Solvent-polarity dependence of ultrafast excited-state dynamics of trans-4-nitrostilbene.

Ultrafast excited-state dynamics of the simplest nitrostilbenes, namely trans-4-nitrostilbene (t-NSB), was studied in solvents of various polarities with ultrafast broadband time-resolved fluorescence and transient absorption spectroscopies, and by quantum-chemical computations. The results revealed that the initially excited S1(ππ*) state deactivation dynamics is strongly influenced by the solvent polarity. Specifically, the t-NSB S1-state lifetime decreases by three orders of magnitude from ∼60 ps in high-polarity solvents to ∼60 fs in nonpolar solvents. The strong solvent-polarity dependence arises from the differences in dipole moments among the S1 and relevant states, including the major intersystem crossing (ISC) receiver triplet states, and therefore, the solvent polarity can modulate their relative energies and ISC rates. In nonpolar solvents, the sub-100 fs lifetime is due to a combination of efficient ISC and internal conversion. In medium-polarity solvents, the S1-state population decays via a competing ISC relaxation mechanism in a biphasic manner, and the ISC rates are found to obey the inverse energy gap law of the strong coupling case. In high-polarity solvents, the S1 state is stabilized to a much lower energy such that ISC becomes energetically infeasible, and the S1 state decays via barrier crossing along the torsion angle of the central ethylenic bond to the nonfluorescent perpendicular configuration. Regardless of the initial S1-state deactivation pathways in various solvents, the excited-state population is ultimately trapped in the metastable T1-state perpendicular configuration, at which a slower ISC occurs to bring the system to the ground state and bifurcate into either trans or cis form of NSB.

Gene polymorphism in IL17A and gene-gene interaction in the IL23R/IL17A axis are associated with susceptibility to coronary artery disease.

AIMS: Studies have confirmed that the IL-23R/IL-17A axis plays an important role in the development of autoimmune and inflammatory diseases. However, its role in coronary artery disease (CAD) remains unclear. Here, we conducted a large sample case-control study to investigate the association between the IL23R/IL17A axis and CAD in the Chinese Han population. METHODS: Two SNPs, rs2275913: G>A (IL17A) and rs6682925: T>C (IL23R), were genotyped in 3042 CAD cases and 3216 controls using the high-resolution melt technology (HRM). Logistic regression analyses were used to adjust the traditional risk factors for CAD and perform the gene interaction analyses. Multiple linear regression analyses were used to study the relationships between the selected SNPs and the levels of serum lipids. In addition, meta-analysis also was performed for the association between rs6682925 and rs2275913 with CAD in different popolations. RESULTS: Our case-control and meta-analysis for single SNPs demonstrated that the frequencies of the alleles and the distribution of the genotypes had no significant differences in CAD cases compared with controls. In the stratified analysis, we observed that the frequency of the IL17A rs2275913-A allele was more epidemic in early-onset CAD than in the controls (Padj = 0.005, OR = 1.209, 95% CI: 1.059-1.382), and the minor allele C of rs6682925 was associated with a decreased level of serum total cholesterol under a recessive model (Padj = 0.011). We demonstrated a significant interaction between rs6682925 and rs2275913 and CAD in the Chinese Han population. Four genotypes (CTGG, CCAA, CCAG, CCGG) were significantly associated with CAD (Padj = 2.94 × 10-4, OR = 0.619, 95% CI: 0.478-0.803; Padj = 0.01, OR = 1.808, 95% CI: 1.152-1.869; Padj = 6 × 10-6, OR = 2.179, 95% CI: 1.558-3.049; Padj = 0.001, OR = 1.883, 95% CI: 1.282-2.762, respectively). CONCLUSION: Our study found no single SNP of rs2275913 in IL17A and rs6682925 in IL23R was associated with CAD in the Chinese population, but the interaction of them were significantly associated with CAD susceptibility, highlighting the key role of the IL-23R/IL-17A axis in the development of CAD. In addition, we also found rs2275913 was associated with early-onset CAD and rs6682925 was associated with total cholesterol levels, which will contribute to the clinical stratified management of this common disease.

Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry.

