The role of exosomal lncRNAs in acetaminophen-induced induced liver injury in SD rats.

Background: Drug-induced liver injury (DILI) is a leading cause of drug development failures during clinical trials and post-market introduction. Current biomarkers, such as ALT and AST, lack the necessary specificity and sensitivity needed for accurate detection. Exosomes, which protect LncRNAs from RNase degradation, could provide reliable and easily accessible options for biomarkers. Materials and methods: RNA-sequencing was used to identify differentially expressed LncRNAs (DE-LncRNAs), followed by isolation of LncRNAs from plasma exosomes in this study. Exosome characterization was conducted by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot (WB). Bioinformatics analysis included functional enrichment and co-expression network analysis. Five rat models were established, and quantitative real-time PCR was used to verify the specificity and sensitivity of two candidate exosomal LncRNAs. Results: The APAP-induced hepatocellular injury model was successfully established for RNA-sequencing, leading to the identification of several differentially expressed exosomal LncRNAs. Eight upregulated exosomal DE-LncRNAs were selected for validation. Among them, NONRATT018001.2 (p < 0.05) and MSTRG.73954.4 (p < 0.05) exhibited a more than 2-fold increase in expression levels. In hepatocellular injury and intrahepatic cholestasis models, both NONRATT018001.2 and MSTRG.73954.4 showed earlier increases compared to serum biomarkers ALT and AST. However, no histological changes were observed until the final time point. In the fatty liver model, NONRATT018001.2 and MSTRG.73954.4 increased earlier than ALT and AST at 21 days. By the 7th day, minor steatosis was evident in liver tissue, while the expression levels of the two candidate exosomal LncRNAs exceeded 2 and 4 times, respectively. In the hepatic fibrosis model, NONRATT018001.2 and MSTRG.73954.4 showed increases at every time point. By the 49th day, hepatocellular necrosis and fibrosis were observed in the liver tissue, with NONRATT018001.2 showing an increase of more than 8 times. The specificity of the identified exosomal DE-LncRNAs was verified using a myocardial injury model and they showed no significant differences between the case and control groups. Conclusion: NONRATT018001.2 and MSTRG.73954.4 hold potential as biomarkers for distinguishing different types of organ injury induced by drugs, particularly enabling early prediction of liver injury. Further experiments, such as siRNA interference or gene knockout, are warranted to explore the underlying mechanisms of these LncRNAs.

Effects of wheat starch content on its flour and frozen dough bread.

The refined wheat flour was mixed with different types of wheat starch in different addition levels, their microstructure, chemical bonds in the dough and baking characteristics of 0-8 weeks frozen dough bread were studied. With the increase of A-Type starch granules and whole wheat starch, the pores of gluten network first decreased and then increased. Conversely, an increase in B-Type starch granules consistently reduced gluten network porosity. With the increase of whole wheat starch, the content of free sulfhydryl group and hydrophobic interaction decreased gradually. Minimal additions of B-Type granules were found to enhance the specific volume of fresh bread, whereas increased quantities improved the specific volume of frozen dough bread. The addition of a small quantity of A- or B-Type granules enhances the freezing stability of bread. This study provides effective information for elucidating the effects of wheat starch on the frozen dough and bread properties in protein-starch matrix.

Prognostic analysis of stage IIIC1p cervical cancer patients.

Background: Stage IIIC1p cervical cancer is characterized by marked heterogeneity and considerable variability in the postoperative prognosis. This study aimed to identify the clinical and pathological characteristics affecting the survival of patients diagnosed with stage IIIC1p cervical cancer. Methods: We retrospectively analyzed patients diagnosed with stage IIIC1p cervical cancer who underwent radical hysterectomy and lymph node dissection between March 2012 and March 2022. Overall survival (OS) was estimated using Kaplan-Meier survival curves. Univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors for OS and forest plots were used to visualize these findings. Nomogram charts were created to forecast survival rates at 3 and 5 years, and the accuracy of predictions was evaluated using Harrell's concordance index (C-index) and calibration curves. Results: The study cohort comprised 186 women diagnosed with stage IIIC1p cervical cancer. The median follow-up duration was 51.1 months (range, 30-91 months), and the estimated 5-year OS rate was 71.5%. Multivariate analysis revealed that concurrent chemoradiotherapy plus adjuvant chemotherapy (CCRT + AC), monocyte-lymphocyte ratio (MLR), ratio of lymph node metastasis (LNM), and squamous cell carcinoma antigen (SCCA) levels independently predicted OS. Conclusions: Significant prognostic disparities exist among patients diagnosed with stage IIIC1p cervical cancer. MLR, ratio of LNM, and SCCA were associated with poor OS. In contrast, the CCRT + AC treatment regimen appeared to confer a survival advantage.

