The bZIP transcription factor SlAREB1 regulates anthocyanin biosynthesis in response to low temperature in tomato.

Low temperature and abscisic acid (ABA) are the two main factors that induce anthocyanin synthesis; however, their potential relationships in governing anthocyanin biosynthesis in Solanum lycopersicum (tomato) seedlings remains unclear. Our study revealed the involvement of the transcription factor SlAREB1 in the low-temperature response of tomato seedlings via the ABA-dependent pathway, for a specific temperature range. The overexpression of SlAREB1 enhanced the expression of anthocyanin-related genes and the accumulation of anthocyanins, especially under low-temperature conditions, whereas silencing SlAREB1 dramatically reduced gene expression and anthocyanin accumulation. There is a direct interaction between SlAREB1 and the promoters of SlDFR and SlF3'5'H, which are structural genes that impact anthocyanin biosynthesis. SlAREB1 can regulate anthocyanins through controlling SlDFR and SlF3'5'H expression. Accordingly, SlAREB1 takes charge of regulating anthocyanin biosynthesis in tomato seedlings via the ABA-dependent pathway at low temperatures.

A case of X-Linked adrenoleukodystrophy caused by a novel mutation with singular clinical manifestation: unilateral lower limb weakness.

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene, leading to the accumulation of very long-chain fatty acids (VLCFAs) in plasma and tissues. It primarily affects the central nervous system white matter and the adrenal cortex. Clinical manifestations include myeloneuropathy, leukodystrophy, and adrenal insufficiency. Reliable methods for diagnosis include VLCFAs and genetic testing. We report the case of a 31-year-old male X-ALD patient who mainly presented with unilateral lower limb weakness. Adrenal insufficiency was not observed, and there was no evidence of peripheral nerve involvement in nerve conduction studies. MRI revealed only mild atrophy of thoracic spinal cord without other relevant abnormalities. Ultimately, Next-Generation Sequencing (NGS) and VLCFAs testing confirmed the diagnosis of X-ALD, and the NGS indicated a novel missense mutation.

Quantitative imaging for predicting hematoma expansion in intracerebral hemorrhage: A multimodel comparison.

BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.

The Efficacy and Safety of Different Targeted Drugs for the Treatment of Generalized Myasthenia Gravis: A Systematic Review and Bayesian Network Meta-analysis.

BACKGROUND: The treatment of generalized myasthenia gravis (gMG) has been transformed by the development and approval of new targeted therapies. This analysis aimed to rank and compare the new therapies for gMG using efficacy and safety data from randomized controlled trials (RCTs). METHODS: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov (up to November 2022) for RCTs of targeted drugs for gMG. We used a Bayesian random-effects network meta-analysis (NMA) model and a Markov chain Monte Carlo (MCMC) model for statistical analysis. The primary outcome was the change in quantitative myasthenia gravis score (QMGS) from baseline, while the secondary outcome was the risk ratio (RR) of adverse events (AEs) during treatment. The surface under the cumulative ranking curve (SUCRA) was used to rank these targeted drugs, with higher SUCRA values indicating better efficacy or lower likelihood of AEs. RESULTS: In total, 13 studies (872 subjects) were included in this analysis evaluating 10 targeted drugs (batoclimab, belimumab, CFZ533, eculizumab, efgartigimod, nipocalimab, rituximab, ravulizumab, rozanolixizumab, and zilucoplan). With regards to the primary outcome, batoclimab [standardized mean difference (SMD), - 1.61; 95% credible interval (CrI), - 2.78, - 0.43] significantly reduced QMGS in patients with gMG when compared with placebo and was ranked as the most efficacious drug. Ranked second and third were eculizumab (SMD, - 0.67; 95% CrI, 1.43, 0.01) and zilucoplan (SMD, - 0.54; 95% CrI, - 1.56, 0.46), respectively. Nipoclimab (SMD, - 0.02; 95% CrI, - 1.04, 1.00) had the worst efficacy and ranked last among all targeted drugs. In our study, except for batoclimab, there was no statistically significant difference in the reduction of patient QMGS for the remaining targeted agents compared with placebo. With regards to the secondary outcomes, only batoclimab (RR, 0.19; 95% CrI, 0, 0.97) led to a significant reduction in the incidence of AEs when compared with the placebo. Belimumab (RR, 0.85; 95% CrI, 0.57, 1.19), CFZ533 (RR, 0.95; 95% CrI, 0.72, 1.25), eculizumab (RR, 0.99; 95% CrI, 0.85, 1.21), and efgartigimod (RR, 0.93; 95% CrI, 0.76, 1.15) also led to a lower incidence of AEs, although these effects were not significantly different from the placebo. CONCLUSIONS: Batoclimab had the best efficacy and safety for the treatment of gMG and was ranked first out of the 10 targeted drugs included in this study. Eculizumab was ranked second, and nipocalimab had the worst efficacy. With the exception of batoclimab, the incidence of AEs for the remaining drugs was not statistically significantly different from placebo. We note, however, that wide CrIs reflect the uncertainty in this analysis owing to the small number of available studies and low numbers of study participants; moreover, batoclimab had the widest CrI of all drugs in this analysis. More well-designed studies with long-term follow-up are needed to further evaluate and compare the efficacy and safety of these drugs in the future.

