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Gene therapy holds great promise for treating a multitude of inherited and acquired diseases by delivering functional genes, comprising DNA or RNA, into targeted cells or tissues to elicit manipulation of gene expression. However, the clinical implementation of gene therapy remains substantially impeded by the lack of safe and efficient gene delivery vehicles. This review comprehensively outlines the novel fastest-growing and efficient non-viral gene delivery vectors, which include liposomes and lipid nanoparticles (LNPs), highly branched poly(β-amino ester) (HPAE), single-chain cyclic polymer (SCKP), poly(amidoamine) (PAMAM) dendrimers, and polyethyleneimine (PEI). Particularly, we discuss the research progress, potential development directions, and remaining challenges. Additionally, we provide a comprehensive overview of the currently approved non-viral gene therapeutics, as well as ongoing clinical trials. With advances in biomedicine, molecular biology, materials science, non-viral gene vectors play an ever-expanding and noteworthy role in clinical gene therapy.

The purpose of this study was to apply infrared-assisted spouted bed drying (IRSBD) technology for Areca taro drying and to investigate the effects of different parameters on its drying quality. Specifically, in order to determine the suitable conditions for IRSBD, the effects of different drying temperatures (45 °C, 50 °C, 55 °C, and 60 °C) and cutting sizes (6 × 6 × 6 mm, 8 × 8 × 8 mm, 10 × 10 × 10 mm, and 12 × 12 × 12 mm) on the drying characteristics, temperature uniformity, and quality properties (including colour, rehydration ratio, total phenol content, total flavonoid content, and antioxidant activity) of Areca taro were studied. The results showed that the optimal drying condition was the sample with a cutting size of 10 × 10 × 10 mm and drying at 50 °C, which yielded the dried sample with the best colour, highest total phenol and flavonoid contents, maximum antioxidant capacity, and rehydration ratio.

In our previous work, we fabricated Ni single-atoms within Beta zeolite (Ni1@Beta-NO3−) using NiNO3·6H2O as a metal precursor without any chelating agents, which exhibited exceptional performance in the selective hydrogenation of furfural. Owing to the confinement effect, the as-encapsulated nickel species appears in the form of Ni0 and Niδ+, which implies its feasibility in metal catalysis and coordination catalysis. In the study reported herein, we further explored the hydrogen production and olefin oligomerization performance of Ni1@Beta-NO3−. It was found that Ni1@Beta-NO3− demonstrated a high H2 generation turnover frequency (TOF) and low activation energy (Ea) in a sodium borohydride (NaBH4) hydrolysis reaction, with values of 331 min−1 and 30.1 kJ/mol, respectively. In ethylene dimerization, it exhibited a high butylene selectivity of 99.4% and a TOF as high as 5804 h−1. In propylene oligomerization, Ni1@Beta-NO3− demonstrated high selectivity (75.21%) of long-chain olefins (≥C6+), overcoming the problem of cracking reactions that occur during oligomerization using H-Beta. Additionally, as a comparison, the influence of the metal precursor (NiCl2) on the performance of the encapsulated Ni catalyst was also examined. This research expands the application scenarios of non-noble metal single-atom catalysts and provides significant assistance and potential for the production of H2 from hydrogen storage materials and the production of valuable chemicals.

Many disease resistance genes have been introgressed into wheat from its wild relatives. However, reduced recombination within the introgressed segments hinders the cloning of the introgressed genes. Here, we have cloned the powdery mildew resistance gene Pm13 , which is introgressed into wheat from Aegilops longissima , using a method that combines physical mapping with radiation-induced chromosomal aberrations and transcriptome sequencing analysis of ethyl methanesulfonate (EMS)-induced loss-of-function mutants. Pm13 encodes a kinase fusion protein, designated MLKL-K, with an N-terminal domain of mixed lineage kinase domain-like protein (MLKL_NTD domain) and a C-terminal serine/threonine kinase domain bridged by a brace. The resistance function of Pm13 is validated through transient and stable transgenic complementation assays. Transient over-expression analyses in Nicotiana benthamiana leaves and wheat protoplasts reveal that the fragment Brace-Kinase 122-476 of MLKL-K is capable of inducing cell death, which is dependent on a functional kinase domain and the three α-helices in the brace region close to the N-terminus of the kinase domain. The powdery mildew resistance gene Pm13 was introgressed into wheat from Aegilops longissima . Here, the authors report the cloning of Pm13 and reveal that it encodes a MLKL_NTD domain-containing kinase.

