Circular RNA vaccines against SARS-CoV-2 and emerging variants.

As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1mΨ-modified mRNA vaccine and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses. Importantly, we found that the circRNARBD-Omicron vaccine induced effective neutralizing antibodies against the Omicron but not the Delta variant. In contrast, the circRNARBD-Delta vaccine protected against both Delta and Omicron or functioned as a booster after two doses of either native- or Delta-specific vaccination, making it a favorable choice against the current variants of concern (VOCs) of SARS-CoV-2.

Maize smart-canopy architecture enhances yield at high densities.

Increasing planting density is a key strategy for enhancing maize yields1-3. An ideotype for dense planting requires a 'smart canopy' with leaf angles at different canopy layers differentially optimized to maximize light interception and photosynthesis4-6, among other features. Here we identified leaf angle architecture of smart canopy 1 (lac1), a natural mutant with upright upper leaves, less erect middle leaves and relatively flat lower leaves. lac1 has improved photosynthetic capacity and attenuated responses to shade under dense planting. lac1 encodes a brassinosteroid C-22 hydroxylase that predominantly regulates upper leaf angle. Phytochrome A photoreceptors accumulate in shade and interact with the transcription factor RAVL1 to promote its degradation via the 26S proteasome, thereby inhibiting activation of lac1 by RAVL1 and decreasing brassinosteroid levels. This ultimately decreases upper leaf angle in dense fields. Large-scale field trials demonstrate that lac1 boosts maize yields under high planting densities. To quickly introduce lac1 into breeding germplasm, we transformed a haploid inducer and recovered homozygous lac1 edits from 20 diverse inbred lines. The tested doubled haploids uniformly acquired smart-canopy-like plant architecture. We provide an important target and an accelerated strategy for developing high-density-tolerant cultivars, with lac1 serving as a genetic chassis for further engineering of a smart canopy in maize.

Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling.

The scarcity of malignant Hodgkin and Reed-Sternberg cells hampers tissue-based comprehensive genomic profiling of classic Hodgkin lymphoma (cHL). By contrast, liquid biopsies show promise for molecular profiling of cHL due to relatively high circulating tumour DNA (ctDNA) levels1-4. Here we show that the plasma representation of mutations exceeds the bulk tumour representation in most cases, making cHL particularly amenable to noninvasive profiling. Leveraging single-cell transcriptional profiles of cHL tumours, we demonstrate Hodgkin and Reed-Sternberg ctDNA shedding to be shaped by DNASE1L3, whose increased tumour microenvironment-derived expression drives high ctDNA concentrations. Using this insight, we comprehensively profile 366 patients, revealing two distinct cHL genomic subtypes with characteristic clinical and prognostic correlates, as well as distinct transcriptional and immunological profiles. Furthermore, we identify a novel class of truncating IL4R mutations that are dependent on IL-13 signalling and therapeutically targetable with IL-4Rα-blocking antibodies. Finally, using PhasED-seq5, we demonstrate the clinical value of pretreatment and on-treatment ctDNA levels for longitudinally refining cHL risk prediction and for detection of radiographically occult minimal residual disease. Collectively, these results support the utility of noninvasive strategies for genotyping and dynamic monitoring of cHL, as well as capturing molecularly distinct subtypes with diagnostic, prognostic and therapeutic potential.

A single dominant GLOBOSA allele accounts for repeated origins of hose-in-hose flowers in Sinningia (Gesneriaceae).

