Preparation, characterisation, and pharmacodynamic study of myricetin pH-sensitive liposomes.

AIMS: Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity. METHODS: The MYR pH-sensitive liposomes (MYR liposomes) were prepared using thin film dispersion method, and assessed by particle size (PS), polydispersed index (PDI), zeta potential (ZP), encapsulation efficiency, drug loading, and in vitro release rate. Pharmacokinetics and anti-hyperuricemic activities were also evaluated. RESULTS: The PS, PDI, ZP, encapsulation efficiency, and drug loading of MYR liposomes were 184.34 ± 1.05 nm, 0.215 ± 0.005, -38.46 ± 0.30 mV, 83.42 ± 1.07%w/w, and 6.20 ± 0.31%w/w, respectively. The release rate of MYR liposomes was higher than free MYR, wherein the cumulative value responded to pH. Besides, the Cmax of MYR liposomes was 4.92 ± 0.20 µg/mL. The level of uric acid in the M-L-H group (200 mg/kg) was reduced by 54.74%w/v in comparison with the model group. CONCLUSION: MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR.

High-order mixed vortex beam generator.

A mixed multi-order vortex beam generator, based on a Reuleaux triangle core fiber chiral grating (RCFG), is proposed. The triangular perturbation and off-axis effects induced by core shape, result in the simultaneous coupling of the core mode with the 1st- and 3rd-order vortex modes. To the best of our knowledge, this is the first time that a mixed vortex beam was generated in a single chiral fiber. The phase matching conditions required for the co-coupling of multi-order vortex beams are analyzed based on the coupled mode theory. Additionally, a cladding shrinkage method is proposed to flexibly adjust the co-coupling wavelength. We found that the key to co-coupling lies in balancing the different order perturbations of the Reuleaux triangle core fiber (RTF). The proposed method offers a new approach for the design of mixed multi-order vortex beam generators, with potential applications in fields such as fiber OAM communications, optical tweezers, and super-resolution imaging.

Identification of a novel GRIN2D variant in a neonate with intractable epileptic encephalopathy-a case report.

BACKGROUND: N-methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. The functional NMDA receptors are heterotetramers consisting mainly of two GluN1 and two GluN2 subunits. GluN2 is encoded by the GRIN2D gene. A few case series have shown that GRIN2D variants are linked to developmental and epileptic encephalopathy. In this article, we report a novel GRIN2D variant, namely c.2021C > A (p.T674K) in a neonate with intractable epileptic encephalopathy. CASE PRESENTATION: A 12-day-old boy who had stiffness of the lower and upper extremities since birth was transferred from a local hospital to our department. On admission, the patient presented with head tilting backwards, staring, apnea and hypertonia of limbs. Video electroencephalogram showed continuous, generalized or multi-focal spike-wave and spike-and-slow wave discharges and hypsarrhythmia. A treatment regimen composed of phenobarbital, midazolam, levetiracetam and clonazepam was administered, which however led to only partial control of the seizure. Whole-exome sequencing identified c.2021C > A (p.T674K) in GRIN2D in the patient while such a mutation was not detected in the parents. The patient was hospitalized for 1 month and died of sudden cardio-respiratory arrest 2 weeks after discharge. CONCLUSIONS: A novel variant of GRIN2D was identified in a neonate with epileptic encephalopathy. Epilepsy associated with this GRIN2D mutation is refractory to conventional anti-epileptic medications.

Disruption of gene SPL35, encoding a novel CUE domain-containing protein, leads to cell death and enhanced disease response in rice.