Background The WRKY gene family is one of the most important families in higher plants. As transcription factors, they actively respond to biotic and abiotic stress and are also involved in plant development. Chinese jujube ( Ziziphus jujuba Mill.) is the largest type of dried fruit tree in China in terms of production, but its production is largely limited by phytoplasma infection, and the information about the role of WRKY genes under phytoplasma stress was still limited. Results We identified 54 ZjWRKYs in the jujube genome and classified them into three subgroups according to conserved WRKY domains and zinc-finger structure. 41 ZjWRKYs were distributed on 11 of 12 pseudo chromosomes in Chinese jujube. The majority of ZjWRKYs were highly expressed in the seven examined tissues, indicating that they play multiple roles in these vegetative and reproductive organs. Transcriptome data showed that most of the characterised ZjWRKYs were highly expressed at later stages of fruit development. RT-qPCR demonstrated that the expression of 23 ZjWRKYs changed following phytoplasma infection, suggesting that they are involved in signalling pathways that respond to phytoplasma stress. Then, STRING analysis and yeast two-hybrid screening proved that some ZjWRKY proteins were interacting with ZjMAPKK proteins, which were also involved in phytoplasma invasion. Moreover, their differential expressions were further confirmed in resistant and susceptible jujube varieties under phytoplasma stress. These results suggest that ZjWRKYs play significant roles in phytoplasma tolerance and should be crucial candidate genes for jujube-phytoplasma interaction. Conclusions 54 ZjWRKYs in Chinese jujube were identified and classified into three subgroups. 41 ZjWRKYs were unevenly distributed along the chromosomes. The majority of ZjWRKYs were highly expressed in various tissues. Most of the ZjWRKYs were positive responses to phytoplasma invasion, and that provided candidate genes for the future studies of jujube-phytoplasma interaction.

Objective This study aimed to comprehensively analyze the detection capacity of non-invasive prenatal testing (NIPT) for chromosomal abnormalities of all 24 chromosomes, as well as high-risk indications for pregnancy and the fetal fraction, in a large cohort. Methods We retrospectively enrolled 118,969 pregnant women who underwent NIPT at Sichuan Provincial Maternity and Child Health Care Hospital from March 2019 to June 2022. The sensitivity, specificity, positive predictive value, negative predictive value, and positive chromosomal abnormality rate were calculated. The fetal fraction based on gestational age, maternal body mass index, and number was examined. Results NIPT demonstrated > 99% sensitivity and specificity for almost all of the common trisomies (T21, T18, and T13), sex chromosomal aneuploidies, rare autosomal trisomies, and microdeletion/microduplication syndromes. Positive predictive values varied from 12.0% to 89.6%. Advanced maternal age was associated with an increased risk of three major aneuploidies. The fetal fraction was positively correlated with gestational age and negatively correlated with the maternal body mass index. Conclusions NIPT can be used to effectively screen for chromosomal abnormalities across all 24 chromosomes. Advanced maternal age is a risk factor for high-risk pregnancy, and careful consideration of the fetal fraction is essential during NIPT.

BackgroundDEAD-Box Helicase 3 X-Linked (DDX3X) is a member of the DEAD-box helicases that play a crucial role in RNA metabolism. Although DDX3X has been shown to contribute to tumorigenesis, the detailed mechanisms by which DDX3X functions in pancreatic ductal adenocarcinoma (PDAC) biogenesis remain poorly understood.AimsThe goal of the present study was to elucidate the molecular mechanisms by which DDX3X contributes to tumorigenesis in PDAC.MethodsKaplan–Meier curves, the log-rank test, t test and Cox regression were used to analyze the relationship between DDX3X expression and the clinicopathological features of PDAC patients. DDX3X and p62 expression in human PDAC tissues was analyzed by immunohistochemistry. Monolayer scratch healing assays, cell migration assays and nude mouse lung metastasis models were used to evaluate the effect of DDX3X on metastasis in vitro and in vivo. Western blot analysis was used to assess the expression of proteins in the signaling pathway.ResultsWe authenticated high DDX3X expression was associated with a poor prognosis in PDAC. The loss of DDX3X attenuated the migratory capacity of PDAC cells in vitro and in vivo. DDX3X was shown to facilitate epithelial-mesenchymal transition (EMT) and the phosphorylation of p65 and eIF2α. Moreover, DDX3X displayed oncogenic activity by promoting p62 accumulation.ConclusionsOur results demonstrated that DDX3X activates NF-κB and promotes metastasis by inducing EMT via p62.