BACKGROUND AND AIMS: Genetic predisposition to autoimmune hepatitis (AIH) in adults is associated with possession of human leukocyte antigen (HLA) class I (A*01, B*08) and class II (DRB1*03, -04, -07, or -13) alleles, depending on geographic region. Juvenile autoimmune liver disease (AILD) comprises AIH-1, AIH-2, and autoimmune sclerosing cholangitis (ASC), which are phenotypically different from their adult counterparts. We aimed to define the relationship between HLA profile and disease course, severity, and outcome in juvenile AILD. APPROACH AND RESULTS: We studied 236 children of European ancestry (152 female [64%], median age 11.15 years, range 0.8-17), including 100 with AIH-1, 59 with AIH-2, and 77 with ASC. The follow-up period was from 1977 to June 2019 (median 14.5 years). Class I and II HLA genotyping was performed using PCR/sequence-specific primers. HLA B*08, -DRB1*03, and the A1-B8-DR3 haplotype impart predisposition to all three forms of AILD. Homozygosity for DRB1*03 represented the strongest risk factor (8.8). HLA DRB1*04, which independently confers susceptibility to AIH in adults, was infrequent in AIH-1 and ASC, suggesting protection; and DRB1*15 (DR15) was protective against all forms of AILD. Distinct HLA class II alleles predispose to the different subgroups of juvenile AILD: DRB1*03 to AIH-1, DRB1*13 to ASC, and DRB1*07 to AIH-2. Possession of homozygous DRB1*03 or of DRB1*13 is associated with fibrosis at disease onset, and possession of these two genes in addition to DRB1*07 is associated with a more severe disease in all three subgroups. CONCLUSIONS: Unique HLA profiles are seen in each subgroup of juvenile AILD. HLA genotype might be useful in predicting responsiveness to immunosuppressive treatment and course.

Comparison of conbercept and ranibizumab combined mitomycin C-augmented trabeculectomy for neovascular glaucoma.

PURPOSE: To compare the efficacy and security of conbercept and ranibizumab combined with trabeculectomy and panretinal photocoagulation for neovascular glaucoma (NVG). METHODS: One hundred and sixty patients with NVG were randomly divided into a conbercept group comprised of 80 patients and a ranibizumab group comprised of 80 patients. The postoperative and preoperative visual acuities, intraocular pressures frequency of anti-glaucoma medications, and surgical complications were recorded. The expressions of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (FLT-1), and placenta-like growth factor (PLGF) in the aqueous humor were determined using an enzyme-linked immunosorbent assay. Examining the fundus and obtaining photographs used indirect ophthalmoscopy. Kaplan-Meier and log-rank analyses estimated the success rates. RESULTS: All patient follow-up periods were at 1 year. The differences observed in IOP and the frequencies of anti-glaucoma medications at various follow-up time points were not statistically significant (all P > 0.05). The differences observed in both the group visual acuities at various follow-up time points were not statistically significant (P > 0.05). Rates of surgery complications were 18.75% and 25.00% in the conbercept group and ranibizumab group, respectively. The expressions of VEGF, FLT-1, and PLGF significantly decreased (all P < 0.05). The recurrence percentages were 30.00% and 36.25% after conbercept and ranibizumab treatment, respectively. CONCLUSION: The conbercept effects were similar with that of ranibizumab. Intravitreal injection of conbercept was effective for NVG treatment, which provides a new therapeutic drug for NVG treatment.

SNP rs2243828 in MPO associated with myeloperoxidase level and atrial fibrillation risk in Chinese Han population.

Previous studies shown that myeloperoxidase (MPO) level is higher in patients with atrial fibrillation (AF); however, no genetic evidence between MPO and AF risk in human population was observed. Therefore, the present study was aimed to investigate the association between rs2243828, a variant in promoter region of MPO and the risk of AF in Chinese GeneID population. The results demonstrated that the minor G allele of rs2243828 showed a significant association with AF in two independent population (GeneID-north population with 694 AF cases and 710 controls, adjusted P-adj = 6.25 × 10-3 with an odds ratio was 0.77, GeneID-central population with 1106 cases and 1501 controls, P-adj = 9.88 × 10-5 with an odds ratio was 0.75). The results also showed G allele was significantly associated with lower plasma concentration of myeloperoxidase in general population. We also observed a significant difference of odds ratio between subgroups of hypertension and non-hypertension. Therefore, our findings identified variant in MPO associated with risk of AF and it may give strong evidence to link the inflammation with the incidence of AF.