Lesion mimic mutants that exhibit spontaneous hypersensitive response (HR)-like necrotic lesions are ideal experimental systems for elucidating molecular mechanisms involved in plant cell death and defence responses. Here we report identification of a rice lesion mimic mutant, spotted leaf 35 (spl35), and cloning of the causal gene by TAIL-PCR strategy. spl35 exhibited decreased chlorophyll content, higher accumulation of H2 O2 , up-regulated expression of defence-related marker genes, and enhanced resistance to both fungal and bacterial pathogens of rice. The SPL35 gene encodes a novel CUE (coupling of ubiquitin conjugation to ER degradation) domain-containing protein that is predominantly localized in cytosol, ER and unknown punctate compartment(s). SPL35 is constitutively expressed in all organs, and both overexpression and knockdown of SPL35 cause the lesion mimic phenotype. SPL35 directly interacts with the E2 protein OsUBC5a and the coatomer subunit delta proteins Delta-COP1 and Delta-COP2 through the CUE domain, and down-regulation of these interacting proteins also cause development of HR-like lesions resembling those in spl35 and activation of defence responses, indicating that SPL35 may be involved in the ubiquitination and vesicular trafficking pathways. Our findings provide insight into a role of SPL35 in regulating cell death and defence response in plants.

Studies on chemical constituents of Ophiopogon japonicus.

Two new and six known steroidal glucosides were isolated from the tuber of Ophiopogon japonicus. The new steroidal glucosides were established as (20R,25R)-26-O-ß-d-glucopyranosyl-3ß,26-dihydroxycholest-5-en-16,22-dioxo-3-O-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-glucopyranoside (1) and 26-O-ß-d-glucopyranosyl-(25R)-furost-5-en-3ß,14α,17α,22α,26-pentaol-3-O-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-glucopyranoside (3) on the basis of spectroscopic data as well as chemical evidence.

Combined replantation of the posterior arch of the atlas and bilateral axial lamina in the treatment of intradural schwannoma: a case report.

Background: Laminotomy and laminar replantation have emerged as novel treatment modalities for intraspinal tumors, aiming to minimize postoperative complications and retain spinal mobility. However, existing research predominantly emphasizes their application in the thoracolumbar spine. The unique anatomy of the atlantoaxial segments necessitates surgical techniques that differ from those used in other spinal regions, and the clinical effect of such procedure remains unknown. Case presentation: A 61-year-old male patient with intradural schwannoma at the atlantoaxial level was operated on. The patient underwent posterior laminectomy, as well as a combined replantation of the posterior arch of the atlas and bilateral axial laminae. Postoperatively, the patient experienced significant neurological improvement, with no deformities or instability on the radiological assessments during the follow-up. Conclusion: Laminotomy with combined replantation of the posterior arch of the atlas and bilateral axial lamina emerges as an effective approach for managing intraspinal tumors at the atlantoaxial level. This technique not only offers ample operating space but also restores the stability of the spinal canal. Moreover, it preserves the mobility of the atlantoaxial segment, minimizes impact on adjacent segments, and mitigates the formation of postoperative fibrosis.

Recent insights into anthocyanin biosynthesis, gene involvement, distribution regulation, and domestication process in rice (Oryza sativa L.).

Anthocyanins are water-soluble natural pigments found broadly in plants. As members of the flavonoid family, they are widely distributed in various tissues and organs, including roots, leaves, and flowers, responsible for purple, red, blue, and orange colors. Beyond pigmentation, anthocyanins play a role in plant propagation, stress response, defense mechanisms, and human health benefits. Anthocyanin biosynthesis involves a series of conserved enzymes encoded by structural genes regulated by various transcription factors. In rice, anthocyanin-mediated pigmentation serves as an important morphological marker for varietal identification and purification, a critical nutrient source, and a key trait in studying rice domestication. Anthocyanin biosynthesis in rice is regulated by a ternary conserved MBW transcriptional complexes comprising MYB transcription factors (TFs), basic-helix-loop-helix (bHLH) TFs, and WD40 repeat protein, which activate the expression of structure genes. Wild rice (Oryza rufipogon) commonly has purple hull, purple stigma, purple apiculus, purple leaf, and red pericarp due to the accumulations of anthocyanin or proanthocyanin. However, most cultivated rice (Oryza sativa) varieties lose the anthocyanin phenotypes due to the function variations of some regulators including OsC1, OsRb, and Rc and the structure gene OsDFR. Over the past decades, significant progress has been made in understanding the molecular and genetic mechanisms of anthocyanin biosynthesis. This review summarizes research progress in rice anthocyanin biosynthetic pathways, genes involvements, distribution regulations, and domestication processes. Furthermore, it discusses future prospects for anthocyanin biosynthesis research in rice, aiming to provide a theoretical foundation for future investigations and applications, and to assist in breeding new rice varieties with organ-targeted anthocyanin deposition.

