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Abstract Background Acute bulbar palsy-plus (ABPp) syndrome is an unusual variant of Guillain-Barré syndrome (GBS). Anti-GT1a and anti-GQ1b antibodies have been reported in patients with ABPp, but without reports related to GD3 antibodies. Methods Clinical data of a patient diagnosed as ABPp syndrome were reviewed clinically. And we summarized the GBS patients with ABP and facial paralysis reported in the literature. Results We reported a 13-year-old girl presented with asymmetric bifacial weakness, bulbar palsy and transient limb numbness, and had positive serum IgG anti-GD3 antibody. Through reviewing the GBS patients with ABP and facial paralysis reported previously, we found that facial palsy could be unilateral or bilateral. The bilateral facial palsy could present successively or simultaneously, and could be symmetrical or asymmetrical. Other common symptoms included ophthalmoplegia, sensory abnormality and ataxia. IgG anti-GT1a and IgG anti-GQ1b antibodies were the most frequent. Most of the patients had full recovery within two weeks to one year of follow-up. Conclusions We reported a patient with asymmetric bifacial palsy and bulbar palsy, which seemed to fit the diagnosis of ABPp syndrome. This was the first report of ABPp variant of GBS with positive serum ganglioside GD3 IgG antibody.

Chromosome rearrangement is a mechanism that can lead to the loss, duplication, translocation and inversion of DNA segments, thereby altering the genomic structure and providing possibilities for creating new variable traits. Accurate identification of plant chromosome rearrangement events contributes to a deeper understanding of the structure and function of the plant genomes as well as their roles in plant evolution and crop breeding. This review delves into the fundamental concepts of plant chromosome rearrangement, presenting both naturally occurring and artificially induced techniques. It elucidates the cytological, molecular genetic and high-throughput sequencing identification methods for plant chromosome rearrangement. We systematically summarize the application of plant chromosome rearrangement techniques in crop genetic breeding, emphasizing the superiority and practical implementation of chromosome rearrangement in increasing genetic diversity, improving essential traits and enhancing environmental adaptability of crops. However, the occurrence probability of chromosome rearrangement is relatively low currently, posing technical challenges that necessitate more precise tools and strategies for the accurate positioning and rearrangement of chromosomal fragments. By comprehensively understanding chromosome rearrangement and its related technologies, researchers and breeders can better leverage the plant genome, providing innovative solutions for global food security and sustainable environmental development. These researches not only open new approach for a deeper understanding of the plant genome but also lay a solid foundation for future innovations in crop breeding. Through tapping into the diversity and plasticity of the plant genome, chromosome rearrangement technology holds the potential to offer more possibilities for cultivating high-yielding, superior-quality and resistant crop varieties, addressing the increasingly critical issues of global food security and climate adaptability.

Paclitaxel (trade name Taxol) is a rare diterpenoid with anticancer activity isolated from Taxus. At present, paclitaxel is mainly produced by the semi-synthetic method using extract of Taxus tissues as raw materials. The studies of regulatory mechanisms in paclitaxel biosynthesis would promote the production of paclitaxel through tissue/cell culture approaches. Here, we systematically identified 990 transcription factors (TFs), 460 microRNAs (miRNAs), and 160 phased small interfering RNAs (phasiRNAs) in Taxus chinensis to explore their interactions and potential roles in regulation of paclitaxel synthesis. The expression levels of enzyme genes in cone and root were higher than those in leaf and bark. Nearly all enzyme genes in the paclitaxel synthesis pathway were significantly up-regulated after jasmonate treatment, except for GGPPS and CoA Ligase. The expression level of enzyme genes located in the latter steps of the synthesis pathway was significantly higher in female barks than in male. Regulatory TFs were inferred through co-expression network analysis, resulting in the identification of TFs from diverse families including MYB and AP2. Genes with ADP binding and copper ion binding functions were overrepresented in targets of miRNA genes. The miRNA targets were mainly enriched with genes in plant hormone signal transduction, mRNA surveillance pathway, cell cycle and DNA replication. Genes in oxidoreductase activity, protein-disulfide reductase activity were enriched in targets of phasiRNAs. Regulatory networks were further constructed including components of enzyme genes, TFs, miRNAs, and phasiRNAs. The hierarchical regulation of paclitaxel production by miRNAs and phasiRNAs indicates a robust regulation at post-transcriptional level. Our study on transcriptional and posttranscriptional regulation of paclitaxel synthesis provides clues for enhancing paclitaxel production using synthetic biology technology.