Plants bearing double flowers have long been cultivated as ornamental plants. Hose-in-hose flowers, bearing 2-whorled corolla tubes in whorls 1 and 2, are uncommon but recur in Sinningia (Gesnerioideae, Gesneriaceae). In this study, we selected 15 hose-in-hose cultivars as materials to explore the underlying molecular and genetic mechanisms of this floral architecture. We found that they originated from different hybridization events within the Dircaea clade. Three B-class MADS-box genes were globally expressed in all floral whorls, but only GLOBOSA1 (GLO1) has accumulated a dominant mutation, i.e., the insertion of a hAT-like miniature inverted-repeat transposable element (MITE) into its promoter, that co-segregated with the hose-in-hose phenotype. In addition, all 15 hose-in-hose cultivars contained the same dominant GLO1 allele. Transient gene expression assays confirmed the role of this MITE insertion in up-regulating the promoter activity of GLO1 by providing several cis-regulatory elements. Genetic transformation in heterologous Chirita pumila (Didymocarpoideae, Gesneriaceae) verified that this dominant GLO1 allele is sufficient to confer the hose-in-hose phenotype. We further demonstrated that both the GLO1 allele and the hAT-like MITE descended from wild S. cardinalis with single flowers. This study highlights the significance of wide hybridization in frequent gains of the dominant GLO1 allele and thereafter repeated occurrence of hose-in-hose flowers in Sinningia.

INDETERMINATE1 autonomously regulates phosphate homeostasis upstream of the miR399-ZmPHO2 signaling module in maize.

The macronutrient phosphorus is essential for plant growth and development. Plants have evolved multiple strategies to increase the efficiency of phosphate (Pi) acquisition to protect themselves from Pi starvation. However, the crosstalk between Pi homeostasis and plant development remains to be explored. Here, we report that overexpressing microRNA399 (miR399) in maize (Zea mays) is associated with premature senescence after pollination. Knockout of ZmPHO2 (Phosphate 2), a miR399 target, resulted in a similar premature senescence phenotype. Strikingly, we discovered that INDETERMINATE1 (ID1), a floral transition regulator, inhibits the transcription of ZmMIR399 genes by directly binding to their promoters, alleviating the repression of ZmPHO2 by miR399 and ultimately contributing to the maintenance of Pi homeostasis in maize. Unlike ZmMIR399 genes, whose expression is induced by Pi deficiency, ID1 expression was independent of the external inorganic orthophosphate status, indicating that ID1 is an autonomous regulator of Pi homeostasis. Furthermore, we show that ZmPHO2 was under selection during maize domestication and cultivation, resulting in a more sensitive response to Pi starvation in temperate maize than in tropical maize. Our study reveals a direct functional link between Pi-deprivation sensing by the miR399-ZmPHO2 regulatory module and plant developmental regulation by ID1.

Phytochromes enhance SOS2-mediated PIF1 and PIF3 phosphorylation and degradation to promote Arabidopsis salt tolerance.

Soil salinity is one of the most detrimental abiotic stresses affecting plant survival, and light is a core environmental signal regulating plant growth and responses to abiotic stress. However, how light modulates the plant's response to salt stress remains largely obscure. Here, we show that Arabidopsis (Arabidopsis thaliana) seedlings are more tolerant to salt stress in the light than in the dark, and that the photoreceptors phytochrome A (phyA) and phyB are involved in this tolerance mechanism. We further show that phyA and phyB physically interact with the salt tolerance regulator SALT OVERLY SENSITIVE2 (SOS2) in the cytosol and nucleus, and enhance salt-activated SOS2 kinase activity in the light. Moreover, SOS2 directly interacts with and phosphorylates PHYTOCHROME-INTERACTING FACTORS PIF1 and PIF3 in the nucleus. Accordingly, PIFs act as negative regulators of plant salt tolerance, and SOS2 phosphorylation of PIF1 and PIF3 decreases their stability and relieves their repressive effect on plant salt tolerance in both light and dark conditions. Together, our study demonstrates that photoactivated phyA and phyB promote plant salt tolerance by increasing SOS2-mediated phosphorylation and degradation of PIF1 and PIF3, thus broadening our understanding of how plants adapt to salt stress according to their dynamic light environment.

CYCLOIDEA-like genes control floral symmetry, floral orientation, and nectar guide patterning.

