Comparative phylogenetic analysis of the mediator complex subunit in asparagus bean (Vigna unguiculata ssp. sesquipedialis) and its expression profile under cold stress.

BACKGROUND: The mediator complex subunits (MED) constitutes a multiprotein complex, with each subunit intricately involved in crucial aspects of plant growth, development, and responses to stress. Nevertheless, scant reports pertain to the VunMED gene within the context of asparagus bean (Vigna unguiculata ssp. sesquipedialis). Establishing the identification and exploring the responsiveness of VunMED to cold stress forms a robust foundation for the cultivation of cold-tolerant asparagus bean cultivars. RESULTS: Within this study, a comprehensive genome-wide identification of VunMED genes was executed in the asparagus bean cultivar 'Ningjiang3', resulting in the discovery of 36 distinct VunMED genes. A phylogenetic analysis encompassing 232 MED genes from diverse species, including Arabidopsis, tomatoes, soybeans, mung beans, cowpeas, and asparagus beans, underscored the highly conserved nature of MED gene sequences. Throughout evolutionary processes, each VunMED gene underwent purification and neutral selection, with the exception of VunMED19a. Notably, VunMED9/10b/12/13/17/23 exhibited structural variations discernible across four cowpea species. Divergent patterns of temporal and spatial expression were evident among VunMED genes, with a prominent role attributed to most genes during early fruit development. Additionally, an analysis of promoter cis-acting elements was performed, followed by qRT-PCR assessments on roots, stems, and leaves to gauge relative expression after exposure to cold stress and subsequent recovery. Both treatments induced transcriptional alterations in VunMED genes, with particularly pronounced effects observed in root-based genes following cold stress. Elucidating the interrelationships between subunits involved a preliminary understanding facilitated by correlation and principal component analyses. CONCLUSIONS: This study elucidates the pivotal contribution of VunMED genes to the growth, development, and response to cold stress in asparagus beans. Furthermore, it offers a valuable point of reference regarding the individual roles of MED subunits.

Percutaneous nephrolithotomy or flexible ureteral lithotripsy, which one is better for patients with upper ureteral calculi of 1.5-2.0 cm in diameter.

PURPOSE: First research to evaluate the clinical efficacy and safety of flexible ureteral lithotripsy (FURSL) and percutaneous nephrolithotomy (PCNL) in the treatment of the upper ureteral stone is between 1.5 cm and 2.0 cm in diameter since there is no consensus with such ureteral stone yet. METHODS: From December 2018 to October 2022, 104 patients with calculi in the upper ureter received percutaneous nephrolithotomy (PCNL)or flexible ureteroscopic lithotripsy (FURSL) in our institution. The clinical data of the patients in the two groups were retrospectively searched. Stone removal rate, operation time, blood loss, postoperative pain score, postoperative inflammatory factor, postoperative complication rates and ureteral obstruction three months after the operation were compared between the two groups. RESULTS: A total of 104 patients were included in the study. The stone clearance rate and the secondary surgery rate were 88.89% and 7.41% in the FURSL group, the figures were 97.96% and 2.0% in the PCNL group (p = 0.067, 0.497). Regarding ureteral obstruction three months after the operation, there were 2 patients in FURSL group and 0 patients in PCNL group(p = 0.497).Compared to patients in FURSL group, patients in the PCNL group had shorter operation time(PCNL 71.81 ± 18.94 min vs. FURSL 86.80 ± 22.49 min, p = 0.0004), fewer complications(PCNL 20.37% vs. FURSL 6.12%), and lower postoperative inflammatory factor(p = 0.0004), yet they got more hemoglobin drop (PCNL 13.14 ± 9.81 g/L vs. FURSL 4.77 ± 3.55 g/L, p < 0.0001), higher postoperative pain scores(p = 0.0017) in the first three postoperative days and longer hospital stay (PCNL 4.96 ± 1.21 days vs. FURSL 3.60 ± 0.83 days). CONCLUSION: Both FURSL and PCNL were effective methods for treating upper ureteral stones of 1.5-2.0 cm in diameter given the extremely high stone clearance rate and a very low secondary surgery rate, as long as rare ureteral obstruction in medium-long term observation. Additionally, FURSL can effectively reduce surgical bleeding, postoperative pain, and hospital stay, while PCNL can decrease operation time, the risk of infection, and complications. Therefore, doctors could select suitable surgical treatment for those patients depending on their different clinical situations based on these findings.