PPR proteins in plants: roles, mechanisms, and prospects for rice research.

Pentatricopeptide repeat (PPR) proteins constitute one of the largest protein families in land plants, with over 300 members in various species. Nearly all PPR proteins are nuclear-encoded and targeted to the chloroplast and mitochondria, modulating organellar gene expression by participating in RNA metabolism, including mRNA stability, RNA editing, RNA splicing, and translation initiation. Organelle RNA metabolism significantly influences chloroplast and mitochondria functions, impacting plant photosynthesis, respiration, and environmental responses. Over the past decades, PPR proteins have emerged as a research focus in molecular biology due to their diverse roles throughout plant life. This review summarizes recent progress in understanding the roles and molecular mechanisms of PPR proteins, emphasizing their functions in fertility, abiotic and biotic stress, grain quality, and chloroplast development in rice. Furthermore, we discuss prospects for PPR family research in rice, aiming to provide a theoretical foundation for future investigations and applications.

Intralesional curettage and surgical adjuvants in the treatment of giant cell tumor of bone: meta-analysis and systematic review.

BACKGROUND: The ideal treatment for giant cell tumor of bone (GCTB) is still controversial. Various surgical adjuvants have been introduced following intralesional curettage to improve local control rates. However, findings from relevant studies are inconsistent, and no consensus has been reached. The purpose of this study is to determine what intraoperative adjuvant is effective in decreasing the recurrence of GCTB. METHODS: We performed a systematic review and meta-analysis of articles published in the PubMed and Embase electronic databases which assessed the recurrence rate of GCTB following intralesional curettage with or without various surgical adjuvants. Two authors independently evaluated all publications. Meta-analysis was performed with Stata/MP (Version 17.0, StataCorp LLC, TX, USA) and Review Manager (RevMan, Version 5.4.1, The Cochrane Collaboration, 2020). Pooled risk ratio (RR) was used for analysis, with P values less than 0.05 considered statistically significant. RESULTS: Twenty-four studies involving 2,579 patients were included in this analysis. The overall recurrence rates for patients treated with or without high-speed burring (HSB) are 11.9% (26/218) and 47.7% (92/193), respectively. The pooled RR for tumor recurrence is 0.33 (95% CI: 0.22 to 0.49, P<0.001). In the meanwhile, the overall recurrence rates for patients treated with or without chemical adjuvants are 23.5% (77/328) and 26.1% (73/280), respectively, with a pooled RR of 0.84 (95% CI: 0.63 to 1.10, P=0.89). Additionally, the overall recurrence rates for patients treated with or without polymethyl methacrylate (PMMA) are 20.4% (205/1,006) and 33.4% (314/939), respectively, with a pooled RR of 0.59 (95% CI: 0.50 to 0.69, P<0.001). CONCLUSIONS: Intraoperative application of HSB or PMMA has an additional antitumor effect, while the use of phenol or H2O2 fails to make any significant difference (PROSPERO: CRD42022344262).

Biomedical analysis of four fixation systems in treatment of type II traumatic spondylolisthesis of the axis: a finite element analysis.

This study aimed to compare the properties and safety of self-designed plates in type II traumatic spondylolisthesis of the axis with those of traditional devices via finite element (FE) analysis. We constructed a hangman's fracture FE model from the occipital bone (C0) level to the C3 level. Then, FE models were constructed for the following four fixation systems: an anterior cervical L-shaped plate with four vertebral screws (4-ACLP), or six screws (6-ACLP), an anterior cervical orion plate (ACOP), and a posterior fixation system. A preloaded compressive force of 50 N and a moment of 1.5 N·m were applied to each model under six working conditions. The mobility of the C2/3 segment decreased significantly in four fixation models. In the Mises stress cloud diagram, 4-ACLP showed a better stress distribution in both the bone graft and fixation system than 6-ACLP and ACOP. The resultant force of 4-ACLP was lower but higher than ACOP in axial force. Additionally, the cage in the 4-ACLP configuration experienced the highest stress in the six working conditions. Hence, this novel self-designed plate has the potential to mitigate the operational difficulties, provide sufficient stability, reduce the risk of plate or screw fractures, and improve bone fusion.