Candidate membrane protein gene families related to chemoreception in a wood-boring beetle, Pharsalia antennata Gahan (Coleoptera: Cerambycidae).

The longhorned beetles are key players for the maintenance of biodiversity in the terrestrial ecosystem. As xylophagous cerambycid insects in Coleoptera, the beetles have evolved specialized olfactory and gustatory systems to recognize chemical cues in the surrounding habitats. Despite over 36,000 described species in the Cerambycidae family including a wood-boring pest Pharsalia antennata, only a limited number of them (<1 %) have been characterized regarding their chemical ecology at the molecular level. Here, we surveyed four membrane protein gene families in P. antennata related to chemoreception through transcriptomics, phylogenetics and expression profiling analyses. In total, 144 genes encoding 72 odorant receptors (ORs), 33 gustatory receptors (GRs), 23 ionotropic receptors (IRs), four sensory neuron membrane proteins (SNMPs) and 12 ionotropic glutamate receptors (iGluRs) were harvested from the transcriptome of multiple tissues including antennae and legs of both sexes. The lineage-specific expansion of PantORs possibly implied a diverse range of host plants in this beetle, supporting this correlation between the host range and olfactory receptor repertoire sizes across cerambycid species. Further phylogenetic analysis revealed that Group 2 was contributed mainly to the large OR gene repertoire in P. antennata, representing 18 genes in Group 2A and eight in Group 2B. On the other hand, some key chemosensory genes were identified by applying a phylogenetics approach, such as PantOR21 close to the 2-phenylethanol receptor in Megacyllene caryae, three carbon dioxide GRs and seven Antennal IRs (A-IRs) clades. We also determined sex- and tissue-specific expression profiles of 69 chemosensory genes, revealing the high expression of most PantORs in antennae. Noticeably, 10 sex-biased genes (six PantORs, three PantIRs and PantSNMP1a) were presented in antennae, five sex-biased PantGRs in legs and 39 sex-biased genes (15 PantORs, 13 PantGRs, eight PantIRs and three PantSNMPs) in abdomens. These findings have greatly enhanced our knowledge about the chemical ecology of P. antennata and identify candidate molecular targets for mediating smell and taste of this beetle.

Reverse remodeling of mitral leaflets after medical treatment in recent-onset dilated cardiomyopathy.

BACKGROUND: The growth of mitral leaflets (MLs) adaptive to left ventricluar (LV) remodeling has been observed. However, the elasticity of MLs upon mechanical stimuli would be supposed if it shrinks with LV reverse remodeling (LVRR). MATERIAL AND METHODS: Patients with idiopathic recent-onset dilated cardiomyopathy (RODCM) (n = 82) and 50 matched normal controls (NC) were prospectively enrolled. Echocardiography was performed at baseline and 6 months of follow-up for the anterior and posterior mitral leaflet (AML and PML) length, mitral annular dimension (MAD), and tenting height (TH). LVRR was measured as a ≥ 15% reduction in LV end-diastolic volume (LVEDV). RESULTS: After 6 months, LVRR was achieved in 69.5% of patients. The AML (28 ± 3 vs. 26 ± 3 mm, p = 0.004) and PML (19 ± 4 vs. 17 ± 3 mm, p < 0.001) decreased in length, as well as the MAD (31 ± 5 vs. 28 ± 5 mm, p = 0.001) and TH (10 ± 3 vs. 8 ± 2 mm, p < 0.001). Compared with the NC group, the AML and PML of the RODCM group were 16.7% and 35.7% longer at baseline and remained 8.3% and 21.2% longer at follow-up, respectively. The change in AML or PML correlated moderately with that in LVEDV (r = 0.487, p < 0.001; r = 0.516, p < 0.001, respectively). The AML and PML length decreased in the LVRR (+) subgroup (AML, 28 ± 3 vs. 26 ± 3 mm, p = 0.001; PML, 20 ± 4 vs. 16 ± 3 mm, p < 0.001), but remained the same in the LVRR (-) subgroup (27 ± 4 vs. 28 ± 4 mm, p = 0.318; 17 ± 3 vs. 17 ± 3 mm, p = 0.790). CONCLUSIONS: Enlarged MLs could reverse accompanied by LV reverse remodeling. This study provided the other facet of ML plasticity adaptive to mechanical stretching.

