Application of eculizumab, a terminal complement inhibitor, in the management of atypical hemolytic uremic syndrome in a 14-month-old Chinese pediatric patient: a case report.

Eculizumab, a recombined humanized monoclonal antibody which possesses high affinity for the complement protein C5, is a therapeutic agent utilized in the treatment of atypical hemolytic uremic syndrome (aHUS) by inhibiting the terminal complement complex C5b-9. In a pediatric patient with aHUS of 14 months, the administration of eculizumab therapy was accompanied by the inclusion of meningococcal vaccine as part of the national immunization program. Notably, no other antibiotics were administered prior to or during the course of eculizumab treatment. Moreover, there were no occurrences of infusion reactions or meningococcal infections observed throughout the course of treatment. Due to the presence of anti-factor H antibodies and insufficient recovery, glucocorticoids and eculizumab were administered at week 0 and week 1, followed by the initiation of mycophenolate mofetil (MMF) at a dosage of 250 mg (approximately 548 mg/m2) per day starting from Day 10. Due to the recovered of complement antibody after 8 doses of eculizumab, the therapeutic interval was extended from once every 3 weeks to once a month since 9th administration. We experienced and successfully treated a rare case of aHUS with eculizumab in a 14-month-old Chinese pediatric patient.

Delayed ventricular septal rupture complicated with ventricular aneurysm in a case of myocardial infarction with non-obstructive coronary arteries.

BACKGROUND: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a rare cause of heart attack, which may not receive sufficient attention from patients during post-discharge treatment, especially among those with normal coronary angiography results. CASE PRESENTATION: We present the case of a 65-year-old woman who was readmitted to the hospital with ventricular septal rupture (VSR) complicated by ventricular aneurysm, occurring 2 weeks after myocardial infarction. During the initial admission, coronary angiography revealed normal coronary arteries, leading to a diagnosis of MINOCA. Epicardial coronary vasospasm or coronary embolism was considered as potential causes; however, the patient did not adhere to standardized treatment upon initial discharge. The delayed VSR led to a decline in cardiac function but did not result in severe hemodynamic impairment. Following correction of heart failure with medications, the patient underwent percutaneous VSR repair 19 days after diagnosis and was discharged with a favorable recovery. CONCLUSIONS: The occurrence of delayed VSR complicated with ventricular aneurysm in patients with MINOCA is rare, highlighting the possibility of serious complications in MINOCA cases. Both cardioprotective therapies and cause-targeted therapies are essential in the management of patients with MINOCA.

Serum exosomal miR-141-3p and miR-3679-5p levels associated with endotype and postoperative recurrence in chronic rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease. Exosomes were involved in different inflammatory diseases, but their roles in CRSwNP were poorly explored. Method: We collected serum samples from 8 CRSwNP patients and 8 healthy controls (HC) and isolated their exosomes. MiRNA sequencing was performed for the exosome samples and differentially expressed miRNAs were identified. The top 3 differentially expressed exosomal miRNAs were confirmed in 2 validation cohorts, and their diagnostic values, predictive values for eosinophilic endotype, and recurrence were evaluated. Results: Distinctive serum exosomal miRNA profiles were observed between CRSwNP and HC groups. Reverse transcription-polymerase chain reaction results in the first validation cohort revealed that serum exosomal miR-141-3p levels were increased, and miR-18a-5p and miR-3679-5p levels were decreased in the CRSwNP group compared to the HC group. These 3 miRNAs were further validated in the second validation cohort, and the results showed that miR-141-3p levels were elevated and miR-3679-5p levels were reduced in the serum exosomes in the eosinophilic CRSwNP group in comparison with the non-eosinophilic CRSwNP group. Receiver operating characteristic (ROC) curves highlighted that exosomal miR-141-3p and miR-3679-5p exhibited promising values for predicting the eosinophilic endotype. The patients in the second cohort were followed up for 2 years, and categorized into recurrence and non-recurrence groups. The serum exosomal miR-141-3p levels were increased and miR-3679-5p levels were reduced in the recurrence group in comparison with the non-recurrence group. ROC curves and Kaplan-Meier survival analysis revealed significant associations between the levels of exosomal miR-141-3p and miR-3679-5p and the risk of postoperative recurrence. Conclusions: This study identified unique miRNA expression patterns in serum exosomes of CRSwNP patients. Circulating exosomal miR-141-3p and miR-3679-5p emerged as novel biomarkers for diagnosing CRSwNP, predicting the eosinophilic endotype, and forecasting postoperative recurrence.