Explore the mechanism of yishenjiangya formula in the treatment of senile hypertension based on multi-omics technology.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yishenjiangya formula (YSJ) is a traditional Chinese medicine (TCM) primarily composed of qi-tonifying components. This classic formula is commonly utilized to treat kidney qi deficiency in elderly patients with hypertension. According to TCM, maintaining a balance between qi and blood is crucial for stable blood pressure. Kidney qi deficiency can disrupt this balance, altering fluid shear force and, ultimately, leading to hypertension, particularly in elderly populations. Despite YSJ's efficacy in treating hypertension, its specific anti-hypertensive mechanisms remain unclear. AIM OF THE STUDY: YSJ is commonly prescribed for elderly patients with hypertension. Earlier metabolomics studies demonstrated that YSJ exerts antihypertensive effects by influencing four key pathways: linoleic acid metabolism, glycerol phospholipid metabolism, arginine and proline metabolism, and steroid hormone biosynthesis. This study aims to combine metabolomic and proteomic analyses to thoroughly understand the molecular biological mechanisms responsible for YSJ's anti-hypertensive properties. METHODS: Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) metabolomics, combined with Label-Free Quantitation (LFQ) proteomics, was employed to analyze serum samples from elderly individuals with and without hypertension pre- and post-YSJ intervention. Serum levels of candidate proteins were assessed using enzyme-linked immunosorbent assay, and receiver operating characteristic curves were used to evaluate the diagnostic performance of the target proteins. RESULTS: Eight differentially expressed metabolites and three differentially expressed proteins were identified as potential therapeutic targets of YSJ. These substances are primarily involved in unsaturated fatty acid metabolism, fluid shear stress and atherosclerosis pathway, primary bile acid biosynthesis, proline metabolism, apoptosis, and endoplasmic reticulum stress. YSJ exerts its therapeutic effects on hypertension in the elderly by modulating these pathways. CONCLUSIONS: YSJ effectively treats senile hypertension. By analyzing the correlation between therapeutic targets and pathways, YSJ's anti-hypertensive effect was achieved by inhibiting lipid peroxidation and matrix degeneration. Combining metabolomics and proteomics provides an effective method for uncovering YSJ's anti-hypertensive mechanisms.

A bibliometric analysis of endoplasmic reticulum stress and atherosclerosis.

The mechanisms underlying the occurrence and development of atherosclerosis (AS) are diverse, among which endoplasmic reticulum stress (ERS) is an important mechanism that should not be overlooked. However, up to now, there has been no bibliometric study on the relationship between ERS and AS. To understand the research progress in ERS and AS, this paper conducted a statistical analysis of publications in this field using bibliometrics. A total of 1,035 records were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, and the R package "bibliometric" were used to analyze the spatiotemporal distribution, countries, authors, institutions, journals, references, and keywords of the literature, and to present the basic information of this field through visualized maps, as well as determine the collaboration relationships among researchers in this field. This field has gradually developed and stabilized over the past 20 years. The current research hotspots in this field mainly include the relationship between ERS and AS-related cells, the mechanisms by which ERS promotes AS, related diseases, and associated cytokines, etc. Vascular calcification, endothelial dysfunction, NLRP3 inflammasome, and heart failure represent the frontier research in this field and are becoming new research hotspots. It is hoped that this study will provide new insights for research and clinical work in the field of ERS and AS.

