Occurrence and risk factors for post-stroke delirium: A systematic review and meta-analysis.

OBJECTIVES: Delirium is a significant health concern in acute stroke patients. We aim to systematically summarize existing evidence to conduct a meta-analysis to quantify the occurrence and risk factors for delirium after acute stroke. METHOD: PubMed, EMBASE and MEDLINE were searched from inception to Feb. 2023 for prospective observational studies that reported the incidence or prevalence of post-stroke delirium and/or evaluated potential risk factors. The search strategy was created using controlled vocabulary terms and text words for stroke and delirium. We performed a meta-analysis of the estimates for occurrence and risk factors using random-effects models. Meta-regression and subgroup meta-analyses were conducted to explore the sources of heterogeneity. Study quality and quality of evidence were assessed using the customized Newcastle-Ottawa Scale and GRADE, respectively. RESULTS: Forty-nine studies that enrolled 12383 patients were included. The pooled occurrence rate of post-stroke delirium was 24.4 % (95 %CI, 20.4 %-28.9 %, I2=96.2 %). The pooled occurrence of hyperactive, hypoactive, and mixed delirium was 8.5 %, 5.7 % and 5.0 %, respectively. Study location, delirium assessment method and stroke type independently affected the heterogeneity of the pooled estimate of delirium. Statistically significant risk factors were older age, low education level, cigarette smoking, alcohol drinking, atrial fibrillation, lower ADL level, higher pre-stroke mRS score, premorbid cognitive impairment or dementia, aphasia, total anterior circulation impairment, higher National Institute of Health Stroke Scale score and infection. CONCLUSIONS: Delirium affected 1 in 4 acute stroke patients, although reported rates may depend on assessment method and stroke type. Timely prevention, recognition and intervention require prioritizing patients with dominant risk factors.

Biosynthesized Selenium Nanoparticles as an Effective Tool to Combat Soil Metal Stresses in Rice (Oryza sativa L.).

Nanotechnology has demonstrated significant potential to improve agricultural production and increase crop tolerance to abiotic stress including exposure to heavy metals. The present study investigated the mechanisms by which aloe vera extract gel-biosynthesized (AVGE) selenium nanoparticles (Se NPs) alleviated cadmium (Cd)-induced toxicity to rice (Oryza sativa L.). AVGE Se NPs, chemically synthesized bare Se NPs, and NaSeO3 as an ionic control were applied to Cd-stressed rice seedlings via root exposure in both hydroponic and soil systems. Upon exposure to AVGE Se NPs at 15 mg Se/L, the fresh root biomass was significantly increased by 100.7% and 19.5% as compared to Cd control and conventional bare Se NPs. Transcriptional analyses highlighted that AVGE Se NPs activated stress signaling and defense related pathways, including glutathione metabolism, phenylpropanoid biosynthesis and plant hormone signal transduction. Specifically, exposure to AVGE Se NPs upregulated the expression of genes associated with the gibberellic acid (GA) biosynthesis by and 4.79- and 3.29-fold as compared to the Cd-alone treatment and the untreated control, respectively. Importantly, AVGE Se NPs restored the composition of the endophyte community and recruit of beneficial species under Cd exposure; the relative abundance of Azospirillum was significantly increased in roots, shoots, and the rhizosphere soil by 0.73-, 4.58- and 0.37-fold, respectively, relative to the Cd-alone treatment. Collectively, these findings highlight the significant potential of AVGE Se NPs to enhance plant growth and to minimize the Cd-induced toxicity in rice and provide a promising nanoenabled strategy to enhance food safety upon crop cultivation in contaminated agricultural soils.

Enhancing the field-of-view of spectral-scanning FMCW LiDAR by multipass configuration with an echelle grating.