Abstract Quantum tunneling is the phenomenon that makes superconducting circuits “quantum”. Recently, there has been a renewed interest in using quantum tunneling in phase space of a Kerr parametric oscillator as a resource for quantum information processing. Here, we report a direct observation of quantum interference induced by such tunneling and its dynamics in a planar superconducting circuit through Wigner tomography. We experimentally elucidate all essential properties of this quantum interference, such as mapping from Fock states to cat states, a temporal oscillation due to the pump detuning, as well as its characteristic Rabi oscillations and Ramsey fringes. Finally, we perform gate operations as manipulations of the observed quantum interference. Our findings lay the groundwork for further studies on quantum properties of superconducting Kerr parametric oscillators and their use in quantum information technologies.

Luteolin is a potent anti-colorectal cancer chemical. However, its effectiveness is hindered by its poor solubility in water and fat, and it is easy to degrade by gastrointestinal enzymes. In this study, a nano-composite carrier, NH2-MIL-101(Fe)@GO (MG), based on aminated MIL-101(Fe) and graphene oxide (GO) was developed and evaluated. This carrier co-delivered luteolin and matrine, while marine was used to balance the pH for the nano-preparation. The loading capacities for luteolin and matrine were approximately 9.8% and 14.1%, respectively. Luteolin's release at pH = 5 was significantly higher than at pH = 7.4, indicating it had an acidic pH response release characteristic. Compared to MOF and GO alone, MG and NH2-MIL-101(Fe)@GO@Drugs (MGD) enhanced anti-cancer activity by inhibiting tumor cell migration, increasing ROS generation, and upregulating the expression of Caspase-3 and Caspase-9. In conclusion, this study contributes new ideas and methods to the treatment strategy of multi-component anti-colorectal cancer therapy. It also advances drug delivery systems and supports the development of more effective and targeted treatment approaches for colorectal cancer.

Abstract Objective Radiation‐induced skin injury (RISI) remains a serious concern during radiotherapy. IL‐10 is considered as an immune suppressive cytokine by inhibiting the secretion of the proinflammatory cytokines in cells. The aim of this study was to evaluate the protective role of Erb (IL10) 2 against ionizing radiation. Methods We fused Interleukin 10 (IL‐10) dimer onto an anti‐epidermal growth factor receptor antibody Cetuximab (Erbitux) to form a new bispecific protein Erb‐(IL10)2. The protective effect and biological activity of Erb‐(IL10)2 was measured in model of RISI. Results Under the condition of 20 Gy irradiation, surviving cells in the IR group decreased significantly compared with the non‐IR group (p = 0.0021). The survival rates of HaCaT (p = 0.0038) and WS1 (p = 0.0003) cells were significantly increased after IL‐10 treatment. The apoptosis rates of HaCaT (p = 0.0048) and WS1 (p = 0.0074) cells in the IL‐10 group were significantly lower compared to the NC group. Under 20 Gy irradiation conditions, IL‐10 fusion protein reduced the level of reactive oxygen in HaCaT (p = 0.0046) and WS1 (p

Abstract Rice quality is one of the main targets of rice breeding and is a complex trait that involves grain appearance, milling, cooking, eating and nutritional quality. For many years, rice breeding has contended with imbalances in rice yield, quality, and disease and lodging resistance. Here, the milling and appearance quality, cooking quality, starch rapid viscosity analyzer (RVA) profile, and nutritional quality of grains of Yuenongsimiao (YNSM), an indica rice variety with high yield, high quality and disease resistance, were determined. YNSM had excellent appearance and quality, with low amylose contents and high gel consistency, and these characteristics exhibited significant correlations with the RVA profile such as hot paste viscosity, cool paste viscosity, setback viscosity, and consistency. Moreover, 5 genes related to length-to-width ratio (LWR) as well as the Wx gene were used to detect the main quality genotype of YNSM. The results showed that YNSM is a semilong-grain rice with a relatively high brown rice rate, milled rice rate and head rice yield and low chalkiness. The results indicated that the LWR and food quality of YNSM might be related to gs3, gw7 and Wx b . This study also reports the quality characteristics of hybrid rice developed using YNSM as a restorer line. The quality characteristics and the genotype for grain quality determined through gene analysis in YNSM may facilitate the breeding of new rice varieties that achieve a balance of grain yield, resistance and quality.

