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1.
Effect of Controlling Nb Content and Cooling Rate on the Microstructure, Precipitation Phases, and Mechanical Properties of Rebar.
Shen, B, Gu, S, Wang, J, Wei, F, Li, Z, Zeng, Z, Zhang, J, Li, C
Materials (Basel, Switzerland). 2024;(7)
Abstract
Seismic anti-seismic rebar, as materials for supporting structures in large buildings, need to have excellent mechanical properties. By increasing the Nb content and controlling the cooling rate, the microstructure and precipitation behavior of the steel are adjusted to develop seismic anti-seismic rebar with excellent mechanical properties. Scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), transmission electron microscopy (TEM), and a universal tensile testing machine were used to characterize the microstructure, precipitation phases, and mechanical properties of the experimental steels. The results show that the ferrite grain size, pearlite lamellae layer (ILS), and small-angle grain boundaries (LAGB) content of the high-Nb steels decreased to 6.39 μm, 0.12 μm, and 48.7%, respectively, as the Nb content was increased from 0.017 to 0.023 wt.% and the cooling rate was increased from 1 to 3 °C·s-1. The strength of the {332}<113>α texture is the highest in the high-Nb steels. The precipitated phase is (Nb, Ti, V)C with a diameter of ~50 nm, distributed on ferrite, and the matrix/precipitated phase mismatch is 8.16%, forming a semicommon-lattice interface between the two. The carbon diffusion coefficient model shows that increasing the Nb content can inhibit the diffusion of carbon atoms and reduce the ILS. The yield strength of the high-Nb steel is 556 MPa, and the tensile strength is 764 MPa.
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2.
Efficacy and pharmacoeconomic advantages of Fufang Huangbai Fluid hydropathic compress in diabetic foot infections: a comparative clinical study with antimicrobial calcium alginate wound dressing.
Yang, G, Wang, G, Li, Z, Deng, L, Wang, N, Wang, X, Zhou, T, Zhang, J, Lei, Y, Wang, T, et al
Frontiers in pharmacology. 2024;:1285946
Abstract
Objective: To compare the intervention effects and pharmacoeconomic advantages of Fufang Huangbai Fluid (FFHB) hydropathic compress versus Antimicrobial Calcium Alginate Wound Dressing (ACAWD) in the treatment of diabetic foot infections (DFI). Methods: Patients with DF who were hospitalized in the peripheral vascular Department of Dongzhimen Hospital of Beijing University of Chinese Medicine from December 2020 to February 2022 and met the inclusion and excluding criteria were allocated into the experimental group and control group through minimization randomization. The experimental group was treated with FFHB hydropathic compress for 2 weeks, while the control group was treated with ACAWD for the same duration. The wound healing of both groups was monitored for 1 month post-discharge. Clinical data from all eligible patients were collected, and differences in various indices between cohorts were analyzed. Results: 22 in the experimental group (including two fell off) and 20 in the control group. After the treatment, the negative rate of wound culture in the experimental group was 30% and that in the control group was 10%, There was no significant difference in the negative rate of wound culture and change trend of minimum inhibitory concentration (MIC) value of drug sensitivity (p > 0.05). The infection control rate of the experimental group was 60%, and that of the control group was 25%. The difference between the two groups was statistically significant (χ2 = 5.013, p = 0.025). The median wound healing rate of the experimental group was 34.4% and that of the control group was 33.3%. There was no significant difference between the two groups (p > 0.05). During the follow-up 1 month later, the wound healing rate in the experimental group was higher, and the difference was statistically significant (p = 0.047). Pharmacoeconomic evaluations indicated that the experimental group had greater cost-effectiveness compared to the control group. Conclusion: In the preliminary study, FFHB demonstrated comparable pathogenic and clinical efficacy to ACAWD in the treatment of mild DF infection, and exhibited superior pharmacoeconomic advantages. With the aid of infection control, the wound healing rate in the FFHB group showed notable improvement. Nevertheless, due to the limited sample size, larger-scale studies are warranted to further validate these findings. Clinical Trial Registration: (https://www.chictr.org.cn/showproj.aspx?proj=66175), identifier (ChiCTR2000041443).
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3.
Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects.
Tong, B, Ba, Y, Li, Z, Yang, C, Su, K, Qi, H, Zhang, D, Liu, X, Wu, Y, Chen, Y, et al
Neurobiology of disease. 2024;:106505
Abstract
Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aβ deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.