We present a spectral-scanning frequency-modulated continuous wave (FMCW) 3D imaging system capable of producing high-resolution depth maps with an extended field of view (FOV). By employing a multipass configuration with an echelle grating, the system achieves an FOV of 5.5° along the grating axis. The resulting depth maps have a resolution of 70 × 40 pixels, with a depth resolution of 5.1 mm. The system employs an echelle grating for beam steering and leverages the multipass configuration for angular FOV magnification. Quantitative depth measurements and 3D imaging results of a static 3D-printed depth variation target are demonstrated. The proposed approach offers a promising solution for enhancing the FOV of spectral-scanning FMCW LiDAR systems within a limited wavelength-swept range, thereby reducing system complexity and cost, paving the way for improved 3D imaging applications.

POEMS syndrome with undetectable M-protein: a case report and literature review.

BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria. CASE PRESENTATION: We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone. CONCLUSIONS: Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren't enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.

Hydrophilic molecularly imprinted lysozyme-BiOBr composite with enhanced visible light utilization for selective removal of trace contaminants in water.

The development of high-efficiency molecularly imprinted photocatalysts is still challenging due to the lack of hydrophilic and suitable functional monomers. In this work, the bio-sourced lysozyme was developed as the hydrophilic functional monomer, and Cu-doped BiOBr was used as the photocatalysts, to prepare a novel hydrophilic molecularly imprinted lysozyme-BiOBr composite (BiOBr-Cu/LyzMIP) with enhanced visible light utilization. Lysozyme could form a transparent layer to mitigate the light transmission obstruction caused by the surface imprinting layer, making it an ideal functional monomer. The prepared BiOBr-Cu/LyzMIP possessed red-shifted visible-light absorption edge and minor reduction of light absorbance, indicating the enhanced utilization of visible light. Accordingly, BiOBr-Cu/LyzMIP demonstrated excellent degradation rate (99.4 % in 20 min), exceptional degradation efficiency (0.211 min-1), and superior reusability. Moreover, BiOBr-Cu/LyzMIP exhibited rapid adsorption equilibrium (20 min), good imprinting factor (2.67), and favourable degradation selectivity (>1.75), indicating the good imprinting effect resulting from abundant functional groups of lysozyme. Versatility experiments on different templates suggested that the proposed approach allowed flexibility in selecting a wide range of hazardous contaminants according to practical requirements. The present work expands the application of lysozyme-based composites in the environmental field, and provides a new one-stop pathway for efficient and sustainable treatment of contaminated water.

Electro-elution-based purification of covalent DNA-protein cross-links.

Covalent DNA-protein cross-links (DPCs) are pervasive DNA lesions that challenge genome stability and can be induced by metabolic or chemotherapeutic cross-linking agents including reactive aldehydes, topoisomerase poisons and DNMT1 inhibitors. The purification of x-linked proteins (PxP), where DNA-cross-linked proteins are separated from soluble proteins via electro-elution, can be used to identify DPCs. Here we describe a versatile and sensitive strategy for PxP. Mammalian cells are collected following exposure to a DPC-inducing agent, embedded in low-melt agarose plugs and lysed under denaturing conditions. Following lysis, the soluble proteins are extracted from the agarose plug by electro-elution, while genomic DNA and cross-linked proteins are retained in the plug. The cross-linked proteins can then be analyzed by standard analytical techniques such as sodium dodecyl-sulfate-polyacrylamide gel electrophoresis followed by western blotting or fluorescent staining. Alternatively, quantitative mass spectrometry-based proteomics can be used for the unbiased identification of DPCs. The isolation and analysis of DPCs by PxP overcomes the limitations of alternative methods to analyze DPCs that rely on precipitation as the separating principle and can be performed by users trained in molecular or cell biology within 2-3 d. The protocol has been optimized to study DPC induction and repair in mammalian cells but may also be adapted to other sample types including bacteria, yeast and tissue samples.

Size Effects of Copper Oxide Nanoparticles on Boosting Soybean Growth via Differentially Modulating Nitrogen Assimilation.

