Exploring the therapeutic potential of rutin through investigating its inhibitory mechanism on lactate dehydrogenase: Multi-spectral methods and computer simulation.

Lactate dehydrogenase (LDH), a crucial enzyme in anaerobic glycolysis, plays a pivotal role in the energy metabolism of tumor cells, positioning it as a promising target for tumor treatment. Rutin, a plant-based flavonoid, offers benefits like antioxidant, antiapoptotic, and antineoplastic effects. This study employed diverse experiments to investigate the inhibitory mechanism of rutin on LDH through a binding perspective. The outcomes revealed that rutin underwent spontaneous binding within the coenzyme binding site of LDH, leading to the formation of a stable binary complex driven by hydrophobic forces, with hydrogen bonds also contributing significantly to sustaining the stability of the LDH-rutin complex. The binding constant (Ka) for the LDH-rutin system was 2.692 ± 0.015 × 104 M-1 at 298 K. Furthermore, rutin induced the alterations in the secondary structure conformation of LDH, characterized by a decrease in α-helix and an increase in antiparallel and parallel ß-sheet, and ß-turn. Rutin augmented the stability of coenzyme binding to LDH, which could potentially hinder the conversion process among coenzymes. Specifically, Arg98 in the active site loop of LDH provided essential binding energy contribution in the binding process. These outcomes might explain the dose-dependent inhibition of the catalytic activity of LDH by rutin. Interestingly, both the food additives ascorbic acid and tetrahydrocurcumin could reduce the binding stability of LDH and rutin. Meanwhile, these food additives did not produce positive synergism or antagonism on the rutin binding to LDH. Overall, this research could offer a unique insight into the therapeutic potential and medicinal worth of rutin.

The potential impact of 6PPD and its oxidation product 6PPD-quinone on human health: A case study on their interaction with human serum albumin.

6PPD and its oxidation product, 6PPD-quinone have garnered widespread attention due to their adverse effects on aquatic ecosystems and human health, and are recognized as emerging pollutants. In this study, we investigated the interaction mechanism between 6PPD/6PPD-quinone and human serum albumin (HSA) through various experiments. Experimental findings reveal that the IC50 values of 6PPD-quinone and 6PPD against HEK293T cells were 11.78 and 40.04 µM, respectively. Additionally, the cytotoxicity of these compounds was regulated by HSA, displaying an inverse correlation with their binding affinity to HSA. Furthermore, 6PPD/6PPD-quinone can spontaneously insert into site I on HSA, forming a binary complex that induces changes in the secondary structure of HSA. However, their effects on the esterase-like activity of HSA exhibit a dichotomy. While 6PPD activates the esterase-like activity of HSA, 6PPD-quinone inhibits it. Molecular docking analyses reveal that both 6PPD and 6PPD-quinone interact with many amino acid residues on HSA, including TRP214, ARG222, ARG218, ALA291, PHE211. The π electrons on the benzene rings of 6PPD/6PPD-quinone play pivotal roles in maintaining the stability of complexes. Moreover, the stronger binding affinity observed between 6PPD and HSA compared to 6PPD-quinone, may be attributed to the larger negative surface potential of 6PPD.

Impacts of Halogen Substitutions on Bisphenol A Compounds Interaction with Human Serum Albumin: Exploring from Spectroscopic Techniques and Computer Simulations.

Bisphenol A (BPA) is an endocrine-disrupting compound, and the binding mechanism of BPA with carrier proteins has drawn widespread attention. Halogen substitutions can significantly impact the properties of BPA, resulting in various effects for human health. Here, we selected tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) to investigate the interaction between different halogen-substituted BPAs and human serum albumin (HSA). TBBPA/TCBPA spontaneously occupied site I and formed stable binary complexes with HSA. Compared to TCBPA, TBBPA has higher binding affinity to HSA. The effect of different halogen substituents on the negatively charged surface area of BPA was an important reason for the higher binding affinity of TBBPA to HSA compared to TCBPA. Hydrogen bonds and van der Waals forces were crucial in the TCBPA-HSA complex, while the main driving factor for the formation of the TBBPA-HSA complex was hydrophobic interactions. Moreover, the presence of TBBPA/TCBPA changed the secondary structure of HSA. Amino acid residues such as Lys199, Lys195, Phe211, Arg218, His242, Leu481, and Trp214 were found to play crucial roles in the binding process between BPA compounds and HSA. Furthermore, the presence of halogen substituents facilitated the binding of BPA compounds with HSA.