A luminescent Cu2I2P2S2-type binuclear complex and its fluorescence sensing for pyridine.

Luminescent CuI complexes are an important class of coordination compounds due to their relative abundance, low cost and ability to display excellent luminescence. The title Cu2I2P2S2-type binuclear complex, di-µ-iodido-bis[(thiourea-κS)(triphenylphosphine-κP)copper(I)], [Cu2I2(CH4N2S)2(C18H15P)2], conventionally abbreviated as Cu2I2TPP2TU2, where TPP and TU represent triphenylphosphine and thiourea, respectively, is described. In this complex, each CuI atom adopts a CuI2PS four-coordination mode and pairs of atoms are connected to each other by two µ2-I ligands to form a centrosymmetric binuclear cluster. It was also found that the paper-based film of this complex exhibited obvious luminescence light-up sensing for pyridine and 4-methylpyridine.

Dual-Locked Enzyme-Activatable Bioorthogonal Fluorescence Turn-On Imaging of Senescent Cancer Cells.

Bioorthogonal pretargeting optical imaging shows the potential for enhanced diagnosis and prognosis. However, the bioorthogonal handles, known for being "always reactive", may engage in reactions at unintended sites with their counterparts, resulting in nonspecific fluorescence activation and diminishing detection specificity. Meanwhile, despite the importance of detecting senescent cancer cells in cancer therapy, current methods mainly rely on common single senescence-associated biomarkers, which lack specificity for differentiating between various types of senescent cells. Herein, we report a dual-locked enzyme-activatable bioorthogonal fluorescence (DEBOF) turn-on imaging approach for the specific detection of senescent cancer cells. A dual-locked bioorthogonal targeting agent (DBTA) and a bioorthogonally activatable fluorescent imaging probe (BAP) are synthesized as the biorthogonal pair. DBTA is a tetrazine derivative dually caged by two enzyme-cleavable moieties, respectively, associated with senescence and cancer, which ensures that its bioorthogonal reactivity ("clickability") is only triggered in the presence of senescent cancer cells. BAP is a fluorophore caged by trans-cyclooctane (TCO), whose fluorescence is only activated upon bioorthogonal reaction between its TCO and the decaged tetrazine of DBTA. As such, the DEBOF imaging approach differentiates senescent cancer cells from nonsenescent cancer cells or other senescent cells, allowing noninvasive tracking of the population fluctuation of senescent cancer cells in the tumor of living mice to guide cancer therapies. This study thus provides a general molecular strategy for biomarker-activatable in vivo bioorthogonal pretargeting imaging with the potential to be applied to other imaging modalities beyond optics.

Placental and fetal enrichment of microplastics from disposable paper cups: implications for metabolic and reproductive health during pregnancy.

