Origin recognition complex 6 overexpression promotes growth of glioma cells.

The discovery of novel oncotargets for glioma is of immense significance. We here explored the expression patterns, biological functions, and underlying mechanisms associated with ORC6 (origin recognition complex 6) in glioma. Through the bioinformatics analyses, we found a significant increase in ORC6 expression within human glioma tissues, correlating with poorer overall survival, higher tumor grade, and wild-type isocitrate dehydrogenase status. Additionally, ORC6 overexpression is detected in glioma tissues obtained from locally-treated patients and across various primary/established glioma cells. Further bioinformatics scrutiny revealed that genes co-expressed with ORC6 are enriched in multiple signaling cascades linked to cancer. In primary and immortalized (A172) glioma cells, depleting ORC6 using specific shRNA or Cas9-sgRNA knockout (KO) significantly decreased cell viability and proliferation, disrupted cell cycle progression and mobility, and triggered apoptosis. Conversely, enhancing ORC6 expression via a lentiviral construct augmented malignant behaviors in human glioma cells. ORC6 emerged as a crucial regulator for the expression of key oncogenic genes, including Cyclin A2, Cyclin B2, and DNA topoisomerase II (TOP2A), within glioma cells. Silencing or KO of ORC6 reduced the mRNA and protein levels of these genes, while overexpression of ORC6 increased their expression in primary glioma cells. Bioinformatics analyses further identified RBPJ as a potential transcription factor of ORC6. RBPJ shRNA decreased ORC6 expression in primary glioma cells, while its overexpression increased it. Additionally, significantly enhanced binding between the RBPJ protein and the proposed ORC6 promoter region was detected in glioma tissues and cells. In vivo experiments demonstrated a significant reduction in the growth of patient-derived glioma xenografts in the mouse brain subsequent to ORC6 KO. ORC6 depletion, inhibited proliferation, decreased expression of Cyclin A2/B2/TOP2A, and increased apoptosis were detected within these ORC6 KO intracranial glioma xenografts. Altogether, RBPJ-driven ORC6 overexpression promotes glioma cell growth, underscoring its significance as a promising therapeutic target.

IFNγ at the early stage induced after cryo-thermal therapy maintains CD4+ Th1-prone differentiation, leading to long-term antitumor immunity.

Introduction: Recently, more and more research illustrated the importance of inducing CD4+ T helper type (Th)-1 dominant immunity for the success of tumor immunotherapy. Our prior studies revealed the crucial role of CD4+ Th1 cells in orchestrating systemic and durable antitumor immunity, which contributes to the satisfactory outcomes of the novel cryo-thermal therapy in the B16F10 tumor model. However, the mechanism for maintaining the cryo-thermal therapy-mediated durable CD4+ Th1-dominant response remains uncovered. Additionally, cryo-thermal-induced early-stage CD4+ Th1-dominant T cell response showed a correlation with the favorable prognosis in patients with colorectal cancer liver metastasis (CRCLM). We hypothesized that CD4+ Th1-dominant differentiation induced during the early stage post cryo-thermal therapy would affect the balance of CD4+ subsets at the late phase. Methods: To understand the role of interferon (IFN)-γ, the major effector of Th1 subsets, in maintaining long-term CD4+ Th1-prone polarization, B16F10 melanoma model was established in this study and a monoclonal antibody was used at the early stage post cryo-thermal therapy for interferon (IFN)-γ signaling blockade, and the influence on the phenotypic and functional change of immune cells was evaluated. Results: IFNγ at the early stage after cryo-thermal therapy maintained long-lasting CD4+ Th1-prone immunity by directly controlling Th17, Tfh, and Tregs polarization, leading to the hyperactivation of Myeloid-derived suppressor cells (MDSCs) represented by abundant interleukin (IL)-1ß generation, and thereby further amplifying Th1 response. Discussion: Our finding emphasized the key role of early-phase IFNγ abundance post cryo-thermal therapy, which could be a biomarker for better prognosis after cryo-thermal therapy.

ATST-Net: A method to identify early symptoms in the upper and lower extremities of PD.