Comparison of Single or Double Titanium Mesh Cage for Anterior Reconstruction After Total En Bloc Spondylectomy for Thoracic and Lumbar Spinal Tumors.

OBJECTIVE: To compare the clinical efficacy of anterior column reconstruction using single or double titanium mesh cage (TMC) after total en bloc spondylectomy (TES) of thoracic and lumbar spinal tumors. METHODS: A retrospective cohort study was performed involving 39 patients with thoracic or lumbar spinal tumors. All patients underwent TES, followed by anterior reconstruction and screw-rod instrumentation via a posterior-only procedure. Twenty-two patients in group A were treated with a single TMC to reconstruct the anterior column, whereas 17 patients in group B were reconstructed with double TMCs. RESULTS: The overall follow-up is 20.5 ± 4.6 months. There is no significant difference between the 2 groups regarding age, sex, body mass index, tumor location, operative time, and intraoperative blood loss. The time for TMC placement was significantly shortened in the double TMCs group (5.2 ± 1.3 minutes vs. 15.6 ± 3.3 minutes, p = 0.004). Additionally, postoperative neural complications were significantly reduced with double TMCs (5/22 vs. 0/17, p = 0.046). The kyphotic Cobb angle and mean intervertebral height were significantly corrected in both groups (p ≤ 0.001), without obvious loss of correction at the last follow-up in either group. The bone fusion rates for single TMC and double TMCs were 77.3% and 76.5%, respectively. CONCLUSION: Using 2 smaller TMCs instead of a single large one eases the placement of TMC by shortening the time and avoiding nerve impingement. Anterior column reconstruction with double TMC is a clinically feasible, and safe alternative following TES for thoracic and lumbar tumors.

GhSWEET42 Regulates Flowering Time under Long-Day Conditions in Arabidopsis thaliana.

Flowering in plants is pivotal for initiating and advancing reproductive processes, impacting regional adaptation and crop yield. Despite numerous cloned and identified flowering time genes, research in cotton remains sparse. This study identified GhSWEET42 as a key determinant of the flowering time in cotton, demonstrating that its heterologous expression in Arabidopsis accelerated flowering under LD conditions compared to WT. Transgenic plants exhibited upregulated expression of the flowering inducers AtFT, AtSOC1, AtGI, and AtFKF1, alongside downregulated expression of the repressors AtTSF, AtFLC, and AtRGL2, correlating with the earlier flowering phenotype. GhSWEET42 showed a constitutive expression pattern, with elevated levels in the leaves, petals, and flower buds, and was notably higher in early-maturing cotton varieties. Subcellular localization assays confirmed GhSWEET42's presence on the cell membrane. Transcriptome analysis between WT and GhSWEET42-overexpressing Arabidopsis plants revealed 2393 differentially expressed genes (DEGs), spanning 221 biological processes, 93 molecular functions, and 37 cellular components according to Gene Ontology (GO) enrichment analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis categorized the DEGs into metabolism and environmental information processing. These findings enhance the understanding of GhSWEET42's function and provide a foundation for elucidating the molecular mechanisms governing flowering time regulation in cotton.

A Novel Free-hand Technique of Pedicle Screw Placement in the Lumbar Spine: Accuracy Evaluation and Preliminary Clinical Results.

