The adult zebrafish spinal cord displays an impressive innate ability to regenerate after traumatic insults, yet the underlying adaptive cellular mechanisms remain elusive. Here, we show that while the cellular and tissue responses after injury are largely conserved among vertebrates, the large-size fast spinal zebrafish motoneurons are remarkably resilient by remaining viable and functional. We also reveal the dynamic changes in motoneuron glutamatergic input, excitability, and calcium signaling, and we underscore the critical role of calretinin (CR) in binding and buffering the intracellular calcium after injury. Importantly, we demonstrate the presence and the dynamics of a neuron-to-neuron bystander neuroprotective biochemical cooperation mediated through gap junction channels. Our findings support a model in which the intimate and dynamic interplay between glutamate signaling, calcium buffering, gap junction channels, and intercellular cooperation upholds cell survival and promotes the initiation of regeneration.
Gap Junctions , Motor Neurons , Spinal Cord Injuries , Spinal Cord , Zebrafish , Animals , Spinal Cord Injuries/metabolism , Spinal Cord/metabolism , Gap Junctions/metabolism , Motor Neurons/metabolism , Calcium/metabolism , Calcium Signaling , Calbindin 2/metabolism , Zebrafish Proteins/metabolism , Zebrafish Proteins/genetics , Glutamic Acid/metabolism , Cell Survival
The field of immunotherapy, particularly immune checkpoint blockade (ICB), holds immense potential in mitigating the progression of cancer. However, the challenges of insufficient tumor antigen production and the immunosuppressive state in the tumor microenvironment substantially impede patients from deriving benefits. In this research, we present a tumor-microenvironment-modulation manganese-based nanosystem, PEG-MnMOF@PTX, aiming to improve the responsiveness of ICB. Under acidic conditions, the released Mn2+ accomplishes multiple objectives. It generates toxic hydroxyl radicals (â¢OH), together with the released paclitaxel (PTX), inducing immunogenic cell death of tumor cells and normalizing tumor blood vessels. Concurrently, it facilitates the in situ generation of oxygen (O2) from hydrogen peroxide (H2O2), ameliorating the microenvironmental immunosuppression and increasing the efficacy of immunotherapy. In addition, this study demonstrates that PEG-MnMOF@PTX can promote the maturation of dendritic cells and augment the infiltration of cytotoxic T lymphocytes through activation of the cyclic guanosine 5'-monophosphate-adenosine 5'-monophosphate synthase (cGAS) and interferon gene stimulator (STING) pathways, namely cGAS-STING pathways, thereby heightening the sensitivity to ICB immunotherapy. The findings of this study present a novel paradigm for the progress in cancer immunotherapy.
BACKGROUND: Auxin response factor (ARF), a transcription factors that controls the expression of genes responsive to auxin, plays a key role in the regulation of plant growth and development. Analyses aimed at identifying ARF family genes and characterizing their functions in Juglans sigillata Dode are lacking. METHODS AND RESULTS: We used bioinformatic approaches to identify members of the J. sigillata ARF gene family and analyze their evolutionary relationships, collinearity, cis-acting elements, and tissue-specific expression patterns. The expression patterns of ARF gene family members under natural drought conditions were also analyzed. The J. sigillata ARF gene family contained 31 members, which were unevenly distributed across 16 chromosomes. We constructed a phylogenetic tree of JsARF genes and other plant ARF genes. Cis-acting elements in the promoters of JsARF were predicted. JsARF28 showed higher expressions in both the roots and leaves. A heat map of the transcriptome data of the cluster analysis under drought stress indicated that JsARF3/9/11/17/20/26 are responsive to drought. The expression of the 11 ARF genes varied under PEG treatment and JsARF18 and JsARF20 were significantly up-regulated. CONCLUSIONS: The interactions between abiotic stresses and plant hormones are supported by our cumulative data, which also offers a theoretical groundwork for comprehending the ARF mechanism and drought resistance in J. sigillata.