【Objective】Heterotrimeric G protein α subunit in rice (Oryza sativa L.) plays important biological roles in plant growth and stress response. Null mutants of Gα protein encoding gene DWARF1 (D1) in Zhonghua 11 (japonica cv.) are created, with a view to providing materials for the studies of functional genomics in rice.【Method】sgRNA was designed to target the exon at D1 locus in Zhonghua 11, and CRISPR/Cas9 vector was constructed to transform the embryonic calli of Zhonghua 11. After selection by adding hygromycin, the calli were induced to differentiate and the regenerated plants were identified.【Result】Three mutant lines harbouring different D1 alleles were identified. Real-time quantitative PCR showed a remarkable decrease in D1 mRNA level, suggesting that nonsense-mediated mRNA decay was also triggered. Progenies without hygromycin resistance or vector backbone were further identified, representing transgene-free and stably inherited d1 mutants. According to the observation results of the growth and development of d1 mutants, d1 mutants in Zhonghua 11 showed significantly shorter plant height and smaller panicles. The plant height and panicle length were only 50%-60% compared with those of the wild-type Zhonghua 11. Smaller and rounder seeds were also shown in d1 mutants, meanwhile, the length/width ratio and 1000-grain weight were decreased by about 40%.【Conclusion】Effective frame-shift d1 mutants in Zhonghua11 are obtained, Which creates the genetic materials for functional studies of G protein and other related genes in the future.

Abstract Background Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of severe disorders that are characterized by early-onset, refractory seizures and developmental slowing or regression. Genetic variations are significant causes of these changes. De novo variants in an increasing number of candidate genes have been found to be causal. The YWHAG gene is one such gene that has been reported to cause developmental and epileptic encephalopathy 56 (DEE56). Here, we report a heterozygous missense variant, c.170G > A (p.R57H), in the YWHAG gene that caused early-onset epilepsy and developmental delay in a Chinese family. Methods We described the clinical manifestations of the proband and his mother in detail. Then, we use trio-based whole-exome sequencing to search the etiology of this family. Results Both the proband and his mother exhibited early-onset seizures, intellectual disability, and developmental delay. While the proband attained seizure control with sodium valproate, his mother's seizures were not well controlled. Trio-based whole-exome sequencing revealed a heterozygous missense variant, c.170G > A (p.R57H), in the YWHAG gene, which was considered as the cause of early-onset epilepsy and developmental delay in this family. Conclusions Our report further confirmed that YWHAG haploinsufficiency results in developmental and epileptic encephalopathy 56.

Investigating the damage and ignition behaviors of polymer-bonded explosive (PBX) under a coupled impact and high-temperature loading condition is required for the safe use of charged PBXs. An improved combined microcrack and microvoid model (CMM) was developed for better describing the thermal effects of deformation, damage, and ignition responses of PBXs. The main features of the model under typical dynamic loadings (i.e. uniaxial tension and compression, and lateral confinement) at different initial temperature were first studied. And then the effects of temperature on impact-shear sensitivity of HMX-based PBXs were investigated. The results showed that the ignition threshold velocity of shear-crack hotspots exhibits an increase from 260 to 270 to 315–325 m/s when initial temperature increases from 301 to 348 K; and then the threshold velocity decreases to 290–300 m/s with the initial temperature continually increasing to 378 K. The predicted ignition threshold velocity level of the explosives under coupled impact and high temperature loading conditions were consistent with the experimental data.

Abstract Background Selective activation of Delta-like 1 (DLL1)-Notch signaling is a new approach to activate CD8+ T cell and suppress tumor growth, while the efficacy remains modest. Lentinan (LNT) is a clinically used immunomodulation agent. Thus, we hypothesized that LNT could improve the efficacy of DLL1. Methods The effects of LNT combined with DLL1 on tumor growth were evaluated by growth curve and tumor weight in EO771 breast and LAP0297 lung tumor models. The impacts on immune cells and gene expression in tumor tissues were determined by flow cytometry, qPCR. Neutrophil depletion was used to investigate the mechanism of the combination therapy on tumor growth. The data sets were compared using unpaired student’s t-test or ordinary one-way ANOVA. Results LNT treatments additively improved the antitumor effects of DLL1 in EO771 breast tumor growth. Remarkably, LNT treatments synergistically enhanced the suppression of DLL1 on LAP0297 lung tumor growth, resulting in tumor regression. Mechanically, the combination of LNT and DLL1 interventions not only promoted the accumulation and activation of CD8+ T cells, but also increased intratumoral CD45+CD11b+Ly6G+ neutrophils. Reduced neutrophils by anti-Gr1 antibody administrations reversed the improved antitumor effects by LNT treatments in LAP0297 lung tumor. These results suggest that LNT treatments improve the inhibition of DLL1 on tumor growth via neutrophils. Conclusions Our findings indicates that LNT and DLL1 may induce synergistical antitumor immunity via simultaneous modulating lymphoid and myeloid cell populations regardless of the type of tumor, providing a potential new strategy to potentiate cancer immunotherapy.