Bradykinesia, a core symptom of motor disorders in Parkinson's disease (PD), is a major criterion for screening early PD patients in clinical practice. Currently, many studies have proposed automatic assessment schemes for bradykinesia in PD. However, existing schemes suffer from problems such as dependence on professional equipment, single evaluation tasks, difficulty in obtaining samples and low accuracy. This paper proposes a manual feature extraction- and neural network-based method to evaluate bradykinesia, effectively solving the problem of a small sample size. This method can automatically assess finger tapping (FT), hand movement (HM), toe tapping (TT) and bilateral foot sensitivity tasks (LA) through a unified model. Data were obtained from 120 individuals, including 93 patients with Parkinson's disease and 27 age- and sex-matched normal controls (NCs). Manual feature extraction and Attention Time Series Two-stream Networks (ATST-Net) were used for classification. Accuracy rates of 0.844, 0.819, 0.728, and 0.768 were achieved for FT, HM, TT, and LA, respectively. To our knowledge, this study is the first to simultaneously evaluate the upper and lower limbs using a unified model that has significant advantages in both model training and transfer learning.

Natural Killer Cells Reprogram Myeloid-Derived Suppressor Cells to Induce TNF-α Release via NKG2D-Ligand Interaction after Cryo-Thermal Therapy.

In our previous studies, a novel cryothermal therapy (CTT) was developed to induce systemic long-term anti-tumor immunity. Natural killer (NK) cells were found to play an important role in CTT-induced long-term immune-mediated tumor control at the late stage after CTT, but the underlying mechanism is unclear. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that have potent immunosuppressive effects on T cells and weaken the long-term benefits of immunotherapy. Consequently, overcoming MDSC immunosuppression is essential for maintaining the long-term efficacy of immunotherapy. In this study, we revealed that NK cells considerably diminish MDSC accumulation at the late stage after CTT, boost T cell production, increase T cell activation, and promote MDSC maturation, culminating in Th1-dominant CD4+ T cell differentiation and enhancing NK and CD8+ T cell cytotoxicity. Additionally, NK cells activate ERK signaling in MDSCs through NKG2D-ligand interaction to increase the activity of tumor necrosis factor (TNF)-α converting enzyme (TACE)-cleaved membrane TNF-α. Furthermore, Increased TACE activity releases more soluble TNF-α from MDSCs to promote MDSC maturation. In our studies, we propose a novel mechanism by which NK cells can overcome MDSC-induced immunosuppression and maintain CTT-induced persistent anti-tumor immunity, providing a prospective therapeutic option to improve the performance of cancer immunotherapy.

All-Inorganic Halide Perovskites Boost High-Ranged Figure-of-Merit in Bi0.4Sb1.6Te3 for Thermoelectric Cooling and Low-Grade Heat Recovery.

The all-inorganic halide perovskite CsPbX3 (X = Cl, Br, or I) offers various advantages, such as tunable electronic structure and high carrier mobility. However, its potential application in thermoelectric materials remains underexplored. In this study, we propose a simple yet effective method to synthesize a CsPbX3/Bi0.4Sb1.6Te3 (BST) nanocomposite by sintering a uniformly mixed raw powder. The intrinsic excitation of the BST system is suppressed by exploiting the rich phase structure and tunable electrical transport properties of CsPbX3, and the thermoelectric properties were synergistically optimized. Notably, for CsPbI3, its phase-transition-induced dislocation arrays together with low group velocities drastically reduce thermal conductivity. As a result, the composite achieves an ultrahigh average figure-of-merit (ZT) of 1.4 from 298 to 523 K. The two-pair TE module demonstrates a superior conversion efficiency of 7.3%. This study expands the potential applications of inorganic halide perovskites, into thermoelectrics.

Janus layers and electronic structure of 1T-(TiSeS)2.