Major vault protein plays important roles in viral infection.

Viral replication and related protein expression inside the host cells, and host antiviral immune responses can lead to the occurrence of diverse diseases. With the outbreak of viral infection, a large number of newly diagnosed and died patients infected with various viruses are still reported every year. Viral infection has already been one of the major global public health issues and lead to huge economic and social burdens. Studying of viral pathogenesis is a very important way to find methods for prevention, diagnosis, and cure of viral infection; more evidence has confirmed that major vault protein (MVP) is closely associated with viral infection and pathogenesis, and this review is intended to provide a broad relationship between viruses and MVP to stimulate the interest of related researchers.

UBC9 regulates cardiac sodium channel Nav1.5 ubiquitination, degradation and sodium current density.

Voltage-gated sodium channel Nav1.5 is critical for generation and conduction of cardiac action potentials. Mutations and expression level changes of Nav1.5 are associated with cardiac arrhythmias and sudden death. The ubiquitin (Ub) conjugation machinery utilizes three enzyme activities, E1, E2, and E3, to regulate protein degradation. Previous studies from us and others showed that Nedd4-2 acts as an E3 ubiquitin-protein ligase involved in ubiquitination and degradation of Nav1.5, however, more key regulators remain to be identified. In this study, we show that UBC9, a SUMO-conjugating enzyme, regulates ubiquitination and degradation of Nav1.5. Overexpression of UBC9 significantly decreased Nav1.5 expression and reduced sodium current densities, whereas knockdown of UBC9 expression significantly enhanced Nav1.5 expression and increased sodium current densities, in both HEK293 cells and primary neonatal cardiomyocytes. Overexpression of UBC9 increased ubiquitination of Nav1.5, and proteasome inhibitor MG132 blocked the effect of UBC9 overexpression on Nav1.5 degradation. Co-immunoprecipitation showed that UBC9 interacts with Nedd4-2. UBC9 with mutation C93S, which suppresses SUMO-conjugating activity of UBC9, was as active as wild type UBC9 in regulating Nav1.5 levels, suggesting that UBC9 regulates Nav1.5 expression levels in a SUMOylation-independent manner. Our findings thus identify a key structural element of the ubiquitin-conjugation machinery for Nav1.5 and provide important insights into the regulatory mechanism for ubiquitination and turnover of Nav1.5.

Significant association of rare variant p.Gly8Ser in cardiac sodium channel ß4-subunit SCN4B with atrial fibrillation.

Atrial fibrillation (AF) affects 33.5 million individuals worldwide. It accounts for 15% of strokes and increases risk of heart failure and sudden death. The voltage-gated cardiac sodium channel complex is responsible for the generation and conduction of the cardiac action potential, and composed of the main pore-forming α-subunit Nav 1.5 (encoded by the SCN5A gene) and one or more auxiliary ß-subunits, including Nav ß1 to Nav ß4 encoded by SCN1B to SCN4B, respectively. We and others identified loss-of-function mutations in SCN1B and SCN2B and dominant-negative mutations in SCN3B in patients with AF. Three missense variants in SCN4B were identified in sporadic AF patients and small nuclear families; however, the association between SCN4B variants and AF remains to be further defined. In this study, we performed mutational analysis in SCN4B using a panel of 477 AF patients, and identified one nonsynonymous genomic variant p.Gly8Ser in four patients. To assess the association between the p.Gly8Ser variant and AF, we carried out case-control association studies with two independent populations (944 AF patients vs. 9,81 non-AF controls in the first discovery population and 732 cases and 1,291 controls in the second replication population). Significant association was identified in the two independent populations and in the combined population (p = 4.16 × 10-4 , odds ratio [OR] = 3.14) between p.Gly8Ser and common AF as well as lone AF (p = 0.018, OR = 2.85). These data suggest that rare variant p.Gly8Ser of SCN4B confers a significant risk of AF, and SCN4B is a candidate susceptibility gene for AF.

Identification of rare variants in cardiac sodium channel ß4-subunit gene SCN4B associated with ventricular tachycardia.