Indoleacetic Acids , Juglans , Indoleacetic Acids/metabolism , Phylogeny , Juglans/genetics , Droughts , Gene Expression Profiling , Gene Expression Regulation, Plant/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Stress, Physiological/genetics
Kaempferol (KA), an natural antioxidant of traditional Chinese medicine (TCM), is extensively used as the primary treatment for inflammatory digestive diseases with impaired redox homeostasis. Severe acute pancreatitis (SAP) was exacerbated by mitochondrial dysfunction and abundant ROS, which highlights the role of antioxidants in targeting mitochondrial function. However, low bioavailability and high dosage of KA leading to unavoidable side effects limits clinical transformation. The mechanisms of KA with poor bioavailability largely unexplored, hindering development of the efficient strategies to maximizing the medicinal effects of KA. Here, we engineered a novel thioketals (TK)-modified based on DSPE-PEG2000 liposomal codelivery system for improving bioavailability and avoiding side effects (denotes as DSPE-TK-PEG2000-KA, DTM@KA NPs). We demonstrated that the liposome exerts profound impacts on damaging intracellular redox homeostasis by reducing GSH depletion and activating Nrf2, which synergizes with KA to reinforce the inhibition of inadequate fission, excessive mitochondrial fusion and impaired mitophagy resulting in inflammation and apoptosis; and then, the restored mitochondrial homeostasis strengthens ATP supply for PAC renovation and homeostasis. Interestingly, TK bond was proved as the main functional structure to improve the above efficacy of KA compared with the absence of TK bond. Most importantly, DTM@KA NPs obviously suppresses PAC death with negligible side effects in vitro and vivo. Mechanismly, DTM@KA NPs facilitated STAT6-regulated mitochondrial precursor proteins transport via interacting with TOM20 to further promote Drp1-dependent fission and Pink1/Parkin-regulated mitophagy with enhanced lysosomal degradation for removing damaged mitochondria in PAC and then reduce inflammation and apoptosis. Generally, DTM@KA NPs synergistically improved mitochondrial homeostasis, redox homeostasis, energy metabolism and inflammation response via regulating TOM20-STAT6-Drp1 signaling and promoting mitophagy in SAP. Consequently, such a TCM's active ingredients-based nanomedicine strategy is be expected to be an innovative approach for SAP therapy.
Kaempferols , Pancreatitis , Humans , Acute Disease , Kaempferols/pharmacology , Kaempferols/metabolism , Protein Kinases/metabolism , Protein Kinases/pharmacology , Pancreatitis/drug therapy , Pancreatitis/metabolism , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , Inflammation/metabolism
The challenges associated with activating ferroptosis for cancer therapy primarily arise from obstacles related to redox and iron homeostasis, which hinder the susceptibility of tumor cells to ferroptosis. However, the specific mechanisms of ferroptosis resistance, especially those intertwined with abnormal metabolic processes within tumor cells, have been consistently underestimated. In response, we present an innovative glutathione-responsive magnetocaloric therapy nanodrug termed LFMP. LFMP consists of lonidamine (LND) loaded into PEG-modified magnetic nanoparticles with a Fe3O4 core and coated with disulfide bonds-bridged mesoporous silica shells. This nanodrug is designed to induce an accelerated ferroptosis-activating state in tumor cells by disrupting homeostasis. Under the dual effects of alternating magnetic fields and high concentrations of glutathione in the tumor microenvironment, LFMP undergoes disintegration, releasing drugs. LND intervenes in cell metabolism by inhibiting glycolysis, ultimately enhancing iron death and leading to synthetic glutathione consumption. The disulfide bonds play a pivotal role in disrupting intracellular redox homeostasis by depleting glutathione and inactivating glutathione peroxidase 4 (GPX4), synergizing with LND to enhance the sensitivity of tumor cells to ferroptosis. This process intensifies oxidative stress, further impairing redox homeostasis. Furthermore, LFMP exacerbates mitochondrial dysfunction, triggering ROS formation and lactate buildup in cancer cells, resulting in increased acidity and subsequent tumor cell death. Importantly, LFMP significantly suppresses tumor cell proliferation with minimal side effects both in vitro and in vivo, exhibiting satisfactory T2-weighted MR imaging properties. In conclusion, this magnetic hyperthermia-based nanomedicine strategy presents a promising and innovative approach for antitumor therapy.