OBJECTIVE: Pedicle screw implantation is the most common technique to achieve stability during spinal surgeries. Current methods for locating the entry point do not have a quantified criteria and highly rely on the surgeons' experience. Therefore, we aim to propose a quantified pedicle screw placement technique in the lumbar spine and to investigate its accuracy and safety in clinical practice. METHODS: We conducted a retrospective study involving 110 patients who received spinal surgery in our hospital from August 2018 to August 2021. All patients included had herniation of a single lumbar disc and were consistently treated with posterior discectomy, inter-body fusion, and transpedicular internal fixation. For 54 patients in the observation group, the pedicle screws were placed with our technique, which is located at 4 mm below the superior edge of the transverse process in line with the lateral margin of the superior articular process. For 56 patients in the control group, pedicle screws were placed according to the traditional crista lambdoidalis method. Comparisons were made in terms of the operation time, blood loss, time for exposure, the accuracy of placement, and postoperative complications. Furthermore, we applied our method to 64 patients with indistinguishable crista lambdoidalis and evaluated the accuracy of screw placement and clinical outcomes according to the visual analogue scale (VAS) and the Japanese Orthopaedic Association (JOA) score. RESULTS: There was no significant difference in intraoperative bleeding, accuracy of placement, and postoperative complications between our technique and the traditional crista lambdoidalis method (P > 0.05). However, the exposure time before screw placement (12.8 ± 0.3 vs. 17.4 ± 0.3, P = 0.001) and the total surgery time (97.2 ± 1.9 vs 102.3 ± 0.9, P = 0.020) were significantly shortened with our method. Additionally, in cases with indistinguishable crista lambdoidalis, our technique showed satisfying accuracy, with 97.6% screws placed in appropriate trajectory on the first attempt and all screws eventually positioned in the safe zone according to the Gertzbein-Robbins grading. All patients experienced steady improvement after surgery. CONCLUSION: Placing pedicle screws at 4 mm below the superior edge of the transverse process in line with the lateral margin of the superior articular process is a viable pedicle screw placement method. With this method, we observed a higher success rate and shorter operation time. In addition, this method can be applied in cases with indistinguishable crista lambdoidalis, and have satisfied success rate and clinical outcome.

[Prospective study on in-hospital mortality and its risk factors in very low birth weight infants requring mechanical ventilation].

OBJECTIVE: To describe the clinical features, treatments and prognosis of very low birth weight infants (VLBWIs) requring mechanical ventilation, to assess the risk factors associated with the mortality of VLBWIs, and to evaluate the significance of the scoring system based on clinical risk index for babies (CRIB) and the score for neonatal acute physiology-perinatal extension II (SNAPPE-II) for predicting mortality risk for premature infants in China. METHODS: Perinatal data were collected from 127 VLBWIs requring mechanical ventilation who were admitted to the neonatal intensive care unit (NICU) from January 2010 to October 2011. RESULTS: The enrolled infants had a mean gestational age of 31±2 weeks, a mean birth weight of 1290±170 g, a male/female ratio of 1.23∶1, and extremely low birth weight infant accounting for 6.3%. Of the 127 cases, 48.0% were administered with pulmonary surfactant (PS), and 49.6% received endotracheal intubation ventilation. The overall in-hospital mortality was 41.7%. Multivariate logistic regression revealed the following independent risk factors for mortality: low birth weight, multiple birth, cesarean section, and low PaO2/FiO2 ratio (OR = 1.611, 7.572, 4.062, and 0.133 respectively; P<0.05). SNAPPE-II and CRIB showed good performance in predicting prognosis, with areas under the ROC curve of 0.806 and 0.777 respectively. CONCLUSIONS: The overall mortality rate of VLBWIs is still relatively high. The high-risk factors for VLBWI mortality include low birth weight, multiple birth, cesarean section, and low PaO2/FiO2 ratio. The neonatal illness severity scoring system (using SNAPPE-II and CRIB) can be used to quantify illness severity in premature infants.

Investigation of key miRNAs and their target genes involved in cell apoptosis during intervertebral disc degeneration development using bioinformatics methods.

