone (P<0.05), with a specificity of 0.718 and a sensitivity of 0.952. CONCLUSIONS: S100 A8/A9 is closely associated with the severity of MPP, and the combination of S100 A8/A9 with CRP is more advantageous for assessing the severity of MPP in children.

CF1 reduces grain-cadmium levels in rice (Oryza sativa).

Rice (Oryza sativa) is a leading source of dietary cadmium (Cd), a non-essential heavy metal that poses a serious threat to human health. There are significant variations in grain-Cd levels in natural rice populations, which make the breeding of low-Cd rice a cost-effective way to mitigate grain-Cd accumulation. However, the genetic factors that regulate grain-Cd accumulation have yet to be fully established, thereby hindering the development of low-Cd varieties. Here, we reported a low-Cd quantitative trait locus, CF1, that has the potential to reduce Cd accumulation in rice grains. CF1 is allelic to the metal transporter OsYSL2, which transports Fe from the roots to the shoots. However, it is incapable of binding Cd, and thus, reduces grain-Cd levels indirectly rather than directly in the form of upward delivery. Further analysis showed that high expression levels of CF1 improve Fe nutrition in the shoots, subsequently inhibiting Cd uptake by systemically inhibiting expression of the main Cd uptake gene OsNramp5 in the roots. Compared with the CF1 allele from '02428' (CF102428 ), higher expression levels of CF1 from 'TQ' (CF1TQ ) increased the Fe contents and decreased Cd levels in rice grains. In natural rice populations, CF1TQ was found to be a minor allele, while CF102428 is present in most japonica rice, suggesting that CF1TQ could be widely integrated into the japonica rice genome to generate low-Cd varieties. Overall, these results broaden our mechanistic understanding of the natural variation in grain-Cd accumulation, supporting marker-assisted selection of low-Cd rice.

Identification of flowering genes in Camellia perpetua by comparative transcriptome analysis.

Camellia perpetua has the excellent characteristic of flowering multiple times throughout the year, which is of great importance to solve the problem of "short flowering period" and "low fresh flower yield" in the yellow Camellia industry at present. Observations of flowering phenology have demonstrated that most floral buds of C. perpetua were formed by the differentiation of axillary buds in the scales at the base of the terminal buds of annual branches. However, the molecular mechanism of flowering in C. perpetua is still unclear. In this study, we conducted a comparative transcriptomic study of the terminal buds and their basal flower buds in March (spring) and September (autumn) using RNA-seq and found that a total of 11,067 genes were significantly differentially expressed in these two periods. We identified 27 genes related to gibberellin acid (GA) synthesis, catabolism, and signal transduction during floral bud differentiation. However, treatment of the terminal buds and axillary buds of C. perpetua on annual branch with GA3 did not induce floral buds at the reproductive growth season (in August) but promoted shoot sprouting. Moreover, 203 flowering genes were identified from the C. perpetua transcriptome library through homology alignment, including flowering integrators LEAFY (LFY) and UNUSUAL FLORAL ORGANS (UFO), as well as MADS-box, SQUAMOSA PROMOTER BINDING PROTEIN-box (SBP-box), and TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) genes, which were specifically upregulated in floral buds and were likely involved in flowering in C. perpetua. The floral inhibitor CperTFL1b was identified and cloned from C. perpetua, and its expression level was specifically regulated in terminal buds in autumn. Ectopic overexpression of CperTFL1b delayed flowering time and produced abnormal inflorescence and floral organs in Arabidopsis, suggesting that CperTFL1b inhibits flowering. In conclusion, this study deepens our understanding of the molecular mechanism of blooms throughout the year in C. perpetua and provides a helpful reference for cultivating new varieties of yellow Camellia with improved flowering traits.

Improved Thermal Stability and Film Uniformity of Halide Perovskite by Confinement Effect brought by Polymer Chains of Polyvinyl Pyrrolidone.

Polyvinyl pyrrolidone (PVP) is doped to PbI2 and organic salt during two-step growth of halideperovskite. It is observed that PVP molecules can interact with both PbI2 and organic salt, reduce the aggregation and crystallization of the two, and then slow down the coarsening rate of perovskite. As doping concentration increases from 0 to 1 mM in organic salt, average crystallite size of perovskite decreases monotonously from 90 to 34 nm; Surface fluctuation reduces from 259.9 to 179.8 nm at first, and then increases; Similarly, surface roughness decreases from 45.55 to 26.64 nm at first, and then rises. Accordingly, a kind of "confinement effect" is resolved to crystallite growth and surface fluctuation/roughness, which helps to build compact and uniform perovskite film. Density of trap states (t-DOS) is cut down by ≈60% at moderate doping  (0.2 mM). Due to the "confinement effect", power conversion efficiency of perovskite solar cells is improved from 19.46 (±2.80) % to 21.50 (±0.99) %, and further improved to 24.11% after surface modification. Meanwhile, "confinement effect" strengthens crystallite/grain boundaries and improves thermal stability of both film and device. T80 of device increases to 120 h, compared to 50 h for reference ones.