The spatiotemporal dynamics of soil nutrients in the crop row zone are critical determinants of crop yield, necessitating precision fertilization for optimal plant growth. However, previous studies have predominantly focused on plant-available nutrient status at the scale of entire cropping systems, yet a granular understanding of their distribution patterns across precise temporal and spatial dimensions remains limited. Therefore, this study investigated maize–legume intercropping systems to quantify the dynamics of soil alkaline-hydrolyzable nitrogen (AN), available phosphorus (AP), and available potassium (AK) across distinct growth stages, soil depths, and row positions. The experiment comprised five treatments: maize–soybean intercropping, maize–peanut intercropping, and monocultures of maize, soybean, and peanut. Throughout the two-year study, maize–soybean intercropping significantly enhanced the plant height of both maize and soybean relative to their respective monocultures (p < 0.05). In contrast, within the maize–peanut system, intercropping significantly promoted peanut plant height but suppressed stem diameter in both species (p < 0.05); these effects were consistent across both study years. Both systems exhibited a “benefit-sacrifice” pattern, where dry matter was preferentially allocated to maize, thereby increasing total system productivity despite suppressing legume growth. Furthermore, during the mid-to-late growth stages, intercropped maize showed an enhanced capacity for nitrogen uptake from deeper soil layers. In contrast, the alkaline-hydrolyzable nitrogen content in intercropped soybean and peanut remained lower than in their respective monocultures throughout the growth period, with reductions ranging from 8.49% to 34.79%. Intercropping significantly increased the soil available phosphorus content in the root zones of maize, soybean, and peanut compared to their respective monocultures. The available phosphorus content in the 0–20 cm soil layer was consistently higher than in monoculture systems, with a maximum increase of 41.70%. Moreover, intercropping effectively mitigated soil potassium depletion, resulting in a smaller decline in available potassium. This effect was most pronounced in the maize–peanut intercropping pattern within the 20–40 cm soil layer. The distribution of soil available nutrients (N, P, K) was also influenced by drip tape placement. The levels of these nutrients for soybean and peanut were higher at 50 cm from the drip tape than at 30 cm, while for maize, levels were higher at 80 cm than at 40 cm. Intercropping increased the thousand-kernel weight of maize and soybean but decreased that of peanut. Overall, the strategic row configuration optimized the yield performance of both intercropping systems, resulting in land equivalent ratios greater than 1, which indicates distinct yield advantages for both intercropping patterns.

Background Chronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We investigated the development of cerebral small vessel disease using in vivo and in vitro models of CKD. Methods CKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We analyzed brain histology using Prussian blue staining to examine formation of cerebral microhemorrhage (CMH), the hemorrhagic component of small vessel disease and the neuropathological substrate of MRI-demonstrable cerebral microbleeds. In cell culture studies, we examined effects of serum from healthy or CKD patients and gut-derived uremic toxins on brain microvascular endothelial barrier. Results CKD was induced in aged C57BL/6J mice with significant increases in both serum creatinine and cystatin C levels ( p  < 0.0001) without elevation of systolic or diastolic blood pressure. CMH was significantly increased and positively correlated with serum creatinine level (Spearman r  = 0.37, p  < 0.01). Moreover, CKD significantly increased Iba-1-positive immunoreactivity by 51% ( p  < 0.001), induced a phenotypic switch from resting to activated microglia, and enhanced fibrinogen extravasation across the blood–brain barrier (BBB) by 34% ( p  < 0.05). On analysis stratified by sex, the increase in CMH number was more pronounced in male mice and this correlated with greater creatinine elevation in male compared with female mice. Microglial depletion with PLX3397 diet significantly decreased CMH formation in CKD mice without affecting serum creatinine levels. Incubation of CKD serum significantly reduced transendothelial electrical resistance (TEER) ( p  < 0.01) and increased sodium fluorescein permeability ( p  < 0.05) across the endothelial monolayer. Uremic toxins (i.e., indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide) in combination with urea and lipopolysaccharide induced a marked drop in TEER compared with the control group ( p  < 0.0001). Conclusions CKD promotes the development of CMH in aged mice independent of blood pressure but directly proportional to the degree of renal impairment. These effects of CKD are likely mediated in part by microglia and are associated with BBB impairment. The latter is likely related to gut-derived bacteria-dependent toxins classically associated with CKD. Overall, these findings demonstrate an important role of CKD in the development of cerebral small vessel disease.

Intestinal dysbiosis and gut-derived toxins in chronic kidney diseases (CKD) are associated with vascular injury. This study examined the relationship between gut dysbiosis and cerebral microhemorrhages (CMH) in young and aged CKD mice (3 vs. 16 months of age) in both sexes. CKD was induced in C57BL/6J mice using a nephrotoxic adenine diet. Serum creatinine, trimethylamine N-oxide (TMAO), indoxyl sulfate (IS) and p-cresyl sulfate (pCS) were measured. CMH was quantified via brain histology, and gut microbial sequencing was analyzed from fecal pellets. Creatinine and uremic toxins were elevated in both young and aged CKD mice compared with controls, and microbial populations were altered by age, sex and CKD status. Age was the most significant factor in microbial variance, with higher levels of IS and pCS in aged CKD mice. Aged male mice had significantly higher creatinine, TMAO and IS than aged females. Males had higher CMH counts than females, and aged CKD males had the highest CMH burden. Age modified the relationship between uremic toxins and CMH burden, with creatinine, TMAO and IS correlating with increased CMH in aged animals. In conclusion, gut dysbiosis in CKD is modulated by sex and age, and gut-derived uremic toxins including TMAO and IS may contribute to vascular injury and CMH development.