Actinomorphic flowers usually orient vertically (relative to the horizon) and possess symmetric nectar guides, while zygomorphic flowers often face horizontally and have asymmetric nectar guides, indicating that floral symmetry, floral orientation, and nectar guide patterning are correlated. The origin of floral zygomorphy is dependent on the dorsoventrally asymmetric expression of CYCLOIDEA (CYC)-like genes. However, how horizontal orientation and asymmetric nectar guides are achieved remains poorly understood. Here, we selected Chirita pumila (Gesneriaceae) as a model plant to explore the molecular bases for these traits. By analyzing gene expression patterns, protein-DNA and protein-protein interactions, and encoded protein functions, we identified multiple roles and functional divergence of 2 CYC-like genes, i.e. CpCYC1 and CpCYC2, in controlling floral symmetry, floral orientation, and nectar guide patterning. CpCYC1 positively regulates its own expression, whereas CpCYC2 does not regulate itself. In addition, CpCYC2 upregulates CpCYC1, while CpCYC1 downregulates CpCYC2. This asymmetric auto-regulation and cross-regulation mechanism might explain the high expression levels of only 1 of these genes. We show that CpCYC1 and CpCYC2 determine asymmetric nectar guide formation, likely by directly repressing the flavonoid synthesis-related gene CpF3'5'H. We further suggest that CYC-like genes play multiple conserved roles in Gesneriaceae. These findings shed light on the repeated origins of zygomorphic flowers in angiosperms.

The evening complex promotes maize flowering and adaptation to temperate regions.

Maize (Zea mays) originated in southern Mexico and has spread over a wide latitudinal range. Maize expansion from tropical to temperate regions has necessitated a reduction of its photoperiod sensitivity. In this study, we cloned a quantitative trait locus (QTL) regulating flowering time in maize and show that the maize ortholog of Arabidopsis thaliana EARLY FLOWERING3, ZmELF3.1, is the causal locus. We demonstrate that ZmELF3.1 and ZmELF3.2 proteins can physically interact with ZmELF4.1/4.2 and ZmLUX1/2, to form evening complex(es; ECs) in the maize circadian clock. Loss-of-function mutants for ZmELF3.1/3.2 and ZmLUX1/2 exhibited delayed flowering under long-day and short-day conditions. We show that EC directly represses the expression of several flowering suppressor genes, such as the CONSTANS, CONSTANS-LIKE, TOC1 (CCT) genes ZmCCT9 and ZmCCT10, ZmCONSTANS-LIKE 3, and the PSEUDORESPONSE REGULATOR (PRR) genes ZmPRR37a and ZmPRR73, thus alleviating their inhibition, allowing florigen gene expression and promoting flowering. Further, we identify two closely linked retrotransposons located in the ZmELF3.1 promoter that regulate the expression levels of ZmELF3.1 and may have been positively selected during postdomestication spread of maize from tropical to temperate regions during the pre-Columbian era. These findings provide insights into circadian clock-mediated regulation of photoperiodic flowering in maize and new targets of genetic improvement for breeding.

Feasibility of hepatitis C elimination by screening and treatment alone in high-income countries.

BACKGROUND AND AIMS: Despite the availability of highly effective direct-acting antiviral therapy, chronic hepatitis C (CHC) continues to cause a major public health burden. In many high-income countries, treatment rates have been declining, which was exacerbated by the impact of the COVID-19 pandemic, threatening the ability to meet the World Health Organization (WHO)'s targets for eliminating HCV as a public health threat by 2030. We sought to model the impact of CHC in Canada, a resource-rich country with ongoing immigration from HCV-endemic regions; which relies exclusively on risk-based screening for case identification. APPROACH AND RESULTS: We developed an agent-based model to characterize the HCV epidemic in a high-income country with ongoing immigration. Combinations of prevention such as harm reduction, screening, and treatment strategies were considered. Model parameters were estimated from the literature and calibrated against historical HCV data. Sensitivity analyses were performed to assess uncertainty. Under the current status quo of risk-based screening, we predict the incidence of CHC-induced decompensated cirrhosis, HCC, and liver-related deaths would decrease by 79.4%, 76.1%, and 62.1%, respectively, between 2015 and 2030, but CHC incidence would only decrease by 11.1%. The results were sensitive to HCV transmission rate and an annual number of people initiating treatment. CONCLUSIONS: Current risk-based screening, and subsequent treatment, will be inadequate to achieve WHO goals. With extensive scale-up in screening, and treatment, the mortality target may be achievable, but the target for preventing new CHC cases is unlikely reachable, highlighting the importance of developing enhanced harm-reduction strategies for HCV elimination.