The disposable paper cups (DPCs) release millions of microplastics (MPs) when used for hot beverages. However, the tissue-specific deposition and toxic effects of MPs and associated toxins remain largely unexplored, especially at daily consumption levels. We administered MPs and associated toxins extracted from leading brand DPCs to pregnant mice, revealing dose-responsive harmful effects on fetal development and maternal physiology. MPs were detected in all 13 examined tissues, with preferred depositions in the fetus, placenta, kidney, spleen, lung, and heart, contributing to impaired phenotypes. Brain tissues had the smallest MPs (90.35 % < 10 µm). A dose-responsive shift in the cecal microbiome from Firmicutes to Bacteroidetes was observed, coupled with enhanced biosynthesis of microbial fatty acids. A moderate consumption of 3.3 cups daily was sufficient to alter the cecal microbiome, global metabolic functions, and immune health, as reflected by tissue-specific transcriptomic analyses in maternal blood, placenta, and mammary glands, leading to neurodegenerative and miscarriage risks. Gene-based benchmark dose framework analysis suggested a safe exposure limit of 2 to 4 cups/day in pregnant mice. Our results highlight tissue-specific accumulation and metabolic and reproductive toxicities in mice at DPC consumption levels presumed non-hazardous, with potential health implications for pregnant women and fetuses.

Migration, transformation of arsenic, and pollution controlling strategies in paddy soil-rice system: A comprehensive review.

Arsenic pollution in paddy fields has become a public concern by seriously threatening rice growth, food security and human health. In this review, we delve into the biogeochemical behaviors of arsenic in paddy soil-rice system, systemically revealing the complexity of its migration and transformation processes, including the release of arsenic from soil to porewater, uptake and translocation of arsenic by rice plants, as well as transformation of arsenic species mediated by microorganism. Especially, microbial processes like reduction, oxidation and methylation of arsenic, and the coupling of arsenic with carbon, iron, sulfur, nitrogen cycling through microbes and related mechanisms were highlighted. Environmental factors like pH, redox potential, organic matter, minerals, nutrient elements, microorganisms and periphyton significantly influence these processes through different pathways, which are discussed in this review. Furthermore, the current progress in remediation strategies, including agricultural interventions, passivation, phytoremediation and microbial remediation is explored, and their potential and limitations are analyzed to address the gaps. This review offers comprehensive perspectives on the complicated behaviors of arsenic and influence factors in paddy soil-rice system, and provides a scientific basis for developing effective arsenic pollution control strategies.

Biotechnological application of Aureobasidium spp. as a promising chassis for biosynthesis of ornithine-urea cycle-derived bioproducts.

The ornithine-urea cycle (OUC) in fungal cells has biotechnological importance and many physiological functions and is closely related to the acetyl glutamate cycle (AGC). Fumarate can be released from argininosuccinate under the catalysis of argininosuccinate lyase in OUC which is regulated by the Ca2+ signaling pathway and over 93.9 ± 0.8 g/L fumarate can be yielded by the engineered strain of Aureobasidium pullulans var. aubasidani in the presence of CaCO3. Furthermore, 2.1 ± 0.02 mg of L-ornithine (L-Orn)/mg of the protein also can be synthesized via OUC by the engineered strains of Aureobasidum melanogenum. Fumarate can be transformed into many drugs and amino acids and L-Orn can be converted into siderophores (1.7 g/L), putrescine (33.4 g/L) and L-piperazic acid (L-Piz) (3.0 g/L), by different recombinant strains of A. melanogenum. All the fumarate, L-Orn, siderophore, putrescine and L-Piz have many applications. As the yeast-like fungi and the promising chassis, Aureobasidium spp, have many advantages over any other fungal strains. Further genetic manipulation and bioengineering will enhance the biosynthesis of fumarate and L-Orn and their derivates.

OUC in fungal cells has biotechnological importance and many physiological functions; OUC is closely related to acetyl glutamate cycle (AGC). Fumarate, L-Orn, siderophore, putrescine and L-Piz produced from OUC have many applications.

Single-cell transcriptomic analysis reveals that the APP-CD74 axis promotes immunosuppression and progression of testicular tumors.