Ventricular tachycardia (VT) causes sudden cardiac death, however, the majority of risk genes for VT remain unknown. SCN4B encodes a ß-subunit, Navß4, for the voltage-gated cardiac sodium channel complex involved in generation and conduction of the cardiac action potential. We hypothesized that genomic variants in SCN4B increase the risk of VT. We used high-resolution melt analysis followed by Sanger sequencing to screen 199 VT patients to identify nonsynonymous variants in SCN4B. Two nonsynonymous heterozygous variants in SCN4B were identified in VT patients, including p.Gly8Ser in four VT patients and p.Ala145Ser in one VT patient. Case-control association studies were used to assess the association between variant p.Gly8Ser and VT in two independent populations for VT (299 VT cases vs. 981 controls in population 1 and 270 VT patients vs. 639 controls in population 2). Significant association was identified between p.Gly8Ser and VT in population 1 (P = 1.21 × 10-4, odds ratio or OR = 11.04), and the finding was confirmed in population 2 (P = 0.03, OR = 3.62). The association remained highly significant in the combined population (P = 3.09 × 10-5, OR = 6.17). Significant association was also identified between p.Gly8Ser and idiopathic VT (P = 1.89 × 10-5, OR = 7.27). Functional analysis with Western blotting showed that both p.Gly8Ser and p.Ala145Ser variants significantly reduced the expression level of Navß4. Based on 2015 ACMG Standards and Guidelines, p.Gly8Ser and p.Ala145Ser can be classified as the pathogenic and likely pathogenic variant, respectively. Our data suggest that SCN4B is a susceptibility gene for common VT and idiopathic VT and link rare SCN4B variants with large effects (OR = 6.17-7.27) to common VT.

Sleep facilitates consolidation of positive emotional memory in healthy older adults.

Evidence has demonstrated that sleep-related memory consolidation declines in ageing. However, little is known about age-related changes to sleep-related emotional memory consolidation, especially when considering the positivity effect observed in older adults. In the present study, we sought to explore whether there is a positive emotional bias in sleep-related memory consolidation among healthy older adults. Young and older adults were randomly assigned either into a sleep or wake condition. All participants encoded positive, negative, and neutral stimuli and underwent recognition tests immediately (test 1), after a 12-hour sleep/wake interval (test 2), and 3 days after test 2 (test 3). Results showed that age-related differences of sleep beneficial effect were modulated by emotion valence. In particular, sleep selectively enhanced positive memory in older adults, while in young adults sleep beneficial effect was manifested in neutral memory. Moreover, the sleep beneficial effect can be maintained at least 3 days in both young and older adults. These findings suggest that older adults had preserved but positive bias of sleep-related memory consolidation, which could be one of the underlying mechanisms for their generally better emotional well-being in daily life. These findings highlight the dynamic interplay among sleep and emotional memory in older adults.

A small proportion of litter-derived nitrogen is assimilated by plant biomass or immobilized in sediments regardless of harvest management as detected by 15N-labeled Phragmites litter in a constructed wetland.

Emergent aquatic macrophytes play an important role in the removal of nutrients in constructed wetlands (CWs). However, plant biomass supplies litter after the onset of senescence. Although litter-derived nitrogen (N) has been considered a nutrient source for the internal loading that may reduce CW performance, little is known about the quantitative N dynamics associated with litter decomposition. Thus, a controversial question remains about whether plant harvest is needed to manage CWs. In this study, we evaluated the decomposition and the fate of N derived from 15N-labeled Phragmites litter in a CW for 1 year. To simulate respective natural conditions, two treatments, including (1) a single winter harvest and (2) no harvest where the latter supplies a greater stem litterfall, were compared. Although the dry weight of the added stem litter was approximately 4.7 times larger in the no harvest plot than in the harvest plot, the total N content of the initial 15N-labeled litter was only 1.2 times higher in the no harvest plot than in the harvest plots because of the low N concentration in the stem litter. The litter functioned as a minor N sink within the first 6 months of decomposition, and it then shifted to functioning as a minor N source after 1 year of decomposition. The recovery of litter-derived N in the sediment and plant biomass was low (less than 10% of the initial litter N), and much of the remaining N might have been released into ambient water or lost through denitrification. Furthermore, our results suggested a potentially low contribution of litter-derived N to internal N loading for at least 1 year regardless of the harvest management treatment.