Meningocele in the Parapharyngeal Space: A Case Report and Review of the Literature.

The parapharyngeal space has been described as an inverted pyramid shape with the base of the skull and the great cornu of the hyoid bone at the top. Tumors of the parapharyngeal space account for 0.5% of head and neck tumors and a wide range of tumor types can occur in this area, 80% of which are benign, the most common being pleomorphic adenomas of the salivary glands and neurogenic tumors. We present a 39-year-old woman who was hospitalized due to left-sided neck pain with a feeling of blockage in the left ear and hearing loss for 10 months. Imaging showed that the mass was not connected to the cranium and the patient underwent surgical resection via a transoral approach, where the contents of the mass were found to be cerebrospinal fluid, and meningocele in the parapharyngeal space is a rare occurrence. The patient presented mainly with painful symptoms, which were eventually relieved by nerve block therapy.

Enhancement of vitamin B6 production driven by omics analysis combined with fermentation optimization.

BACKGROUND: Microbial engineering aims to enhance the ability of bacteria to produce valuable products, including vitamin B6 for various applications. Numerous microorganisms naturally produce vitamin B6, yet the metabolic pathways involved are rigorously controlled. This regulation by the accumulation of vitamin B6 poses a challenge in constructing an efficient cell factory. RESULTS: In this study, we conducted transcriptome and metabolome analyses to investigate the effects of the accumulation of pyridoxine, which is the major commercial form of vitamin B6, on cellular processes in Escherichia coli. Our omics analysis revealed associations between pyridoxine and amino acids, as well as the tricarboxylic acid (TCA) cycle. Based on these findings, we identified potential targets for fermentation optimization, including succinate, amino acids, and the carbon-to-nitrogen (C/N) ratio. Through targeted modifications, we achieved pyridoxine titers of approximately 514 mg/L in shake flasks and 1.95 g/L in fed-batch fermentation. CONCLUSION: Our results provide insights into pyridoxine biosynthesis within the cellular metabolic network for the first time. Our comprehensive analysis revealed that the fermentation process resulted in a remarkable final yield of 1.95 g/L pyridoxine, the highest reported yield to date. This work lays a foundation for the green industrial production of vitamin B6 in the future.

Metal telluride nanosheets by scalable solid lithiation and exfoliation.

Transition metal tellurides (TMTs) have been ideal materials for exploring exotic properties in condensed-matter physics, chemistry and materials science1-3. Although TMT nanosheets have been produced by top-down exfoliation, their scale is below the gram level and requires a long processing time, restricting their effective application from laboratory to market4-8. We report the fast and scalable synthesis of a wide variety of MTe2 (M = Nb, Mo, W, Ta, Ti) nanosheets by the solid lithiation of bulk MTe2 within 10 min and their subsequent hydrolysis within seconds. Using NbTe2 as a representative, we produced more than a hundred grams (108 g) of NbTe2 nanosheets with 3.2 nm mean thickness, 6.2 µm mean lateral size and a high yield (>80%). Several interesting quantum phenomena, such as quantum oscillations and giant magnetoresistance, were observed that are generally restricted to highly crystalline MTe2 nanosheets. The TMT nanosheets also perform well as electrocatalysts for lithium-oxygen batteries and electrodes for microsupercapacitors (MSCs). Moreover, this synthesis method is efficient for preparing alloyed telluride, selenide and sulfide nanosheets. Our work opens new opportunities for the universal and scalable synthesis of TMT nanosheets for exploring new quantum phenomena, potential applications and commercialization.

Regioselective super-assembly of Prussian blue analogue.