TiS2-TiSe2 is one of the most studied titanium based solid solution systems. However, so far, all research on it has only focused on its disordered phase. Here, we systematically investigate its ordered phases. Using a structure search method based on the particle swarm optimization (CALYPSO) algorithm, we identify TiSeS-156 and discover a new structure (1T-(TiSeS)2). Based on first principles theory, their phonon spectra, formation energy, mechanical, electronic, thermal, and optical properties, as well as chemical bond analysis and synthetic pathways, have been investigated. The primitive cell of TiSeS-156 has three atoms and has a space group of P3m1 (no. 156). 1T-(TiSeS)2 has six atoms and has P3̄m1 symmetry (no. 164). TiSeS-156 and 1T-(TiSeS)2 are constructed by stacking the S-Ti-Se Janus layer materials. TiSeS-156 and 1T-(TiSeS)2 are narrow-gap semiconductors. The localized nature of the Ti(3d) states of TiSeS-156 and 1T-(TiSeS)2 leads to their semiconductor properties. 1T-(TiSeS)2 and TiSeS-156 have very similar mechanical, electronic, thermal, and optical properties of 1T-TiS2 and 1T-TiSe2, and are members of the 2D hexagonal lattice transition metal dichalcogenide layered material family. However, compared with 1T-TiS2 and 1T-TiSe2, TiSeS-156 and 1T-(TiSeS)2 have a wider range of potential applications, such as photovoltaic devices and photocatalysis, due to their S-Ti-Se Janus layer structure. They also provide a pathway for the preparation of Janus TiSeS monolayer and multi-layer materials. Moreover, our findings provide crucial insights for understanding the rich and complex crystal structures of the TiS2-TiSe2 system, which have broad implications for further exploration of this class of promising materials.

Infant gut DNA bacteriophage strain persistence during the first 3 years of life.

Bacteriophages are key components of gut microbiomes, yet the phage colonization process in the infant gut remains uncertain. Here, we establish a large phage sequence database and use strain-resolved analyses to investigate DNA phage succession in infants throughout the first 3 years of life. Analysis of 819 fecal metagenomes collected from 28 full-term and 24 preterm infants and their mothers revealed that early-life phageome richness increases over time and reaches adult-like complexity by age 3. Approximately 9% of early phage colonizers, which are mostly maternally transmitted and infect Bacteroides, persist for 3 years and are more prevalent in full-term than in preterm infants. Although rare, phages with stop codon reassignment are more likely to persist than non-recoded phages and generally display an increase in in-frame reassigned stop codons over 3 years. Overall, maternal seeding, stop codon reassignment, host CRISPR-Cas locus prevalence, and diverse phage populations contribute to stable viral colonization.

Infant microbiome cultivation and metagenomic analysis reveal Bifidobacterium 2'-fucosyllactose utilization can be facilitated by coexisting species.

The early-life gut microbiome development has long-term health impacts and can be influenced by factors such as infant diet. Human milk oligosaccharides (HMOs), an essential component of breast milk that can only be metabolized by some beneficial gut microorganisms, ensure proper gut microbiome establishment and infant development. However, how HMOs are metabolized by gut microbiomes is not fully elucidated. Isolate studies have revealed the genetic basis for HMO metabolism, but they exclude the possibility of HMO assimilation via synergistic interactions involving multiple organisms. Here, we investigate microbiome responses to 2'-fucosyllactose (2'FL), a prevalent HMO and a common infant formula additive, by establishing individualized microbiomes using fecal samples from three infants as the inocula. Bifidobacterium breve, a prominent member of infant microbiomes, typically cannot metabolize 2'FL. Using metagenomic data, we predict that extracellular fucosidases encoded by co-existing members such as Ruminococcus gnavus initiate 2'FL breakdown, thus critical for B. breve's growth. Using both targeted co-cultures and by supplementation of R. gnavus into one microbiome, we show that R. gnavus can promote extensive growth of B. breve through the release of lactose from 2'FL. Overall, microbiome cultivation combined with genome-resolved metagenomics demonstrates that HMO utilization can vary with an individual's microbiome.

Development of a Skeletal Mechanism of a Four-Component Diesel Surrogate Fuel Using the Decoupling Method.

