Strategies of invasive snail Pomacea canaliculata during hibernation in rice fields of south China: effects of body size, sex, and soil depth.

BACKGROUND: The invasive freshwater snail Pomacea canaliculata is an agricultural pest with a certain level of tolerance to abiotic stress. After the harvest of late rice, the snails usually burrow themselves into the soil surface layers to overwinter and pose a renewed threat to rice production in the following year. Revealing the response of snails to environmental stresses is crucial for developing countermeasures to control their damage and spread. RESULTS: In this study, we conducted a 120-day in situ experiment during the winter to investigate the survival and physiological changes of hibernating snails in 0-5 and 5-10 cm soil depths, aiming to explore their overwintering strategies. Our results showed that 73.61%, 87.50%, and 90.28% of male, female, and juvenile snails survived after hibernation for 120 days in 0-10 cm soil depth, respectively. The differences in survival rates based on sex and size of snails potentially reflect the countermeasures of snails to rapidly reproduce after hibernation. Simultaneously, the hibernating snails exhibited the ability to maintain a certain level of body weight. During this period, the snails increased their antioxidant enzyme activities to cope with oxidative stress, and enhanced their lipid storage. The hibernation survival of snails was not significantly affected by different soil depths, indicating that they have the potential to hibernate into deeper soils. Furthermore, snails were capable of increasing their contents of bound water and glycerol to cope with sudden cold spells during hibernation. CONCLUSION: Our findings emphasize the adaptive changes of P. canaliculata snails overwintering in paddy soils. In future studies, the vulnerabilities of P. canaliculata during hibernation (e.g. shell characteristics, nutrient reserves, and dehydration tolerance, etc.,) should be investigated to develop effective control methods for this period. © 2024 Society of Chemical Industry.

Antioxidant, Antimicrobial, and Anti-Inflammatory Effects of Liriodendron chinense Leaves.

Liriodendron chinense has been widely utilized in traditional Chinese medicine to treat dispelling wind and dampness and used for alleviating cough and diminishing inflammation. However, the antioxidant, antimicrobial, and anti-inflammatory effects of L. chinense leaves and the key active constituents remained elusive. So, we conducted some experiments to support the application of L. chinense in traditional Chinese medicine by investigating the antioxidant, antibacterial, and anti-inflammatory abilities, and to identify the potential key constituents responsible for the activities. The ethanol extract of L. chinense leaves (LCLE) was isolated and extracted, and assays measuring ferric reducing antioxidant power, total reducing power, DPPH•, ABTS•+, and •OH were used to assess its in vitro antioxidant capacities. Antimicrobial activities of LCLE were investigated by minimal inhibitory levels, minimum antibacterial concentrations, disc diffusion test, and scanning electron microscope examination. Further, in vivo experiments including macro indicators examination, histopathological examination, and biochemical parameters measurement were conducted to investigate the effects of LCLE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. LCLE was further isolated and purified through column chromatography, and LPS-induced RAW264.7 cells were constructed to assess the diminished inflammation potential of the identified chemical composites. ABTS•+ and •OH radicals were extensively neutralized by the LCLE treatment. LCLE administration also presented broad-spectrum antimicrobial properties, especially against Staphylococcus epidermidis by disrupting cell walls. LPS-induced ALI in mice was significantly ameliorated by LCLE intervention, as evidenced by the histological changes in the lung and liver tissues as well as the reductions of nitric oxide (NO), TNF-α, and IL-6 production. Furthermore, three novel compounds including fragransin B2, liriodendritol, and rhamnocitrin were isolated, purified, and identified from LCLE. These three compounds exhibited differential regulation on NO accumulation and IL-10, IL-1ß, IL-6, TNF-α, COX-2, and iNOS mRNA expression in RAW264.7 cells induced by LPS. Fragransin B2 was more effective in inhibiting TNF-α mRNA expression, while rhamnocitrin was more powerful in inhibiting IL-6 mRNA expression. LCLE had significant antioxidant, antimicrobial, and anti-inflammatory effects. Fragransin B2, liriodendritol, and rhamnocitrin were probably key active constituents of LCLE, which might act synergistically to treat inflammatory-related disorders. This study provided a valuable view of the healing potential of L. chinense leaves in curing inflammatory diseases.