Testicular tumors represent the most common malignancy among young men. Nevertheless, the pathogenesis and molecular underpinning of testicular tumors remain largely elusive. We aimed to delineate the intricate intra-tumoral heterogeneity and the network of intercellular communication within the tumor microenvironment. A total of 40,760 single-cell transcriptomes were analyzed, encompassing samples from six individuals with seminomas, two patients with mixed germ cell tumors, one patient with a Leydig cell tumor, and three healthy donors. Five distinct malignant subclusters were identified in the constructed landscape. Among them, malignant 1 and 3 subclusters were associated with a more immunosuppressive state and displayed worse disease-free survival. Further analysis identified that APP-CD74 interactions were significantly strengthened between malignant 1 and 3 subclusters and 14 types of immune subpopulations. In addition, we established an aberrant spermatogenesis trajectory and delineated the global gene alterations of somatic cells in seminoma testes. Sertoli cells were identified as the somatic cell type that differed the most from healthy donors to seminoma testes. Cellular communication between spermatogonial stem cells and Sertoli cells is disturbed in seminoma testes. Our study delineates the intra-tumoral heterogeneity and the tumor immune microenvironment in testicular tumors, offering novel insights for targeted therapy. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Diverse Microstructures and Quasi-Ionic Liquid-like Transport Mechanisms in Concentrated "Water-in-Salt" Lithium Salt Electrolytes: A Molecular Dynamics Study.

"Water-in-salt"(WIS) electrolytes as potential green and nonflammable electrolytes are currently applied in various energy storage devices, such as lithium-ion batteries and supercapacitors. However, the microstructure at molecular scale and fast ion transport mechanism in such aqueous electrolytes are still under heavy debate due to the complex interactions among ions and water. Here, molecular dynamics simulations are used to study the microstructure and ion transport behaviors from the very dilute LiTFSI/water solution to the highly concentrated WIS electrolytes. It revealed that the diverse microstructures such as completely hydrated ions, ion complexes, and bridge-water molecules are jointly responsible for the electrochemical stability of WIS electrolytes. Diffusion model analysis showed that the Li+ ions exhibit a vehicular transport mechanism with first shell water molecules and structural diffusion mechanism with TFSI- anions. The lithium ion and its first hydration shell act as a single cationic entity. The entity forms a quasi-ionic liquid-like dynamic transport structure with associated anions. Our study challenges previous findings that the high transport dynamics of lithium ions arises from their transport in water-rich nanodomains in high-concentration WIS systems.

Formation of Aluminum-Fluoride Complexes Compromises Defluoridation Efficiency of Aluminum-Based Coagulation.

Aluminum-based coagulation has long been regarded as a reliable and cost-effective process for the defluoridation of industrial effluents. However, such a well-recognized viewpoint is challenged by the underestimation of fluoride levels in treated effluents. Herein, we developed a systematic protocol to distinguish different fluoride species, including free F-, exchangeable fluoride (EF), and nonexchangeable fluoride (NEF). We demonstrated that EF forms complexes with octahedral aluminum (AlO6) on the surface of polyaluminum and can be exchanged with (1,2-cyclohexylenedinitrilo)-tetraacetic acid (CDTA). However, NEF is incorporated with tetrahedral aluminum (AlO4) at the core of polyaluminum, as confirmed by 19F/23Al NMR and ESI-MS analysis, and cannot be exchanged with CDTA due to steric hindrance. Increasing the aluminum coagulant dosage effectively reduced free F- levels in photovoltaic and electroplating effluents to below 1 mg/L. However, the total fluoride content, with over half in the form of EF and NEF, was above 2 mg/L, exceeding the discharge limit regulated by many local governments of China. Furthermore, both EF and NEF can gradually transform to free F- in natural waters. Our findings indicate that aluminum-based coagulation inevitably accompanies the formation of substantial amounts of EF and NEF, compromising its defluoridation efficiency toward industrial effluents.

SSVEP-based visual acuity threshold estimation: linear extrapolation to noise level baseline with various noise definition criteria.