The construction of high-asymmetrical structures demonstrates significant potential in improving the functionality and distinctness of nanomaterials, but remains a considerable challenge. Herein, we develop a one-pot method to fabricate regioselective super-assembly of Prussian blue analogue (PBA) -- a PBA anisotropic structure (PBA-AS) decorated with epitaxial modules--using a step-by-step epitaxial growth on a rapidly self-assembled cubic substrate guided by thiocyanuric acid (TCA) molecules. The epitaxial growth units manifest as diverse geometric shapes, which are predominantly concentrated on the {100}, {111}, or {100}+{111} crystal plane of the cubic substrate. The crystal plane and morphology of epitaxial module can be regulated by changing the TCA concentration and reaction temperature, enabling a high level of controllability over specific assembly sites and structures. To illustrate the advantage of the asymmetrical structure, phosphated PBA-AS demonstrates improved performance in the oxygen evolution reaction compared to simple phosphated PBA nanocube. This method offers valuable insights for designing asymmetrical nanomaterials with intricate architectures and versatile functionalities.

Effect of Resin Content on the Structure, Water Resistance and Mechanical Properties of High-Density Bamboo Scrimbers.

Bamboo scrimber is acknowledged for its eco-friendly potential as a structural material. Its properties are significantly affected by both its density and resin content, but the effect of resin content on the properties under high density is not yet known. In this study, the microstructure, water resistance, mechanical properties, and thermal stability of bamboo scrimbers with varying resin content at a density of 1.30 g/cm3 were investigated. The results unearthed that phenolic resin assisted in the densification of bamboo cells during hot pressing, and a higher resin content could effectively reduce the cracks in the scrimber. The inherent cellulose I structure remained unaffected, but an increase in resin content led to a noticeable decline in crystallinity. Additionally, an increase in resin content pronouncedly improved the water resistance and dimensional stability of bamboo scrimbers. The water absorption and thickness swelling were as low as 9.67% and 7.62%, respectively. The modulus of rupture (MOR) exhibited a marginal increase with the amount of resin, whereas the compressive strength and short-beam shearing strength first increased and then decreased. Their peak strengths were 327.87 MPa at a resin content of 15 wt.%, and 168.85 MPa and 25.96 MPa at 11 wt.%, respectively. However, phenolic resin accelerated the thermal decomposition of bamboo scrimbers, and more resin worsened the thermal stability. These research outcomes offer a dual advantage, providing both a theoretical foundation and concrete data that can inform the production and practical application of high-density bamboo scrimbers.

Rapid Construction of Double Crystalline Prussian Blue Analogue Hetero-Superstructure.

The controllable construction of complex metal-organic coordination polymers (CPs) merits untold scientific and technological potential, yet remains a grand challenge of one-step construction and modulating simultaneously valence states of metals and topological morphology. Here, a thiocyanuric acid (TCA)-triggered strategy is presented to one-step rapid synthesis a double-crystalline Prussian blue analogue hetero-superstructure (PBA-hs) that comprises a Co3[Fe(CN)6]2 cube overcoated with a KCo[Fe(CN)6] shell, followed by eight self-assembled small cubes on vertices. Unlike common directing surfactants, TCA not only acts as a trigger for the fast growth of KCo[Fe(CN)6] on the Co3[Fe(CN)6]2 phase resulting in a PBA-on-PBA hetero-superstructure, but also serves as a flange-like bridge between them. By combining experiments with simulations, a deprotonation-induced electron transfer (DIET) mechanism is proposed for formation of second phase in PBA-hs, differing from thermally and photo-induced electron transfer processes. To prove utility, the calcined PBA-hs exhibits enhanced oxygen evolution reaction performance. This work provides a new method to design of novel CPs for enriching chemistry and material science. This work offers a practical approach to design novel CPs for enriching chemistry and material science.

Causal Relationship Between Body Mass Index and Risk of Otitis Media with Effusion in Children: A Mendelian Randomization Study.