Exomic and Epigenomic Analyses in a Pair of Monozygotic Twins Discordant for Cryptorchidism.

Cryptorchidism represents one of the most common human congenital anomalies. In most cases, its etiology remains unclear and seems to be multifactorial. In the present study, a pair of monozygotic twins discordant for cryptorchidism was identified. Twin zygosity was confirmed by microsatellite genotyping. Whole exome sequencing and methylated DNA immunoprecipitation sequencing (MeDIP-Seq) of DNA extract from leucocytes were performed to, respectively, evaluate their exomes and epigenomes. No differences in exome sequencing data were found between the twins after validation. MeDIP-Seq analysis detected 5,410 differentially hypermethylated genes and 2,383 differentially hypomethylated genes. Bioinformatic analysis showed that these genes belonged to several biological processes and signaling pathways, including regulation of actin cytoskeleton, which has been previously implicated in the etiology of cryptorchidism. The findings of the present study suggest that non-genetic factors might contribute to the pathogenesis of cryptorchidism.

Effect of Phragmites japonicus harvest frequency and timing on dry matter yield and nutritive value.

Phragmites is a cosmopolitan perennial emergent macrophyte that is distributed worldwide. In recent years, Phragmites has attracted attention for its potential use as roughage. Given the increasing demand for feed and the number of constructed wetlands (CWs) vegetated with Phragmites, Phragmites is expected to play an important role in roughage production. Thus, it is vital to understand the effects of harvest timing and frequency on dry matter yield, nutritive value, and nitrogen (N) removal to establish appropriate vegetation management. In two CWs in Southwest China, four treatments with different harvesting frequencies were evaluated in monospecific areas of P. japonicus. The four treatments included no harvest, single harvest at 6 months, two harvests at 2 and 4 months, and three harvests at 2, 4, and 6 months. A sharp decline in the total digestible nutrients (TDN) concentration and the rate of increase in dry matter (DM) yield was associated with the heading timings, and the seasonal variations in TDN were likely influenced by carbohydrate accumulation in the stems. The three harvest treatment contributed to substantially improve the N and DM yields without decreasing the nutritive value but negatively affected the growth in the following year. Therefore, not only the combinations of harvest timing and frequency but also other management practices, including partial harvesting, may be needed to optimize CW performance and roughage production.

Safety in Treating Primary Acute Angle-closure Glaucoma under High Intraocular Pressure by Compound Trabeculectomy.

In clinical practice, Primary Acute Angle-closure Glaucoma (APACG) is a common disease with an increasing incidence rate and blind rate, and has attracted attention of medical researchers. When a patient suffers both primary acute glaucoma and high tension glaucoma, drug therapy can achieve limited efficacy, and operative treatment is necessary on this occasion. This research mainly explored the safety in treating high tension APACG by compound trabeculectomy, and observed the clinical treatment effect and incident rate of postoperative complications after compound trabeculectomy. The compound trabeculectomy can effectively control the intraocular pressure and decrease the incident rate of postoperative complications, accelerating the rehabilitation of patients.

Autoantibody and human leukocyte antigen profiles in children with autoimmune liver disease and their first-degree relatives.

OBJECTIVE: Familial clustering of juvenile autoimmune liver disease (AILD), including autoimmune hepatitis and autoimmune sclerosing cholangitis (ASC), is rare, despite a high prevalence of autoimmune disorders in AILD families. METHODS: To investigate this discrepancy, we measured autoantibodies diagnostic for AILD, anti-nuclear, anti-smooth muscle, anti-liver kidney microsomal type 1, anti-liver cytosol type 1, and anti-soluble liver antigen antibodies, and human leukocyte antigen profiles in 31 patients and 65 of their first-degree relatives (FDR). The autoantibody profile was compared with that of 42 healthy subjects (HS). RESULTS: Autoantibodies were detected in 71% (22/31) patients. Anti-nuclear antibody or anti-smooth muscle antibody were present in 4/65 FDR (6.2%). HS were negative for all autoantibodies. The frequencies of homozygous HLA DRB1*0301 (DR3) genes and haplotype A1-B8-DR3 were higher in the patients (25% and 43%) than in FDR (9% and 27%) and HS (0% and 16%). The frequencies of disease-protective genes DR4 and/or DR15 were lower in the patients (25%) than in FDR (42%) and HS (42%). Only 1 family contained 2 patients with AILD, 1 with ASC and 1 with primary sclerosing cholangitis. Both patients possessed A1-B8-DR3 genes, the ASC being homozygous and the primary sclerosing cholangitis heterozygous. Six FDR had nonhepatic autoimmune disorders, none being autoantibody positive. CONCLUSIONS: Homozygosity for DR3 plays a major role in the predisposition to juvenile AILD. Diagnostic autoantibodies for AILD are rare among patients' FDR and not linked to clinical manifestation of AILD.