Alkylcyclohexanes with a long alkyl chain account for more than 30% of diesel fuel but seldom used in the oxidation mechanism of diesel surrogate fuel due to the lack of a reduced skeletal mechanism. Hence, a four-component diesel surrogate fuel was developed with n-butylcyclohexane (NBCH) as the representative of alkylcyclohexanes with a long alkyl chain in real diesel. The surrogate fuel can reproduce the physicochemical characteristics of real diesel, especially the distillation range. The reduced mechanism of NBCH was developed, and the skeletal mechanism of the surrogate fuel was formulated including 80 species and 251 reactions based on the decoupling method. The mechanism was validated under a wide range of conditions with the experimental results of ignition delay time (IDT), laminar flame speed, and species concentrations of both pure components and diesel. The accuracy of the mechanism on the spray and ignition performance was further validated against the experimental data obtained in a constant volume combustion chamber system. The calculated results showed a satisfactory agreement, in which the maximum error of flame lift-off length is 7.82 mm and that of IDTs is 0.16 ms. It was proven that the mechanism is suitable to reproduce the physicochemical properties of diesel and further predict the diesel spray and ignition performance.

General Syntheses of High-Performance Thermoelectric Nanostructured Solids without Post-Synthetic Ligand Stripping.

Ligand-assisted wet chemical synthesis is a versatile methodology to produce controllable nanocrystals (NCs). The post-treatment of ligands is significant for the performance of functional devices. Herein, a method that retains ligands of colloidal-synthesized nanomaterials to produce thermoelectric nanomaterials is proposed, which differs from the conventional methods that strip ligands using multistep cumbersome processes. The ligand-retention method can control the size and dispersity of nanocrystals during the consolidation of the NCs into dense pellets, in which retained ligands are transformed into organic carbon within the inorganic matrices, establishing clear organic-inorganic interfaces. Characterizations of the nonstripped and stripped samples confirm that this strategy can affect electric transport slightly but reduce the thermal conductivity largely. As a result, the materials (e.g., SnSe, Cu2-xS, AgBiSe2, and Cu2ZnSnSe4) with ligands retained achieve higher peak zT and better mechanical properties. This method can be applied to other colloidal thermoelectric NCs and functional materials.

Soluble epoxide hydrolase inhibitor promotes the healing of oral ulcers.

OBJECTIVE: Oral ulcers are a lesion in the oral mucosa that impacts chewing or drinking. Epoxyeicosatrienoic Acids (EETs) have enhanced angiogenic, regenerative, anti-inflammatory, and analgesic effects. The present study aims to evaluate the effects of 1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea (TPPU), a soluble epoxide hydrolase inhibitor for increasing EETs level, on the healing of oral ulcers. METHODS: The chemically-induced oral ulcers were established in Sprague Dawley rats. The ulcer area was treated with TPPU to evaluate the healing time and pain threshold of ulcers. The expression of angiogenesis and cell proliferation-related protein in the ulcer area was detected using immunohistochemical staining. The effects of TPPU on migration and angiogenesis capability were measured with scratch assay and tube formation. RESULTS: Compared with the control group, TPPU promoted wound healing of oral ulcers with a shorter healing time, and raised pain thresholds. Immunohistochemical staining showed that TPPU increased the expression of angiogenesis and cell proliferation-related protein with reduced inflammatory cell infiltration in the ulcer area. TPPU enhanced cell migration and tube-forming potential in vitro. CONCLUSIONS: The present results support the potential of TPPU with multiple biological effects for the treatment of oral ulcers by targeting soluble epoxide hydrolase.

Combining Cryo-Thermal Therapy with Anti-IL-6 Treatment Promoted the Maturation of MDSCs to Induce Long-Term Survival in a Mouse Model of Breast Cancer.