Background: Body mass index(BMI) in children appears to be associated with Otitis media with effusion(OME) in observational studies, but the causal relationship is not clear. Methods: A two-sample Mendelian randomization (MR) study was used to explore the causal relationship between childhood BMI and OME in people of European ancestry. Genome-wide association studies (GWAS) of childhood BMI were used as exposures (n = 61,111), while GWAS of OME were used as outcomes (n = 429,290). The weighted inverse variance method (IVW) was used as a baseline method to test for causality. In addition, MR-Egger, simple mode analysis, weighted median, and weighted mode were used as complementary methods.MR-PRESSO analysis, MR-Egger intercept analysis, and Cochran's Q statistical analysis were also used to detect possible directional heterogeneity and polymorphism. To assess this association, we used ratios (OR) with 95% confidence intervals (ci). All statistical analyses were performed in R. Results: We selected 22 genome-wide significant single nucleotide polymorphisms (SNPs) from GWAS as instrumental variables (IVW). the IVW approach showed evidence supporting a causal relationship between BMI and OME in children (ß = 0.265, SE = 0.113, P = 0.018). MR-Egger regression showed that targeted polymorphisms were unlikely to bias the results bias (intercept=-0.022; P = 0.488), but there was no causal relationship between BMI and OME (ß = 0.584, SE = 0.465, P = 0.224). Although the results of the IVW and MR Egger analyses were not consistent, the IVW analysis maintained higher precision, and the Cochran Q test, heterogeneity and polymorphism tests showed no heterogeneity, no directionality and no polymorphism. Conclusions: MR studies suggest that genetically predicted body mass index in childhood is associated with an increased risk of OME. Notably, given the limitations of this study, the mechanism of association between body mass index and OME in childhood needs further investigation. These results support the importance of effective management of obesity, which may reduce OME occurrence and decrease OME recurrence.

Healthy lifestyles, systemic inflammation and breast cancer risk: a mediation analysis.

BACKGROUND: Despite the known association between healthy lifestyles and reduced risk of breast cancer, it remains unclear whether systemic inflammation, as a consequence of unhealthy lifestyles, may mediate the association. METHODS: A cohort study of 259,435 female participants in the UK Biobank was conducted to estimate hazard ratio (HR) for breast cancer according to 9 inflammation markers using Cox regression models. We further estimated the percentage of total association between healthy lifestyle index (HLI) and breast cancer that is mediated by these inflammation markers. RESULTS: During 2,738,705 person-years of follow-up, 8,889 cases of breast cancer were diagnosed among 259,435 women in the UK Biobank cohort. Higher level of C-reactive protein (CRP), systemic immune-inflammation index (SII), CRP-to-albumin Ratio (CAR), CRP-to-lymphocyte Ratio (CLR), monocyte-to-HDL-c ratio (MHR), and neutrophil-to-HDL-c ratio (NHR) were associated with increased breast cancer risk, while a higher lymphocyte-to-monocyte ratio (LMR) was associated with a lower risk. The inverse association between HLI and breast cancer was weakly mediated by CRP (8.5%), SII (1.71%), CAR (8.66%), CLR (6.91%), MHR (6.27%), and NHR (7.33%). When considering individual lifestyle factors, CRP and CAR each mediated 16.58% and 17.20%, respectively, of the associations between diet score and breast cancer risk, while the proportion mediated for physical activity and breast cancer were 12.13% and 11.48%, respectively. Furthermore, MHR was found to mediate 13.84% and 12.01% of the associations between BMI, waist circumference, and breast cancer. CONCLUSION: The association of HLI and breast cancer is weakly mediated by the level of inflammation, particularly by CRP and CAR. Systemic inflammatory status may be an intermediate in the biological pathway of breast cancer development.

CDK6 inhibits de novo lipogenesis in white adipose tissues but not in the liver.

Increased de novo lipogenesis (DNL) in white adipose tissue is associated with insulin sensitivity. Under both Normal-Chow-Diet and High-Fat-Diet, mice expressing a kinase inactive Cyclin-dependent kinase 6 (Cdk6) allele (K43M) display an increase in DNL in visceral white adipose tissues (VAT) as compared to wild type mice (WT), accompanied by markedly increased lipogenic transcriptional factor Carbohydrate-responsive element-binding proteins (CHREBP) and lipogenic enzymes in VAT but not in the liver. Treatment of WT mice under HFD with a CDK6 inhibitor recapitulates the phenotypes observed in K43M mice. Mechanistically, CDK6 phosphorylates AMP-activated protein kinase, leading to phosphorylation and inactivation of acetyl-CoA carboxylase, a key enzyme in DNL. CDK6 also phosphorylates CHREBP thus preventing its entry into the nucleus. Ablation of runt related transcription factor 1 in K43M mature adipocytes reverses most of the phenotypes observed in K43M mice. These results demonstrate a role of CDK6 in DNL and a strategy to alleviate metabolic syndromes.

