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To evaluate the association between serum uric acid (SUA) and kidney function decline. Data was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older population for analysis. The kidney function decline was defined as an annual estimated glomerular filtration rate (eGFR) decrease by > 3 mL/min per 1.73 m2. Multivariable logistic regression was applied to determine the association between SUA and kidney function decline. The shape of the association was investigated by restricted cubic splines. A total of 7,346 participants were included, of which 1,004 individuals (13.67%) developed kidney function decline during the follow-up of 4 years. A significant dose-response relation was recorded between SUA and the kidney function decline (OR 1.14, 95% CI 1.03–1.27), as the risk of kidney function decline increased by 14% per 1 mg/dL increase in SUA. In the subgroup analyses, such a relation was only recorded among women (OR 1.22, 95% CI 1.03–1.45), those aged < 60 years (OR 1.22, 95% CI 1.05–1.42), and those without hypertension and without diabetes (OR 1.22, 95% CI 1.06–1.41). Although the dose-response relation was not observed in men, the high level of SUA was related to kidney function decline (OR 1.83, 95% CI 1.05–3.17). The restricted cubic spline analysis indicated that SUA > 5 mg/dL was associated with a significantly higher risk of kidney function decline. The SUA level was associated with kidney function decline. An elevation of SUA should therefore be addressed to prevent possible kidney impairment and dysfunction. [ABSTRACT FROM AUTHOR]

The five-year survival rate for patients with hepatocellular carcinoma (HCC) is only 20 %, highlighting the urgent need to identify new therapeutic targets and develop potential therapeutic options to improve patient prognosis. One promising approach is inhibiting autophagy as a strategy for HCC treatment. In this study, we established a virtual docking conformation of the autophagy promoter ULK1 binding XST-14 derivatives. Based on this conformation, we designed and synthesized four series of derivatives. By evaluating their affinity and anti-HCC effects, we confirmed that these compounds exert anti-HCC activity by inhibiting ULK1. The structure-activity relationship was summarized, with derivative A4 showing 10 times higher activity than XST-14 and superior efficacy to sorafenib against HCC. A4 has excellent effect on reducing tumor growth and enhancing sorafenib activity in HepG2 and HCCLM3 cells. Moreover, we verified the therapeutic effect of A4 in sorafenib-resistant HCC cells both in vivo and in vitro. These results suggest that inhibiting ULK1 to regulate autophagy may become a new treatment method for HCC and that A4 will be used as a lead drug for HCC in further research. Overall, A4 shows good drug safety and efficacy, offering hope for prolonging the survival of HCC patients. [ABSTRACT FROM AUTHOR]

Pseudomyxoma peritonei (PMP) is an extremely rare condition. Information regarding the disease burden of PMP in developing countries is limited. This study aimed to determine the epidemiology of PMP in China. PMP data were extracted from the national databases of Urban Basic Medical Insurance. All cases were identified using the International Classification of Diseases (ICD) codes and Chinese diagnostic terms. The national prevalence from 2012 to 2016 and incidence in 2016 were estimated. In total, 153 patients with PMP were identified. The crude prevalence of PMP in 2016 was 2.47 (95% confidence interval [CI] 1.71 to 3.23) per million person-year, with a higher prevalence in females than males. Prevalence increased with age, with the first peak in those aged 15–29 years and the highest in those aged >80 years. The crude incidence of PMP in 2016 was 1.19 (95% CI 0.59 to 1.78) per million person-years. Similar to the prevalence, the rates were higher in women than in men. The incidence also increased with age, with the highest prevalence in those aged >80 years. Besides, the most frequent comorbidities before and after the first diagnosis of PMP were unspecified secondary malignancies and malignancies of unspecified sites, followed by abdominal malignant tumours. The rate of PMP was lower in mainland China than in European countries and increased with advancing age. Women were more likely to have PMP than men. Furthermore, an insufficient understanding of this rare disease presents a major challenge in accurately evaluating the disease burden. [ABSTRACT FROM AUTHOR]