IntroductionHemiplegic migraine (HM) is a rare subtype of migraine. HM in children may be atypical in the initial stage of the disease, which could easily lead to misdiagnosis.MethodsWe report two cases of atypical hemiplegic migraine that onset as an acute encephalopathy. And a comprehensive search was performed using PubMed, Web of Science, and Scopus. We selected only papers that reported complete clinical information about the patients with CACNA1A or ATP1A2 gene mutation.ResultsPatient #1 showed a de novo mutation, c.674C>A (p. Pro225His), in exon 5 of the CACNA1A gene. And patient #2 showed a missense mutation (c.2143G>A, p. Gly715Arg) in exon 16 of the ATP1A2. Together with our two cases, a total of 160 patients (73 CACNA1A and 87 ATP1A2) were collected and summarized finally.DiscussionAcute encephalopathy is the main manifestation of severe attacks of HM in children, which adds to the difficulty of diagnosis. Physicians should consider HM in the differential diagnosis of patients presenting with somnolence, coma, or convulsion without structural, epileptic, infectious, or inflammatory explanation. When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis and treatment. Early recognition and treatment of the disease can help improve the prognosis.

Claudin 18.2 (CLDN18.2)-targeting chimeric antigen receptor (CAR)-modified T cells are one of the few cell therapies currently producing an impressive therapeutic effect in treating solid tumors; however, their long-term therapeutic efficacy is not satisfactory with a short duration of response. Transgenic expression of interleukin (IL)-15 has been reported to promote T-cell expansion, survival, and function and enhance the antitumor activity of engineered T cells in vitro and in vivo. Therefore, this study aimed to explore whether IL-15 modification would increase the antitumor activity of CLDN18.2-targeting CAR-modified T (CAR-T) cells in immunocompetent murine tumor models. CLDN18.2-specific CAR-T cells with (H9 CAR-IL15) or without transgenic IL-15 expression (H9 CAR) were generated by retroviral transduction of mouse splenic T cells. In vitro, compared with H9 CAR T cells, H9 CAR-IL15 T cells exhibited better expansion and viability in the absence of antigen stimulation, with a less differentiated and T-cell exhausted phenotype; although IL-15 modification did not affect the production of effector cytokines and cytotoxic activity in the short-term killing assay, it moderately improved the in vitro recursive killing activity of CAR-T cells against CLDN18.2-expressing tumor cells. In vivo, H9 CAR T cells showed no antitumor activity against CLDN18.2-expressing pancreatic tumors in immunocompetent mice without lymphodepleting pretreatment; however, H9 CAR-IL15 T cells produced significant tumor-suppressive effects. Furthermore, H9 CAR-IL15 T cells exhibited greater in vivo expansion and tumor infiltration when combined with lymphodepleting preconditioning, resulting in superior antitumor activity in two murine tumor models and a survival advantage in one tumor model. We further demonstrated that recurrent tumors following H9 CAR-IL15 T-cell therapy downregulated CLDN18.2 expression, suggesting immune escape through the selection of antigen-negative cells under persistent CAR-T-cell immune pressure. In conclusion, our findings provide preclinical evidence supporting the clinical evaluation of IL-15-expressing CLDN18.2 CAR-T cells in patients with CLDN18.2-positive tumors.

With increasing public health awareness and the unprecedented global health crisis, consumers' demand for in vitro diagnostic (IVD) reagents is gradually increasing. However, consumer mistrust remains a significant barrier to purchasing and using IVD products. Pharmaceutical companies and governments prioritizing direct-to-consumer (DTC) marketing have recognized the impact of visual packaging elements on consumer perception. Thus, we researched whether visual packaging elements systematically influence consumers' perceived credibility of IVD products' credence attributes, namely, their ability to protect personal and public health. Combining previous related studies, this study was conducted experimentally with rapid diagnostic test (RDT) kits, assuming that the visual elements (i.e., typeface, color, pattern, and information) of packaging can influence consumers' perceived credibility of RDT kits and explored which elements are more credible. Questionnaires were randomly selected and assigned to 216 participants. The results indicated that all four elements influenced the participants’ perceived credibility. Specifically, a sans serif typeface, realistic pattern, chromatic color, and more information made the participants feel more credible. Our research results fill a gap in the consumer perception of over-the-counter (OTC) pharmaceutical products by providing new insights into dissecting consumer perceptions. This offers a novel design strategy for online and offline marketing and promotional efforts by different companies and governmental organizations.