Preparation, structural characteristics and pharmacological activity of polysaccharides from Polygala tenuifolia: A review.

Polygala tenuifolia is a traditional Chinese medicine with a long history of application, with the efficacy of suppressing cough, calming asthma, tranquilizing the mind, and benefiting the intellect. It is classified as a top-quality medicine in Shennong's Classic of Materia Medica. Polysaccharide is an important active ingredient in Polygala tenuifolia, which consists of several monosaccharides, including Ara, Gal, Glc, and so on. In this review, the preparation methods, structural characteristics, and biological activities of polysaccharides from Polygala tenuifolia are summarized, and the problems in the current studies are discussed to support further research, development, and utilization.

Case report: Rapid clinical improvement in acute exacerbation of MuSK-MG with efgartigimod.

Myasthenia gravis with positive MuSK antibody often involves the bulbar muscles and is usually refractory to acetylcholinesterase inhibitors. For MuSK-MG patients who experience acute exacerbations and do not respond to conventional treatments, there is an urgent need to find more suitable treatment options. With the advent of biologic agents, efgartigimod has shown promising results in the treatment of MG. We report a 65-year-old MuSK-MG patient who presented with impaired eye movements initially, and the symptoms rapidly worsened within a week, affecting the limbs and neck muscles, and had difficulties in chewing and swallowing. Lymphoplasmapheresis did not achieve satisfactory results, but after a cycle of efgartigimod treatment, the patient's symptoms gradually improved and remained in a good clinical state for several months.

A comprehensive prediction model predicts perihematomal edema growth in the acute stage after intracerebral hemorrhage.

BACKGROUND: Perihematomal edema (PHE) is regarded as a potential intervention indicator of secondary injury following intracerebral hemorrhage (ICH). But it still lacks a comprehensive prediction model for early PHE formation. METHODS: The included ICH patients have received an initial Computed Tomography scan within 6 hours of symptom onset. Hematoma volume and PHE volume were computed using semiautomated computer-assisted software. The volume of the hematoma, edema around the hematoma, and surface area of the hematoma were calculated. The platelet-to-lymphocyte ratio (PLR) was calculated by dividing the platelet count by the lymphocyte cell count. All analyses were 2-tailed, and the significance level was determined by P <0.05. RESULTS: A total of 226 patients were included in the final analysis. The optimal cut-off values for PHE volume increase to predict poor outcomes were determined as 5.5 mL. For clinical applicability, we identified a value of 5.5 mL as the optimal threshold for early PHE growth. In the multivariate logistic regression analyses, we finally found that baseline hematoma surface area (p < 0.001), expansion-prone hematoma (p < 0.001), and PLR (p = 0.033) could independently predict PHE growth. The comprehensive prediction model demonstrated good performance in predicting PHE growth, with an area under the curve of 0.841, sensitivity of 0.807, and specificity of 0.732. CONCLUSION: In this study, we found that baseline hematoma surface area, expansion-prone hematoma, and PLR were independently associated with PHE growth. Additionally, a risk nomogram model was established to predict the PHE growth in patients with ICH.

SlGAD2 is the target of SlTHM27, positively regulates cold tolerance by mediating anthocyanin biosynthesis in tomato.

Cold stress significantly limits the yield and quality of tomato. Deciphering the key genes related to cold tolerance is important for selecting and breeding superior cold-tolerant varieties. γ-aminobutyric acid (GABA) responds to various types of stress by rapidly accumulating in plant. In this study, glutamic acid decarboxylase (GAD2) was a positive regulator to enhance cold stress tolerance of tomato. Overexpression of SlGAD2 decreased the extent of cytoplasmic membrane damage and increased the endogenous GABA content, antioxidant enzyme activities, and reactive oxygen species (ROS) scavenging capacity in response to cold stress, whereas Slgad2 mutant plants showed the opposite trend. In addition, SlGAD2 induced anthocyanin biosynthesis in response to cold stress by increasing the content of endogenous GABA. Further study revealed that SlGAD2 expression was negatively regulated by the transcription factor SlTHM27. However, the transcript levels of SlTHM27 were repressed under cold stress. Antioxidant enzyme activities, SlGAD2 transcript levels, GABA and anthocyanin contents were significantly increased in Slthm27 mutant plants. Further, our study demonstrated that SlTHM27 decreases SlGAD2-promoted cold resistance in tomato by repressing SlGAD2 transcription. Overall, our results showed that the SlTHM27-SlGAD2 model regulates the cold tolerance in tomato by regulating GABA and anthocyanin.