Ulinastatin ameliorates the malignant progression of prostate cancer cells by blocking the RhoA/ROCK/NLRP3 pathway.

Prostate cancer is a male malignant tumor disease with high incidence and mortality. This study was designed to explore the effects of ulinastatin (UTI) on the malignant progression of prostate cancer and its relevant mechanism of action. Human prostate cancer cell line PC-3 was applied to investigate the anticancer activity of UTI. PC-3 cells were treated with increasing concentrations (400, 800, and 1600 U/ml) of UTI. Cell proliferation, migration, invasion, and apoptosis were determined by cell counting kit-8 (CCK-8), colony formation, wound-healing, Transwell assay, and flow cytometry analysis, respectively. The expression level of corresponding proteins was detected by western blot. In addition, PC-3 cells were pretreated with RhoA agonist CN03 (1 µg/ml) or NLRP3 agonist nigericin (10 µM) before UTI treatment, and the cellular behaviors above were detected again. It was demonstrated that UTI significantly suppressed cell proliferation, migration, and invasion but promoted apoptosis in PC-3 cells in a concentration-dependent manner. Meanwhile, UTI could block RhoA/ROCK/NLRP3 inflammasome pathway in PC-3 cells, and the activation of RhoA or NLRP3 inflammasome partly weakened the impacts of UTI on cell proliferation, migration, and apoptosis in PC-3 cells, respectively. In summary, our study demonstrated the antitumor activity of UTI against prostate cancer by regulating RhoA/NLRP3 inflammasome pathway, providing a promising candidate drug for the therapeutic treatment of prostate cancer.

5-ALA Improves the Low Temperature Tolerance of Common Bean Seedlings through a Combination of Hormone Transduction Pathways and Chlorophyll Metabolism.

Low-temperature stress is a key factor limiting the yield and quality of the common bean. 5-aminolevulinic acid (5-ALA), an antioxidant in plants, has been shown to modulate plant cold stress responses. However, the molecular mechanisms of 5-ALA-induced physiological and chemical changes in common bean seedlings under cold stress remains unknown. This study explored the physiological and transcriptome changes of common bean seedlings in response to cold stress after 5-ALA pretreatment. Physiological results showed that exogenous 5-ALA promotes the growth of common bean plants under cold stress, increases the activity of antioxidant enzymes (superoxide dismutase: 23.8%; peroxidase: 10.71%; catalase: 9.09%) and proline content (24.24%), decreases the relative conductivity (23.83%), malondialdehyde (33.65%), and active oxygen content, and alleviates the damage caused by cold to common bean seedlings. Transcriptome analysis revealed that 214 differentially expressed genes (DEGs) participate in response to cold stress. The DEGs are mainly concentrated in indole alkaloid biosynthesis, carotenoid biosynthesis, porphyrin, and chlorophyll metabolism. It is evident that exogenous 5-ALA alters the expression of genes associated with porphyrin and chlorophyll metabolism, as well as the plant hormone signal transduction pathway, which helps to maintain the energy supply and metabolic homeostasis under low-temperature stress. The results reveal the effect that applying exogenous 5-ALA has on the cold tolerance of the common bean and the molecular mechanism of its response to cold tolerance, which provides a theoretical basis for exploring and improving plant tolerance to low temperatures.

CaSPDS, a Spermidine Synthase Gene from Pepper (Capsicum annuum L.), Plays an Important Role in Response to Cold Stress.

Spermidine synthase (SPDS) is a key enzyme in the polyamine anabolic pathway. SPDS genes help regulate plant response to environmental stresses, but their roles in pepper remain unclear. In this study, we identified and cloned a SPDS gene from pepper (Capsicum annuum L.), named CaSPDS (LOC107847831). Bioinformatics analysis indicated that CaSPDS contains two highly conserved domains: an SPDS tetramerisation domain and a spermine/SPDS domain. Quantitative reverse-transcription polymerase chain reaction results showed that CaSPDS was highly expressed in the stems, flowers, and mature fruits of pepper and was rapidly induced by cold stress. The function of CaSPDS in cold stress response was studied by silencing and overexpressing it in pepper and Arabidopsis, respectively. Cold injury was more serious and reactive oxygen species levels were greater in the CaSPDS-silenced seedlings than in the wild-type (WT) seedlings after cold treatment. Compared with the WT plants, the CaSPDS-overexpression Arabidopsis plants were more tolerant to cold stress and showed higher antioxidant enzyme activities, spermidine content, and cold-responsive gene (AtCOR15A, AtRD29A, AtCOR47, and AtKIN1) expression. These results indicate that CaSPDS plays important roles in cold stress response and is valuable in molecular breeding to enhance the cold tolerance of pepper.