Nanoscale agrochemicals have been widely used in sustainable agriculture and may potentially affect the nitrogen fixation process in legume crops. The present study investigated the size-effects of copper oxide nanoparticles (CuO NPs) on nitrogen assimilation in soybean (G. max (L.) Merrill) plants, which were treated with different sizes (20 and 50 nm) of CuO NPs at low use doses (1 and 10 mg/kg) for 21 days under greenhouse conditions. The results showed that 50 nm CuO NPs significantly increased the fresh biomass more than 20 nm CuO NPs achieved at 10 mg/kg. The activities of N assimilation-associated enzymes and the contents of nitrogenous compounds, including nitrates, proteins, and amino acids, in soybean tissues were greatly increased across all the CuO NP treatments. The use doses of two sizes of CuO NPs had no impact on the Cu contents in shoots and roots but indeed increased the Cu contents in soils in a dose-dependent fashion. Overall, our findings demonstrated that both 20 and 50 nm CuO NPs could positively alter soybean growth and boost N assimilation, furthering our understanding that the application of nanoscale micro-nutrient-related agrochemicals at an optimal size and dose will greatly contribute to increasing the yield and quality of crops.

O-GlcNAcylation Facilitates the Interaction between Keratin 18 and Isocitrate Dehydrogenases and Potentially Influencing Cholangiocarcinoma Progression.

Glycosylation plays a pivotal role in the intricate landscape of human cholangiocarcinoma (CCA), actively participating in key pathophysiological processes driving tumor progression. Among the various glycosylation modifications, O-linked ß-N-acetyl-glucosamine modification (O-GlcNAcylation) emerges as a dynamic regulator influencing diverse tumor-associated biological activities. In this study, we employed a state-of-the-art chemical proteomic approach to analyze intact glycopeptides, unveiling the critical role of O-GlcNAcylation in orchestrating Keratin 18 (K18) and its interplay with tricarboxylic acid (TCA) cycle enzymes, specifically isocitrate dehydrogenases (IDHs), to propel CCA progression. Our findings shed light on the mechanistic intricacies of O-GlcNAcylation, revealing that site-specific modification of K18 on Ser 30 serves as a stabilizing factor, amplifying the expression of cell cycle checkpoints. This molecular event intricately fosters cell cycle progression and augments cellular growth in CCA. Notably, the interaction between O-GlcNAcylated K18 and IDHs orchestrates metabolic reprogramming by down-regulating citrate and isocitrate levels while elevating α-ketoglutarate (α-KG). These metabolic shifts further contribute to the overall tumorigenic potential of CCA. Our study thus expands the current understanding of protein O-GlcNAcylation and introduces a new layer of complexity to post-translational control over metabolism and tumorigenesis.

Benefit of cardiac rehabilitation in acute heart failure patients with cognitive impairment.

Aims: This study aimed to evaluate the prevalence of cognitive impairment among patients with acute heart failure (AHF), its prognosis, and the effects of cardiac rehabilitation (CR) on these patients' outcomes. Methods: Overall, 247 consecutive AHF patients (median age, 60 years; males, 78.5 %) were evaluated from March 2015 to May 2021. Patients received an AHF disease management program coordinated by an HF specialist nurse and underwent a Luria-Nebraska Neuropsychological battery-screening test (LNNB-S) assessment during admission. Cognitive impairment was defined as an LNNB-S score ≥10. Patients who underwent at least one session of phase II CR and continued with the home-based exercise program were considered to have received CR. The primary endpoint was composite all-cause mortality or readmission after a 3.30-year follow-up (interquartile range, 1.69-5.09 years). Results: Cognitive impairment occurred in 53.0 % and was associated with significantly higher composite endpoint, all-cause mortality, and readmission rates (p=<0.001, 0.001, and 0.015, respectively). In the total cohort, 40.9 % of patients experienced the composite endpoint. Multivariate analysis showed that the peak VO2 was a significant predictor of the composite endpoint. After adjustment, CR significantly decreased the event rate of the composite endpoint and the all-cause mortality in patients with cognitive impairment (log-rank p = 0.024 and 0.009, respectively). However, CR did not have a significant benefit on the composite endpoint and the all-cause mortality in patients without cognitive impairment (log-rank p = 0.682 and 0.701, respectively). Conclusion: Cognitive impairment is common in AHF patients and can lead to poor outcomes. CR is a standard treatment to improve prognosis.