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Safety and efficacy of melatonin supplementation as an add-on treatment for infantile epileptic spasms syndrome: A randomized, placebo-controlled, double-blind trial.
Sun, Y, Chen, J, Shi, X, Li, Z, Wan, L, Yan, H, Chen, Y, Wang, J, Wang, J, Zou, L, et al
Journal of pineal research. 2024;(1):e12922
Abstract
This was a prospective, randomized, double-blind, single-center placebo-controlled trial to assess the efficacy and safety of melatonin as an add-on treatment for infantile epileptic spasms syndrome (IESS). Participants aged 3 months to 2 years with a primary diagnosis of IESS were recruited and assigned to two groups in a 1:1 ratio. Both treatment groups received a combination of adrenocorticotrophic hormone (ACTH) and magnesium sulfate (MgSO4 ) for 2 weeks, and the treatment group also received melatonin (3 mg) between 20:00 and 21:00 daily, 0.5-1 h before bedtime. The study's primary endpoint was the average reduction rate in spasm frequency assessed by seizure diaries. Secondary endpoints included assessment of the response rate, EEG hypsarrhythmia (Kramer score), and psychomotor development (Denver Developmental Screening Test, DDST). Sleep quality was assessed by using the Brief Infant Sleep Questionnaire (BISQ), the Infant Sleep Assessment Scale (ISAS), and actigraphy. Safety parameters were also evaluated. Statistical analyses were conducted on intention-to-treat and per-protocol populations. The trial is registered at Clinicaltrials.gov (ChiCTR2000036208). Out of 119 screened patients, 70 were randomized and 66 completed treatments. In the intention-to-treat population, there were no significant differences in the average percentage reduction of spasm frequency (median [interquartile range, IQR: Q3-Q1], 100% [46.7%] vs. 66.7% [55.3%], p = .288), the 3-day response rate (51.4% vs. 37.1%, p = .229), the 28-day response rate (42.9% vs. 28.6%, p = .212), EEG Kramer scores (2 [3.5] vs. 2 [3], p = .853), or DDST comprehensive months (5 [2.5] vs. 6 [6], p = .239) between the melatonin (n = 35) and placebo (n = 35) groups. However, caregivers reported improved sleep quality after melatonin treatment, with 85.7% reporting regular sleep compared to 42.9% with placebo (42.9%, p < .001). The melatonin group had lower ISAS scores in 4-11-month-old patients compared to the placebo (mean ± SD, 29.3 ± 4.4 vs. 35.2 ± 5.9, p < .001). Moreover, the median (IQR) value of sleep-onset latency was shortened by 6.0 (24.5) min after melatonin treatment, while that in the placebo group was extended by 3.0 (22.0) min (p = .030). The serum melatonin (6:00 h) level (pg/mL) of the children in the melatonin group after treatment was significantly higher than in the placebo group (median [IQR], 84.8 [142] vs. 17.5 [37.6], p < .001). No adverse effects related to melatonin were observed in the study, and there were no significant differences in adverse effects between the melatonin and placebo groups. Although not statistically significant, the results of this randomized clinical trial proved that melatonin supplementation, as an add-on treatment, can improve spasm control rate in the treatment of IESS. For IESS children treated with ACTH, the addition of melatonin was found to improve sleep quality, shorten sleep onset latency, and increase blood melatonin levels. Moreover, it was observed to be a safe treatment option.
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5.
Non-coding RNAs and leaf senescence: Small molecules with important roles.
Li, S, Zhao, Y, Tan, S, Li, Z
Plant physiology and biochemistry : PPB. 2024;:108399
Abstract
Non-coding RNAs (ncRNAs) are a special class of functional RNA molecules that are not translated into proteins. ncRNAs have emerged as pivotal regulators of diverse developmental processes in plants. Recent investigations have revealed the association of ncRNAs with the regulation of leaf senescence, a complex and tightly regulated developmental process. However, a comprehensive review of the involvement of ncRNAs in the regulation of leaf senescence is still lacking. This manuscript aims to summarize the molecular mechanisms underlying ncRNAs-mediated leaf senescence and the potential applications of ncRNAs to manipulate the onset and progression of leaf senescence. Various classes of ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are discussed in terms of their regulatory mechanisms in leaf senescence. Furthermore, we explore the interactions between ncRNA and the key regulators of senescence, including transcription factors as well as core components in phytohormone signaling pathways. We also discuss the possible challenges and approaches related to ncRNA-mediated leaf senescence. This review contributes to a further understanding of the intricate regulatory network involving ncRNAs in leaf senescence.