Electro-absorption modulated 53 Gbps widely tunable laser based on half-wave V-coupled cavities.

In this paper, a 53 Gbps widely tunable transmitter is experimentally demonstrated for the first time, to our knowledge. An InGaAlAs/InP multiple-quantum-well (MQW) wafer is used with an identical layer structure for both the V-coupled cavity laser (VCL) and the electro-absorption modulator (EAM). The VCL uses a shallow-etched waveguide to reduce loss, while the EAM uses a deep-etched waveguide to increase the 3-dB modulation bandwidth. With the temperature varying from 19.5 to 30°C, the transmitter achieves wavelength tuning of 42 channels with a spacing of 100 GHz, corresponding to a tuning range of 32.6 nm from 1538.94 to 1571.54 nm. The static extinction ratio (ER) for all channels is higher than 14 dB. The measured 3-dB electro-optic (E0) bandwidth of the transmitter is over 40 GHz, which fits well with the calculated 3-dB bandwidth. At a fixed peak-to-peak driving voltage of 2.4 V, all channels exhibit clearly an open eye diagram with a 53 Gbps non-return-to-zero (NRZ) signal, while the dynamic ER is higher than 4.5 dB.

Enhanced editing efficiency in Arabidopsis with a LbCas12a variant harboring D156R and E795L mutations.

Cas12a (Cpf1), a Class 2 Type V CRISPR/Cas nuclease, has several unique attributes for genome editing and may provide a valuable alternative to Cas9. However, a low editing efficiency due to temperature sensitivity and insufficient cleavage activity of the Cas12a nuclease are major obstacles to its broad application. In this report, we generated two variants, ttAsCas12 Ultra and ttLbCas12a Ultra harboring three (E174R, M537R, and F870L) or two (D156R and E795L) mutations, respectively, by combining the mutations from the temperature-tolerant variants ttAsCas12a (E174R) and ttLbCas12a (D156R), and those from the highly active variants AsCas12a Ultra (M537R and F870L) and LbCas12a Ultra (E795L). We compared editing efficiencies of the five resulting Cas12a variants (LbCas12a, ttLbCas12a, ttLbCas12a Ultra, AsCas12a Ultra, and ttAsCas12 Ultra) at six target sites of four genes in Arabidopsis (Arabidopsis thaliana). The variant ttLbCas12a Ultra, harboring the D156R and E795L mutations, exhibited the highest editing efficiency of all variants tested in Arabidopsis and can be used to generate homozygous or biallelic mutants in a single generation in Arabidopsis plants grown at 22 °C. In addition, optimization of ttLbCas12a Ultra, by varying nuclear localization signal sequences and codon usage, further greatly improved editing efficiency. Collectively, our results indicate that ttLbCas12a Ultra is a valuable alternative to Cas9 for editing genes or promoters in Arabidopsis. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00144-w.

Clinical characteristics of membranous nephropathy after allogeneic hematopoietic stem cell transplantation: A real-world multicenter study.

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.

The nicotine demethylase CYP82E4 is essential for the formation of red dapples on flue-cured leaves of cherry-red tobacco.

Common flue-cured tobacco (Nicotiana tabacum L.) primarily accumulates nicotine, and its flue-cured leaves exhibit a lemon appearance. In contrast, a spontaneous cherry-red variant (CR60) primarily accumulates nornicotine, accompanied by distinctive red dapples on the cured leaves. In this study, suppression of conversion of nicotine to nornicotine by genome editing resulted in decreased nornicotine and N-acyl nornicotines (NacNNs), and the subsequent disappearance of red dapples in CR60. Conversely, overexpression of CYP82E4 increased nornicotine and NacNNs accumulation, inducing a red dapple phenotype in common tobacco. Notably, nicotine conversion triggered significant alterations in leaf total sugars, alkaloids, and nitrogens. Metabolome analyses using 1352 identified compounds indicated nicotine conversion dramatically affected the entire metabolic network and induced unique metabolic responses across diverse genetic backgrounds. Further WGCNA analysis revealed that nicotine conversion caused substantial contents variation of alkaloids, flavonoids and amino acids and derivatives in cured leaves. Overall, this research provides valuable insights into the mechanisms underlying red dapple formation in cherry-red tobacco, elucidating profound influence of nicotine conversion on entire metabolic network.