Ultrasound image-based nomogram combining clinical, radiomics, and deep transfer learning features for automatic classification of ovarian masses according to O-RADS.

Background: Accurate and rapid discrimination between benign and malignant ovarian masses is crucial for optimal patient management. This study aimed to establish an ultrasound image-based nomogram combining clinical, radiomics, and deep transfer learning features to automatically classify the ovarian masses into low risk and intermediate-high risk of malignancy lesions according to the Ovarian- Adnexal Reporting and Data System (O-RADS). Methods: The ultrasound images of 1,080 patients with 1,080 ovarian masses were included. The training cohort consisting of 683 patients was collected at the South China Hospital of Shenzhen University, and the test cohort consisting of 397 patients was collected at the Shenzhen University General Hospital. The workflow included image segmentation, feature extraction, feature selection, and model construction. Results: The pre-trained Resnet-101 model achieved the best performance. Among the different mono-modal features and fusion feature models, nomogram achieved the highest level of diagnostic performance (AUC: 0.930, accuracy: 84.9%, sensitivity: 93.5%, specificity: 81.7%, PPV: 65.4%, NPV: 97.1%, precision: 65.4%). The diagnostic indices of the nomogram were higher than those of junior radiologists, and the diagnostic indices of junior radiologists significantly improved with the assistance of the model. The calibration curves showed good agreement between the prediction of nomogram and actual classification of ovarian masses. The decision curve analysis showed that the nomogram was clinically useful. Conclusion: This model exhibited a satisfactory diagnostic performance compared to junior radiologists. It has the potential to improve the level of expertise of junior radiologists and provide a fast and effective method for ovarian cancer screening.

Bilateral Production Shield Enabling Highly Efficient Perovskite Photovoltaics.

Enhancing the intrinsic stability of perovskite and through encapsulation to isolate water, oxygen, and UV-induced decomposition are currently common and most effective strategies in perovskite solar cells. Here, the atomic layer deposition process is employed to deposit a nanoscale (≈100 nm), uniform, and dense Al2O3 film on the front side of perovskite devices, effectively isolating them from the erosion caused by water and oxygen in the humid air. Simultaneously, nanoscale (≈100 nm) TiO2 films are also deposited on the glass surface to efficiently filter out the ultraviolet (UV) light in the light source, which induces degradation in perovskite. Ultimately, throughthe collaborative effects of both aspects, the stability of the devices is significantly improved under conditions of humid air and illumination. As a result, after storing the devices in ambient air for 1000 h, the efficiency only declines to 95%, and even after 662 h of UV exposure, the efficiency remains at 88%, far surpassing the performance of comparison devices. These results strongly indicate that the adopted Al2O3 and TiO2 thin films play a significant role in enhancing the stability of perovskite solar cells, demonstrating substantial potential for widespread industrial applications.

Robust Gaussian Process Regression Method for Efficient Tunneling Pathway Optimization: Application to Surface Processes.

Simulation of surface processes is a key part of computational chemistry that offers atomic-scale insights into mechanisms of heterogeneous catalysis, diffusion dynamics, and quantum tunneling phenomena. The most common theoretical approaches involve optimization of reaction pathways, including semiclassical tunneling pathways (called instantons). The computational effort can be demanding, especially for instanton optimizations with an ab initio electronic structure. Recently, machine learning has been applied to accelerate reaction-pathway optimization, showing great potential for a wide range of applications. However, previous methods still suffer from numerical and efficiency issues and were not designed for condensed-phase reactions. We propose an improved framework based on Gaussian process regression for general transformed coordinates, which has improved efficiency and numerical stability, and we propose a descriptor that combines internal and Cartesian coordinates suitable for modeling surface processes. We demonstrate with 11 instanton optimizations in three representative systems that the improved approach makes ab initio instanton optimization significantly cheaper, such that it becomes not much more expensive than a classical transition-state theory rate calculation.