Simulation of Lower Limb Muscle Activation Using Running Shoes with Different Heel-to-Toe Drops Using Opensim.

BACKGROUND: Although numerous studies have been conducted to investigate the acute effects of shoe drops on running kinematics and kinetic variables, their effects on muscle forces remain unknown. Thus, the primary aim of this study was to compare the muscle force, kinematics, and kinetic variables of habitually rearfoot runners with heel-to-toe drops of negative 8 mm shoes (minimalist shoes) and positive 9 mm shoes (normal shoes) during the running stance phase by using musculoskeletal modeling and simulation techniques. METHODS: Experimental data of lower limb kinematics, ground reaction force, and muscle activation from 16 healthy runners with rearfoot strike patterns were collected and analyzed in OpenSim. Using Matlab, the statistical parameter mapping paired t-test was used to compare the joint angle, moment, and muscle force waveform. RESULTS: The results revealed differences in the sagittal ankle and hip angles and sagittal knee moments between the different heel-to-toe drops of running shoes. Specifically, it showed that the negative 8 mm running shoes led to significantly smaller values than the positive 9 mm running shoes in terms of the angle of ankle dorsiflexion, ankle eversion, knee flexion, hip flexion, and hip internal and hip external rotation. The peak ankle dorsiflexion moment, ankle plantarflexion moment, ankle eversion moment, knee flexion moment, knee abduction moment, and knee internal rotation also decreased obviously with the minimalist running shoes, while the lateral gastrocnemius, Achilleas tendon, and extensor hallucis longus muscles were obviously greater in the minimalist shoes compared to normal shoes. The vastus medialis, vastus lateralis and extensor digitorum longus muscles force were smaller in the minimalist shoes. CONCLUSIONS: Runners may shift to a midfoot strike pattern when wearing negative running shoes. High muscle forces in the gastrocnemius lateral, Achilleas tendon, and flexor hallucis longus muscles may also indicate an increased risk of Achilleas tendonitis and ankle flexor injuries.

Comparison of 10 obesity-related indices for predicting hypertension based on ROC analysis in Chinese adults.

Objective: To compare the predictive performance of the percentage body fat (PBF), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), waist-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), abdominal volume index (AVI), and conicity index (CI) for identifying hypertension. Methods: A cross-sectional study was conducted among 2,801 adults (1,499 men and 1,302 women) aged 18 to 81 in Ningbo, China. The receiver operator characteristic (ROC) analysis and multiple non-parametric Z tests were used to compare the areas under the curve (AUC). The maximum Youden's indices were used to determine the optimal cut-off points of 10 obesity-related indices (ORI) for hypertension risk. Results: The AUC of all the indices were statistically significant (P < 0.05). The AUC of all the indices in men and women were 0.67-0.73 and 0.72-0.79, respectively. Further non-parametric Z tests showed that WHR had the highest AUC values in both men [0.73 (95% CI: 0.70, 0.76)] and women (0.79 (95% CI: 0.75, 0.83)], and several central ORI (men: WHR, WC, BRI, AVI, and CI, 0.71-0.73; women: WC, WHR, and AVI, 0.77-0.79) were higher than general ORI (PBF and BMI, 0.68 in men; 0.72-0.75 in women), with adjusted P < 0.05. The optimal cut-off points for identifying hypertension in men and women were as follows: PBF (23.55%, 32.55%), BMI (25.72 kg/m2, 23.46 kg/m2), HC (97.59 cm, 94.82 cm), WC (90.26 cm, 82.78 cm), WHR (0.91, 0.88), WHtR (0.51, 0.55), ABSI (0.08 m7/6/kg2/3, 0.08 m7/6/kg2/3), BRI (4.05, 4.32), AVI (16.31 cm2, 13.83 cm2), and CI (1.23 m2/3/kg1/2, 1.27 m2/3/kg1/2). Multivariate logistic regression models showed that all indices were statistically significant (P < 0.05) with the adjusted ORs (per 1-SD increase) at 1.39-2.06 and ORs (over the optimal cut-off points) at 1.80-2.64. Conclusions: All 10 ORI (PBF, BMI, HC, WC, WHR, WHtR, ABSI, BRI, AVI, and CI) can effectively predict hypertension, among which WHR should be recommended as the best predictor. Central ORI (WHR, WC, and AVI) had a better predictive performance than general ORIs (PBF and BMI) when predicting the risk of hypertension.