Mechanistic analysis of the hardening process of the thorns on stems of Bougainvillea glabra "Elizabeth Angus".

Introduction: Bougainvillea glabra "Elizabeth Angus" is a thorny woody vine or shrub. However, the hard thorns are considered a deficiency in its ornamental value. Methods: To find the genes and pathways related to the hardening process of the thorns on the stems of B. glabra, the eukaryotic unreferenced transcriptome sequencing analysis was conducted to explore the 3 stages of the thorn-hardening process. Total RNA was extracted from thorns and stems, and transcriptome libraries were constructed and sequenced using unreferenced Illumina sequencing. Results: Gene function annotation was performed using various databases, resulting in 8937 co-annotated genes. The density distribution of Fragments Per Kilobase of transcript per Million mapped reads (FPKM) depicted the overall gene expression patterns. The study found that stage 2 as the period of highest gene expression activity during the thorns hardening process in B. glabra. Differential expression analysis revealed that during thorn-hardening, 1045 genes up-regulated and 391 genes down-regulated significantly in thorns at stage 2 compared to stage 1 (early stage of thorns formation). Meanwhile, 938 genes up-regulated and 784 genes down-regulated significantly in stems. At stage 3, as thorns became harder, 63 genes exhibited notable expression increase and 98 genes' expression decreased obviously within thorns, and 46 genes up-regulated and 29 genes down-regulated in stems, compared to stage 2. Phenylpropanoid biosynthesis was the key step in the hardening process of the thorns of B. glabra. The formation and hardening of thorns on the stem of B. glabra was a process in which lignin gradually accumulated in the thorns, and several genes were involved in this process. They include PAL (EC:4.3.1.24), CYP73A (EC:1.14.14.91), 4CL (EC:6.2.1.12), CCR (EC:1.2.1.44), CAD (EC:1.1.1.195) and POX (EC:1.11.1.7). Discussion: This transcriptome analysis offers insights into the molecular mechanisms underlying thorns development in this plant species.

Chemerin in caudal division of nucleus tractus solitarius increases sympathetic activity and blood pressure.

Chemerin is an adipokine that contributes to metabolism regulation. Nucleus tractus solitarius (NTS) is the first relay station in the brain for accepting various visceral afferent activities for regulating cardiovascular activity. However, the roles of chemerin in the NTS in regulating sympathetic activity and blood pressure are almost unknown. This study aimed to determine the role and potential mechanism of chemerin in the NTS in modulating sympathetic outflow and blood pressure. Bilateral NTS microinjections were performed in anaesthetized adult male Sprague-Dawley rats. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were continuously recorded. Chemerin and its receptor chemokine-like receptor 1 (CMKLR1) were highly expressed in caudal NTS (cNTS). Microinjection of chemerin-9 to the cNTS increased RSNA, MAP and HR, which were prevented by CMKLR1 antagonist α-NETA, superoxide scavenger tempol or N-acetyl cysteine, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodonium or apocynin. Chemerin-9 increased superoxide production and NADPH oxidase activity in the cNTS. The increased superoxide production induced by chemerin-9 was inhibited by α-NETA. The effects of cNTS microinjection of chemerin-9 on the RSNA, MAP and HR were attenuated by the pretreatment with paraventricular nucleus (PVN) microinjection of NMDA receptor antagonist MK-801 rather than AMPA/kainate receptor antagonist CNQX. These results indicate that chemerin-9 in the NTS increases sympathetic outflow, blood pressure and HR via CMKLR1-mediated NADPH oxidase activation and subsequent superoxide production in anaesthetized normotensive rats. Glutamatergic inputs in the PVN are needed for the chemerin-9-induced responses.

Clinical trial evidence supporting FDA approval of novel orphan drugs between 2017 and 2023.

Characterization analysis of 87 pivotal clinical trials for 72 novel orphan drugs (76 orphan indications) approved by the FDA from 2017 to 2023 revealed that the clinical trial evidence supporting FDA orphan drug approvals often lacked high-quality designs, which frequently did not incorporate randomization, blinding, placebo or no treatment control, or clinical endpoint-driven methodologies. Additionally, regulatory flexibility was observed in the quantity of clinical trial evidence required, which included choices such as a single trial plus confirmatory evidence, one large multicenter trial or at least two trials. Furthermore, the overall strength of the clinical trial evidence exhibited variations across different orphan drugs and indications, influenced by features such as the therapeutic area and whether the orphan drug was granted accelerated approvals.