Predictive Value of Insulin Resistance as Determined by Homeostasis Model Assessment in Acute Ischemic Stroke Patients: A Systematic Review and Meta-Analysis.

Studies on association between homeostasis model assessment of insulin resistance (HOMA-IR) and adverse outcomes have yielded conflicting results in patients with acute ischemic stroke (AIS). This meta-analysis aimed to assess the predictive value of HOMA-IR in AIS patients. Two authors comprehensively searched PubMed and Embase databases until February 28, 2021. All observational studies investigating the association between HOMA-IR and adverse outcomes in AIS patients were included. Outcome measures were poor functional outcome (Modified Rankin Scale≥3), all-cause mortality, stroke recurrence, and neurologic worsening. Seven studies (eight articles) involving 8330 AIS patients were identified. For the highest versus lowest HOMA-IR, the pooled risk ratio (RR) of poor functional outcome was 2.55 (95% CI 1.76-3.70) after adjustment of conventional confounding factors. In addition, elevated HOMA-IR was associated with higher risk of neurologic worsening (RR 1.93; 95% CI 1.15-3.26). However, there were conflicting findings on the association of HOMA-IR with stroke recurrence and all-cause mortality. This meta-analysis confirms that HOMA-IR is significantly associated with an increased risk of poor functional outcome in patients with AIS. However, interpretation of the results of mortality, stroke recurrence, and neurologic worsening should be done with caution due to small number of studies available.

Potential of C1QTNF1-AS1 regulation in human hepatocellular carcinoma.

The aim of our study is to explore the regulation of C1QTNF1-AS1 on its target miR-221-3p/SOCS3 in human hepatocellular carcinoma (HCC). To explore the underlying molecular regulation of non-coding RNA for HCC, differentially expressed patterns of lncRNAs and genes were examined by RNA-seq. GO and KEGG pathway analysis were done based on the function of mRNAs that mediated by differentially expressed lncRNAs. RT-qPCR and western blot were conducted to detect the mRNA and protein level expression of C1QTNF1-AS1, miR-221-3p, SOCS3 and key proteins in JAK/STAT signaling pathway in HCC tissues and cells. The target miRNA of differentially expressed C1QTNF1-AS1 and SOCS3 was miR-221-3p predicted by bioinformatics analysis. C1QTNF1-AS1 and SOCS3 was downregulated and miR-221-3p was upregulated in HCC tissues and cells. In HepG2 and Huh-7 cells, the overexpression of C1QTNF1-AS1 or SOCS3, and silencing of miR-221-3p inhibited proliferation, migration, invasion and JAK/STAT signaling pathway, while promoted cell apoptosis. The results of dual-luciferase assay indicated that C1QTNF1-AS1 regulated miR-221-3p and miR-221-3p targeted SOCS3 by directly binding. And the growth of HCC in vivo was impeded when C1QTNF1-AS1 was upregulated. Overexpression of C1QTNF1-AS1 could downregulate miR-221-3p thereby inhibited the proliferation, migration and invasion of HCC cells.

Involvement of WNK1-mediated potassium channels in the sexual dimorphism of blood pressure.

Potassium homeostasis plays an essential role in the control of blood pressure. It is unknown, however, whether potassium balance is involved in the gender-associated blood pressure differences. We therefore investigated the possible mechanism of sexual dimorphism in blood pressure regulation by measuring the blood pressure, plasma potassium, renal actions of potassium channels and upstream regulator in male and female mice. Here we found that female mice exhibited lower blood pressure and higher plasma K+ level as compared to male littermates. Western blot analyses of mouse kidney extract revealed a significant decrease in renal outer medullary potassium (ROMK) channel expression, while large-conductance Ca2+-activated K+ (BK) channel and Na-K-2Cl cotransporter (NKCC2) as well as the upstream regulator with-no-lysine kinase 1 (WNK1) enhanced in female mice under normal condition. Surprisingly, both dietary K+ loading and K+ depletion eliminated the differences in plasma K+ and blood pressure between females and males, and the differences of renal K+ channels and WNK1 also attenuated in both groups of mice. These findings indicated the existence of a close correlation between K+ homeostasis and sex-associated blood pressure. Moreover, the differential regulation of ROMK, BK-α and NKCC2 between female and male mice, at least, were partly mediated via WNK1 pathway, which may contribute to the sexual dimorphism of plasma K+ and blood pressure control.