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6.
Mechanical Behavior and Microstructure Evaluation of Quicklime-Activated Cement Kiln Dust-Slag Binder Pastes.
Hu, M, Dong, T, Cui, Z, Li, Z
Materials (Basel, Switzerland). 2024;(6)
Abstract
Cement kiln dust (CKD) is a by-product of cement production, which has the shortcomings of low utilization and high-temperature activation. This study combined CKD and slag as precursors for preparing pastes through quicklime activation under ambient conditions. The effects of quicklime and CKD content on the workability (flowability and setting time), macro-mechanical properties, and micro-structure of the CKD-slag binders were analyzed. The experimental results showed that the rapid precipitation of Ca2+, Si4+, and Al3+ ions from the CKD provided more nucleation sites for the formation of calcium aluminosilicate hydrate (C-(A)-S-H) gel and enhanced the reactivity of the binder system under the influence of the activator (CaO). The specimens had the highest unconfined compressive strength (UCS) (24.6 MPa) after 28 days with 10% quicklime content and 60% CKD content; scanning electron microscopy with energy-dispersive X-ray (SEM-EDX) analysis showed that the Ca/Si ratio of the C-(A)-S-H gel was minimized, leading to a denser microstructure and better binding ability under this mixing proportion. Therefore, this study may provide novel binder materials with a high proportion of CKD under ambient conditions.
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7.
Graphormer supervised de novo protein design method and function validation.
Mu, J, Li, Z, Zhang, B, Zhang, Q, Iqbal, J, Wadood, A, Wei, T, Feng, Y, Chen, HF
Briefings in bioinformatics. 2024;(3)
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Abstract
Protein design is central to nearly all protein engineering problems, as it can enable the creation of proteins with new biological functions, such as improving the catalytic efficiency of enzymes. One key facet of protein design, fixed-backbone protein sequence design, seeks to design new sequences that will conform to a prescribed protein backbone structure. Nonetheless, existing sequence design methods present limitations, such as low sequence diversity and shortcomings in experimental validation of the designed functional proteins. These inadequacies obstruct the goal of functional protein design. To improve these limitations, we initially developed the Graphormer-based Protein Design (GPD) model. This model utilizes the Transformer on a graph-based representation of three-dimensional protein structures and incorporates Gaussian noise and a sequence random masks to node features, thereby enhancing sequence recovery and diversity. The performance of the GPD model was significantly better than that of the state-of-the-art ProteinMPNN model on multiple independent tests, especially for sequence diversity. We employed GPD to design CalB hydrolase and generated nine artificially designed CalB proteins. The results show a 1.7-fold increase in catalytic activity compared to that of the wild-type CalB and strong substrate selectivity on p-nitrophenyl acetate with different carbon chain lengths (C2-C16). Thus, the GPD method could be used for the de novo design of industrial enzymes and protein drugs. The code was released at https://github.com/decodermu/GPD.
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Association between leisure sedentary behaviors and hypertension risk: A prospective cohort study and two-sample Mendelian randomization analysis in Europeans.
Li, Z, Zhong, W, Gao, J, Zhang, X, Lin, G, Qi, C, Mao, C, Zhou, H
Preventive medicine. 2024;:107915
Abstract
OBJECTIVE This study aimed to investigate the potential causal relationship between domain-specific sedentary behaviors (including television watching, computer use, and driving) and hypertension risk in European populations. METHODS Initially, we conducted a multivariable Cox regression analysis to evaluate the associations between domain-specific sedentary behaviors and the risk of developing hypertension using data from 261,829 hypertension-free participants in the UK Biobank. To validate the findings of observational analysis, we employed two-sample univariable mendelian randomization (UVMR) analysis utilizing summary statistics from genome-wide association study conducted on European populations. We then performed multivariable mendelian randomization (MVMR) analysis to account for the influence of the risk factors for hypertension. RESULTS In this prospective observational analysis, individuals who spent >3 h per day watching television had significantly higher risk of developing hypertension (HR = 1.24, 95% CI: 1.20-1.29, P < 0.001) compared to those who watched television for 0-1 h per day. The mendelian randomization analysis provided consistent evidence for a causal relationship between prolonged television watching time and hypertension risk (OR = 1.45, 95% CI: 1.25-1.69, P < 0.001; all PMVMR < 0.05) in both UVMR and MVMR results. No significant associations were found between computer use, driving behaviors and the risk of hypertension in either the observational or UVMR/MVMR analyses. CONCLUSIONS These findings provide evidence for a causal effect specifically linking higher television watching time to an increased risk of hypertension and indicate the potential effectiveness of reducing television viewing time as a preventive measure to mitigate the risk of hypertension.