Ferroptosis , Neoplasms , Humans , Glutathione , Iron , Lactic Acid , Glucose , Disulfides , Neoplasms/drug therapy , Cell Line, Tumor , Reactive Oxygen Species , Tumor Microenvironment
Juglans sigillata Dode is one of the important tree species in southwest China, and it has significant economic and ecological value. However, there is still a lack of effective methods to identify the functional genes of J. sigillata. By verifying the model plant tobacco, the pTRV2::JsPDS vector was able to cause photobleaching. This study showed that photobleaching occurred 24 and 30 d after the silencing vector was infected with aseptic seedlings and fruits of J. sigillata, respectively. When the OD600 was 0.6, and the injection dose was 500 µL, the gene silencing efficiency of aseptic seedlings was the highest at 16.7 %, significantly better than other treatments. Moreover, when the OD600 was 0.8, and the injection dose was 500 µL, the gene silencing efficiency in the walnut fruit was the highest (20 %). In addition, the VIGS system was successfully used to silence JsFLS2 and JsFLS4 genes in J. sigillata. This study also showed that the flavonol content and gene expression in the treatment group were decreased compared to the control group. In addition, the proteins transcribed and translated from the JsFLS4 gene may have higher catalytic activity for dihydroquercetin. The above results indicate that the TRV-mediated VIGS system can be an ideal tool for studying J. sigillata gene function.
Juglans , Plant Viruses , Juglans/genetics , Gene Silencing , Phenotype , Fruit , Nicotiana , Seedlings/genetics , Gene Expression Regulation, Plant , Plant Viruses/genetics
SUMMARY: The objective of this study was to investigate the therapeutic wound healing potential and molecular mechanisms of shikonin as small molecules in vitro. A mouse burn model was used to explore the potential therapeutic effect of shikonin; we traced proliferating cells in vivo to locate the active area of skin cell proliferation. Through the results of conventional pathological staining, we found that shikonin has a good effect on the treatment of burned skin and promoted the normal distribution of skin keratin at the damaged site. At the same time, shikonin also promoted the proliferation of skin cells at the damaged site; importantly, we found a significant increase in the number of fibroblasts at the damaged site treated with shikonin. Most importantly, shikonin promotes fibroblasts to repair skin wounds by regulating the PI3K/AKT signaling pathway. This study shows that shikonin can effectively promote the proliferation of skin cell, and local injection of fibroblasts in burned skin can play a certain therapeutic role.
El objetivo de este trabajo fue investigar el potencial terapéutico de cicatrización de heridas y los mecanismos moleculares de la shikonina como moléculas pequeñas in vitro. Se utilizó un modelo de quemaduras en ratones para explorar el posible efecto terapéutico de la shikonina; Rastreamos las células en proliferación in vivo para localizar el área activa de proliferación de células de la piel. A través de los resultados de la tinción para patología convencional, encontramos que la shikonina tiene un buen efecto en el tratamiento de la piel quemada y promueve la distribución normal de la queratina de la piel en el sitio dañado. Al mismo tiempo, la shikonina también promovió la proliferación de células de la piel en el sitio dañado. Es importante destacar que encontramos un aumento significativo en la cantidad de fibroblastos en el sitio dañado tratado con shikonina. Lo más importante es que la shikonina promueve la función reparadora de fibroblastos en las heridas de la piel regulando la vía de señalización PI3K/ AKT. Este estudio muestra que la shikonina puede promover eficazmente la proliferación de células de la piel y que la inyección local de fibroblastos en la piel quemada puede desempeñar un cierto papel terapéutico.