The inferior parathyroid gland (IPTG) is widely distributed; effective techniques for its safe exploration and protection during thyroid surgery have not been documented. The thyrothymic ligament (TTL) is a connective tissue located between the thymic tongue and thyroid. This study aims to introduce a novel meticulous thyrothymic ligament dissection technique and assess its role in proactive exploration and situ preservation of IPTG. 737 patients undergoing initial thyroid surgery between 2017 and 2021 in the Department of General Surgery of the First Affiliated Hospital of Nanjing Medical University were retrospectively recruited for this clinical study. In 391 of the recruited patients, the TTL was dissected, and the number and location of IPTG were recorded. Among them, 214 patients underwent total/near-total thyroidectomy (TT) plus central neck dissection (CND) were assigned to the observation group. The control group included 346 consecutive patients who underwent conventional TT plus CND. After 1:1 propensity score matching, each group contained 206 patients. The incidence of postoperative hypoparathyroidism was recorded. Among the 391 patients, 596 sides were dissected, out of which 436 sides (73.2%) had TTL, and approximately 90.1% of IPTG were located and identified. A statistically significant difference in incidence of temporary (27.7 vs. 49.0%, P < 0.001) and permanent hypoparathyroidism (0 vs. 8.2%, P = 0.047) was noted between the observation group and the control group. The meticulous thyrothymic ligament dissection technique helps to protect IPTG in situ and reduce the incidence of postoperative hypoparathyroidism. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To develop and validate 2 iodine maps based radiomics nomograms for preoperatively predicting cervical lymph node metastasis (LNM) and central lymph node metastasis (CLNM) in papillary thyroid cancer (PTC).Materials and Methods: A total of 346 patients with PTC were enrolled and allocated to training (242) and validation (104) sets. Radiomics features were extracted from arterial and venous phase iodine maps, respectively. Aggregated machine-learning strategy was applied for features selection and construction of 2 radiomics scores (LN rad-score; CLN rad-score). Logistic regression model was employed to establish two radiomics nomograms (nomogram 1: predicting LNM; nomogram 2: predicting CLNM) after incorporating LN or CLN rad-score with clinical predictors. Nomograms performance was determined by discrimination, calibration and clinical usefulness.Results: Nomogram 1 incorporated LN rad-score, age (categorized by 55) and CT reported LN status; Nomogram 2 incorporated CLN rad-score, capsule contact >25% and CT reported CLN status. 2 nomograms both showed good discrimination and calibration in the training (AUC = 0.847; AUC = 0.837) and validation cohorts (AUC = 0.807; AUC = 0.795). Significant improved AUC, net reclassification index (NRI) and integrated discriminatory improvement (IDI) confirmed additional great predictive value of 2 rad-scores, compared with clinical models without radiomics. Decision curve analysis indicated clinical utility of nomograms. 2 nomograms both demonstrated favorable predictive efficacy in CT reported LN or CLN negative subgroup (AUC = 0.766; AUC = 0.744).Conclusion: The presented 2 radiomics nomograms are useful tools for preoperative prediction of LNM and CLNM in PTC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Laminaria japonica is shown to bind with VEGF by HerboChip screening platform. • Laminaria japonica suppresses VEGF-induced angiogenesis and related signalings. • Laminaria japonica may act as a potential therapeutic agent for prevention and clinical treatment of angiogenesis-related diseases. Laminaria japonica (LJ) is a common seaweed, which has been widely used as functional food and medicine, but its pharmaceutical activities in angiogenic regulation are unclear. Here, different lines of studies provide evidence to the suppressive effects of LJ extract in VEGF-medicated angiogenic function. In cellular level, LJ extract significantly inhibited VEGF-mediated endothelial cell proliferation, migration, invasion and tube formation. For in vivo verification, LJ extract suppressed the VEGF-induced formation of sub-intestinal vessels in zebrafish embryo model. In signalling cascades, LJ extract decreased the amount of phosphorylated VEGF receptor-2, as triggered by VEGF, and subsequently some key related downstream elements were obviously inactivated. In parallel, NO production and ROS formation, as induced by VEGF, were significantly attenuated. Thus, these preclinical findings promoted the possible development of LJ extract as a potential therapeutic agent for prevention and clinical treatment of angiogenesis-related diseases. [ABSTRACT FROM AUTHOR]