Rice blast disease, caused by the fungal pathogen Magnaporthe oryzae, is a major threat to rice production worldwide. This study investigates the role of long non-coding RNAs (lncRNAs) in rice’s response to this destructive disease, with a focus on their impacts on disease resistance and yield traits. Three specific lncRNAs coded by M. oryzae infection-responsive lncRNAs (MOIRAs), MOIRA1, MOIRA2, and MOIRA3, were identified as key regulators of rice’s response to M. oryzae infection. Strikingly, when MOIRA1 and MOIRA2 were overexpressed, they exhibited a dual function: they increased rice’s susceptibility to blast fungus, indicating a negative role in disease resistance, while simultaneously enhancing tiller numbers and single-plant yield, with no adverse effects on other yield-related traits. This unexpected improvement in productivity suggests the possibility of overcoming the traditional trade-off between disease resistance and crop yield. These findings provide a novel perspective on crop enhancement, offering a promising solution to global food security challenges by developing rice varieties that effectively balance disease resistance and increased productivity.

Here, we aimed to optimize the ethanol extraction technology for Yujin powder (YJP) and evaluate its safety. The ultrasonic-assisted ethanol reflux extraction method refluxing was used to extract YJP. The parameters were optimized through a combination of single-factor and response surface methodology (RSM). The comprehensive Y value score calculated using the content of 13 active ingredients in YJP ethanolic extracts (YEEs) and the yield of the dry extract were used as measuring criteria. RSM with a Box–Behnken design using three factors and three levels was adopted to optimize the ethanol extraction technology for YJP. Finally, acute and subchronic toxicity tests were performed to evaluate its safety. The results revealed the best technological parameters: a liquid–material ratio of 24:1, an ethanol concentration of 69%, assistance of ultrasound (40 °C, 50 kHZ, 30 min), reflux time of 53 min, and reflux temperature of 50 °C. In acute toxicity tests, the maximum administration dosage in mice was 28.21 g/kg, which is higher than 10 times the clinical dosage. Adverse effects in the acute and subchronic toxicity tests were not observed. All clinical indexes were normal. In conclusion, the RSM based on AHP–CRITIC weight analysis could be used to optimize the ethanol extraction technology for YJP and YEEs prepared under the above conditions and ensure high safety.

Noncoding RNAs constitute a substantial portion of the transcriptome and play pivotal roles in plant growth and development. Among these processes, flowering stands out as a crucial trait, ensuring reproductive success and seed set, and is meticulously controlled by genetic and environmental factors. With remarkable advancements in the identification and characterization of noncoding RNAs in plants, it has become evident that noncoding RNAs are intricately linked to the regulation of flowering time. In this article, we present an overview of the classification of plant noncoding RNAs and delve into their functions in the regulation of flowering time. Furthermore, we review their molecular mechanisms and their involvement in flowering pathways. Our comprehensive review enhances the understanding of how noncoding RNAs contribute to the regulation of flowering time and sheds light on their potential implications in crop breeding.

Abstract Cell senescence is a basic aging mechanism. Previous studies have found that the cellular senescence in adipose tissue and other tissues, such as the pancreas, muscle and liver, is associated with the pathogenesis and progression of type 2 diabetes; however, strong evidence of whether diabetes directly causes neuronal senescence in the brain is still lacking. In this study, we constructed a high glucose and palmitic acid (HGP) environment on PC12 neuronal cells and primary mouse cortical neurons to simulate diabetes. Our results showed that after HGP exposure, neurons exhibited obvious senescence-like phenotypes, including increased NRSF/REST level, mTOR activation and cell autophagy suppression. Downregulation of NRSF/REST could remarkably alleviate p16, p21 and γH2A.X upregulations induced by HGP treatment, and enhance mTOR-autophagy of neurons. Our results suggested that the diabetic condition could directly induce neuronal senescence, which is mediated by the upregulation of NRSF/REST and subsequent reduction of mTOR-autophagy.

Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.