Immunosuppression plays a significant role in tumor recurrence and metastasis, ultimately causing poor survival outcomes. Overcoming immunosuppression and stimulating durable antitumor immunity are essential for tumor treatment. In our previous study, a novel cryo-thermal therapy involving liquid nitrogen freezing and radiofrequency heating could reduce the proportion of Myeloid-derived suppressor cells (MDSCs), but the remaining MDSCs produced IL-6 by the NF-κB pathway, resulting in an impaired therapeutic effect. Therefore, here we combined cryo-thermal therapy with anti-IL-6 treatment to target the MDSC-dominant immunosuppressive environment, thereby optimizing the efficacy of cryo-thermal therapy. We found that combinational treatment significantly increased the long-term survival rate of breast cancer-bearing mice. Mechanistic investigation revealed that combination therapy was capable of reducing the proportion of MDSCs in the spleen and blood while promoting their maturation, which resulted in increased Th1-dominant CD4+ T-cell differentiation and enhancement of CD8+ T-mediated tumor killing. In addition, CD4+ Th1 cells promoted mature MDSCs to produce IL-7 through IFN-γ, indirectly contributing to the maintenance of Th1-dominant antitumor immunity in a positive feedback loop. Our work suggests an attractive immunotherapeutic strategy targeting the MDSC-dominant immunosuppressive environment, which would offer exciting opportunities for highly immunosuppressive and unresectable tumors in the clinic.

Using strain-resolved analysis to identify contamination in metagenomics data.

BACKGROUND: Metagenomics analyses can be negatively impacted by DNA contamination. While external sources of contamination such as DNA extraction kits have been widely reported and investigated, contamination originating within the study itself remains underreported. RESULTS: Here, we applied high-resolution strain-resolved analyses to identify contamination in two large-scale clinical metagenomics datasets. By mapping strain sharing to DNA extraction plates, we identified well-to-well contamination in both negative controls and biological samples in one dataset. Such contamination is more likely to occur among samples that are on the same or adjacent columns or rows of the extraction plate than samples that are far apart. Our strain-resolved workflow also reveals the presence of externally derived contamination, primarily in the other dataset. Overall, in both datasets, contamination is more significant in samples with lower biomass. CONCLUSION: Our work demonstrates that genome-resolved strain tracking, with its essentially genome-wide nucleotide-level resolution, can be used to detect contamination in sequencing-based microbiome studies. Our results underscore the value of strain-specific methods to detect contamination and the critical importance of looking for contamination beyond negative and positive controls. Video Abstract.

Contamination source modeling with SCRuB improves cancer phenotype prediction from microbiome data.

Sequencing-based approaches for the analysis of microbial communities are susceptible to contamination, which could mask biological signals or generate artifactual ones. Methods for in silico decontamination using controls are routinely used, but do not make optimal use of information shared across samples and cannot handle taxa that only partially originate in contamination or leakage of biological material into controls. Here we present Source tracking for Contamination Removal in microBiomes (SCRuB), a probabilistic in silico decontamination method that incorporates shared information across multiple samples and controls to precisely identify and remove contamination. We validate the accuracy of SCRuB in multiple data-driven simulations and experiments, including induced contamination, and demonstrate that it outperforms state-of-the-art methods by an average of 15-20 times. We showcase the robustness of SCRuB across multiple ecosystems, data types and sequencing depths. Demonstrating its applicability to microbiome research, SCRuB facilitates improved predictions of host phenotypes, most notably the prediction of treatment response in melanoma patients using decontaminated tumor microbiome data.

Risk factors for femoral overgrowth after femoral shortening osteotomy in children with developmental dysplasia of the hip.