To evaluate the effects of incretin-based therapies on body weight as the primary outcome, as well as on body mass index (BMI) and waist circumference (WC) as secondary outcomes. Databases including Medline, Embase, the Cochrane Library, and clinicaltrials.gov (www.clinicaltrials.gov) were searched for randomized controlled trials (RCTs). Standard pairwise meta-analysis and network meta-analysis (NMA) were both carried out. The risk of bias (ROB) tool recommended by the Cochrane handbook was used to assess the quality of studies. Subgroup analysis, sensitivity analysis, meta-regression, and quality evaluation based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were also performed. A total of 292 trials were included in this study. Compared with placebo, dipeptidyl-peptidase IV inhibitors (DPP-4Is) increased weight slightly by 0.31 kg [95% confidence interval (CI): 0.05, 0.58] and had negligible effects on BMI and WC. Compared with placebo, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lowered weight, BMI, and WC by –1.34 kg (95% CI : –1.60, –1.09), –1.10 kg/m2 (95% CI : –1.42, –0.78), and –1.28 cm (95% CI : –1.69, –0.86), respectively. GLP-1 RAs were more effective than DPP-4Is in lowering the three indicators. Overall, the effects of GLP-1 RAs on weight, BMI, and WC were favorable. [ABSTRACT FROM AUTHOR]

Rare diseases encompass a diverse group of genetic disorders that affect a small proportion of the population. Identifying the underlying genetic causes of these conditions presents significant challenges due to their genetic heterogeneity and complexity. Conventional short-read sequencing (SRS) techniques have been widely used in diagnosing and investigating of rare diseases, with limitations due to the nature of short-read lengths. In recent years, long read sequencing (LRS) technologies have emerged as a valuable tool in overcoming these limitations. This minireview provides a concise overview of the applications of LRS in rare disease research and diagnosis, including the identification of disease-causing tandem repeat expansions, structural variations, and comprehensive analysis of pathogenic variants with LRS. [ABSTRACT FROM AUTHOR]

Background Over 80% of head and neck cancer patients suffer from radiotherapy-induced xerostomia (dry mouth). Xerostomia affects cancer patients' quality of life, and xerostomia sometimes persists throughout the patients' lifetime. This review aimed to evaluate the effectiveness and safety of Chinese herbs in relieving radiotherapy induced xerostomia. Methods Systematic searches were conducted on 6 databases (English and Chinese). Studies published up till May 2017 were considered for inclusion. Results A final 14 RCTs (total 994 head and neck cancer patients undergoing radiotherapy) compared Chinese herbs with no herbs, were included in analysis. Very low to moderate quality of evidence found Chinese herbal treatment may relief radiotherapy-induced xerostomia and other related complications (such as oral mucositis and loss of appetite) in head and neck cancer patients. Conclusion There is limited evidence that Chinese herbal treatment may relief radiotherapy-induced xerostomia and other related complications in head and neck cancer patients. [ABSTRACT FROM AUTHOR]

Protein chemical synthesis can provide the homogeneous atypical ubiquitin chains that are usually difficult to obtain by other methods. Herein, we report a new one-pot ligation approach for the synthesis of atypical Ub chains based on the Tfacm-protected isoUb building block with operational simplicity and high efficiency. The key intermediate, the Tfacm-protected isoUb building block can be readily prepared by Fmoc SPPS. The practicality and efficiency of the new method is demonstrated by the successful preparation of K11-linked di-Ub. [ABSTRACT FROM AUTHOR]

Background: Isolated distal deep venous thrombosis (IDDVT) is a common complication after ischemic stroke. However, there is a paucity of evidence regarding the clinical features and risk factors of IDDVT in patients with acute ischemic stroke. This study aimed to establish and validate a clinical prediction scale of IDDVT at an early stage of ischemic stroke development.Methods: We retrospectively studied consecutive patients with stroke admitted to our neurology department between January and December 2016. Selected clinical variables were assessed by multivariable logistic regression to determine the independent risk factors for IDDVT. A prediction scale was developed and verified by the receiver operating characteristic curve.Results: A total of 671 patients with ischemic stroke were included in the study, with 450 patients allocated into the derivation group and 221 patients into the validation group. A substantial proportion (22.1%) of patients developed IDDVT. A 16-point prediction scale (female gender = 2, older age [≥60 years] = 3, atrial fibrillation = 2, acute infection = 2, active cancer = 5, and higher [≥2.6 mmol/L] level of low-density lipoprotein = 2) derived from a multivariable logistic regression model was highly predictive of 10-day risk of IDDVT in both the validation group (c statistic = .70, 95% confidence interval [CI], .63-0.78, P < .0001) and the derivation group (c statistic = .68, 95% CI, .63-0.74, P < .0001).Conclusions: This prediction scale may help to identify patients with ischemic stroke who are at a higher risk of developing IDDVT. [ABSTRACT FROM AUTHOR]