A two-stage genome-wide association study identifies novel germline genetic variations in CACNA2D3 associated with radiotherapy response in nasopharyngeal carcinoma.

BACKGROUND: Radiotherapy (RT) is the standard treatment for nasopharyngeal carcinoma (NPC). However, due to individual differences in radiosensitivity, biomarkers are needed to tailored radiotherapy to cancer patients. However, comprehensive genome-wide radiogenomic studies on them are still lacking. The aim of this study was to identify genetic variants associated with radiotherapy response in patients with NPC. METHODS: This was a large­scale genome-wide association analysis (GWAS) including a total of 981 patients. 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant loci were further genotyped using MassARRAY system and TaqMan SNP assays in the validation stages of 847 patients. This study used logistic regression analysis and multiple bioinformatics tools such as PLINK, LocusZoom, LDBlockShow, GTEx, Pancan-meQTL and FUMA to examine genetic variants associated with radiotherapy efficacy in NPC. RESULTS: After genome-wide level analysis, 19 SNPs entered the validation stage (P < 1 × 10- 6), and rs11130424 ultimately showed statistical significance among these SNPs. The efficacy was better in minor allele carriers of rs11130424 than in major allele carriers. Further stratified analysis showed that the association existed in patients in the EBV-positive, smoking, and late-stage (III and IV) subgroups and in patients who underwent both concurrent chemoradiotherapy and induction/adjuvant chemotherapy. CONCLUSION: Our study showed that rs11130424 in the CACNA2D3 gene was associated with sensitivity to radiotherapy in NPC patients. TRIAL REGISTRATION NUMBER: Effect of genetic polymorphism on nasopharyngeal carcinoma chemoradiotherapy reaction, ChiCTR-OPC-14005257, Registered 18 September 2014, http://www.chictr.org.cn/showproj.aspx?proj=9546 .

Roles of ApoE4 on the Pathogenesis in Alzheimer's Disease and the Potential Therapeutic Approaches.

The Apolipoprotein E ε4 (ApoE ε4) allele, encoding ApoE4, is the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD). Emerging epidemiological evidence indicated that ApoE4 contributes to AD through influencing ß-amyloid (Aß) deposition and clearance. However, the molecular mechanisms of ApoE4 involved in AD pathogenesis remains unclear. Here, we introduced the structure and functions of ApoE isoforms, and then we reviewed the potential mechanisms of ApoE4 in the AD pathogenesis, including the effect of ApoE4 on Aß pathology, and tau phosphorylation, oxidative stress; synaptic function, cholesterol transport, and mitochondrial dysfunction; sleep disturbances and cerebrovascular integrity in the AD brains. Furthermore, we discussed the available strategies for AD treatments that target to ApoE4. In general, this review overviews the potential roles of ApoE4 in the AD development and suggests some therapeutic approaches for AD. ApoE4 is genetic risk of AD. ApoE4 is involved in the AD pathogenesis. Aß deposition, NFT, oxidative stress, abnormal cholesterol, mitochondrial dysfunction and neuroinflammation could be observed in the brains with ApoE4. Targeting the interaction of ApoE4 with the AD pathology is available strategy for AD treatments.

Construction and analysis of a nomogram prediction model for post-infectious bronchiolitis obliterans in children with adenovirus pneumonia after invasive mechanical ventilation.

BACKGROUND: Post-infectious bronchiolitis obliterans (PIBO) is the most common sequelae in children with adenovirus pneumonia (ADVP). However, there are few studies on the risk factors for PIBO occurrence. This study aims to investigate the risk factors for PIBO in pediatric patients with severe ADVP, especially after invasive mechanical ventilation (IMV), as well as to build a nomogram prediction model. METHODS: The clinical data, laboratory and imaging features, and treatment of 863 children with ADVP under 3 years old who were admitted to our hospital from January to December 2019 were retrospectively analyzed. Among them, 66 children with severe ADVP received IMV treatment. The situation and the influencing factors of PIBO in children with severe ADVP were explored, and a nomogram prediction model was constructed. RESULTS: Among the 863 cases of ADVP, 46 cases (5.33%) developed PIBO. Duration of fever, IMV, complications, and neutrophil percentage were independent risk factors for PIBO in children with ADVP. Among the 66 patients with ADVP who underwent IMV, 33 patients (50.0%) developed PIBO. Gender, duration of fever, adenovirus (ADV) load, and mixed fungal coinfections were independent risk factors for PIBO. In the nomogram prediction model analysis, the area under the curve (AUC) was 0.857; in addition, Hosmer‒Lemeshow (H-L) detection reflected good alignment (χ2 = 68.75, P < 0.01). CONCLUSIONS: A nomogram prediction model, which can be utilized to predict PIBO occurrence in pediatric patients with ADVP after IMV at an early time period, was successfully built.