The Effects of Breastfeeding for Four Months on Thinness, Overweight, and Obesity in Children Aged 3 to 6 Years: A Retrospective Cohort Study from National Physical Fitness Surveillance of Jiangsu Province, China.

Objective: To explore the effects of breastfeeding during the first four months of life on thinness, overweight, and obesity and to analyze the influential factors in children aged three to six years in eastern China. Methods: This study was designed as a retrospective cohort study, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were followed. A total of 8053 subjects were included in this secondary analysis of data from the 2015 "Physical Fitness Surveillance data of Jiangsu, China". The subjects were classified into three groups on the basis of feeding patterns: breastfeeding, mixed feeding, and formula feeding. The International Obesity Task Force (IOTF) definitions of BMI were used to define thinness, overweight, and obesity. Multivariate logistic regression models and subgroup analysis were used to assess the association between feeding patterns and childhood thinness, overweight, obesity, and overweight/obesity, adjusted for potential confounders (sex, age grade, area, region/economy, gestational age, birthweight, childbearing age, mother's education, and caretaker). Results: The prevalence of breastfeeding was 63.8%, and the prevalence of thinness, overweight, obesity, and overweight/obesity reached 2.7%, 11.2%, 4.7%, and 15.9%, respectively. Breastfeeding participants had a lower risk of overweight and overweight/obesity with adjusted ORs of 0.652 (95% CI: 0.533, 0.797; p < 0.001) and 0.721 (95% CI: 0.602, 0.862; p < 0.001), respectively; however, there was no difference in thinness and obesity (both p > 0.05) compared with formula feeding. There was no statistical difference between mixed and formula feeding, in terms of thinness, overweight, obesity, or overweight/obesity (all p > 0.05). Subgroup analysis showed that breastfeeding for three years, preterm, and a childbearing age of 25−29 years had higher adjusted ORs for thinness, and in 5−6 years, urban areas, southern/developed economy regions, post-mature, childbearing age ≥ 25 years, and other caretakers had higher and invalid breastfeeding-adjusted ORs (all p > 0.05 except overweight in the urban grade) for both overweight and overweight/obesity. Conclusions: Breastfeeding during the first four months was not associated with the thinness of children aged 3−6 years in eastern China, and the protective effect of breastfeeding against overweight or overweight/obesity could be confirmed. However, the effects of breastfeeding on thinness, overweight, and obesity may change or become invalid in some subgroups, suggesting that there may be potential interactions between feeding patterns and influential factors.

Normal activated partial thromboplastin time in Chinese patients with mild hemophilia B.

OBJECTIVES: Hemophilia B (HB, OMIM: 300746) is one of the most common bleeding disorders with an X-linked recessive inheritance pattern, caused by the deficiency of coagulation factor IX (FIX). FIX is encoded by the F9 gene located on Xq27.1. Diagnosis of HB is primarily suspected by prolonged activated partial thromboplastin time (APTT), decreased FIX activity (FIX:C) or genetic test of the F9 gene. We herein described a Chinese family with patients of mild HB. METHODS: Sanger sequencing of the F9 gene was applied to identify mutation. Coagulation tests were performed. RESULTS: The proband was a 5-year-old boy. He suffered prolonged bleeding after tonsillectomy recently and circumcision last year as well. His grandfather experienced prolonged bleeding after gastric surgery. Both patients showed normal APTT, though they had significantly decreased FIX:C. Sanger sequencing of the F9 gene revealed a novel hemizygous F9 c.639C > A (p.Asn213Lys) missense mutation in both patients. The proband's mother carried heterozygous mutation. This mutation was located in the activation peptide domain of FIX. CONCLUSION: In conclusion, we confirmed that APTT could be normal in mild HB patients. Highly sensitive APTT for mild HB and molecular genetic test could confirm the diagnosis of mild HB.

Structural Diversity of Copper(I) Cluster-Based Coordination Polymers with Pyrazine-2-thiol Ligand.