CAP-Gly domain of dynactin, a microtubule-associated activator of dynein motor, participates in multiple cellular processes, and its point mutations are associated with neurodegenerative diseases. Recently, we have demonstrated that conformational plasticity is an intrinsic property of CAP-Gly. To understand its origin, we addressed internal dynamics of CAP-Gly assembled on polymeric microtubules, bound to end-binding protein EB1 and free, by magic angle spinning NMR and molecular dynamics simulations. The analysis of residue-specific dynamics of CAP-Gly on time scales spanning nano- through milliseconds reveals its unusually high mobility, both free and assembled on polymeric microtubules. On the contrary, CAP-Gly bound to EB1 is significantly more rigid. Molecular dynamics simulations indicate that these motions are strongly temperature-dependent, and loop regions are surprisingly mobile. These findings establish the connection between conformational plasticity and internal dynamics in CAP-Gly, which is essential for the biological functions of CAP-Gly and its ability to bind to polymeric microtubules and multiple binding partners. In this work, we establish an approach, for the first time, to probe atomic resolution dynamic profiles of a microtubule-associated protein assembled on polymeric microtubules. More broadly, the methodology established here can be applied for atomic resolution analysis of dynamics in other microtubule-associated protein assemblies, including but not limited to dynactin, dynein, and kinesin motors assembled on microtubules. [ABSTRACT FROM AUTHOR]

Highlights: [•] TEVp is a unique enzyme with the specific enzymatic activity. [•] Hg2+ induced the increased hydrophobicity around the chromophores in TEVp. [•] Hg2+ quenched the fluorescence of TEVp mainly in a static process. [•] TEVp and Hg2+ possibly formed a complex with the molar ratio of 1:1. [•] Hg2+ may bind to the residues His46 and Cys151 and increase β-sheet in TEVp. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the incidence of Ketoconazole associated hepatotoxicity and related factors. Methods: Literature retrieval was conducted by using multi-databases for meta-analysis on Ketoconazole associated hepatotoxicity. The data were collected with a standardized form. Overall estimation of incidence of hepatotoxicity for specific study type was calculated by using a DerSimonian-Laird random-effects model owing to the substantial differences among the studies. Results: Totally 204 eligible studies were included in the analysis. The incidence of Ketoconazole associated hepatotoxicity was 3.6%-4.2%. The dosage and duration specific subgroup analyses did not show any significant difference among groups, while the age specific subgroup analysis showed the incidence in children and people aged >60 years was 1.4% (95% CI: 0.5%-4.2%) and 3.2% (95% CI: 1.1%-8.7%) respectively. Additionally, the incidence of the hepatotoxicity was higher in people who had oral administration of ketoconazole beyond the provisions of the usage instructions, and the incidence was 5.7% (95% CI: 4.5%-7.2%). Conclusion: Ketoconazole associated hepatotoxicity was common. Off-label use might increase the risk of liver damage. Well-designed large sample studies are needed to identify the risk factors in future. [Copyright &y& Elsevier]

Abstract: Three-dimensional (3D) quantitative structure–activity relationship (QSAR) and docking studies of 43 tubulin inhibitors, 2-phenylindole derivatives with anticancer activity against human breast cancer cell line MDA-MB 231, have been carried out. The established 3D-QSAR model from the comparative molecular field analysis (CoMFA) in training set shows not only significant statistical quality, but also satisfying predictive ability, with high correlation coefficient value (R 2 =0.910) and cross-validation coefficient value (q 2 =0.705). Moreover, the predictive ability of the CoMFA model was further confirmed by a test set, giving the predictive correlation coefficient (R 2 pred) of 0.688. Based on the CoMFA contour maps and docking analyses, some key structural factors responsible for anticancer activity of this series of compounds were revealed as follows: the substituent R1 should have higher electronegativity; the substituent R2 should be linear alkyl with four or five carbon atoms in length; and the substituent R3 should be selected to OCH3-kind group whereas should not be selected to CF3-kind group. Meanwhile, the interaction information between target and ligand was presented in detail. Such results can offer some useful theoretical references for understanding the action mechanism, designing more potent inhibitors and predicting their activities prior to synthesis. [Copyright &y& Elsevier]