Yadanziolide A Inhibits Proliferation and Induces Apoptosis of Hepatocellular Carcinoma via JAK-STAT Pathway: A Preclinical Study.

Liver cancer is a significant global health concern, prompting the search for innovative therapeutic solutions. Yadanziolide A (Y-A), a natural derivative of Brucea javanica, has emerged as a promising candidate for cancer treatment; however, its efficacy and underlying mechanisms in liver cancer remain incompletely understood. In this study, we conducted a comprehensive evaluation of Y-A's effects on liver cancer cells using a range of in vitro assays and an orthotopic liver cancer mouse model. Our findings reveal that Y-A exerts dose-dependent cytotoxic effects on liver cancer cells, significantly inhibiting proliferation, migration, and invasion at concentrations ≥ 0.1 µM. Furthermore, Y-A induces apoptosis, as evidenced by increased apoptotic cell populations and apoptosome formation. In vivo studies confirm that Y-A inhibits tumor growth and reduces liver damage in mouse models. Mechanistically, Y-A targets the TNF-α/STAT3 pathway, inhibiting STAT3 and JAK2 phosphorylation, thereby activating apoptotic pathways and suppressing tumor cell growth. These results suggest that Y-A has promising anticancer activity and potential utility in liver cancer therapy.

Comparative Transcriptome Analysis Reveals Different Responses in Three Developmental Stages of Mythimna loreyi to Cold Stress.

The loreyi leafworm Mythimna loreyi (Lepidoptera: Noctuidae) is a serious pest of agriculture that causes particular damage to Gramineae crops in Asia, Europe, Australia, Africa, and the Middle East. Low temperature is one of the important environmental factors that limits the survival, distribution, colonization, and abundance of M. loreyi. However, the metabolic synthesis pathways of cold-tolerant substances in M. loreyi and the key genes involved in the regulation under cold stress remain largely unknown. In this study, we sequenced the transcriptomes of three developmental stages (larvae, pupae, and adults) of M. loreyi to discover the molecular mechanisms of their responses to cold stress. In total, sequencing generated 120.64 GB of clean data from 18 samples, of which 19,459 genes and 1740 differentially expressed genes (DEGs) were identified. The enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that many DEGs were mainly enriched in pathways associated with energy metabolism and hormone metabolism. Among these, genes encoding multiple metabolic enzymes, cuticle proteins (CPs), and heat shock proteins (HSPs) were differentially expressed. These results indicate that there are significant differences among the three developmental stages of M. loreyi exposed to cold stress and provide a basis for further studying the molecular mechanisms of cold tolerance in insects.

Multi-omics data analysis reveals the complex roles of age in differentiated thyroid cancer.

Aims: Age is a major risk factor for differentiated thyroid cancer (DTC); however, the mechanisms underlying aging-regulated progression of DTC remains unclear. Methods: Based on multi-omics data (transcriptional files, somatic mutation files, methylation files) derived from the TCGA database, we comprehensively investigated the genomic and biological features associated with aging in patients with DTC. Results: We confirmed that age was an independent risk factor for overall survival and progression-free survival of patients with DTC, and confirmed that 55 years of age (adopted in the 8th AJCC staging system) is an appropriate cutoff for patients with DTC rather than 45 years (adopted in the 7th AJCC staging system). Using 55 years as the cutoff, we demonstrated DNA methylation-driven transcriptional regulation during aging, and identified the landscape of somatic mutations in young and old patients with DTC along with two aging-related mutations: TTN and EIF1AX. Subsequently, we investigated the infiltration of immune cells in DTC, and found that old patients exhibited decreased CD8+ T cells infiltration with lower cytotoxicity. Finally, we constructed a prognosis prediction model based on three age-related genes (PTK2B, E2F1, and GHR) that showed satisfactory performance in predicting patients prognosis. Conclusions: We comprehensively investigated the complex interplay between age and biological features of DTC, which may provide new insights into the role of aging in DTC.