This study aimed to explore the effect of various noise definition criteria in linear extrapolation technique to noise level baseline on steady-state visual evoked potential (SSVEP)-based visual acuity assessment. Four noise definition criteria on frequency-domain, i.e., the mean amplitude at the two adjacent bins of the target frequency, the mean amplitude of a narrow frequency band on either side of the target frequency, the mean amplitude at a broad frequency band except for the target frequency and its harmonic frequencies, and the mean amplitude at a broad frequency band at resting state, corresponding to noise 1, noise 2, noise 3, and noise 4, were introduced to calculate noise level baselines. Then, two experiments were implemented. In experiment 1, electroencephalography (EEG) signals of resting state were recorded for fourteen subjects. In experiment 2, the visual stimuli of vertical sinusoidal gratings at six spatial frequency steps were used to induce SSVEPs for twelve subjects. Finally, SSVEP visual acuity was obtained via the SSVEP visual acuity threshold estimation of linear extrapolation technique to noise level baseline with various noise definition criteria. The bland-Altman analysis found that the difference between subjective Freiburg Visual Acuity and Contrast Test (FrACT) and objective SSVEP visual acuity was - 0.0892, - 0.1071, - 0.0745, and - 0.0804 logMAR and the 95% limit of agreement was 0.2150, 0.2146, 0.2046, and 0.2189 logMAR for noise 1, noise 2, noise 3, and noise 4, respectively, indicating that visual acuity of noise 3 definition criterion, i.e., the mean amplitude at a broad frequency band except for the target frequency and its harmonic frequencies, showed the best performance. This study recommended noise definition criterion 3 of the mean amplitude at a broad frequency band to calculate the noise level baseline in the linear extrapolation of SSVEP-based visual acuity assessment.

Suppression of SMXL4 and SMXL5 confers enhanced thermotolerance through promoting HSFA2 transcription in Arabidopsis.

Identifying the essential factors and underlying mechanisms regulating plant heat stress (HS) responses is crucial for mitigating the threat posed by HS on plant growth, development, distribution, and productivity. Here, we found that the Arabidopsis (Arabidopsis thaliana) super-killer2 (ski2) dicer-like4 (dcl4) mutant, characterized by RNA processing defects and accumulation of abundant 22-nt small interfering RNAs (siRNAs) derived from protein-coding transcripts, displayed significantly increased expression levels of HS-responsive genes and enhanced thermotolerance. These traits primarily resulted from the suppression of SMAX1-LIKE4 (SMXL4) and SMXL5, which encode two putative transcriptional regulators that belong to the SMXL protein family. While smxl4 and smxl5 single mutants were similar to wild type, the smxl4 smxl5 double mutant displayed substantially heightened seedling thermotolerance. Further investigation demonstrated that SMXL4 and SMXL5 repressed the transcription of HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2), encoding a master regulator of thermotolerance, independently of EAR motifs. Moreover, SMXL4 and SMXL5 interacted with HSFA1d and HSFA1e, central regulators sensing and transducing HS stimuli, and antagonistically affected their transactivation activity. In addition, HSFA2 directly bound to the SMXL4 and SMXL5 promoters, inducing their expression during recovery from HS. Collectively, our findings elucidate the role of the SMXL4/SMXL5-HSFA2 regulatory module in orchestrating plant thermotolerance under HS.

MASS cohort: Multicenter, longitudinal, and prospective study of the role of microbiome in severe pneumonia and host susceptibility.

The MASS cohort comprises 2000 ICU patients with severe pneumonia, covering community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, sourced from 19 hospitals across 10 cities in three provinces. A wide array of samples including bronchoalveolar lavage fluid, sputum, feces, and whole blood are longitudinally collected throughout patients' ICU stays. The cohort study seeks to uncover the dynamics of lung and gut microbiomes and their associations with severe pneumonia and host susceptibility, integrating deep metagenomics and transcriptomics with detailed clinical data.