Abstract: Studies on the electronic structures and trend in DNA-binding affinities of a series of Co(Ш) complexes have been carried out, using the density functional theory (DFT) at the B3LYP/LanL2DZ level. The optimized geometric structures of these Co(Ш) complexes in aqueous solution are more close to experimental data than those in vacuo. The electronic structures of these Co(Ш) complexes were analyzed on the basis of their geometric structures optimized in aqueous solution, and the trend in the DNA-binding constants (K b) was reasonably explained. In addition, the electronic absorption spectra of these complexes were calculated and simulated in aqueous solution using the time dependent DFT (TDDFT) at the B3LYP/LanL2DZ level. The calculated absorption spectra of these Co(Ш) complexes in aqueous solution are in satisfying agreement with experimental results, and the properties of experimental absorption bands have been theoretically explained in detail. Meanwhile, in order to explore the solvent effect on the absorption spectra of these Co(Ш) complexes, their absorption spectra in vacuo were also calculated, and the results show that the calculated absorption spectra of Co(Ш) complexes are greatly influenced by the solvent effect. [Copyright &y& Elsevier]

Abstract: The quantitative structure–activity relationship (QSAR) of 32 flavone and isoflavone derivatives with cytotoxicity expressed as pGC50, which is defined as the negative value of the logarithm of necessary molar concentration of this series of compounds to cause 50% growth inhibition against the human cervical epithelioid carcinoma cell line (HeLa), has been studied by using the density functional theory (DFT), molecular mechanics (MM2) and statistical methods. In order to obtain QSAR model with high predictive ability, the original dataset was randomly divided into a training set comprising 26 compounds and a test set comprising the rest 6 compounds. An optimal model for the training set with significant statistical quality () and predictive ability (q 2 =0.818) was established. The same model was further applied to predict pGC50 values of the 6 compounds in the test set, and the resulting predictive correlation coefficient reaches 0.738, further showing that this QSAR model has high predictive ability. It is very interesting to find that the cytotoxicities of these compounds against HeLa appear to be mainly governed by two quantum-chemical factors, i.e., the energy (E LUMO) of the lowest unoccupied molecular orbital (LUMO) and the net charges of C atom at site 6 on aromatic rings (Q C6). Here the possible action mechanism of these compounds was analyzed and discussed in detail, in particular, the fact why the flavone derivatives have considerably higher cytotoxicity than isoflavone derivatives was reasonably explained. Based on this QSAR equation, 5 new compounds with higher cytotoxicity have been theoretically designed. Such results can offer useful theoretical references for experimental works. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the sensitivity of serum tartrate-resistant acid phosphatase 5b(Tracp5b) activity in monitoring bisphosphonate treatment results of bone metastasis in breast cancer(BC) patients. Methods: The serum activities of Tracp5b, CEA, CA153 were measured in 58 BC patients, including 26 without bone metastasis, 32 with bone metastasis. The serum activities of Tracp5b, CEA, CA153 were also measured in 19 patients with bone metastasis after 3 months of bisphosphonate treatment. Eighteen healthy women with age from 34 to 70 served as control. Results: Serum Tracp5b was significantly elevated in patients with bone metastasis compared with that in all any other groups(P < 0.05). The sensitivity of Tracp5b was 78.13% and the specificity was 86.36%. The sensitivity of CA153 was 37.50% and the specificity was 77.27%. The sensitivity of CEA was 21.88% and the specificity was 84.09%. The serum activity of Tracp5b decreased significantly(P < 0.05) after 3 months of bisphosphonate treatment, while the levels of CA153 and CEA were unchanged. Conclusion: Serum Tracp5b activity is a useful diagnostic marker for bone metastasis in BC patients and can be used to evaluate the treatment results of bisphosphonate. [Copyright &y& Elsevier]