Animals , Mice , Wound Healing/drug effects , Burns/drug therapy , Naphthoquinones/administration & dosage , Skin , In Vitro Techniques , Naphthoquinones/pharmacology , Phosphatidylinositol 3-Kinases , Cell Proliferation/drug effects , Disease Models, Animal , Proto-Oncogene Proteins c-akt , Fibroblasts , Mice, Inbred C57BL
BACKGROUND: Previous classifications in polydactyly of the thumb were by the level of duplication on radiography. This study aimed to develop a practical algorithm based on physical characteristics for treatment guidelines. METHODS: The polydactylies were stratified using four physical characteristics: floating, symmetry, dominant side, and joint angulation/nail size. The algorithm identified the hypoplastic type and then stratified the polydactylies as symmetric and asymmetric. The asymmetric type was divided into ulnar dominant and radial dominant. The symmetric type was divided into adequate type and inadequate type. The prediction of treatments was studied retrospectively by the distribution of surgical procedures in 500 patients with 545 affected thumbs, by the new classification and the Wassel-Flatt classification. RESULTS: Of the 545 polydactylies, 78 (14.5%) were categorized as the hypoplastic type, 369 (67.5%) as the ulnar-dominant type, 8 (1.5%) as the radial-dominant type, 70 (12.8%) as the symmetric adequate nail type, and 20 (3.7%) as the symmetric inadequate type. Treatments were excision and reconstruction in 403 polydactylies (73.9%), simple excision in 135 polydactylies (24.8%), and the Bilhaut-Cloquet procedure, ray amputation, and on-top plasty procedures were only performed in 7 polydactylies (1.3%). The distribution of surgical procedures was distinct among the new classification types and was similar among the Wassel-Flatt types. CONCLUSIONS: The new classification stratified polydactylies by physical findings in a stepwise manner. Though surgical technical details are not included, this simple classification is useful for paediatricians and parents to understand how a surgical decision is made. LEVEL OF EVIDENCE: Diagnostic Level IV.
Plastic Surgery Procedures , Polydactyly , Thumb/abnormalities , Humans , Thumb/diagnostic imaging , Thumb/surgery , Retrospective Studies , Polydactyly/diagnostic imaging , Polydactyly/surgery
BACKGROUND: Established associated factors for DDH include female sex, breech presentation, family history, congenital malformations, oligohydramnios, and maternal hyperthyroidism. However, evidence for environmental factors that may contribute to DDH is limited and inconsistent. METHODS: A systematic review of medical literature was conducted to collect data on environmental factors, including latitude, longitude, average yearly precipitation, average yearly temperature, minimum monthly temperature, and maximum monthly temperature, from all institutions that published articles on DDH. Univariate linear regression analysis was used to examine the correlation between environmental factors and DDH incidence, while multiple regression analysis was conducted to identify significant associated factors for DDH incidence. RESULTS: Data from a total of 93 unique manuscripts were analyzed, revealing a significant negative correlation between DDH incidence and temperature, including average yearly temperature (r = -0.27, p = 0.008), minimum monthly temperature (r = -0.28, p = 0.006), and maximum monthly temperature (r = -0.23, p = 0.029). Additionally, there was a significant positive correlation between DDH incidence and latitude (r = 0.27, p = 0.009), and a significant negative correlation between DDH incidence and average yearly precipitation (r = -0.29, p = 0.004). In the final multiple regression analysis, temperature, including average yearly temperature, minimum monthly temperature, and maximum monthly temperature, were identified as significant associated factors for DDH incidence. CONCLUSION: The findings of this study suggest an association between cold weather and DDH incidence. Further research should explore the link between cold weather and DDH incidence, offering insights into potential interventions for cold climates.