The transcription factor bZIP68 negatively regulates cold tolerance in maize.

Maize (Zea mays) originated in tropical areas and is thus susceptible to low temperatures, which pose a major threat to maize production. Our understanding of the molecular basis of cold tolerance in maize is limited. Here, we identified bZIP68, a basic leucine zipper (bZIP) transcription factor, as a negative regulator of cold tolerance in maize. Transcriptome analysis revealed that bZIP68 represses the cold-induced expression of DREB1 transcription factor genes. The stability and transcriptional activity of bZIP68 are controlled by its phosphorylation at the conserved Ser250 residue under cold stress. Furthermore, we demonstrated that the bZIP68 locus was a target of selection during early domestication. A 358-bp insertion/deletion (Indel-972) polymorphism in the bZIP68 promoter has a significant effect on the differential expression of bZIP68 between maize and its wild ancestor teosinte. This study thus uncovers an evolutionary cis-regulatory variant that could be used to improve cold tolerance in maize.

Heavy metal ions exchange driven protein phosphorylation cascade functions in genomic instability in spermatocytes and male infertility.

DNA double-strand breaks (DSBs) are functionally linked to genomic instability in spermatocytes and to male infertility. The heavy metal cadmium (Cd) is known to induce DNA damage in spermatocytes by unknown mechanisms. Here, we showed that Cd ions impaired the canonical non-homologous end-joining (NHEJ) repair pathway, but not the homologous recombination (HR) repair pathway, through stimulation of Ser2056 and Thr2609 phosphorylation of DNA-PKcs at DSB sites. Hyper-phosphorylation of DNA-PKcs led to its premature dissociation from DNA ends and the Ku complex, preventing recruitment of processing enzymes and further ligation of DNA ends. Specifically, this cascade was initiated by the loss of PP5 phosphatase activity, which results from the dissociation of PP5 from its activating ions (Mn), that is antagonized by Cd ions through a competitive mechanism. In accordance, in a mouse model Cd-induced genomic instability and consequential male reproductive dysfunction were effectively reversed by a high dosage of Mn ions. Together, our findings corroborate a protein phosphorylation-mediated genomic instability pathway in spermatocytes that is triggered by exchange of heavy metal ions.

Serum GSDMD for Early Diagnosis of Bloodstream Infection and Differentiating Bacterial from Fungal Infections.

BACKGROUND: The role of Gasdermin D (GSDMD) in bloodstream infection (BSI) diagnosis is unknown. METHODS: Serum GSDMD levels were measured in BSI patients. Endothelial cells and PBMCs were isolated, infected with bacteria/fungi, and intracellular/extracellular GSDMD concentrations were measured. An animal model was established to investigate the association between serum GSDMD levels and BSI incidence/progression. RESULTS: ROC curve analysis indicated that GSDMD could be a potential early diagnostic biomarker for BSI (AUC = 0.9885). Combining GSDMD with procalcitonin (PCT) improved the differential diagnosis of Gram-positive and Gram-negative bacteria (AUC = 0.6699, 66.15% specificity), and early diagnosis of Gram-positive bacteria (98.46% sensitivity), while PCT was not significantly elevated. The combined GSDMD and G-test had higher sensitivity (AUC = 0.7174) for differential diagnosis of bacterial and fungal infections, and early detection of fungal infections (98.44% sensitivity). In vitro and in vivo experiments confirmed that GSDMD levels increased significantly within 2 hours, peaked at 16 hours, and exhibited a time-dependent upward trend. CONCLUSIONS: Serum GSDMD, alone or combined with other biomarkers, has potential for early diagnosis and differential diagnosis of BSI caused by various pathogens. This finding offers a new strategy for early detection and treatment of BSI.