Effect of plasma exosome lncRNA on isoproterenol hydrochloride-induced cardiotoxicity in rats.

Isoprenaline hydrochloride (IH) is a ß-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases. This study aimed to investigate whether abnormal lncRNA expression is involved in IH-mediated cardiotoxicity. First, the Sprague-Dawley (SD) rat myocardial injury model was established. Circulating exosomes were extracted from the plasma of rats and identified. In total, 108 differentially expressed (DE) lncRNAs and 150 DE mRNAs were identified by sequencing. These results indicate that these lncRNAs and mRNAs are substantially involved in chemical cardiotoxicity. Further signaling pathway and functional studies indicated that lncRNAs and mRNAs regulate several biological processes, such as selective mRNA splicing through spliceosomes, participate in sphingolipid metabolic pathways, and play a certain role in the circulatory system. Finally, we obtained 3 upregulated lncRNAs through reverse transcription-quantitative PCR (RT-qPCR) verification and selected target lncRNA-mRNA pairs according to the regulatory relationship of lncRNA/mRNA, some of which were associated with myocardial injury. This study provides valuable insights into the role of lncRNAs as novel biomarkers of chemical-induced cardiotoxicity.

Association of iron deficiency with chronic suppurative otitis media in adults.

BACKGROUND: Chronic suppurative otitis media (CSOM) is a prevalent chronic inflammatory disease globally. Current research suggests a possible association between anaemia and the development of CSOM. OBJECTIVES: The objective of this trial was to investigate the relationship between iron metabolism and chronic suppurative otitis media (CSOM) in adults aged 20-60 years. MATERIALS AND METHODS: A consecutive sampling case-control study was used. The study participants were divided into a case group (42 children diagnosed with CSOM) and a control group (42 children with normal ears). Haemoglobin (Hb), Hematocrit (Hct), mean corpuscular volume of erythrocytes (MCV), serum iron level (SI), unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), transferrin (TF), ferritin (Fer) were tested in all the participants, and the results were compared with the normal ranges of the World Health Organization (WHO). The comparative analysis of cases and controls was performed using the Fisher extract test, independence t-test, or Mann-Whitney U test. p-value <.05 was considered statistically significant for correlation. RESULTS: There were 61 patients with CSOM and 61 controls included in the study. In the case group, 16 out of 61 patients (26.2%) had low ferritin levels and in the control group, 1 out of 61 patients (1.6%) had low ferritin levels (p < .001). In the case group, 6 (9.8%) of 61 patients had IDA, and in the control group, there were no patients with IDA among 61 patients (p = .027). There were significant differences in SI, UIBC, and Fer parameters between the groups. CONCLUSIONS: In adult patients, the incidence of iron deficiency was higher in CSOM patients than in controls. Iron deficiency may be considered a potential risk factor for chronic suppurative otitis media, and serum iron parameters should be evaluated in these CSOM patients and further studies should be conducted to better understand the potential link between iron deficiency and CSOM.

A Potent SOS1 PROTAC Degrader with Synergistic Efficacy in Combination with KRASG12C Inhibitor.

AMG510, as the first approved inhibitor for KRASG12C mutation, has shown promising efficacy in nonsmall-cell lung cancer and colorectal cancer harboring KRASG12C mutation. However, the moderate response rate and the rapid emergence of acquired resistance limit the therapeutic potential of AMG510, highlighting the need for the development of combination strategies. Here, we observed the suppression of RAS-MAPK signaling induced by AMG510 was prolonged and enhanced by SOS1 knockdown. Thus, we design, synthesize, and characterize a potent and specific SOS1 degrader 23. Compound 23 showed efficient SOS1 degradation in KRAS-driven cancer cells and achieved significant antiproliferative potency. Importantly, the combination of 23 with AMG510 suppressed RAS signaling feedback activation, showing synergistic effects against KRASG12C mutant cells in vitro and in vivo. Our findings demonstrated that KRASG12C inhibition plus SOS1 degradation as a potential therapeutic strategy to improve antitumor response and overcome acquired resistance to KRASG12C inhibitor.