Cisplatin resistance-related transcriptome and methylome integration identifies PCDHB4 as a novel prognostic biomarker in small cell lung cancer.

Platinum-based chemo-resistance is the major issue for the treatment of small cell lung cancer (SCLC). The integrative analysis of multi-omics data is a reliable approach for discovering novel biomarkers associated with chemo-resistance. Here, multi-omics integrative analysis and Cox regression found that higher expression of PCDHB4 was associated with poorer survival of SCLC patients who received chemotherapy. PCDHB4 gene was hypomethylated and upregulated in SCLC, which was validated in the levels of promoter methylation, mRNA, and protein expression. Mechanistically, using bulk RNA-seq data, functional enrichment analysis indicated that higher PCDHB4 expression was associated with lower immune infiltration. The analysis of single-cell RNA-seq (scRNA-seq) found that SCLC cells with PCDHB4 expression exhibited the characteristics of stemness and EMT. In addition, the high expression and hypomethylation of PCDHB4 were also significantly associated with poor survival in lung squamous cell carcinoma. In summary, PCDHB4 is a potential prognostic biomarker of platinum-based chemotherapy in SCLC.

Occurrence and health risks of multiple emerging bisphenol S analogues in pregnant women from South China.

Recently, there has been increasing concern regarding the emergence of bisphenol S analogues (BPSs) due to their potential toxicity. However, their exposure levels and associated health risks in susceptible populations remain unknown. In our study, we analyzed bisphenol A (BPA), along with 11 common BPA analogues (BPAs), and nine emerging BPSs in urine samples collected from 381 pregnant women in South China. All nine BPSs were first detected in pregnant women's urine. In addition to BPA, two BPAs, three BPSs including Diphenylsulfone (DPS), Bis(phenylsulfonyl)phenol (DBSP) and Bis(3-allyl-4-hydroxyphenyl)sulfone (TGSA), were identified as the predominant bisphenols, with detection frequencies ranging from 53-100 %. BPA still exhibited the highest median concentration at 0.624 ng/mL, followed by DPS (0.169 ng/mL), BPS (0.063 ng/mL) and DBSP (0.023 ng/mL). Importantly, mothers with higher levels of BPA, DBSP, DPS, and TGSA in their urine are statistically more likely to give birth to premature infants with shorter lengths at birth or smaller head circumference (p < 0.05). Although the median exposure to 21 bisphenols did not exceed the tolerable daily intake (TDI) of BPA, it did surpass the recently proposed BPA TDI (0.2 ng/kg bw/day) by a factor ranging from 1.1-99 times. This study signifies the first report unveiling the prevalence of multiple bisphenols, particularly emerging BPSs, in the urine of pregnant women in South China.

Unraveling the molecular complexity: Wtap/Ythdf1 and Lcn2 in novel traumatic brain injury secondary injury mechanisms.

The primary aim of this research was to explore the functions of Wtap and Ythdf1 in regulating neuronal Lipocalin-2 (Lcn2) through m6A modification in traumatic brain injury (TBI). By employing transcriptome sequencing and enrichment analysis, we identified the Wtap/Ythdf1-mediated Lcn2 m6A modification pathway as crucial in TBI. In our in vitro experiments using primary cortical neurons, knockout of Wtap and Ythdf1 led to the inhibition of Lcn2 m6A modification, resulting in reduced neuronal death and inflammation. Furthermore, overexpression of Lcn2 in cortical neurons induced the activation of reactive astrocytes and M1-like microglial cells, causing neuronal apoptosis. In vivo experiments confirmed the activation of reactive astrocytes and microglial cells in TBI and importantly demonstrated that Wtap knockdown improved neuroinflammation and functional impairment. These findings underscore the significance of Wtap/Ythdf1-mediated Lcn2 regulation in TBI secondary injury and suggest potential therapeutic implications for combating TBI-induced neuroinflammation and neuronal damage.