Multifocal Papillary thyroid carcinoma (PTC) is a very common condition. In certain cases, it is possible to find tens to hundreds of foci with a diffuse intrathyroidal spread in the whole thyroid with no stromal fibrosis. Herein, PTC with such features was nominated as diffuse disseminate variant (DDV) PTC. The aim of the present study was to investigate the histopathological characteristics, molecular features, and biological behavior of DDV and compare the characteristics of DDV to diffuse sclerosing variant (DSV) PTC. Thirty-four DDV and 23 DSV cases were identified from consecutive surgical specimens diagnosed with PTC between 2014 and 2019. Targeted next-generation sequencing (NGS) was applied to investigate the mutation spectrum of DDV and DSV. DDV was commonly diagnosed in young patients and exhibited high rates of LNM (100 %), ETE (61.8 %), and LVI (44.1 %); however, they did not differ from DSV (P > 0.05). Male patients were more frequently diagnosed with DDV than with DSV (P < 0.001). The size of the largest tumor was significantly greater in DDV than in DSV patients (P = 0.008). In addition, BRAFV600E mutation was significantly higher in the DDV than in the DSV group (P < 0.001). The RET/PTC rearrangement was more frequent in DSV than in DDV patients; however, the difference was not statistically significant (P = 0.106). Moreover, DDV had a higher rate of recurrence compared to DSV treated with the same protocol (total thyroidectomy followed by radioactive iodine (RAI) treatment) (47.1 % and 8.7 %, P = 0.002). DDV should be regarded as a novel aggressive variant of PTC with distinct clinicopathological characteristics, aggressive biological behaviors, and a high recurrence. [ABSTRACT FROM AUTHOR]

[Display omitted] Hyperglycaemic memory refers to the damages occurred under early hyperglycaemic environment in organs of diabetic patients persisting after intensive glycaemic control. Mammalian sterile 20-like kinase 1 (Mst1) contributes to the development of diabetic cardiomyopathy. Here, we investigated the role of Mst1 in hyperglycaemic memory and test the effect of XMU-MP-1, a Mst1 inhibitor, on hyperglycaemic memory in hearts. Eight weeks after induction of type 1 diabetes by injection with streptozotocin (STZ) in mice, glycaemic control was obtained by means of insulin treatment and maintained for 4 additional weeks. In the diabetic mice, insulin treatment alone did not reduce phosphorylation of Mst1 or improve cardiac function. Treatment with XMU-MP-1 alone immediately after induction of diabetes for 12 weeks did not improve myocardial function in mice. But treatment with XMU-MP-1 for the later 4 weeks relieved myocardial dysfunction when glycaemic control was obtained by insulin treatment simultaneously. Mst1 deficiency and glycaemic control synergistically improved myocardial function and reduced apoptosis in myocardium of diabetic mice. Mechanistically, when Mst1 was deficient or inhibited by XMU-MP-1, AMPK was activated and mitochondrial dysfunction was attenuated. In vitro, treatment with AMPK activator reversed the detrimental effects of Mst1 overexpression in cultured cardiomyocytes. XMU-MP-1 might thus be envisaged as a complement for insulin treatment against diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

• Isoflavone puerarin supplement prevents intestinal damage. • Puerarin decreased permeability of intestinal epithelial cell. • Puerarin inhibited the NF-κB pathway, and activated the MAPK-ERK pathways. Increasing functional food ingredients such as flavonoids have been confirmed to exhibit significant effects on improving the function of intestinal barrier. Puerarin, an isoflavone extracted from Pueraria, was reported to play an active role in many diseases. Our previous research found that puerarin can improve enteritis by increasing mucin secretion and increase intestinal tight connectivity in mice. In this study, Caco-2 cell model was utilized to investigate the protective effects of puerarin on ethanol-induced intestinal tight junction injury. Results exhibited that puerarin could protect the integrity of the Caco-2 monolayer and inhibit the down-regulation of tight junction proteins (Z0-1, Claudin-1 and Occludin) expression induced by ethanol. Moreover, the puerarin administration exerted antagonistic function in regulating the alterations of tight junction related signalling pathways (NF-κB, ERK1 and ERK2) induced by ethanol, which may pave the way for puerarin might function as a candidate supplement to enhance intestinal barrier function. [ABSTRACT FROM AUTHOR]