The study of pentagonal chain with respect to schultz index, modified schultz index, schultz polynomial and modified schultz polynomial.

Distance-based topological indices are numerical parameters that are derived from the distances between atoms in a molecular structure, and they provide a quantitative measure of the topology and geometry of a molecule. The distance-based topological indices uses to predict various properties of molecules, including their boiling points, melting points, and solubility. It also predicts the biological activity of molecules, including their pharmacological and toxicological properties. Pentagonal chain molecules are organic compounds that consist of a linear chain of five-membered (pentagons) connected by carbon and bonds. These molecules have unique structural and electronic properties that make them useful in a variety of applications. Motivated by the pentagonal chain molecules, we have considered a pentagonal chain graph and it is denoted by Pn. We have computed some distance based topological indices for Pn. The paper focuses on a pentagonal chain molecules denoted by G, and derives several distance-based topological indices. These indices compromise insights into physicochemical properties, aid in identifying structural characterizations, and enhance understanding of molecular properties.

Multi-objective optimization using improved NSGA-II for integrated process planning and scheduling problems in a machining job shop for large-size valve.

This paper studied an integrated process planning and scheduling problem from a machining workshop for large-size valves in a valve manufacturing plant. Large-size valves usually contain several key parts and are generally produced in small-series production. Almost all the parts need to be manufactured in the same workshop at the same time in the plant. Facilities have to handle various items in one order, including different models, sizes, and types. It is a classical NP-hard problem on a large scale. An improved NSGA-II algorithm is suggested to obtain satisfactory solutions for makespan and manufacturing costs, which involve large optimization parameters and interactions. A two-section encoding method and an inserting greedy decoding method are chosen to enable the algorithm. The dynamic population update strategy based on dynamic population update and the adaptive mutation technique depending on the population entropy changing rate are selected for enhancing both the solution quality and population diversity. The methodology was successfully implemented in a real-life case at a major valve machining workshop operated by Yuanda Valve Company in China. By taking into account realistic factors and restrictions that have been identified from a real-world manufacturing setting, this technique aids in bridging the knowledge gap between present IPPS research and practical valve production implementations.

On topological indices and entropy measures of beryllonitrene network via logarithmic regression model.

Chemical graph theory, a subfield of graph theory, is used to investigate chemical substances and their characteristics. Chemical graph analysis sheds light on the connection, symmetry, and reactivity of molecules. It supports chemical property prediction, research of molecular reactions, drug development, and understanding of molecular networks. A crucial part of computational chemistry is chemical graph theory, which helps researchers analyze and manipulate chemical structures using graph algorithms and mathematical models. Beryllonitrene , a compound of interest due to its potential applications in various fields, is examined through the lens of graph theory and mathematical modeling. The study involves the calculation and interpretation of topological indices and graph entropy measures, which provide valuable insights into the structural and energetic properties of Beryllonitrene's molecular graph. Logarithmic regression models are employed to establish correlations between these indices, entropy, and other relevant molecular attributes. The results contribute to a deeper understanding of Beryllonitrene's complex characteristics, facilitating its potential applications in diverse scientific and technological domains. In this study, degree-based topological indices TI are determined, as well as the entropy of graphs based on these TI .

Tumor necrosis factor-α attenuates starvation-induced apoptosis through upregulation of ferritin heavy chain in hepatocellular carcinoma cells.