Six novel copper(I) cluster-based coordination polymers (CPs) [Cu9(pzt)7Cl2]n (1), [Cu2(pzt)Cl]n (2), [Cu4(pzt)3Br]n (3), [Cu(pzt)]n (4), [Cu4(pzt)3I]n (5), and [Cu7(pzt)6I]n (6) were solvothermally synthesized using Hpzt (Hpzt = pyrazine-2-thiol) ligand and well-characterized by elemental analysis, infrared (IR) spectroscopy, powder X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SCXRD). Six CPs exhibit either 2D (4 and 6) or 3D (1-3, and 5) network based on diverse multinuclear {CuxSy} clusters. The structural evolutions of 1-6 are greatly influenced by types of metal halides and the ligand-to-metal molar ratio used in the reaction. Among them, compound 1 displays interesting temperature-dependent photoluminescence arising from triplet cluster-centered (3CC) excited state from the cluster metal core. Compounds 1-6 also exhibit photocurrent responses upon visible-light illumination (λ = 420 nm) in the order 6 > 5 > 3 > 1 > 4 > 2. This work not only shows the structural diversity of {CuxSy} clusters-based CPs but also provides an interesting insight into structural modulation using crystal engineering concept.

A highly robust heterometallic TbIII/NiII-organic framework for C2 hydrocarbon separation and capture.

The exquisite combination of hetreometallic [TbIIINiII(COO)3(H2O)] clusters with a designed hexatopic ligand generates one highly robust three-dimensional heterometallic TbIII/NiII-organic framework material {[TbNi(HTDP)(H2O)]·3DMF·2H2O}n (NUC-2; H6TDP = 2,4,6-tri(2,4-dicarboxyphenyl)pyridine). Gas adsorption measurements reveal that the activated NUC-2 exhibits ultrahigh C2H2 adsorption capacity but negligible uptake of C2H4, which is ascribed to its high stability and ultrahigh functional internal surface. Furthermore, dynamic breakthrough experiments confirm that NUC-2 can effectively fulfill the separation of a C2H2/C2H4 (1 : 99) mixture. Such excellent performance makes NUC-2 a promising adsorbent for practical C2H2/C2H4 separation and provides new insights into heterometallic MOFs for gas separation.

5,10,15,20-Tetrakis(4-carboxylphenyl)porphyrin modified nickel-cobalt layer double hydroxide nanosheets as enhanced photoelectrocatalysts for methanol oxidation under visible-light.

The development of low-cost noble metal-free and high-active electrocatalysts for methanol electrooxidation is highly worthwhile but remains a challenge. In this paper, 5, 10, 15, 20-tetrakis(4-carboxylphenyl)porphyrin (H2TCPP) modified nickel-cobalt layer double hydroxides nanosheets (NiCo-LDH) were prepared by one-pot hydrothermal method and characterized by the powder X-ray diffraction (XRD), the scanning electron microscopy (SEM) and X-ray photoelectron spectra (XPS), etc. H2TCPP/NiCo-LDH was demonstrated as superior a photoelectrocatalyst towards methanol oxidation in the alkaline media. Due to the introduction of H2TCPP photosensitizer, H2TCPP/NiCo-LDH exhibits the outstanding photoeletrocatalytic activity toward methanol oxidation under the visible-light irradiation. The great enhancement in the photoelectrocatalytic activity are attributed to high exposed surface active sites, efficient widen adsorption wavelength of H2TCPP in visible region, as well as efficient electron transfer between the electrode surface and the active sites. The H2TCPP/NiCo-LDH nanosheets show mass activity of 246.6 mA mg-1 and specific activity of 34.9 mA cm-2 for methanol oxidation under visible-light, which are 2.32 times higher than that of NiCo-LDH at the same conditions. The developing catalytic activity of H2TCPP/NiCo-LDH for methanol oxidation are attributed to the synergistic effect of H2TCPP and NiCo-LDH. This study may offer new ideas for developing highly effective noble metal-free catalysts for the application in methanol oxidation.

Cobalt Nanoparticles Embedded into N-Doped Carbon from Metal Organic Frameworks as Highly Active Electrocatalyst for Oxygen Evolution Reaction.