This study aimed to characterize the immunopotentiating effects and immune receptors for Coriolus versicolor mushroom polysaccharides (CVP), a Chinese medicinal fungus that exerts anti-tumor activities by enhancing host immunity. Proliferation assays were used to determine whether CVP could activate splenocytes. Flow cytometry analysis and IgM and IgG detection were used to characterize CVP-binding cells. Immune receptors were analyzed in immunoprecipitation and western blot assays. The downstream signaling pathways were identified by western blotting or immunostaining. CVP significantly stimulated the proliferation of mouse splenocytes. Fluorescence-labeled CVP (fl-CVP) selectively stained mouse B cells, but not T cells. CVP induced the production of IgM and IgG1 with or without exogenous IL-4. Membrane Ig (B cell antigen-receptor, BCR) was identified as a CVP-binding protein in immunoprecipitation and western blot experiments. CVP-induced B cell proliferation could be significantly inhibited by anti-mouse immunoglobulin (Ig) blocking antibody (Fab) or in cells from TLR4-mutant mice (C3H/HeJ). Phosphorylation of ERK-1/2 and p38 MAPK were clearly increased in a time-dependent manner, as was the nuclear translocation of the cytosolic NF-κB p65 subunit after CVP stimulation. Together, we demonstrate that CVP can bind and induce B cell activation using membrane Ig and TLR-4 as potential immune receptors. CVP activates mouse B cells through the MAPK and NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]

The fall armyworm, Spodoptera frugiperda , poses a significant threat as a highly destructive agricultural pest in many countries. Understanding the complex interplay between the insect immune system and entomopathogens is critical for optimizing biopesticide efficacy. In this study, we identified a novel microbial binding protein, SfMBP, in S. frugiperda. However, the specific role of SfMBP in the immune response of S. frugiperda remains elusive. Encoded by the LOC118269163 gene, SfMBP shows significant induction in S. frugiperda larvae infected with the entomopathogen Beauveria bassiana. Consisting of 115 amino acids with a signal peptide, an N-terminal flexible region and a C-terminal β-sheet, SfMBP lacks any known functional domains. It is expressed predominantly during early larval stages and in the larval epidermis. Notably, SfMBP is significantly induced in larvae infected with bacteria and fungi and in SF9 cells stimulated by peptidoglycan. While recombinant SfMBP (rSfMBP) does not inhibit bacterial growth, it demonstrates binding capabilities to bacteria, fungal spores, peptidoglycan, lipopolysaccharides, and polysaccharides. This binding is inhibited by monosaccharides and EDTA. Molecular docking reveals potential Zn2+-interacting residues and three cavities. Furthermore, rSfMBP induces bacterial agglutination in the presence of Zn2+. It also binds to insect hemocytes and SF9 cells, enhancing phagocytosis and agglutination responses. Injection of rSfMBP increased the survival of S. frugiperda larvae infected with B. bassiana, whereas blocking SfMBP with the antibody decreased survival. These results suggest that SfMBP acts as a pattern recognition receptor that enhances pathogen recognition and cellular immune responses. Consequently, this study provides valuable insights for the development of pest control measures. • SfMBP is a novel pattern recognition receptor in S. frugiperda. • SfMBP binds to microorganisms, peptidoglycan, lipopolysaccharide and polysaccharide. • SfMBP binds to insect hemocytes and SF9 cells. • SfMBP can enhance phagocytosis and agglutination of hemocytes. • SfMBP can increase survival of S. frugiperda infected by B. bassiana. [ABSTRACT FROM AUTHOR]