In Vivo Self-Sorting of Peptides via In Situ Assembly Evolution.

Despite significant progress achieved in artificial self-sorting in solution, operating self-sorting in the body remains a considerable challenge. Here, we report an in vivo self-sorting peptide system via an in situ assembly evolution for combined cancer therapy. The peptide E3C16-SS-EIY consists of two disulfide-connected segments, E3C16SH and SHEIY, capable of independent assembly into twisted or flat nanoribbons. While E3C16-SS-EIY assembles into nanorods, exposure to glutathione (GSH) leads to the conversion of the peptide into E3C16SH and SHEIY, thus promoting in situ evolution from the nanorods into self-sorted nanoribbons. Furthermore, incorporation of two ligand moieties targeting antiapoptotic protein XIAP and organellar endoplasmic reticulum (ER) into the self-sorted nanoribbons allows for simultaneous inhibition of XIAP and accumulation surrounding ER. This leads to the cytotoxicity toward the cancer cells with elevated GSH levels, through activating caspase-dependent apoptosis and inducing ER dysfunction. In vivo self-sorting of E3C16-SS-EIY decorated with ligand moieties is thoroughly validated by tissue studies. Tumor-bearing mouse experiments confirm the therapeutic efficacy of the self-sorted assemblies for inhibiting tumor growth, with excellent biosafety. Our findings demonstrate an efficient approach to develop in vivo self-sorting systems and thereby facilitating in situ formulation of biomedical agents.

High-Strength MOF-Based Polymer Electrolytes with Uniform Ionic Flow for Lithium Dendrite Suppression.

The uneven formation of lithium dendrites during electroplating/stripping leads to a decrease in the utilization of active lithium, resulting in poor cycling stability and posing safety hazards to the battery. Herein, introducing a 3D continuously interconnected zirconium-based metal-organic framework (MOF808) network into a polyethylene oxide polymer matrix establishes a synergistic mechanism for lithium dendrite inhibition. The 3D MOF808 network maintains its large pore structure, facilitating increased lithium salt accommodation, and expands anion adsorption at unsaturated metal sites through its diverse large-space cage structure, thereby promoting the flow of Li+. Infrared-Raman and synchrotron small-angle X-ray scattering results demonstrate that the transport behavior of lithium salt ion clusters at the MOF/polymer interface verifies the increased local Li+ flux concentration, thereby raising the mobility number of Li+ to 0.42 and ensuring uniform Li+ flux distribution, leading to dendrite-free and homogeneous Li+ deposition. Furthermore, nanoindentation tests reveal that the high modulus and elastic recovery of MOF-based polymer electrolytes contribute to forming a robust, dendrite-resistant interface. Consequently, in symmetric battery systems, the system exhibits minimal overpotential, merely 35 mV, while maintaining stable cycling for over 1800 h, achieving low-overpotential lithium deposition. Moreover, it retains redox stability under high voltages up to 5.3 V.

Genetic variation in the aquaporin TONOPLAST INTRINSIC PROTEIN 4;3 modulates maize cold tolerance.

Cold stress is a major abiotic stress that threatens maize (Zea mays L.) production worldwide. Understanding the molecular mechanisms underlying cold tolerance is crucial for breeding resilient maize varieties. Tonoplast intrinsic proteins (TIPs) are a subfamily of aquaporins in plants. Here, we report that TIP family proteins are involved in maize cold tolerance. The expression of most TIP genes was responsive to cold stress. Overexpressing TIP2;1, TIP3;2 or TIP4;3 reduced the cold tolerance of maize seedlings, while loss-of-function mutants of TIP4;3 exhibited enhanced cold tolerance. Candidate gene-based association analysis revealed that a 328-bp transposon insertion in the promoter region of TIP4;3 was strongly associated with maize cold tolerance. This transposon insertion conferred cold tolerance by repressing TIP4;3 expression through increased methylation of its promoter region. Moreover, TIP4;3 was found to suppress stomatal closure and facilitate reactive oxygen species (ROS) accumulation under cold stress, thereby inhibiting the expression of cold-responsive genes, including DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR 1 (DREB1) genes and a subset of peroxidase genes, ultimately attenuating maize cold tolerance. This study thus elucidates the mechanism underlying TIP-mediated cold tolerance and identifies a favourable TIP4;3 allele as a potential genetic resource for breeding cold-tolerant maize varieties.