Breech Presentation , Developmental Dysplasia of the Hip , Hip Dislocation, Congenital , Pregnancy , Humans , Female , Incidence , Regression Analysis , Risk Factors
The escalating global climate change significantly threatens plant growth, development, and production through salinity stress. Flavonoids, a crucial category of secondary metabolites, have been extensively studied for their role in modulating plant growth and development mechanisms in the face of biological and abiotic stress. The flavonol synthetase (FLS) gene plays a key role in the biosynthesis and accumulation of flavonoids. To investigate the correlation between salt tolerance and flavonol synthesis, JsFLS5 was overexpressed in the callus of Juglans sigillata cv. "Qianhe-7." This study shows that the upregulation of JsFLS5 significantly elevates the overall flavonoid content by modulating the expression of genes associated with flavonoid synthesis under salinity stress conditions. Additionally, the overexpressing callus exhibited enhanced resistance to salt stress compared to the wild-type callus, as evidenced by reduced levels of reactive oxygen species accumulation, electrolyte leakage, and malondialdehyde content in the overexpressing callus relative to the wild type (WT). Moreover, the overexpressing callus showed higher antioxidant enzyme activity and a more efficient ascorbic acid-glutathione cycle. Furthermore, the concentration of Na+ in the overexpressing callus was lower than WT, resulting in a decreased Na+ /K+ ratio. These findings suggest that JsFLS5 overexpression in calli effectively mitigates the oxidative damage induced by osmotic stress and reduces Na+ toxicity by enhancing flavonoid synthesis under salt stress conditions. Consequently, this study offers a novel perspective for comprehending the role of JsFLS5 in the response to abiotic stress in J. sigillata.
Juglans , Salt Tolerance , Reactive Oxygen Species/metabolism , Salt Tolerance/genetics , Juglans/genetics , Juglans/metabolism , Plants, Genetically Modified/genetics , Antioxidants/metabolism , Stress, Physiological/genetics , Ions/metabolism , Sodium/metabolism , Flavonoids/metabolism , Flavonols/metabolism , Flavonols/pharmacology , Salinity , Gene Expression Regulation, Plant
The widespread use of ultra-thin mulch films has been considered the root cause of China's difficulties in recycling waste mulch films and their severe residue and pollution. Therefore, environmental regulation to guide farmers to use and recycle high-standard mulch has become a key measure to prevent and control mulch pollution at the source. In this paper, we review environmental regulation measures for mulch pollution and their implementation characteristics in the northwest dry farming restoration region as a case study, and explore their impact on the use and recycling of high-standard mulch. âThe results show that China's environmental regulations on mulch use and recycling can be classified into three types: guidance, incentives, and restrictions. However, the measures implemented so far primarily consist of guidance, while the restrictive and incentive regulations are inadequate. The percentage of farmers using and recycling high-standard mulch under environmental regulations is relatively high (88.18% and 79.83%, respectively), but there is still room for improvement. The study also reveals that while environmental regulations promote the use of high-standard plastic film and its recycling, not all measures are equally effective. Specifically, the implementation of measures such as benefits publicity, price subsidies, technical training, behavior supervision, and punishment mechanisms can be effective in improving farmers' adoption of high-standard plastic mulch; publicizing the hazards of mulch residue, training on recycling techniques, establishing recycling sites, regulating recycling practices, and penalizing violations can effectively help increase the recycling rate of used mulch film. Finally, this study provides a valuable reference for improving regulatory policies for mulch pollution control.
Agriculture , Environmental Pollution , Recycling , China , Government
Canna indica, which produce conspicuous and colorful flowers, are widely appreciated as ornamental plants. We used Pacific Biosciences sequencing (PacBio) and chromosome conformation capture (Hi-C) genome scaffolding to build a high-quality chromosome-scale genome assembly of C. indica and the genome assembly was 821Mb with a contig N50 of 48Mb assembled into nine chromosomes. The genome of C. indica was predicted to contain 31,130 genes and 30,816 genes were functionally annotated. Genome annotation identified 522 Mb (63.59 %) as repetitive sequences. Genome evolution analysis showed that whole-genome duplication occurred 53.4 million years ago. Transcriptome analysis revealed that petal coloration was linked with the expression of genes encoding enzymes involved in anthocyanin biosynthesis, carotenoid biosynthesis, and the methylerythritol phosphate (MEP) pathway. Furthermore, modules of co-expressed genes and hub genes were identified via weighted gene co-expression network analysis. These results suggested that, in Canna indica, deep red petal coloration was regulated by CHS2 and yellow petal coloration was associated with expression of ARF6 and NAC14. Considered together, the current study revealed a high-quality reference genome which may provide new insights into the molecular basis of flower coloration in Canna indica and help enhance the conservation and breeding of ornamental plants in general.