BACKGROUND: Tumor microenviroment is characteristic of inflammation, ischemia and starvation of nutrient. TNF-α, which is an extraordinarily pleiotropic cytokine, could be an endogenous tumor promoter in some tumor types. The basic objective of this study was to investigate the effects of TNF-α on the cell viability and apoptosis of hepatocellular carcinoma cells under serum starvation, and to identify the molecular mechanisms involved. METHODS: For this purpose, five different concentrations of TNF-α and two different serum settings (serum-cultured and serum-deprived) were used to investigate the effects of TNF-α on the cell viability and apoptosis of Hep3B and SMMC-7721 cells. RESULTS: TNF-α (10 ng/ml) attenuated serum starvation-induced apoptosis of hepatocellular carcinoma cells, and autophagy conferred this process. BAY11-7082, a specific inhibitor of NF-κB, reversed the suppression of serum starvation-induced apoptosis by TNF-α. Moreover, TNF-α-induced NF-κB transactivation was suppressed by autophagy inhibitor 3-MA. In addition, TNF-α up-regulated Ferritin heavy chain (FHC) transiently by NF-κB activation and FHC levels were correlated with the TNF-α-induced protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells. Furthermore, FHC-mediated inhibition of apoptosis depended on suppressing ROS accumulation. CONCLUSIONS: Our findings suggested that autophagy conferred the TNF-α protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells, the mechanism involved with the activation of the TNF-α/ NF-κB /FHC signaling pathway.

Effect of Decompressive Craniectomy with Stepwise Decompression of the Intracranial Compartment on Postoperative Neurologic Function, Hemodynamics, and Glasgow Outcome Scale Score of Patients with Severe Traumatic Brain Injury.

BACKGROUND: We assess the effects of standard decompressive craniectomy with stepwise decompression of the intracranial compartment on the postoperative neurologic function, hemodynamics, and Glasgow Outcome Scale (GOS) score of patients with severe traumatic brain injury (sTBI). METHODS: One hundred sTBI patients admitted from July 2017 to February 2019 were enrolled and randomly divided into step and standard groups (n = 50) using a random number table. The standard group received traditional standard decompression during surgery, while the step group underwent multistep decompression during surgery. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured immediately after surgery (T0), 3 hours after surgery (T1), 6 hours after surgery (T2), and 12 hours after surgery (T3). The postoperative Glasgow Coma Scale (GCS) score, neurologic function deficit score, and GOS score were evaluated. RESULTS: After treatment, the excellent/good rate of neurologic function improvement and GCS and GOS scores of the step group significantly exceeded those of the standard group (p < 0.05). Compared with the standard group, the HR, SBP, DBP, and MAP decreased significantly in the step group at T1, T2, and T3 (p < 0.05). CONCLUSION: Standard decompressive craniectomy under multistep decompression can markedly improve the neurologic function, hemodynamics, and prognosis of patients.

Sleep quality after stroke: A systematic review and meta-analysis.

BACKGROUND: Sleep-related problems are debilitating and long-lasting conditions in individuals with stroke. We aimed to estimate the prevalence of poor sleep quality after stroke by conducting a systematic review and meta-analysis. METHODS: Five databases (PubMed, Embase, Web of Science, Scopus, and CINHAL) were searched for literature published before November 2022. Studies recruiting participants with stroke, using a validated scale to measure sleep quality and in English were included. We used the Agency for Healthcare Research and Quality Scale and Newcastle-Ottawa Scale to assess the quality of eligible studies. Pooled prevalence and subgroup analyses were performed to understand the variation in sleep quality among studies. We followed the PRISMA checklist to report the study. RESULTS: Thirteen studies were included for analysis (n = 3886). The pooled prevalence of poor sleep quality was 53% (95% CI 41-65%). Studies using PSQI with a cutoff point of 7 had a prevalence of 49% (95% CI 26-71%), whereas those with a cutoff point of 5 had a higher prevalence of 66% (95% CI 63-69%) (P = .13). Geographical location could explain the prevalence variation between studies. The majority of included studies had a medium level quality of evidence (10/13). CONCLUSION: Poor sleep quality appears to be common in patients with stroke. Considering its negative impact on health, effective measures should be taken to improve their quality of sleep. Longitudinal studies should be conducted to examine the contributing factors and investigate the mechanisms that lead to poor sleep quality.

The association between iron metabolism with the change of blood pressure and risk of hypertension: A large cross-sectional study.