A SARS-CoV-2-Related Virus from Malayan Pangolin Causes Lung Infection without Severe Disease in Human ACE2-Transgenic Mice.

Coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most severe emerging infectious disease in the current century. The discovery of SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins in South Asian countries indicates that SARS-CoV-2 likely originated from wildlife. To date, two SARSr-CoV-2 strains have been isolated from pangolins seized in Guangxi and Guangdong by the customs agency of China, respectively. However, it remains unclear whether these viruses cause disease in animal models and whether they pose a transmission risk to humans. In this study, we investigated the biological features of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin (Manis javanica) captured by the Guangxi customs agency, termed MpCoV-GX, in terms of receptor usage, cell tropism, and pathogenicity in wild-type BALB/c mice, human angiotensin-converting enzyme 2 (ACE2)-transgenic mice, and human ACE2 knock-in mice. We found that MpCoV-GX can utilize ACE2 from humans, pangolins, civets, bats, pigs, and mice for cell entry and infect cell lines derived from humans, monkeys, bats, minks, and pigs. The virus could infect three mouse models but showed limited pathogenicity, with mild peribronchial and perivascular inflammatory cell infiltration observed in lungs. Our results suggest that this SARSr-CoV-2 virus from pangolins has the potential for interspecies infection, but its pathogenicity is mild in mice. Future surveillance among these wildlife hosts of SARSr-CoV-2 is needed to monitor variants that may have higher pathogenicity and higher spillover risk. IMPORTANCE SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health. Several SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins have been identified since the SARS-CoV-2 outbreak. It is therefore important to assess their potential of crossing species barriers for better understanding of their risk of future emergence. In this work, we investigated the biological features and pathogenicity of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin, named MpCoV-GX. We found that MpCoV-GX can utilize ACE2 from 7 species for cell entry and infect cell lines derived from a variety of mammalian species. MpCoV-GX can infect mice expressing human ACE2 without causing severe disease. These findings suggest the potential of cross-species transmission of MpCoV-GX, and highlight the need of further surveillance of SARSr-CoV-2 in pangolins and other potential animal hosts.

Widely tunable S-band ring-cavity Tm3+-doped fluorotellurite fiber laser.

Tm3+-doped fluorotellurite fibers (TDFTFs) are fabricated by using a rod-in-tube method. A 2.1 m long TDFTF is used as the gain medium, in which both ends of the TDFTF are connected to a short piece of a silica fiber by direct fusion splicing. By inserting the above TDFTF and a tunable optical bandpass filter into a ring cavity and employing a 1400/1570 nm dual-wavelength pumping technique, tunable lasing from 1460 to 1526 nm is obtained, which almost covers the whole S-band. To the best of our knowledge, this is the first report of tunable Tm3+-doped fiber laser with a tunable range almost covering the whole S-band. Furthermore, by removing the tunable optical bandpass filter from the ring cavity, free-running multi-wavelength lasers at 1500 and 1901 nm are achieved. Our results show that TDFTFs are promising gain media for constructing S-band fiber lasers.

ETV6::ACSL6 translocation-driven super-enhancer activation leads to eosinophilia in acute lymphoblastic leukemia through IL-3 overexpression.