BACKGROUND: Soft tissue release (STR) is an established treatment for spastic hip displacement, but recurrence of hip displacement is not uncommon. This study aims to (1) evaluate the recurrence of hip displacement after STR, (2) define associated factors of recurrence, and (3) elucidate the effects of guided growth on hip displacement recurrence. METHODS: The study subjects included 66 individuals with spastic cerebral palsy treated by STR with or without guided growth for hip displacement. The treatment goal was the maintenance of migration percentage (MP) to <40%. Recurrence was defined by a rebound of the MP by 5% or more after the first postoperative year. Children with recurrence were compared with those without recurrence using the Mann-Whitney U test and the χ 2 test. The risk factors for recurrence were evaluated using multiple logistic regression analysis. RESULTS: Nineteen individuals (29%) had a recurrence of hip displacement after the first postoperative year. They sustained a 2-fold increase in the rate of treatment failure ( P < 0.001) and reoperation ( P = 0.04). Age, sex, motor function, and preoperative radiographic parameters were comparable between individuals with and without recurrence. The use of guided growth was associated with less risk of recurrence than without (5% and 39%, respectively, odds ratio = 0.01 to 0.45, respectively) despite the similar risk of failure (35% and 48%, respectively, odds ratio = 0.15 to 4.82). CONCLUSIONS: Recurrence of the MP >5% after the first postoperative year is an important early indicator for failure to control MP to <40% and reoperation. Guided growth not only decreases coxa valga but also reduces the risk of recurrent hip displacement after STR. LEVEL OF EVIDENCE: Level III; case-control study.
Cerebral Palsy , Hip Dislocation , Child , Humans , Hip Dislocation/surgery , Muscle Spasticity/complications , Case-Control Studies , Treatment Failure , Cerebral Palsy/complications
OBJECTIVE: To investigate the correlation between single-nucleotide polymorphism (SNP) of ARID5B gene and resistance to methotrexate (MTX) in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 144 children with ALL who were treated in General Hospital of Ningxia Medical University from January 2015 to November 2021 were enrolled and divided into MTX resistant group and non-MTX resistant group, with 72 cases in each group. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) technology was used to measure the SNP of ARID5B gene in all children and analyze its correlation with MTX resistant. RESULTS: There were no significant differences in the genotype and gene frequency of rs7923074, rs10821936, rs6479778, and rs2893881 between MTX resistant group and non-MTX resistant group (P>0.05). The frequency of C/C genotype in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T/T genotype was opposite (P<0.05). The frequency of C allele in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T allele was opposite (P<0.05). Multivariate logistic regression analysis showed that ARID5B gene rs4948488 TT genotype and T allele frequency were risk factors for MTX resistant in ALL children (P<0.05). CONCLUSION: The SNP of ARID5B gene is associated with MTX resistant in ALL children.
DNA-Binding Proteins , Drug Resistance, Neoplasm , Polymorphism, Single Nucleotide , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Transcription Factors , Child , Humans , DNA-Binding Proteins/genetics , Gene Frequency , Genotype , Methotrexate , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Transcription Factors/genetics
Walnut and Rosa roxburghii are important arbor and shrub fruit trees cultivated in the southwest mountainous area of China. Furthermore, those two species are compound cultivated in this area. In this study, we investigated the growth, yield, fruit quality, photosynthesis, and soil fertility of R. roxburghii in a 7-year typical 'Qianhe 7'/ 'Guinong 5' compound planting pattern in Guizhou. The results showed that compared with the monoculture, photosynthetic pigment content and photosynthetic rate of R. roxburghii leaves were significantly lower in the compound plantation. The growth and yield of R. roxburghii decreased significantly, with a 77.7% reduction of yield. Fruit quality of R. roxburghii was improved. The content of ascorbic acid (Vc), total phenol, carbohydrate, K, Ca, Mg, Fe, Mn, Zn, and other substances increased significantly. Fruit Vc and Mn content increased by 34.1% and 64.1%, respectively. The contents of total N, available N and K in the soil increased by 45.8%, 34.8% and 67.8%, respectively. The abundance of soil microorganisms and functional bacteria increased significantly, with the increase of bacteria and fungi being more than 36.0%. The increase of potassium bacteria and nitrogen fixing bacteria was 71.3% and 124.8%, respectively. However, the contents of organic matter, carbon-nitrogen ratio, total P, total K, available mineral nutrient (P, Ca, Mg, Fe, Mn, Cu, Zn) contents decreased. While the activities of soil urease and catalase were increased, the activities of other soil enzymes (sucrase, cellulase, protease, phosphatase) were significantly reduced. In summary, with continuous growth of walnuts in the walnut/R. roxburghii compound plantation, there was obvious shade and soil fertility competition for R. roxburghii, which affected its yield, but had a improvement effect on fruit quality.