Abstract: Theoretical studies on the DNA-binding, DNA-photocleavage and spectral properties of Co(III) polypyridyl complexes [Co(phen)2(L)]3+ (L=pip, hpip, hnaip) have been carried out, using the density functional theory (DFT), Hartree–Fock (HF) and configuration interaction singles (CIS) methods. The optimized geometric structures of these Co(III) complexes in aqueous solution are more close to experimental data than those in vacuo at the B3LYP/LanL2DZ level. Based on the optimized geometric structures in solution, the electronic structures of these Co(III) complexes were analyzed and the trend in the DNA-binding constants (K b) was reasonably explained. In particular, via the analysis of natural charges of the complexes in ground state and excited state, it is very interesting to find the following: under UV or visible light irradiation, the Co(Ш) polypyridyl complexes undergo an intra-molecular electron transfer from S0 state to T1 state, and the positive charges on the main-ligand in the T1 state are greatly increased, so as to form a radical cation with strong oxidation ability. Meanwhile, the change in geometry of the complexes under light irradiation also helps to the radical cation easily approaching and further oxidating DNA-base-pairs. These results offer the theoretical explanation for the photo-induced oxidation–reduction mechanism which was experimentally proposed on DNA-photocleavage by Co(Ш) polypyridyl complexes. In addition, the electronic absorption spectra of these complexes were calculated and simulated in aqueous solution using the time dependent DFT (TDDFT) method, in satisfying agreement with experimental results, and the properties of experimental absorption bands have been theoretically explained in detail. [ABSTRACT FROM AUTHOR]

Abstract: Theoretical studies on the spectral and DNA-photocleavage properties of Co(III) and Ru(II) polypyridyl complexes [M(phen)2(pyip)] n + (M=Co(III) and Ru(II), n =3 and 2, respectively) have been carried out, using DFT, HF and CIS methods. The electronic absorption spectra of the two complexes were calculated and simulated using TDDFT and CPCM model. The calculated results show that both the geometric structure and spectra of the Co(III) complex are greatly affected by the solvent effect, whereas those of the Ru(II) complex are affected only slightly by the solvent effect. The calculated and simulated spectra of these complexes in solution are in satisfying agreement with experimental ones, and the characters of the interested spectral bands are deeply discussed. In addition, the photo-induced oxidation–reduction mechanisms on the DNA-photocleavage by Co(Ш) and Ru(II) polypyridyl complexes are also preliminarily explained in theory. [ABSTRACT FROM AUTHOR]

Abstract: The hydrolysis process of Ru(III) complex [TzH][trans-RuCl4(DMSO)(Tz)]·(DMSO) (TzNAMI), a potential antitumor complex similar to the well-known antitumor agent NAMI-A, has been investigated by using density functional theory (DFT) method, and the solution effect was also considered and calculated by conductor-like polarizable calculation model (CPCM). The structural characteristics and the detailed energy profiles for the hydrolysis processes of this complex have been obtained. The analysis of thermodynamic and kinetic characteristics of hydrolysis reaction suggests the following: for the 1st hydrolysis step, the complex TzNAMI with thiazole ligand has slightly lower hydrolysis rate than NAMI-A with imidazole ligands, and such a calculated result is in good agreement with experimental one and reasonably explained in theory. For the 2nd hydrolysis step, the formation of cis-diaqua species is thermodynamically preferred to that of trans isomer. In addition, based on the analysis of electronic characteristics of species in the hydrolysis process, the trend in nucleophilic attack abilities (A) of hydrolysis products by pertinent biomolecules is revealed. [Copyright &y& Elsevier]

Abstract: Studies on the electronic structures and related properties of a series of Co(Ш) complexes have been carried out, using the density functional theory (DFT) at the B3LYP/LanL2DZ level. The effect of the ancillary ligands on their electronic structures, DNA-binding affinities and spectra was revealed. The results show that an ancillary ligand has quite important effect on electronic structures and DNA-binding properties of these Co(Ш) complexes. The ancillary ligand possessing a great conjugated structure can effectively improve the DNA-binding affinity of the complex. Meanwhile, introducing a stronger electronegative N atom on the skeleton of ancillary ligand can obviously reduce the LUMO energy of the complex. Based on these findings, a designed complex 4 can be expected to have the greatest K b value in complexes 1–4. So it may be able to control the interaction between the complex and DNA-base-pairs via varying ancillary ligands. In addition, the electronic absorption spectra of these complexes were calculated and simulated in aqueous solution using the time-dependent DFT (TDDFT) method and the effect of the ancillary ligands on the spectra was also explored. The calculated absorption spectra of these complexes in aqueous solution are in a satisfying agreement with the experimental results, and the properties of experimental absorption bands were theoretically explained in detail. [Copyright &y& Elsevier]