Objective: Developmental dysplasia of the hip (DDH) refers to a series of deformity of acetabulum and proximal femur and abnormal relationship between them, it represents the most common hip disease in children. Overgrowth and limb length discrepancy (LLD) was common complication in children undergoing femoral shortening osteotomy. Therefore, the purpose of this study was to explore the risk factors of overgrowth after femoral shortening osteotomy in children with DDH. Methods: We included 52 children with unilateral DDH who underwent pelvic osteotomy combined with femoral shortening osteotomy between January 2016 and April 2018, including seven males (six left and one right hip) and 45 females (33 left and 12 right hips) with an average age of 5.00 ± 2.48 years, and an average follow-up time of 45.85 ± 6.22 months. The amount of overgrowth and limb length discrepancies (LLDs) were calculated. The risk factors of femoral overgrowth ≥1 cm and LLD ≥ 1 cm were analyzed. Results: There were statistical differences in age (p < 0.001) and operation duration (p = 0.010) between the two groups with femoral overgrowth <1 cm and ≥1 cm. There was a statistical difference in operation duration (p < 0.001) between the two groups. Age (p < 0.001) was an independent influencing factor of femoral overgrowth in children with unilateral DDH after pelvic osteotomy and femoral shortening osteotomy, and a risk factor (p = 0.008) of LLD in these children. Conclusion: The overgrowth and LLD of children with developmental dislocation of hip after pelvic osteotomy and femoral shortening osteotomy are significantly related to age. There was no significant difference between different pelvic osteotomies for femoral overgrowth in children. Therefore, surgeons should consider the possibility of LLD after femoral shortening osteotomy in children of a young age.

Risk factors for postoperative avascular necrosis of the femoral head in children with developmental dysplasia of the hip.

Aim: To investigate factors associated with postoperative avascular necrosis of the femoral head (ANFH) in developmental dysplasia of the hip (DDH) patients, and if or how the associations varied among different subpopulations of age, sex and surgical method. Methods: Patients with DDH were enrolled between October 31, 2016 and July 15, 2020 in this retrospective cohort study. The average follow-up time was 21.42 ± 10.02 months. The outcome was postoperative ANFH. The main study variables were the DDH classification, Tonnis grade, International Hip Dysplasia Institute (IHDI) classification, and preoperative traction. Multivariate logistic regression was employed to assess the associations between main study variables and postoperative ANFH. Subgroup analysis was carried out based on age at reduction, sex and surgical method. Odds ratio (ORs) and 95% confidence intervals (CIs) were calculated. Results: A total of 427 children with DDH were included, with 92 (21.55%) in the ANFH group, and 335 (78.45%) in the non-ANFH group. DDH classification was positively correlated with the risk of postoperative ANFH (OR = 4.14, 95% CI, 1.08-15.77, P = 0.038). Children with preoperative traction had a significantly decreased risk of postoperative ANFH in contrast to those without preoperative traction (OR = 0.37, 95% CI, 0.22-0.61, P < 0.001). Children aged 1-3 years who received preoperative traction has a significantly reduced risk of postoperative ANFH than those who did not receive preoperative traction (OR = 0.28, 95% CI, 0.15-0.51, P < 0.001). For children aged >3 years, positive association was found between DDH classification and the risk of postoperative ANFH (OR = 3.75, 95% CI, 1.51-9.31, P = 0.004). Girls with a more severe DDH type had a significantly higher risk of postoperative ANFH (OR = 3.80, 95% CI, 1.80-8.02, P < 0.001). Receiving preoperative traction was associated with a significantly decreased risk of postoperative ANFH in girls (OR = 0.37, 95% CI, 0.22-0.61, P < 0.001). For children undergoing open reduction, DDH classification was positively associated with the risk of postoperative ANFH (OR = 3.01, 95% CI, 1.65-5.50, P < 0.001), and those with preoperative traction had a lower risk of postoperative ANFH compared with those without preoperative traction (OR = 0.35, 95% CI, 0.20-0.61, P < 0.001). Conclusion: DDH classification and preoperative traction were associated with the risk of postoperative ANFH, and these associations varied across DDH patients with different ages, sexes and surgical methods.

Application of optimized convolutional neural networks for early aided diagnosis of essential tremor: Automatic handwriting recognition and feature analysis.