Juglans , Rosa , Fruit , Soil , Nuts
An efficient genetic transformation system is of great significance for verifying gene function and improving plant breeding efficiency by gene engineering. In this study, a stable Agrobacterium mediated genetic transformation system of Juglans sigillata Dode 'Qianhe-7' was investigated using callus and negative pressure-assisted and ultrasonic-assisted transformation selection. The results showed that the axillary shoot leaves were suitable to induce callus and the callus proliferation rate could reach 516.27% when induction calli were cultured on DKW medium containing 0.5 mg L-1 indole-3-butyric acid, 1.2 mg L-1 2,4-dichlorophenoxyacetic acid and 0.5 mg L-1 kinetin for 18 d. In addition, negative pressure infection was the optimal infection method with the lowest browning rate (0.00%), high GFP conversion rate (16.67%), and better growth status. To further prove the feasibility of this genetic transformation system, the flavonol synthetase (JsFLS5) gene was successfully transformed into the into leaf-derived callus of 'Qianhe-7'. JsFLS5 expression and the content of total flavonoids in transformed callus were improved significantly compared with the untransformed callus, which proved that we had an efficient and reliable genetic transformation system using leaf-derived callus of Juglans sigillata.
Agrobacterium , Juglans , Agrobacterium/genetics , Juglans/genetics , Plants, Genetically Modified , Transformation, Genetic , Plant Breeding
Ecological management has been implemented to improve individual well-being. However, it remains unclear whether this management has improved health inequality over time. Aiming to examine whether health inequality is caused by ecological management in China, we harnessed a macro-level dataset from 2001 to 2019 across 31 Chinese provinces-combined with gene and dietary culture data-and utilized a bilateral approach to pair provincial data. Empirical results of system Generalized Method of Moments (sys-GMM) estimations in benchmark and extensive models which suggest a negative and statistically significant causal effect of ecological management on health inequality. Specifically, ecological management contributes to decreasing the inequality in the population death rate, the death rate among pregnant women, the underweight newborn rate, the child malnutrition rate, and the infectious disease mortality. The results are robust to weak instruments in the sys-GMM setting and a delayed effect of ecological management. Additionally, the heterogeneity analysis shows that the causal effect of ecological management on decreasing regional health inequality is more significant and higher for subsamples in identical regions than in different regions.
Child Nutrition Disorders , Health Status Disparities , Infant, Newborn , Child , Humans , Female , Pregnancy , China , Thinness
BACKGROUND: The Wassel classification is commonly used for cases of radial polydactyly but has not been used to predict surgical outcomes. This study aimed to investigate the predictive factors of surgical outcomes using the Wassel type and symmetry of duplication. METHODS: Forty-five patients with 47 radial polydactylies were reviewed using the Japanese Society for Surgery of the Hand (JSSH) scores 4.6 years after minor thumb excision and reconstructive surgery. The symmetry index was defined as the metaphyseal width ratio of the minor thumb to the dominant thumb. The relationships between the JSSH scores and operation age, sex, side, follow-up duration, Wassel type, symmetric index, divergent angle, and joint angulation were analyzed by linear regression. RESULTS: The mean JSSH score of the 47 thumbs was 18.3 points (range, 15-20). Five thumbs had fair or poor outcomes (scores <17), all of which were Wassel type IV. The hypoplastic type had a better JSSH score (19.4) than other Wassel types. The symmetric index had a negative relationship with JSSH scores, especially for Wassel type IV (r=-0.68, P =0.001). Linear regression revealed that the symmetric index was the only independent factor significantly associated with JSSH scores among Wassel type IV polydactylies ( P <0.05). The receiver operating characteristic curve suggested a symmetric index <0.74 could predict good or excellent outcomes. CONCLUSION: The symmetry of the 2 duplicated thumbs is an important factor for surgical outcomes. The Wassel type IV polydactylies with a symmetric index >0.74 are at greater risk of fair or poor outcomes after excision and reconstruction, and further studies are warranted to confirm whether the Bilhaut-Cloquet procedure is a good choice. LEVEL OF EVIDENCE: Level IV-Case-control study.