Cystosepiment-like cobalt nanoparticles@N-doped carbon composite named Co-NPs@NC with highly efficient electrocatalytic performance for oxygen evolution reaction was prepared from carbonization of N-doped Co-MOFs. The optimized Co-NPs@NC-600 shows overpotentials of 315 mV to afford a current density of 10 mA·cm-2. Meanwhile, the electrocatalys presents excellent long-term durability. The outstanding electrocatalytic performance can be attributed to the unique cystosepiment-like architecture with high specific surface area (214 m2/g), high conductivity of N-doped carbon and well-distributed active sites.

Highly sensitive colorimetric detection of glucose through glucose oxidase and Cu2+-catalyzed 3,3',5,5'-tetramethylbenzidine oxidation.

We develop a glucose oxidase (GOx)-mediated strategy for detecting glucose based on oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB), which is generated from Cu2+-catalyzed 3,3',5,5'-tetramethylbenzidine (TMB)-H2O2 reaction, as colorimetric readout. The sensing system involves two processes: generation of H2O2 from GOx-catalyzed oxidation of glucose, and H2O2-induced the oxidization of TMB via the catalysis of Cu2+. The H2O2 formed by GOx-catalyzed oxidation of glucose oxidizes colorless TMB to blue oxTMB, thus enhancing the absorbance intensity at 670 nm. Therefore, we draw a conclusion that the enhancement in colorimetric signal relies directly on H2O2 concentration, which, in turn, depends on glucose concentration. This color change can be used not only for visual detection of glucose by naked eyes but for reliable glucose quantification in the range from 1 to 100 nM with a detection limit of 0.21 nM. The method possesses the following advantages: simple design, low experimental cost, and no any additional experimental equipment for heating, illuminating, or bubbling.

Colorimetric adenosine aptasensor based on DNA cycling amplification and salt-induced aggregation of gold nanoparticles.

An aptamer based assay is described for the colorimetric detection of adenosine. The presence of adenosine triggers the deformation of hairpin DNA oligonucleotide (HP1) containing adenosine aptamer and then hybridizes another unlabeled hairpin DNA oligonucleotide (HP2). This leads to the formation of a double strand with a blunt 3' terminal. After exonuclease III (Exo III)-assisted degradation, the guanine-rich strand (GRS) is released from HP2. Hence, the adenosine-HP1 complex is released to the solution where it can hybridize another HP2 and initiate many cycles of the digestion reaction with the assistance of Exo III. This leads to the generation of a large number of GRS strands after multiple cycles. The GRS stabilize the red AuNPs against aggregation in the presence of potassium ions. If, however, GRS forms a G-quadruplex, it loses its ability to protect gold nanoparticles (AuNPs) from salt-induced AuNP aggregation. Therefore, the color of the solution changes from red to blue which can be visually observed. This colorimetric assay has a 0.13 nM detection limit and a wide linear range that extends from 5 nM to 1 µM. Graphical abstract Schematic presentation of a colorimetric aptamer biosensor for adenosine detection based on DNA cycling amplification and salt-induced aggregation of gold nanoparticles.

[Effect of icariin on learning and memory abilities and activity of cholinergic system of senescence-accelerated mice SAMP10].

OBJECTIVE: To investigate the effect of icariin (ICA) on learning and memory abilities and cholinergic system in senescence-accelerated mice SAMP10. METHOD: The 8-month-old senescence-accelerated mice were randomly divided into the model SAMP10 group and the positive Donepezil group (1 mg x kg(-1)) and ICA groups (50, 100, 200 mg x kg(-1)), with 12 mice in each group. Another 12 8-month-old mice SAMR1 were selected as the normal control group. After 30 days of oral administration, Morris water maze, SMG-2 water maze and experimental platform were used to test the effects of ICA on learning and memory abilities of SAMP10 groups. By colorimetric determination of AChE activity in the cortex, enzyme-linked immunosorbent assay detection of ACh, ChAT, MCBC of the cerebral cortex, the effect of ICA on the cholinergic system of SAMP10 was observed. RESULT: ICA could improve the abilities of space exploration and positioning navigation of SAMP10, shorten the latency in SMG-2 water maze, enhance their jumping ability in response to the passive test, and increase levels of ACh, ChAT, MCBC in the cerebral cortex of SAMP10. But its active effect on AChE in SAMP10 cortex was not obvious. CONCLUSION: Different doses of icariin can improve learning and memory abilities of SAMP10 to varying degrees, which may be related to its effect on the cholinergic system.