Tibial neuropathy, a rare manifestation of hereditary neuropathy with liability to pressure palsy: A case report.

Hereditary neuropathy with liability to pressure palsy (HNPP) is characterized by acute, painless and recurrent mononeuropathies. Genetic testing shows PMP22 gene deletion of chromosome 17p11.2 can provide evidence for the diagnosis of HNPP. Reports on tibial neuropathy as the main manifestation of HNPP are very rare. We report a 14-year-old girl who was admitted to our hospital due to plantar foot numbness and plantar flexion weakness of her left foot. The patient had a history of lateral dorsal numbness and right foot drop when she was 3 years old. Clinical symptoms, and neurological examination demonstrated tibial neuropathy. Electromyography showed extensive peripheral nerve, including median nerve, ulnar nerve, tibial nerve and peroneal nerve, were involved. The diagnosis of HNPP was confirmed by genetic testing which disclosed a deletion of PMP22 gene. She was completely asymptomatic in one month after neurotrophic drug treatments.

Transcription Factor SlAREB1 Is Involved in the Antioxidant Regulation under Saline-Alkaline Stress in Tomato.

Basic leucine zipper (bZIP) transcription factors of the ABA-responsive element binding factor/ABA-responsive element binding proteins (ABF/AREB) subfamily have been implicated in abscisic acid (ABA) and abiotic stress responses in plants. However, the specific function of ABF/AREB transcription factors under saline-alkaline stress is unclear. Here, we identified four ABF/AREB transcription factors in tomato and found that SlAREB1 strongly responded to both ABA and saline-alkaline stress. To further explore the function of SlAREB1 under saline-alkaline stress, SlAREB1-overexpressing lines were constructed. Compared with wild-type plants, SlAREB1-overexpressing transgenic tomato plants showed reduced malondialdehyde content, increased the relative water content, and alleviated the degradation of chlorophyll under saline-alkaline stress. Importantly, SlAREB1 directly physically interacted with SlMn-SOD, which improved the activity of antioxidant enzymes and increased the scavenging of excess reactive oxygen species. Overall, the overexpression of SlAREB1 increased the antioxidant capacity of the transgenic tomato under saline-alkaline stress.

Exogenous 5-aminolevulinic acid alleviates low-temperature damage by modulating the xanthophyll cycle and nutrient uptake in tomato seedlings.

5-Aminolevulinic acid (ALA), an antioxidant existing in plants, has been widely reported to participate in the process of coping with cold stress of plants. In this study, exogenous ALA promoted the growth of tomato plants and alleviated the appearance of purple tomato leaves under low-temperature stress. At the same time, exogenous ALA improved antioxidant enzyme activities, SlSOD gene expression, Fv/Fm, and proline contents and reduced H2O2 contents, SlRBOH gene expression, relative electrical conductivity, and malondialdehyde contents to alleviate the damage caused by low temperature to tomato seedlings. Compared with low-temperature stress, spraying exogenous ALA before low-temperature stress could restore the indicators of photochemical quenching, actual photochemical efficiency, electron transport rate, and nonphotochemical quenching to normal. Exogenous ALA could increase the total contents of the xanthophyll cycle pool, the positive de-epoxidation rate of the xanthophyll cycle and improved the expression levels of key genes in the xanthophyll cycle under low-temperature stress. In addition, we found that exogenous ALA significantly enhanced the absorption of mineral nutrients, promoted the transfer and distribution of mineral nutrients to the leaves, and improved the expression levels of mineral nutrient absorption-related genes, which were all conducive to the improved adaptation of tomato seedlings under low-temperature stress. In summary, the application of exogenous ALA can increase tomato seedlings' tolerance to low-temperature stress by improving the xanthophyll cycle and the ability of the absorption of mineral nutrients in tomato seedlings.