Polydactyly , Thumb , Humans , Infant , Thumb/surgery , Case-Control Studies , Polydactyly/surgery , Treatment Outcome
Aim To investigate the effect of silencing circRNA ciRS-7 on cisplatin resistance of gastric cancer cells and its related mechanism. Methods Cisplatin-resistant gastric cancer cells HGC-27/DDP were constructed, ciRS-7 was silenced and HGC-27/DDP cells were treated with cisplatin. Real-time quantitative PCR (qRT-PCR) was used to detect the expression levels of ciRS-7 and microrNA-944 (miR-944). Cell counting kit-8 (CCK-8) was used to detect cell survival rate. Clone formation assay was used to detect the number of clones. Western blot was used to detect the protein expression levels of CyclinD1, proliferating cell nuclear antigen (PCNA), B-lymphocytoma-2-associated X protein (Bax), B-lymphocytoma-2 (Bcl-2) and cleaved aspartate-specific cysteine proteinase 3 (cleaved-caspase-3). Flow cytometry was used to detect cell apoptosis rate. In situ end labeling (TUNEL) was used to detect apoptosis index. Dual luciferase assay was used to verify the targeting relationship between ciRS-7 and miR-944. Results CiRS-7 was highly expressed in cisplatin-resistant gastric cancer tissues and cells, while miR-944 was low expressed in cisplatin-resistant gastric cancer tissues and cells. The survival rate, clonal formation number, protein expression levels of CyclinD1, PCNA and Bcl-2 in cisplatin-treated HGC-27/DDP cells were significantly reduced by silencing ciRS-7, while ciRS-7 expression level, apoptosis rate, apoptosis index, Bax, cleaved-caspase-3 protein expression levels of cisplatin-treated HGC-27/DDP cells were significantly raised. CiRS-7 targetedly inhibited the expression of miR-944. Conclusions Silencing ciRS-7 can reverse cisplatin resistance of gastric cancer cells, and the mechanism may be related to the promotion of miR-944 expression by silencing ciRS-7.
OBJECTIVE@#To investigate the correlation between single-nucleotide polymorphism (SNP) of ARID5B gene and resistance to methotrexate (MTX) in children with acute lymphoblastic leukemia (ALL).@*METHODS@#A total of 144 children with ALL who were treated in General Hospital of Ningxia Medical University from January 2015 to November 2021 were enrolled and divided into MTX resistant group and non-MTX resistant group, with 72 cases in each group. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) technology was used to measure the SNP of ARID5B gene in all children and analyze its correlation with MTX resistant.@*RESULTS@#There were no significant differences in the genotype and gene frequency of rs7923074, rs10821936, rs6479778, and rs2893881 between MTX resistant group and non-MTX resistant group (P>0.05). The frequency of C/C genotype in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T/T genotype was opposite (P<0.05). The frequency of C allele in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T allele was opposite (P<0.05). Multivariate logistic regression analysis showed that ARID5B gene rs4948488 TT genotype and T allele frequency were risk factors for MTX resistant in ALL children (P<0.05).@*CONCLUSION@#The SNP of ARID5B gene is associated with MTX resistant in ALL children.
Child , Humans , DNA-Binding Proteins/genetics , Gene Frequency , Genotype , Methotrexate , Polymorphism, Single Nucleotide , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Transcription Factors/genetics , Drug Resistance, Neoplasm