Predicting postoperative pain in children: an observational study using the pain threshold Index.

Objective: While the pain threshold index (PTI) holds potential as a tool for monitoring analgesia-pain equilibrium, its precision in forecasting postoperative pain in children remains unconfirmed. This study's primary aim was to assess the PTI's predictive precision for postoperative pain. Methods: Children (aged 2-16 years) undergoing general surgery under general anesthesia were included. Within 5 min prior to the patient's emergence from surgery, data including PTI, wavelet index (WLI), heart rates (HR) and mean arterial pressure (MAP) were collected. Subsequently, a 15-min pain assessment was conducted following the patient's awakening. The accuracy of these indicators in discerning between mild and moderate to severe postoperative pain was evaluated through receiver operating characteristic (ROC) analysis. Results: The analysis encompassed data from 90 children. ROC analysis showed that PTI was slightly better than HR, MAP and WLI in predicting postoperative pain, but its predictive value was limited. The area under the curve (AUC) was 0.659 [0.537∼0.780] and the optimal threshold was 65[64-67]. Sensitivity and specificity were determined at 0.90 and 0.50, respectively. In a multivariable logistic regression model, a higher predictive accuracy was found for a multivariable predictor combining PTI values with gender, BMI, HR and MAP (AUC, 0.768; 95%CI, 0.669-0.866). Upon further scrutinizing the age groups, PTI's AUC was 0.796 for children aged 9-16, 0.656 for those aged 4-8, and 0.601 for younger individuals. Conclusions: PTI, when used alone, lacks acceptable accuracy in predicting postoperative pain in children aged 2 to 16 years. However, when combined with other factors, it shows improved predictive accuracy. Notably, PTI appears to be more accurate in older children.

Cationic Foldamer-Catalyzed Asymmetric Synthesis of Inherently Chiral Cages.

The stereochemistry of shape-persistent molecular cages, particularly those resembling prisms, exerts significant influence on their application-specific functionalities. Although methods exist for fabricating inherently chiral prism-like cages, strategies for catalytic asymmetric synthesis of these structures in a diversity-oriented fashion remain unexplored. Herein, we introduce an unprecedented organocatalytic desymmetrization approach for the generation of inherently chiral prism-like cages via phosphonium-containing foldamer-catalyzed SNAr reactions. This methodology establishes a topological connection, enabling the facile assembly of a wide range of versatile stereogenic-at-cage building blocks possessing two highly modifiable groups. Furthermore, subsequent stereospecific transformations of the remaining chlorides and/or ethers afford convenient access to numerous functionally relevant chiral-at-cage molecules.

Conserved features and diversity attributes of chimeric RNAs across accessions in four plants.

As a non-collinear expression form of genetic information, chimeric RNAs increase the complexity of transcriptome in diverse organisms. Although chimeric RNAs have been identified in plants, few common features have been revealed. Here, we systemically explored the landscape of chimeric RNAs across multi-accession and multi-tissue using pan-genome and transcriptome data of four plants: rice, maize, soybean, and Arabidopsis. Among the four species, conserved characteristics of breakpoints and parental genes were discovered. In each species, chimeric RNAs displayed a high level of diversity among accessions, and the clustering of accessions using chimeric events was generally concordant with clustering based on genomic variants, implying a general relationship between genetic variations and chimeric RNAs. Through mass spectrometry, we confirmed a fusion protein OsNDC1-OsGID1L2 and observed its subcellular localization, which differed from the original proteins. Phenotypic cues in transgenic rice suggest the potential functions of OsNDC1-OsGID1L2. Moreover, an intriguing chimeric event Os01g0216500-Os01g0216900, generated by a large deletion in basmati rice, also exists in another accession without the deletion, demonstrating its convergence in evolution. Our results illuminate the characteristics and hint at the evolutionary implications of plant chimeric RNAs, which serve as a supplement to genetic variations, thus expanding our understanding of genetic diversity.