Lysozyme 1 Inflamed CCR2+ Macrophages Promote Obesity-Induced Cardiac Dysfunction.

BACKGROUND: Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage's role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response. METHODS AND RESULTS: Though analyzing in-depth cardiac macrophage clusters identified by single macrophage RNA-sequencing, we find that the Ccr2 cluster undergoes a functional transition from homeostatic maintenance to proinflammation. Our data highlight specific changes in macrophage behavior during cardiac dysfunction under metabolic challenge. Consistently, inducible ablation of CCR2+CX3CR1+ macrophages by a dual recombinase-based lineage-tracing approach or selective deletion of macrophage C-C chemokine receptor 2 (CCR2) prevents obesity-induced cardiac dysfunction. At the mechanistic level, we demonstrate that the obesity-induced functional shift of CCR2-expressing macrophages is mediated by the CCR2/ATF3/lysozyme 1/NF-κB (nuclear factor kappa B) signaling. Finally, we uncover a noncanonical role for lysozyme 1 as a transcription activator, binding to the RelA promoter, driving NF-κB signaling, and strongly promoting inflammation and cardiac dysfunction in obesity. CONCLUSIONS: Our findings suggest that lysozyme 1 may represent a potential target for the diagnosis of obesity-induced inflammation and the treatment of obesity-induced heart disease.

Comparison of the Effects of Adductor Canal and Femoral Nerve Blocks on Postoperative Opioid Consumption and Inflammatory Factor Levels in Elderly Patients After Total Knee Arthroplasty: A Prospective Observational Study.

Purpose: Total Knee Arthroplasty (TKA) is a highly invasive procedure causing severe postoperative pain, which hampers early mobility. Effective pain management is crucial for optimal recovery. This study aimed to evaluate how adductor canal block (ACB) and femoral nerve block (FNB) affect opioid use and inflammation factor levels in elderly TKA patients. Methods: This prospective observational study included 120 patients who received TKA, and divided them into three groups, based on the different nerve block technique: ACB, FNB, and no intervention before general anesthesia (CON). Postoperative opioid consumption, pain assessment, inflammation factor, knee function recovery and other clinical indicators were recorded. Results: The CON group had significantly higher cumulative sufentanil consumption compared to the ACB and FNB groups at both 12 h and 48h postoperative (P<0.001). Compared with the CON group, the ACB and FNB groups persistently had lower pain scores until 12 h at rest and 24 h during motion after surgery. The ACB group showed significantly lower serum concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) compared to the CON group at 24 h postoperative (P=0.017, P=0.009), and IL-6 levels remained significantly lower at 72 h postoperative (P=0.005). Both ACB and FNB groups achieved earlier ambulation compared to the CON group (P=0.002). On the first day postoperative, both the ACB and FNB groups showed significantly better knee motion (P<0.001), quadriceps strength (P<0.001), and daily mobilization (P<0.001) compared to the CON group. Additionally, the ACB group exhibited superior quadriceps strength (P<0.001) and daily mobilization (P<0.001) compared to the FNB group. Conclusion: The ACB and FNB groups exhibited comparable clinical efficacy outcomes in terms of pain scores and opioid consumption. However, the ACB group experienced reduced postoperative inflammation and improved knee recovery, especially in quadriceps strength.

A Soldering Flux Tackles Complex Defects Chemistry in Sn-Pb Perovskite Solar Cells.

Developing tin-lead (Sn-Pb) narrow-bandgap perovskites is crucial for the deployment of all-perovskite tandem solar cells, which can help to exceed the limits of single-junction photovoltaics. However, the Sn-Pb perovskite suffers from a large number of bulk traps and interfacial nonradiative recombination centers, with unsatisfactory open-circuit voltage and the consequent device efficiency. Herein, for the first time, it is shown that abietic acid (AA), a commonly used flux for metal soldering, effectively tackles complex defects chemistry in Sn-Pb perovskites. The conjugated double bond within AA molecule plays a key role for self-elimination of Sn4+-Pb0 defects pair, via a redox process. In addition, C═O group is able to coordinate with Sn2+, leading to the improved antioxidative stability of Sn-Pb perovskites. Consequently, a ten-times longer carrier lifetime is observed, and the defects-associated dual-peak emission feature at low temperature is significantly inhibited. The resultant device achieves a power conversion efficiency improvement from 22.28% (Ref) to 23.42% with respectable stability under operational and illumination situations.