Two lysin motif extracellular (LysMe) proteins are deployed in rice to facilitate arbuscular mycorrhizal symbiosis.

During arbuscular mycorrhizal (AM) symbiosis, plant innate immunity is modulated to a prime state to allow for fungal colonization. The underlying mechanisms remain to be further explored. In this study, two rice genes encoding LysM extracellular (LysMe) proteins were investigated. By obtaining OsLysMepro:GUS transgenic plants and generating oslysme1, oslysme2 and oslysme1oslysme2 mutants via CRISPR/Cas9 technique, OsLysMe genes were revealed to be specifically induced in the arbusculated cells and mutations in either gene caused significantly reduced root colonization rate by AM fungus Rhizophagus irregularis. Overexpression of OsLysMe1 or OsLysMe2 dramatically increased the colonization rates in rice and Medicago truncatula. The electrophoretic mobility shift assay and dual-luciferase reporter assay supported that OsLysMe genes are regulated by OsWRI5a. Either OsLysMe1 or OsLysMe2 can efficiently rescue the impaired AM phenotype of the mtlysme2 mutant, supporting a conserved function of LysMe across monocotyledonous and dicotyledonous plants. The co-localization of OsLysMe proteins with the apoplast marker SP-OsRAmy3A implies their probable localization to the periarbuscular space (PAS) during symbiosis. Relative to the fungal biomass marker RiTEF, some defense-related genes showed disproportionately high expression levels in the oslysme mutants. These data support that rice plants deploy two OsLysMe proteins to facilitate AM symbiosis, likely by diminishing plant defense responses.

Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity.

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti-B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8+ CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.

Regulating microbial redox reactions towards enhanced removal of refractory organic nitrogen from wastewater.

Biotechnology for wastewater treatment is mainstream and effective depending upon microbial redox reactions to eliminate diverse contaminants and ensure aquatic ecological health. However, refractory organic nitrogen compounds (RONCs, e.g., nitro-, azo-, amide-, and N-heterocyclic compounds) with complex structures and high toxicity inhibit microbial metabolic activity and limit the transformation of organic nitrogen to inorganic nitrogen. This will eventually result in non-compliance with nitrogen discharge standards. Numerous efforts suggested that applying exogenous electron donors or acceptors, such as solid electrodes (electrostimulation) and limited oxygen (micro-aeration), could potentially regulate microbial redox reactions and catabolic pathways, and facilitate the biotransformation of RONCs. This review provides comprehensive insights into the microbial regulation mechanisms and applications of electrostimulation and micro-aeration strategies to accelerate the biotransformation of RONCs to organic amine (amination) and inorganic ammonia (ammonification), respectively. Furthermore, a promising approach involving in-situ hybrid anaerobic biological units, coupled with electrostimulation and micro-aeration, is proposed towards engineering applications. Finally, employing cutting-edge methods including multi-omics analysis, data science driven machine learning, technology-economic analysis, and life-cycle assessment would contribute to optimizing the process design and engineering implementation. This review offers a fundamental understanding and inspiration for novel research in the enhanced biotechnology towards RONCs elimination.

Nanoparticles targeting OPN loaded with BY1 inhibits vascular restenosis by inducing FTH1-dependent ferroptosis in vascular smooth muscle cells.

Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.

Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis.

Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated to target the destruction of cancer cells. We find that MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization to generate metabolites in the kynurenine (Kyn) pathway is reduced. Depriving MYC-driven tumors of Trp through a No-Trp diet not only prevents tumor growth but also restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unhindered in liver cancer cells. We define a crucial role for the Trp-derived metabolite indole 3-pyruvate (I3P) in liver tumor growth. I3P supplementation effectively restores the growth of liver cancer cells starved of Trp. These findings suggest that I3P is a potential therapeutic target in MYC-driven cancers. Developing methods to target this metabolite represents a potential avenue for liver cancer treatment.