ETV6::ACSL6 represents a rare genetic aberration in hematopoietic neoplasms and is often associated with severe eosinophilia, which confers an unfavorable prognosis requiring additional anti-inflammatory treatment. However, since the translocation is unlikely to produce a fusion protein, the mechanism of ETV6::ACSL6 action remains unclear. Here, we performed multi-omics analyses of primary leukemia cells and patient-derived xenografts from an acute lymphoblastic leukemia (ALL) patient with ETV6::ACSL6 translocation. We identified a super-enhancer located within the ETV6 gene locus, and revealed translocation and activation of the super-enhancer associated with the ETV6::ACSL6 fusion. The translocated super-enhancer exhibited intense interactions with genomic regions adjacent to and distal from the breakpoint at chromosomes 5 and 12, including genes coding inflammatory factors such as IL-3. This led to modulations in DNA methylation, histone modifications, and chromatin structures, triggering transcription of inflammatory factors leading to eosinophilia. Furthermore, the bromodomain and extraterminal domain (BET) inhibitor synergized with standard-of-care drugs for ALL, effectively reducing IL-3 expression and inhibiting ETV6::ACSL6 ALL growth in vitro and in vivo. Overall, our study revealed for the first time a cis-regulatory mechanism of super-enhancer translocation in ETV6::ACSL6ALL, leading to an ALL-accompanying clinical syndrome. These findings may stimulate novel treatment approaches for this challenging ALL subtype.

OAM mode-division multiplexing IM/DD transmission at 4.32†Tbit/s with a low-complexity adaptive-network-based fuzzy inference system nonlinear equalizer.

Stochastic nonlinear impairment is the primary factor that limits the transmission performance of high-speed orbital angular momentum (OAM) mode-division multiplexing (MDM) optical fiber communication systems. This Letter presents a low-complexity adaptive-network-based fuzzy inference system (LANFIS) nonlinear equalizer for OAM-MDM intensity-modulation direct-detection (IM/DD) transmission with three OAM modes and 15 wavelength division multiplex (WDM) channels. The LANFIS equalizer could adjust the probability distribution functions (PDFs) of the distorted pulse amplitude modulation (PAM) symbols to fit the statistical characteristics of the WDM-OAM-MDM transmission channel. Therefore, although the transmission symbols in the WDM-OAM-MDM system are subjected to a stochastic nonlinear impairment, the proposed LANFIS equalizer can effectively compensate the distorted signals. The proposed equalizer outperforms the Volterra equalizer with improvements in receiver sensitivity of 2, 1.5, and 1.3 dB for three OAM modes at a wavelength of 1550.12 nm, respectively. It also outperforms a CNN equalizer, with improvements in receiver sensitivity of 1, 0.5, and 0.3 dB, respectively. Moreover, complexity reductions of 67%, 74%, and 99.9% are achieved for the LANFIS equalizer compared with the Volterra, CNN, and ANFIS equalizers, respectively. The proposed equalizer has high performance and low complexity, making it a promising candidate for a high-speed WDM-OAM-MDM system.

3D Covalent Organic Framework Membranes for Molecular Separations.

Membrane separation has become an indispensable separation technology in social production, playing an important role in drug production, mineral exploitation, water purification, etc. The key core of membranes lies in achieving efficient and precise sieving between substances. As a result, a typical trade-off arises: highly permeable membranes usually sacrifice selectivity and vice versa. To address this dilemma, long-term research has focused on comprehensive understanding and modelling of synthetic membranes at various scales. A significant advancement in this arena is the advent of three-dimensional covalent organic framework (3D COF) membranes, a novel category of long-range ordered porous organic polymer materials. Characterized by an abundance of interconnected channels, diverse pore wall properties, tunable structures, and robust thermal and chemical resilience, 3D COF membranes offer a promising approach for efficient substance separation. This review undertakes a meticulous investigation of the synthesis and physicochemical properties of 3D COF membranes, accentuating the underlying design principles, fabrication methods, and application attempts. A comprehensive assessment of their research trajectory and current standing in the field of membrane processes is provided. The review culminates in a forward-looking outlook, summarizing future research directions and highlighting the substantial potential of this innovative work to shape the future of efficient membrane separation processes.