Safety and efficacy of baricitinib in steroid-resistant or relapsed immune thrombocytopenia: An open-label pilot study.

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

PE6c greatly enhances prime editing in transgenic rice plants.

Prime editing is a versatile CRISPR/Cas-based precise genome-editing technique for crop breeding. Four new types of prime editors (PEs) named PE6a-d were recently generated using evolved and engineered reverse transcriptase (RT) variants from three different sources. In this study, we tested the editing efficiencies of four PE6 variants and two additional PE6 constructs with double-RT modules in transgenic rice (Oryza sativa) plants. PE6c, with an evolved and engineered RT variant from the yeast Tf1 retrotransposon, yielded the highest prime-editing efficiency. The average fold change in the editing efficiency of PE6c compared with PEmax exceeded 3.5 across 18 agronomically important target sites from 15 genes. We also demonstrated the feasibility of using two RT modules to improve prime-editing efficiency. Our results suggest that PE6c or its derivatives would be an excellent choice for prime editing in monocot plants. In addition, our findings have laid a foundation for prime-editing-based breeding of rice varieties with enhanced agronomically important traits.

Long-Term Stimulation of the Left Dorsal Branch of the Thoracic Nerve Improves Ventricular Electrical Remodeling in a Canine Model of Chronic Myocardial Infarction.

PURPOSE: To evaluate the ventricular electrophysiologic effects of long-term stimulation of the left dorsal branch of thoracic nerve (LDTN) derived from the left stellate ganglion (LSG) in a canine model of chronic myocardial infarction (MI). METHODS: Seventeen adult male beagles were randomly divided into three groups: the sham group (sham operated, n = 6), the MI group (n = 6), and the MI + LDTN group (MI plus LDTN stimulation, n = 5). The canine model of chronic MI was induced by the occlusion of the left anterior descending artery (LADO). The LDTN was separated and intermittently stimulated immediately after LADO for 2 months. The heart rate variability (HRV) analysis, in vivo electrophysiology, the evaluation of LSG function and neural activity, histological staining, and western blotting (WB) assay were performed to evaluate the effect of LDTN stimulation on the heart. RESULTS: The canine MI model was successfully established by LADO, and the LDTN was separated and stimulated immediately after LADO. The HRV analysis showed that LDTN stimulation reversed the increased LF value and LF/HF ratio of the MI group. LDTN stimulation prolonged the shortening ERP and APD90, decreased the dispersion of ERP and APD90, and increased the VFT. Additionally, LDTN stimulation inhibits the LSG function and neural activity. Furthermore, LDTN stimulation suppressed the activation of Wnt/ß-catenin signaling, which contributed to the LSG neuronal apoptosis by upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-2. CONCLUSION: LDTN stimulation could attenuate cardiac sympathetic remodeling and improve ventricular electrical remodeling, which may be mediated by suppressing the activated Wnt/ß-catenin signaling pathway and then promoting the LSG neuronal apoptosis.

Progressive encephalomyelitis with rigidity and myoclonus: a pediatric case report and literature review.

BACKGROUND: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and life-threatening autoimmune disease of the central nervous system. So far, only ten cases of PERM have been reported in children worldwide, including the one in this study. CASE PRESENTATION: We report a case of an 11-year-old boy with PERM with an initial presentation of abdominal pain, skin itching, dysuria, urinary retention, truncal and limb rigidity, spasms of the trunk and limbs during sleep, deep and peripheral sensory disturbances, and dysphagia. A tissue-based assay using peripheral blood was positive, demonstrated by fluorescent staining of mouse cerebellar sections. He showed gradual and persistent clinical improvement after immunotherapy with intravenous immunoglobulin, steroids, plasmapheresis and rituximab. CONCLUSIONS: We summarized the diagnosis and treatment of a patient with PERM and performed a literature review of pediatric PERM to raise awareness among pediatric neurologists. A better comprehension of this disease is required to improve its early diagnosis, treatment, and prognosis.

SETDB1 regulates short interspersed nuclear elements and chromatin loop organization in mouse neural precursor cells.

BACKGROUND: Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive. RESULTS: In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo. CONCLUSIONS: In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.