BACKGROUND: The aim of this study was to identify important miRNAs and their target genes involved in cell apoptosis in intervertebral disc degeneration (IDD) patients. METHODS: The dataset, GSE63492, was obtained from the gene expression omnibus platform. After preprocessing, the differentially expressed miRNAs (DEMs) and their target genes were identified using the Limma package and miRWalk2.0 database, respectively. The clusterProfiler package in R was used to perform functional enrichment analysis of these target genes. Subsequently, protein-protein interaction (PPI) network and subnet clusters of the coregulated genes were conducted using the STRING database and MCODE, respectively. Further, the co-regulatory network of the key miRNAs and PPI networks were visualized using Cytoscape. Finally, cell apoptosis-related pathways and the genes enriched in these pathways were identified. RESULTS: The genes targeted by the upregulated (hsa-miR-302c-5p, hsa-miR-631, hsa-let-7f-1-3p, hsa-miR-3675-3p, and hsa-miR-585-3p) and downregulated miRNAs (hsa-miR-185-5p, hsa-miR-486-5p, hsa-miR-4306, and hsa-miR-4674) were interrelated with cell apoptosis-related pathways. MAPK1 and MAPK3 were targeted by hsa-miR-185-5p, while GSK3B was targeted hsa-miR-4306, hsa-miR-486-5p, hsa-miR-185-5p, hsa-let-7f-1-3p, and hsa-miR-631. Besides, MAPK3 and VEGFA were regulated by hsa-miR-3675-3p and hsa-miR-631, respectively. CONCLUSIONS: The expression of GSK3B may be coregulated by miR-4306, miR-185-5p, miR-486-5p, hsa-let-7f-1-3p, and miR-631 and may affect IDD development. Besides, miR-185-5p and miR-3675-3p may control nucleus pulposus (NP) cell apoptosis through the MAPK signaling pathway in IDD patients. VEGFA expression may be regulated by miR-631, and help maintain NP cell survival in IDD patients. Our findings may help guide further research into the role of miRNAs in IDD progression.

Three-dimensional finite element analysis of a novel interzygapophyseal fusion device for lower cervical spine.

PURPOSE: A three-dimensional finite element model of the lower cervical spine was established to evaluate the biomechanical stability and stress distribution of the new lower cervical interzygapophyseal fusion device (IZFD) developed by ourselves under different construct. The aim of this study was to provide theoretical basis for further clinical application. METHODS: A normal fresh cadaveric specimen (male, 35 years old) was used to establish an intact three-dimensional finite element model of C3-C6. On this basis, the comparative finite element models of the lateral mass screw rod (LMSR) system and LMSR+IZFD were established. Only C4-C5 is fixed in the lateral mass. The range of motion (ROM) and stress distribution in the flexion,extension, lateral bending and rotation of the C4-C5 segment under the three constructs were analyzed. RESULTS: The ROM and stress distribution of the three-dimensional finite element model under load construct were within a reasonable range, which proved the validity and reliability of the model. The ROM and stress distribution of C4-C5 segment was significantly decreased in both LMSR and LMSR+IZFD constructs than those in the intact construct. The ROM and stresss distribution were even smaller in LMSR+IZFD construct than in LMSR construct. CONCLUSIONS: The IZFD combined with LMSR system can provide satisfactory stability for the lower cervical spine, and the IZFD can further improve the fixation effect of the LMSR system.

A New Type of Hierarchical Honeycomb in-Plane Impact Study.

Honeycomb materials have low density, high specific strength and stiffness, impact resistance, and good sound insulation effect, and therefore are widely used in aerospace, automobile, and ship field applications. In this paper, we study the in-plane impact response of a second-order hierarchical honeycomb (SHH) material. Its main structure is a hexagonal honeycomb, and the substructure is composed of an augmented double arrow honeycomb (ADAH) negative Poisson's ratio unit. Through a finite element simulation, the failure stress of an hierarchical honeycomb in two directions of quasi-static crushing and dynamic crushing was analyzed; the failure stress of the hierarchical honeycomb under different densities, different speeds, and different substructures was discussed; and the theoretical failure stress was verified. The numerical analysis results show that a second-order hierarchical honeycomb (SHH) has better collapse stress than a first-order regular hexagonal honeycomb (FHH) and an augmented double arrow honeycomb (ADAH).

MicroRNA-211-5p attenuates spinal cord injury via targeting of activating transcription factor 6.