Essential tremor (ET) is one of the most common neurological disorders, and its mainly clinical symptoms, including patient hand's kinetic tremor, dystonia, ataxia, etc., would influence the daily life of patients inordinately. Current ET diagnosis highly replies on the clinical evaluation and neurological examination, so the objective measurement indicators are particularly important in the auxiliary diagnosis of ET. In this research, the Archimedes spiral line freehand sketching samples without template assistance is collected and the Convolutional Neural Network (CNN) model of optimized structure is adopted to fully analyze the tremor, spacing of turns, shape, etc. shown in the handwriting samples of patients with ET, including the following main process: characteristics extraction, model visualization and subregional relevance evaluation. Dropout is used as a regularization technique in the network structure. The test group consisted of 50 patients with confirmed ET and the control group consisted of 40 healthy individuals. The main research objectives of this paper comprise two points: on the one hand, to achieve effective automatic classification of patients with ET and healthy controls using a scheme combining deep learning and simple hand mapping for the purpose of primary disease screening; on the other hand, to design sub-regional automatic classification experiments to demonstrate that Archimedean spiral hand drawings of patients with ET do have distinct local features, and to lay the experimental foundation for future hand drawing-based automatic aid for the identification of a variety of neurodegenerative diseases. Our model's average accuracy rate in test set reaches 89.3%, and average AUC is 0.972, with favorable stability and generalization performance. Besides, subregional characteristics recognition proofs that the spiral line samples of most of the patients with ET show more category-related characteristics in the local area of upper right, which provides evidences and theory update for predecessors' medical research.

Ascorbic acid-mediated reactive oxygen species homeostasis modulates the switch from tapetal cell division to cell differentiation in Arabidopsis.

The major antioxidant L-ascorbic acid (AsA) plays important roles in plant growth, development, and stress responses. However, the importance of AsA concentration and the regulation of AsA metabolism in plant reproduction remain unclear. In Arabidopsis (Arabidopsis thaliana) anthers, the tapetum monolayer undergoes cell differentiation to support pollen development. Here, we report that a transcription factor, DEFECTIVE IN TAPETAL DEVELOPMENT AND FUNCTION 1 (TDF1), inhibits tapetal cell division leading to cell differentiation. We identified SKEWED5-SIMILAR 18 (SKS18) as a downstream target of TDF1. Enzymatic assays showed that SKS18, annotated as a multicopper oxidase-like protein, has ascorbate oxidase activity, leading to AsA oxidation. We also show that VITAMIN C DEFECTIVE1 (VTC1), an AsA biosynthetic enzyme, is negatively controlled by TDF1 to maintain proper AsA contents. Consistently, either knockout of SKS18 or VTC1 overexpression raised AsA concentrations, resulting in extra tapetal cells, while SKS18 overexpression in tdf1 or the vtc1-3 tdf1 double mutant mitigated their defective tapetum. We observed that high AsA concentrations caused lower accumulation of reactive oxygen species (ROS) in tapetal cells. Overexpression of ROS scavenging genes in tapetum restored excess cell divisions. Thus, our findings demonstrate that TDF1-regulated AsA balances cell division and cell differentiation in the tapetum through governing ROS homeostasis.

Comparison of Surgical Treatment Outcomes of Pediatric Medial Epicondyle Fractures With and Without Elbow Dislocation.

PURPOSE: The aim of this study was to compare surgical treatment outcomes of pediatric medial epicondyle fractures with and without elbow dislocation. METHODS: A total of 139 patients (75 boys and 64 girls; mean ± SD age, 9.6 ± 3.3 years) who received surgical treatment for medial epicondyle fractures at the Children's Hospital of Nanjing Medical University from January 2012 to December 2018 were included in our study. There were 99 cases that had a medial epicondyle fracture alone (group A) and 40 cases had a concomitant elbow dislocation (group B). Pain, ulnar nerve palsy, and stability of the elbow joint were recorded. Robert's criteria was used to assess elbow function. RESULTS: The prevalence of ulnar nerve palsy was lower in group A compared to group B, both before and after surgery. More patients underwent ulnar nerve transposition in group B than in group A. The incidence of elbow valgus instability was higher in group B than in group A. At the final follow-up, all patients had achieved good radiographic restoration of the elbow joint. Clinical outcomes in group A, according to Robert's criteria, were better than those in group B. CONCLUSIONS: Elbow dislocation was associated with poorer functional outcomes following surgical treatment of medial epicondyle fractures in children. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.