Clinical assessment of reformed lumbar microdiscectomy.

The aim of this study was to evaluate the clinical outcomes of the reformed lumbar microdiscectomy preserving more ligamentum flavum than the traditional microdiscectomy does. A prospective, randomized, controlled clinical study was conducted. Patients with unilateral lumbar disc herniation were randomly divided into two groups. The control group underwent traditional lumbar microdiscectomy, and the test group patients underwent the same procedure but with a curved incision of the lumbodorsal fascia and with more preservation of the ligamentum flavum. Visual analogue scale (VAS) scores and Oswestry scale scores were used to appraise the outcomes. Both groups' clinical parameters were significantly improved after the operation. The VAS scores in the test group showed a less intensity than that in the control group at 3 days, 12 weeks after the operation (P < 0.05), while at 1 year, showed no significant difference. Both groups' postoperative leg pain was significantly relieved (P < 0.05). The VAS scores for leg pain had no significant difference between the two groups at any testing time point after the surgery (P > 0.05). The Oswestry scale scores showed a better lumbar function state in the test group than that in the control group at 12 weeks and 1 year after the operation (P < 0.05). In both groups, there was no patient who had a lumbar disc reherniation. Preserving more ligamentum flavum is helpful to improve the clinical outcomes, and this improvement maybe resulted from the prevention of the fibrosis-related complication and the stability of the spine.

Childhood Adversities and Caregiving for Older Parents: Building Capacity for a Caring Society.

OBJECTIVES: This study investigates the relationships between childhood adversities and the provision of informal care for older parents in later life in China. METHODS: The data came from 4 waves of the China Health and Retirement Longitudinal Study (N = 20,047). Using multilevel logistic regression models, we examined the relationships between adverse experiences in childhood and both the propensity and intensity of caregiving for older parents. Drawing on the regression results, we then estimated the total number of caregivers for older parents in China. RESULTS: Experiencing 1 additional childhood adversity was associated with a decrease of 8% in the odds of providing informal care (p < .001). The association between childhood adversity and caregiving remained significant after sociodemographic factors and later-life outcomes were controlled for. We estimated that 58.3 million middle-aged adults in China were providing care for parents in 2020. Had people experienced 1 fewer adversity in their childhood, there would have been 2.2 million more caregivers in 2020. Had they experienced 2 fewer adversities, there would have been 3.4 million more caregivers. DISCUSSION: The factors associated with informal caregiving can be traced back to early-life experiences. To address the shortage of informal care supply, it is crucial to foster a caring culture from the very beginning of human development.

Bioinformatics analysis for the identification of Sprouty-related EVH1 domain-containing protein 3 expression and its clinical significance in thyroid carcinoma.