The recovery of spinal cord injury (SCI) involves multiple factors, of which miRNAs take an important part. In this study, we evaluated the function of microRNA-211-5p (miR-211-5p) on SCI in a rat model. SCI model was established using modified Allen's weight-drop method and Basso-Bcattie-Bresnahan score was applied to assess the locomotor function. MiR-211-5p agomir was utilized to increase miR-211-5p expression and endoplasmic reticulum (ER) stress inhibitor, 4-PBA (4-phenylbutyric acid), was utilized to suppress ER stress. Neuron apoptosis and the expressions of miR-211-5p, activating transcription factor 6 (ATF6), apoptosis-related proteins, pro-inflammatory cytokines and endoplasmic reticulum stress-related proteins were detected. Dual luciferase reporter gene assay was performed to verify the binding between miR-211-5p and ATF6. The results showed that miR-211-5p directly targeted ATF6. MiR-211-5p was down-regulated and ATF6 was up-regulated in SCI rats. Both interferences with miR-211-5p agomir and 4-PBA effectively attenuated neuron apoptosis and reversed the expressions of apoptosis, inflammation and endoplasmic reticulum stress-related molecules post SCI in rats. These findings demonstrated that miR-211-5p could effectively alleviate SCI-induced neuron apoptosis and inflammation via directly targeting ATF-6 and regulating ER stress.

Novel GLDC Compound Heterozygous Variant Leading to Nonketotic Hyperglycinemia: Case Report and Literature Review.

Nonketotic hyperglycinemia (NKH) is a lethal autosomal recessive disease resulting from alterations in glycine metabolism, commonly caused by mutations in glycine decarboxylase (GLDC). The symptoms of NKH usually manifest in the neonatal period, and can be categorized into severe NKH and attenuated NKH based on the clinical outcome. To date, only a few NKH cases have been reported in China. We here report a case of a neonate with severe NKH carrying a novel compound heterozygous variant in GLDC. The patient was a 68-h-old girl who had progressive lethargy, no crying, and poor sucking ability from birth, and was therefore transferred to our department. On admission, the patient was supported by intubation and ventilation and presented with profound coma. Metabolic investigation indicated a markedly increased glycine concentration both in the plasma and cerebrospinal fluid (CSF). Symptomatic treatments were administered, but the patient's condition did not improve substantially. Whole-exome sequencing identified compound heterozygous mutations (c.1261G>C, p.G421R and c.450 C>G, p.N150K) in GLDC, which were inherited from the mother and the father, respectively. The patient was hospitalized for 8 days in our department and died 2 days after discharge. We further summarize the clinical features, genetic characteristics, administered treatment, and prognosis of previously reported Chinese NKH patients for context. Our results highlight that due to the non-specific clinical phenotypes of NKH and difficulty in obtaining CSF samples, genetic testing is a crucial tool, not only for a diagnosis but also for predicting the clinical outcome and can potentially help to determine the optimal therapeutic strategy.

Effect of combination therapy with neural stem cell transplantation and teramethylpyrazine in rats following acute spinal cord injury.

OBJECTIVES: This study was to explore the effects of teramethylpyrazine (TMP) administered in conjunction with neural stem cell transplantation on motor function, pathological lesions and the Janus kinase (JAK)2/signal transducer and activator of transcription 3 signal transduction pathway in rats following acute spinal cord injury (SCI). METHODS: Female Sprague-Dawley rats were randomly divided into sham, model, neural stem cells (NSCs) and NSCs+TMP groups. Motor function was evaluated using the Basso, Beattie, Bresnahan scale. Spinal cord neuropathies and neuron apoptosis were observed by HE and TUNEL staining. The brain-derived neurotrophic factor (BDNF), Nogo-A, JAK2 and p-JAK2 protein levels were measured by western blot analysis. RESULTS: NSCs+TMP significantly improved rat motor function, attenuated impaired spinal cords, and decreased cellular apoptosis, compared with NSCs therapy alone (P < 0.05). In addition, expression of BDNF protein was significantly higher in NSCs+TMP rats compared with other groups regardless of time postinjury (P < 0.05). The highest expression levels of Nogo-A protein were observed in the model group. The expression of p-JAK2 in the NSCs+TMP group was relatively lower than the model and NSCs groups (P < 0.05). CONCLUSIONS: In rats with SCI, NSCs+TMP effectively improved motor function and offered spinal cord protection by increasing BDNF and decreasing Nogo-A levels, as well as inhibiting the JAK2/STAT3 signal transduction pathway, suggesting that TMP could be a useful agent in NSCs transplantation in the treatment of SCI.