Over-expression of spermidine synthase 2 (SlSPDS2) in tomato plants improves saline-alkali stress tolerance by increasing endogenous polyamines content to regulate antioxidant enzyme system and ionic homeostasis.

Endogenous spermidine can improve the resistance of plants to saline-alkali stress. SlSPDS1 and SlSPDS2 are the main spermidine synthase (SPDS) genes in tomatoes. In comparison with SlSPDS1, SlSPDS2 plays an important role in wild-type tomato seedling under saline-alkali stress. However, limited research has focused on the role of SlSPDS2 in saline-alkali stress. Wild-type (WT) and SPDS gene (SlSPDS2) transgenic over-expression tomato seedlings were used to explore the function of endogenous spermidine on the saline-alkali resistance of tomato seedlings. The results show that SlSPDS2 overexpression under normal conditions and saline-alkali stress increased the content of endogenous free polyamines and the expression levels of polyamine synthesis-related genes in tomato seedlings. Under saline-alkali stress, SlSPDS2 overexpression significantly reduced Na+/K+ ratio, relative electrical conductivity, O2·-, H2O2, and malondialdehyde content, increased Seedling index, relative water content, antioxidant enzyme activities (peroxidase, superoxide dismutase, and catalase), and the contents of proline and soluble sugar in tomato leaf, and mitigated the adverse effect of saline-alkali stress on tomato seedlings. In summary, the overexpression of SlSPDS2 tomato seedlings regulated the ionic homeostasis, antioxidant enzyme system, and osmotic regulatory substances of tomato seedlings living in saline-alkali environment by increasing endogenous free polyamine content, thereby improving the resistance of tomato seedlings against saline-alkali stress.

Removal Mechanism of Oxide Layer on the Surface of Sn-0.4Ti Alloy for Quartz Glass Sealing.

The oxide layer on the surface of Sn-0.4Ti alloy and its removal mechanism were investigated by coalitional analyses, using XPS and TEM technologies. The results show that a compact SnO1.65 oxide layer of less than 4 nm in thickness exists on the surface of Sn-0.4Ti alloy. A large number of TiO2 nanoparticles with scale of several to tens of nanometers were grown in Sn-0.4Ti matrix by depleting SnO1.65 while welding at 800 °C. These nanoparticles were adhered to the interfacial layer between Sn-0.4Ti alloy and quartz glass, which was formed by the reaction of Sn-0.4Ti and SiO2 after SnO1.65 removal from the Sn-0.4Ti. This work may promote further works on Sn-Ti design to further improve the welding quality between Sn-Ti alloy and quartz glass, and also provide a feasible research idea to remove the oxide layer on the surfaces of solders.

Effects of a Soluble Epoxide Hydrolase Inhibitor on Lipopolysaccharide-Induced Acute Lung Injury in Mice.

OBJECTIVES: Inflammation plays a key role in the pathogenesis of acute lung injury (ALI). Soluble epoxide hydrolase (sEH) is suggested as a vital pharmacologic target for inflammation. In this study, we determined whether a sEH inhibitor, AUDA, exerts lung protection in lipopolysaccharide (LPS)-induced ALI in mice. METHODS: Male BALB/c mice were randomized to receive AUDA or vehicle intraperitoneal injection 4 h after LPS or phosphate buffered saline (PBS) intratracheal instillation. Samples were harvested 24 h post LPS or PBS administration. RESULTS: AUDA administration decreased the pulmonary levels of monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-α. Improvement of oxygenation and lung edema were observed in AUDA treated group. AUDA significantly inhibited sEH activity, and elevated epoxyeicosatrienoic acids (EETs) levels in lung tissues. Moreover, LPS induced the activation of nuclear factor (NF)-κB was markedly dampened in AUDA treated group. CONCLUSION: Administration of AUDA after the onset of LPS-induced ALI increased pulmonary levels of EETs, and ameliorated lung injury. sEH is a potential pharmacologic target for ALI.