BACKGROUND: The relationship between iron metabolism and variations in blood pressure and hypertension risk is still not clear. This study aimed to determine whether iron metabolism is associated with changes in blood pressure and hypertension prevalence in the general United States population. METHODS: The National Health and Nutrition Examination Survey (NAHNES) database contains data on 116876 Americans from 1999 to 2020 years. Data from the NHANES database were used to examine the relationships between iron metabolism (serum iron [SI], serum ferritin [SF], and soluble transferrin receptor [sTfR]) and changes in blood pressure and hypertension prevalence. Generalized linear models and restricted cubic spline (RCS) plot curves were used to estimate the relationship between iron metabolism and hypertension. Further, generalized additive models with smooth functions were used to identify the relationship between iron metabolism and blood pressure. Finally, a stratified subgroup analysis was performed. RESULTS: A total of 6710 participants were included in our analysis. The RCS plot showed a linear relationship between SI, as well as sTfR, and hypertension prevalence. SF and hypertension prevalence were associated in a J-shape. In addition, the relationship between SI and systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased initially and then increased. A correlation between SF, SBP, and DBP first decreased, then increased, and finally decreased. A positive linear correlation existed between sTfR and SBP, but it increased and then decreased with DBP. CONCLUSION: The correlation between SF and hypertension prevalence displayed a J-curve. In contrast, the correlation between SI, as well as sTfR, and hypertension risk was negative and positive, respectively.

NO and GSH Alleviate the Inhibition of Low-Temperature Stress on Cowpea Seedlings.

Low-temperature stress in early spring seriously affects the growth and development of cowpea seedlings. To study the alleviative effect of the exogenous substances nitric oxide (NO) and glutathione (GSH) on cowpea (Vigna unguiculata (Linn.) Walp.) seedlings under 8 °C low-temperature stress, 200 µmol·L-1 NO and 5 mmol·L-1 GSH were sprayed on cowpea seedlings whose second true leaf was about to unfold to enhance the tolerance of cowpea seedlings to low temperature. Spraying NO and GSH can eliminate excess superoxide radicals (O2-) and hydrogen peroxide (H2O2) to varying degrees, reduce the content of malondialdehyde and relative conductivity, delay the degradation of photosynthetic pigments, increase the content of osmotic regulating substances such as soluble sugar, soluble protein, and proline, and improve the activity of antioxidant enzymes such as superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, dehydroascorbate reductase, and monodehydroascorbate reductase. This study revealed that the mixed use of NO and GSH played an important role in alleviating low temperature stress, and the effect of spraying NO alone was better than that of spraying GSH.

A prospective observational study on utility of serum mesencephalic astrocyte-derived neurotrophic factor as a promising prognostic biomarker of severe traumatic brain injury in humans.

BACKGROUND: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is released under endoplasmic reticulum stress, thereby exerting neuroprotective effects. We determined whether serum MANF may be a prognostic biomarker of human severe traumatic brain injury (sTBI). METHODS: Serum MANF concentrations of 137 sTBI patients and 137 controls were quantified in this prospective cohort study. Patients with extended Glasgow outcome scale (GOSE) scores of 1-4 at post-traumatic 6 months were considered to have poor prognosis. Relationships between serum MANF concentrations and severity plus prognosis were investigated using multivariate analyses. Area under receiver operating characteristic curve (AUC) was calculated for reflecting prognostic efficiency. RESULTS: As compared to controls, there was a significant increase of serum MANF concentrations after sTBI (median, 18.5 ng/ml versus 3.0 ng/ml; P < 0.001), which was independently correlated with Glasgow coma scale (GCS) scores [ß, -3.000; 95% confidence interval (CI), -4.525--1.476; VIF, 2.216; P = 0.001], Rotterdam computed tomography (CT) scores (ß, 4.020; 95% CI, 1.446-6.593; VIF, 2.234; P = 0.002) and GOSE scores (ß, -0.056; 95% CI, -0.089--0.023; VIF, 1.743; P = 0.011). Serum MANF concentrations substantially distinguished risk of poor prognosis with AUC of 0.795 (95% CI, 0.718-0.859) and its concentrations > 23.9 ng/ml was predictive of poor prognosis with 67.7% sensitivity and 81.9% specificity. Serum MANF concentrations combined with GCS scores and Rotterdam CT scores displayed markedly higher prognostic predictive ability than each of them (all P < 0.05). Using restricted cubic spline, there was a linear correlation between serum MANF concentrations and poor prognosis (P = 0.256). Serum MANF concentrations > 23.9 ng/ml was independently associated with poor prognosis (odds ratio, 2.911; 95% CI, 1.057-8.020; P = 0.039). A nomogram was built, where serum MANF concentrations > 23.9 ng/ml, GCS scores and Rotterdam CT scores were integrated. Hosmer and Lemeshow test, calibration curve and decision curve analysis demonstrated such a prediction model was comparatively stable and was of relatively high clinical benefit. CONCLUSIONS: Substantially increased serum MANF concentrations after sTBI are highly correlated with traumatic severity and are independently predictive of long-term poor prognosis, suggesting that serum MANF may represent a useful prognostic biochemical marker of human sTBI.