An epilepsy-associated CILK1 variant compromises KATNIP regulation and impairs primary cilia and Hedgehog signaling.

Mutations in human CILK1 (ciliogenesis associated kinase 1) are linked to ciliopathies and epilepsy. Homozygous point and nonsense mutations that extinguish kinase activity impair primary cilia function, whereas mutations outside the kinase domain are not well understood. Here, we produced a knock-in mouse equivalent of the human CILK1 A615T variant identified in juvenile myoclonic epilepsy (JME). This residue is in the C-terminal region of CILK1 separate from the kinase domain. Mouse embryo fibroblasts (MEF) with either heterozygous or homozygous A612T mutant alleles exhibited a higher ciliation rate, shorter individual cilia and up-regulation of ciliary Hedgehog signaling. Thus, a single A612T mutant allele was sufficient to impair primary cilia and ciliary signaling in MEFs. Gene expression profiles of wild type versus mutant MEFs revealed profound changes in cilia-related molecular functions and biological processes. CILK1 A615T mutant protein was not increased to the same level as the wild type protein when co-expressed with scaffold protein KATNIP (katanin-interacting protein). Our data show that KATNIP regulation of a JME-associated single residue variant of CILK1 is compromised and this impairs the maintenance of primary cilia and Hedgehog signaling.

Decitabine cytotoxicity is promoted by dCMP deaminase DCTD and mitigated by SUMO-dependent E3 ligase TOPORS.

The nucleoside analogue decitabine (or 5-aza-dC) is used to treat several haematological cancers. Upon its triphosphorylation and incorporation into DNA, 5-aza-dC induces covalent DNA methyltransferase 1 DNA-protein crosslinks (DNMT1-DPCs), leading to DNA hypomethylation. However, 5-aza-dC's clinical outcomes vary, and relapse is common. Using genome-scale CRISPR/Cas9 screens, we map factors determining 5-aza-dC sensitivity. Unexpectedly, we find that loss of the dCMP deaminase DCTD causes 5-aza-dC resistance, suggesting that 5-aza-dUMP generation is cytotoxic. Combining results from a subsequent genetic screen in DCTD-deficient cells with the identification of the DNMT1-DPC-proximal proteome, we uncover the ubiquitin and SUMO1 E3 ligase, TOPORS, as a new DPC repair factor. TOPORS is recruited to SUMOylated DNMT1-DPCs and promotes their degradation. Our study suggests that 5-aza-dC-induced DPCs cause cytotoxicity when DPC repair is compromised, while cytotoxicity in wild-type cells arises from perturbed nucleotide metabolism, potentially laying the foundations for future identification of predictive biomarkers for decitabine treatment.

A Review on The Phytochemistry and Pharmacology of The Genus Sterculia.

The Sterculia genus is comprised of approximately 300 species, which have been widely used as traditional medicines to treat inflammation, snake bites, gastrointestinal diseases, skin diseases, microbial infections and many other diseases. To gain a comprehensive understanding of the therapeutic potential of Sterculia plants, an extensive literature search was conducted in CNKI, Bing, Wanfang Database, Springer Database, Elsevier Database, Google Scholar, Baidu Scholar, PubMed, and other similar websites from January 1971 to March 2024. The research indicated that Sterculia species predominantly contain flavonoids, terpenoids, phenylpropanoids, fatty acids, alkaloids and other chemical components. A wide range of pharmacologic activities such as anti-inflammatory, antioxidant, antibacterial and other biological activities have been reported. Nevertheless, there isn't much scholarly research on the therapeutic material basis of the genus Sterculia. This review reports the ethnobotany, phytochemicals, and biological activities of the plants in the Sterculia genus as herbal remedies.