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Osteoporosis and Primary Biliary Cholangitis: A Trans-ethnic Mendelian Randomization Analysis.
Wu, Y, Qian, Q, Liu, Q, Wang, R, Pu, X, Li, Y, Zhang, H, You, Z, Miao, Q, Xiao, X, et al
Clinical reviews in allergy & immunology. 2024
Abstract
Osteoporosis is a major clinical problem in many autoimmune diseases, including primary biliary cholangitis (PBC), the most common autoimmune liver disease. Osteoporosis is a major cause of fracture and related mortality. However, it remains unclear whether PBC confers a causally risk-increasing effect on osteoporosis. Herein, we aimed to investigate the causal relationship between PBC and osteoporosis and whether the relationship is independent of potential confounders. We performed bidirectional Mendelian randomization (MR) analyses to investigate the association between PBC (8021 cases and 16,489 controls) and osteoporosis in Europeans (the UK Biobank and FinnGen Consortium: 12,787 cases and 726,996 controls). The direct effect of PBC on osteoporosis was estimated using multivariable MR analyses. An independent replication was conducted in East Asians (PBC: 2495 cases and 4283 controls; osteoporosis: 9794 cases and 168,932 controls). Trans-ethnic meta-analysis was performed by pooling the MR estimates of Europeans and East Asians. Inverse-variance weighted analyses revealed that genetic liability to PBC was associated with a higher risk of osteoporosis in Europeans (OR, 1.040; 95% CI, 1.016-1.064; P = 0.001). Furthermore, the causal effect of PBC on osteoporosis persisted after adjusting for BMI, calcium, lipidemic traits, and sex hormones. The causal relationship was further validated in the East Asians (OR, 1.059; 95% CI, 1.023-1.096; P = 0.001). Trans-ethnic meta-analysis confirmed that PBC conferred increased risk on osteoporosis (OR, 1.045; 95% CI, 1.025-1.067; P = 8.17 × 10-6). Our data supports a causal effect of PBC on osteoporosis, and the causality is independent of BMI, calcium, triglycerides, and several sex hormones.
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Synthesis of New Derivatives of Berberine Canagliflozin and Study of Their Antibacterial Activity and Mechanism.
Li, J, Hou, X, Xiao, J, Zhu, L, Deng, Y, Li, Z, Zhao, Z, Luo, Z, Wei, H
Molecules (Basel, Switzerland). 2024;(1)
Abstract
The isoquinoline alkaloid berberine, derived from Coptidis rhizoma, exhibits antibacterial, hypoglycemic, and anti-inflammatory properties. Canagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. We synthesized compounds B9OC and B9OBU by conjugating canagliflozin and n-butane at the C9 position of berberine, aiming to develop antimicrobial agents for combating bacterial infections worldwide. We utilized clinically prevalent pathogenic bacteria, namely Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, to investigate the antibacterial efficacy of B9OC. This was accomplished through the determination of the MIC80 values, analysis of bacterial growth curves, evaluation of biofilm formation using crystal violet staining, assessment of impact on bacterial proteins via SDS-PAGE analysis, and observation of alterations in bacterial morphology utilizing field emission scanning electron microscopy. Meanwhile, the ADMET of compound B9OC was predicted using a computer-aided method. The findings revealed that B9OC exhibited lower minimal inhibitory concentrations against all three bacteria compared to berberine alone or in combination with canagliflozin. The minimal inhibitory concentrations (MICs) of B9OC against the three experimental strains were determined to be 0.035, 0.258, and 0.331 mM. However, B9OBu exhibited a lower level of antimicrobial activity compared to berberine. The compound B9OC exhibits a broad spectrum of antibacterial activity by disrupting the integrity of bacterial cell walls, leading to cellular rupture and the subsequent degradation of intracellular proteins.