XPA Enhances Temozolomide Resistance of Glioblastoma Cells by Promoting Nucleotide Excision Repair.

Glioblastoma is the most frequent, as well as aggressive kind of high-grade malignant glioma. Chemoresistance is posing a significant clinical barrier to the efficacy of temozolomide-based glioblastoma treatment. By suppressing xeroderma pigmentosum group A (XPA), a pivotal DNA damage recognition protein implicated in nucleotide excision repair (NER), we devised a novel method to enhance glioblastoma therapy and alleviate temozolomide resistance. On the basis of preliminary assessment, we found that XPA dramatically increased in glioblastoma compared with normal cells and contributed to temozolomide resistance. By constructing XPA stably knockdown cells, we illustrate that XPA protects glioma cells from temozolomide-triggered reproductive cell death, apoptosis, as well as DNA repair. Besides, XPA silencing remarkably enhances temozolomide efficacy in vivo. This study revealed a crucial function of XPA-dependent NER in the resistance of glioma cells to temozolomide.

Serum Sulfonylurea Receptor-1 Levels After Acute Supratentorial Intracerebral Hemorrhage: Implication for Prognosis.

Objective: Sulfonylurea receptor-1 (SUR1) is implicated in acute brain injury. This study was designed to determine relationship between serum SUR1 levels and severity, early neurologic deterioration (END) plus clinical outcome after intracerebral hemorrhage (ICH). Methods: Serum SUR1 levels of 131 ICH patients and 131 healthy controls were quantified in this prospective, observational study. END was defined as an increase of 4 or more points in the National Institutes of Health Stroke Scale (NIHSS) score or death within 24 hours after admission. Patients with a modified Rankin scale (mRS) score of 3-6 at 90 days following onset were considered to experience a poor outcome. Results: Serum SUR1 levels were substantially higher in patients than in controls. Serum SUR1 levels of patients were highly correlated with NIHSS score, Glasgow Coma Scale score, hematoma volume and ICH score. Compared with patients with END or mRS score of 0-2, other remainders had significantly elevated serum SUR1 levels. Serum SUR1 levels independently predicted END and 90-day poor outcome. Under receiver operating characteristic curve, serum SUR1 levels significantly predicted END and a poor outcome at 90 days after hemorrhagic stroke and its predictive value was similar to those of NIHSS score, Glasgow coma scale score, hematoma volume and ICH score. Conclusion: Serum SUR1 levels are highly correlated with severity, END and poor outcome after hemorrhagic stroke, indicating that serum SUR1 may be useful for risk stratification and prognostic prediction of ICH.

Elevated Serum Complement C1q Levels After Traumatic Brain Injury and Its Association with Poor Prognosis.

OBJECTIVE: Complement C1q is implicated in neuroinflammation. We intended to discern the relationship between serum C1q levels and severity in addition to prognosis following traumatic brain injury (TBI). METHODS: In this prospective, observational study, serum C1q levels were quantified in 188 TBI patients and 188 healthy controls. Glasgow coma scale (GCS) and Rotterdam computed tomography (CT) classification were used as clinical and radiological indicators of severity. Patients with extended Glasgow outcome scale (GOSE) score of 1-4 at 6 months after trauma were considered to have a poor outcome. Multiple logistic regression model was built to ascertain the independent association of serum C1q levels with 6-month poor outcome. Receiver operating characteristic (ROC) curve was configured for analysis of prognostic capability with respect to serum C1q levels. RESULTS: TBI patients exhibited substantially higher serum C1q levels than controls (median, 223.9 mg/l versus 75.4 mg/l). Serum C1q levels of patients were tightly correlated with GCS score (r = -0.671), Rotterdam CT classification (r = 0.604) and GOSE score (r = -0.581). An area under the ROC curve was yielded of 0.793 (95% confidence interval = 0.728-0.849), and serum C1q levels above 345.5 mg/l discriminated the risk of 6-month poor outcome with 59.6% sensitivity and 92.6% specificity. Serum C1q levels above 345.5 mg/l retained as an independent predictor for 6-month poor outcome with odds ratio of 4.922 (95% confidence interval = 1.552-15.606; P = 0.017). CONCLUSION: Elevated serum C1q levels are closely correlated with traumatic severity and independently predicted the risk of long-term poor prognosis after TBI.