The poorly differentiated thyroid carcinoma (THCA) subtype is associated with an aggressive disease course, a less favorable overall prognosis, and an increased risk of distant organ metastasis. In this study, our objective was to explore the potential utility of the Sprouty-related EVH1 domain-containing protein 3 (SPRED3) as a biomarker for early diagnosis and prognosis in THCA patients. The differentially expressed prognostic-related genes associated with THCA were identified by querying The Cancer Genome Atlas (TCGA) database. The difference in the expression of the SPRED3 gene between thyroid carcinoma (THCA) tissues and normal tissues was analyzed using data from The Cancer Genome Atlas (TCGA) and further validated through immunohistochemistry. Univariate and multivariate Cox regression models were used, along with clinical information from THCA patients, to analyze the prognostic value of the SPRED3 gene in THCA patients. Functional enrichment analysis was subsequently performed to elucidate the molecular mechanisms underlying the regulatory effects of the SPRED3 gene on thyroid carcinoma. Additionally, we calculated the percentage of infiltrating immune cells in THCA patients and evaluated their correlation with SPRED3 gene expression. Compared with those in noncancerous thyroid tissue, the gene and protein expression levels of SPRED3 were found to be elevated in thyroid carcinoma tissues. Furthermore, the expression of SPRED3 in thyroid carcinoma exhibited significant correlations with tumor location, histological grade, pathological stage, and tumor node metastasis classification (TNM) stage. Univariate and multivariate Cox proportional hazards (Cox) regression analyses demonstrated that SPRED3 could serve as an independent prognostic factor for predicting the overall survival of THCA patients. The results of functional enrichment analysis suggested the potential involvement of SPRED3 in the regulation of extracellular matrix organization, epidermal development, signaling receptor activator activity, skin development, receptor ligand activity, glycosaminoglycan binding, neuroactive ligand‒receptor interaction, the IL-17 signaling pathway, and the PI3K-Akt signaling pathway. Additionally, there were significant correlations between the expression level of the SPRED3 gene and the infiltration of various immune cells (eosinophils, central memory T cells, neutrophils, macrophages, and NK cells) within the thyroid tumor microenvironment. SPRED3 can be used as a prognostic biomarker in patients with THCA could potentially be therapeutic target for THCA.

Structure elucidation and anticancer activity of a heteropolysaccharide from white tea.

White tea, one of the six traditional teas in China, is made only through natural withering and low-temperature drying processes. It demonstrates diverse pharmacological and health-promoting effects, including antioxidant, antiviral, anticancer, and hypolipidemic activities. Despite the significance of polysaccharides in white tea leaves, their fine structure and physiological functions remain unexplored. In this study, the polysaccharide fragment WTP-80a with anticancer activity was isolated and purified from white tea through water extraction, alcohol precipitation, DEAE-52 ion exchange column chromatography, and sephacryl S-200 dextran gel column chromatography. WTP-80a exhibited a molecular weight of 1.14 × 105 Da and consisted of galactose (Gal), arabinose (Ara), rhamnose (Rha), and glucuronic acid (Glc-UA). The main chain skeleton of WTP-80a contained 3,6)-ß-Galp-(1→, 3)-α-Galp-(1→, 5)-α-Araf-(1 â†’ and 3)-α-Glcp-UA-(1→. Branch chains included α-Araf-(1 â†’ and ß-Rhap-(1 â†’ connected to the C3 and C6 positions of →3,6)-ß-Galp-(1→, respectively. In vitro anticancer experiments revealed that WTP-80a effectively hindered the proliferation, colony formation, migration, and invasion of B16F10 cells. Additionally, it induced apoptosis in B16F10 cells by blocking the G2/M phase, increasing active oxygen content, and reducing mitochondrial membrane potential. These findings provide a solid theoretical foundation for the application of white tea polysaccharides as anticancer products.

Therapeutic potential of cannabidiol (CBD) in anxiety disorders: A systematic review and meta-analysis.

Cannabidiol (CBD), as one of the phytocannabinoids, has a wide range of therapeutic properties for various neuropsychiatric disorders due to central nervous system effects. These therapeutic properties demonstrated by preclinical and clinical studies encompass more than just anticonvulsant, anti-arthritic, analgesic, anti-inflammatory, antioxidant, antitumor, antiemetic, antipsychotic and neuroprotective effects. It has been hypothesized that CBD holds potential in the treatment of various neuropsychiatric and anxiety disorders. Thus, PRISMA was used as a guide for our systematic review. Eight of the 1550 articles screened in June 2023 were eligible for meta-analysis. Based on the 316 participants included in these eight articles, this meta-analysis revealed a substantial significant impact of CBD on anxiety with a considerable effect size (Hedges' g = -0.92, 95% CI -1.80 to -0.04). In addition, this meta-analysis focuses on the efficacy of CBD in treating anxiety disorders such as generalized anxiety disorder (GAD), social anxiety disorder (SAD), and post-traumatic stress disorder (PTSD). However, caution should be exercised in interpreting our findings due to the limited size of the clinical sample, and additional trials ought to be carried out if deemed necessary.