Dipole Effect on Oxygen Evolution Reaction of 2D Janus Single-Atom Catalysts: A Case of Rh Anchored on the P6m2-NP Configurations.

Catalytic performance of single-atom catalysts (SACs) relies fundamentally on the electronic nature and local coordination environment of the active site. Here, based on a machine-learning (ML)-aided density functional theory (DFT) method, we reveal that the intrinsic dipole in Janus materials has a significant impact on the catalytic activity of SACs, using 2D γ-phosphorus carbide (γ-PC) as a model system. Specifically, a local dipole around the active site is a key degree to tune the catalytic activity and can be used as an important descriptor with a high feature importance of 17.1% in predicting the difference of adsorption free energy (ΔGO* - ΔGOH*) to assess the activity of the oxygen evolution reaction. As a result, the catalytic performance of SACs can be tuned by an intrinsic dipole, in stark contrast to those external stimuli strategies previously used. These results suggest that dipole engineering and the revolutionary DFT-ML hybrid scheme are novel approaches for designing high-performance catalysts.

EARLY FLOWERING is a dominant gain-of-function allele of FANTASTIC FOUR 1/2c that promotes early flowering in tomato.

Flowering time, an important factor in plant adaptability and genetic improvement, is regulated by various genes in tomato (Solanum lycopersicum). In this study, we characterized a tomato mutant, EARLY FLOWERING (EF), that developed flowers much earlier than its parental control. EF is a dominant gain-of-function allele with a T-DNA inserted 139 bp downstream of the stop codon of FANTASTIC FOUR 1/2c (FAF1/2c). The transcript of SlFAF1/2c was at elevated levels in the EF mutant. Overexpressing SlFAF1/2c in tomato plants phenocopied the early flowering trait of the EF mutant. Knocking out SlFAF1/2c in the EF mutant reverted the early flowering phenotype of the mutant to the normal flowering time of the wild-type tomato plants. SlFAF1/2c promoted the floral transition by shortening the vegetative phase rather than by reducing the number of leaves produced before the emergence of the first inflorescence. The COP9 signalosome subunit 5B (CSN5B) was shown to interact with FAF1/2c, and knocking out CSN5B led to an early flowering phenotype in tomato. Interestingly, FAF1/2c was found to reduce the accumulation of the CSN5B protein by reducing its protein stability. These findings imply that FAF1/2c regulates flowering time in tomato by reducing the accumulation and stability of CSN5B, which influences the expression of SINGLE FLOWER TRUSS (SFT), JOINTLESS (J) and UNIFLORA (UF). Thus, a new allele of SlFAF1/2c was discovered and found to regulate flowering time in tomato.

Hemostasis after transradial coronary intervention by rotary compression device with sterile gauze is associated with more adverse events: a retrospective study.

OBJECTIVE: We investigated the relationship between using a rotary compression device (RCD) with or without sterile gauze and adverse events in transradial access (TRA) for coronary intervention. METHODS: In this study involving 933 patients at Yueyang Hospital, we recorded TRA-related adverse events, such as bleeding, forearm hematoma, swollen palms, radial artery occlusion (RAO) and others. Logistic regression was applied to assess the association. RESULTS: Of the 933 patients (66.7% males, average age 67.8 years), 511 used RCD with sterile gauze, whereas 422 used RCD without sterile gauze. The most common adverse events were radial artery hemorrhage (7.4%), hand swelling (4.8%) and RAO (4.6%). Logistic regression analysis revealed that the use of RCD with sterile gauze was associated with a higher prevalence of adverse events [odds ratio (OR), 1.74; 95% confidence interval (CI), 1.22-2.49), even with the adjustment of potential confounders (OR, 1.71; 95% CI, 1.19-2.45). Moreover, patients who used RCD with sterile gauze exhibited an increased risk of radial artery hemorrhage (OR, 1.83; 95% CI, 1.07-3.12), swelling of the hand (OR, 1.96; 95% CI, 1.02-3.75) and RAO (OR, 3.17; 95% CI, 1.49-6.72). CONCLUSIONS: The use of RCD with sterile gauze in TRA is associated with a higher incidence of adverse events.