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Chlorinated paraffins (CP) are complex molecular mixtures occurring in a wide range of isomers and homologs of environmental hazards, whose analytical complexity demand advanced mass spectrometry (MS) methods for their characterization. The reported formation of chlorinated olefins (COs) and other transformation products during CP biotransformation and degradation can alter the MS analysis, increasing the high resolution required to distinguish CPs from their degradation products. An advanced setup hyphenating a plasma ionization source and an external high-performance data acquisition and processing system to the legacy hybrid LTQ Orbitrap XL mass spectrometer is reported. First, the study demonstrated the versatility of a liquid sampling atmospheric pressure glow discharge, as a soft ionization technique, for CP analysis. Second, enhanced resolution and sensitivity provided by the absorption mode Fourier transform spectral representation on this legacy mass spectrometer are shown. The developed Orbitrap-based platform allowed the detection of new isotopic clusters and CPs and COs to be distinguished at medium resolution (setting 30,000 at m/z 400, ~ 400 ms transients), and even chlorinated di-olefins (CdiOs) at higher resolution (setting 100,000 at m/z 400, ~ 1500 ms transients). Overall, such proof-of-principle instrumental improvements are promising for environmental and analytical research in the field of CP analysis.
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Recently, certain challenges and accompanying drawbacks have emerged in the preparation of high-strength and tough polymer hydrogels. Insights from wood science highlight the role of the intertwined molecular structure of lignin and crystalline cellulose in contributing to wood's strength. Herein, we immersed prestretched poly(vinyl alcohol) (PVA) polymer hydrogels into a solution of nanosized lignosulfonate sodium (LS), a water-soluble anionic polyelectrolyte, to creatively reconstruct this similar structure at the molecular scale in hydrogels. The nanosized LS effectively fixed and bundled the prestretched PVA polymers while inducing the formation of dense crystalline domains within the polymer matrix. Consequently, the interwoven structure of crystalline PVA and LS conferred good strength to the composite hydrogels, exhibiting a tensile strength of up to â¼23 MPa, a fracture strain of â¼350%, Young's modulus of â¼17 MPa, toughness of â¼47 MJ/m3, and fracture energy of â¼42 kJ/m2. This hydrogel far outperformed previous hydrogels composed directly of lignin and PVA (tensile strength <1.5 MPa). Additionally, the composite hydrogels demonstrated excellent antifreezing properties (<-80 °C). Notably, the LS-assisted reconstruction technology offers opportunities for the secondary fixation of PVA hydrogel shapes and high-strength welding of hydrogel components. This work introduces an approach for the high-value utilization of LS, a green byproduct of pulp production. LS's profound biomimetic strategy will be applied in multifunctional hydrogel fields.
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OBJECTIVES: The association between loneliness and disability is a growing public health priority. While the University of California Los Angeles Loneliness Scale (UCLA-LS) has been internationally used as an indicator for assessing loneliness, its optimal cutoff point in relation to disability occurrence has not yet been examined. Therefore, we aimed to determine the optimal cutoff point of the UCLA-LS regarding future disability. METHODS: This longitudinal cohort study was conducted in Tokai City, Aichi Prefecture, Japan. Overall, 4536 community-dwelling older adults (age: 73.8 ± 5.5 years; females: 55.2%) were followed up for 2 years. The area under the curve of the receiver operating characteristic analysis was calculated to evaluate the optimal cutoff point of the UCLA-LS in relation to future disability occurrence using the Youden index, which maximized the sensitivity and specificity of the UCLAS-LS. A survival analysis was conducted to test this cutoff value's external validity, using the presence or absence of disability occurrence as the dependent variable. RESULTS: The cutoff score of the UCLA-LS in relation to future disability was 44 points. An association was found between new disability occurrence and loneliness based on this cutoff value (hazard ratio: 1.67, 95% confidence interval: 1.29-2.16). CONCLUSIONS: Although cultural context should be taken into account, the optimal cutoff scores for the loneliness scale related to disability identified in this study may be a useful indicator for early recognition of loneliness as a global public health problem and for promoting social participation as one of the disability prevention strategies.
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Personas con Discapacidad , Soledad , Humanos , Femenino , Soledad/psicología , Masculino , Anciano , Japón , Estudios Longitudinales , Personas con Discapacidad/psicología , Anciano de 80 o más Años , Curva ROC , Escalas de Valoración Psiquiátrica/normas , Vida Independiente , Tamizaje Masivo/métodos , Sensibilidad y Especificidad , Reproducibilidad de los Resultados , Pueblos del Este de AsiaRESUMEN
Gel permeation chromatography coupled with light scattering (GPC-LS) is among the most common methods for determining the molar masses of polymers. GPC-LS is widely used in polymer science research and has been adopted for many industrial applications owing to its high sensitivity, accuracy, and precision. The determination of polymer molar masses using GPC-LS is an important experimental component of the "Polymer Physics Experiments" course. However, the present GPC-LS experimental teaching content tends to be overly simplistic and lacking in depth. Herein, the original experimental content is expanded and multiple sets of experiments are redesigned: (1) Using commercial polystyrene as an experimental sample, the molar mass, molar mass distribution, radius of gyration, and other molecular structure parameters are determined using GPC-LS; (2) Using two polyacrylonitriles with similar molecular structure parameters, subtle differences in the molar mass distributions of the samples are explored using differential mass distribution curves; (3) By comparing the chromatograms of a series of polyethylene glycols with different molar masses, the effect of molar mass on chromatographic peaks is investigated; and (4) For three different polymers (polyacrylonitrile, poly(methyl methacrylate), and poly(ß-cyclodextrin)), the polymer chain conformations are analyzed using conformation plots (i.e., radius of gyration vs. molar mass). In addition, the experimental teaching method is modified to convert passive learning into active learning, thereby improving the students' self-directed learning ability. This experimental teaching reform will help students obtain a more comprehensive understanding of GPC-LS principles and applications, stimulate their enthusiasm for learning, and improve the teaching quality of the experimental course.
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BACKGROUND: There is a dearth of studies investigating the efficacy of hydroxychloroquine in the treatment of either anogenital lichen sclerosus or extragenital lichen sclerosus, a condition that, if left untreated, could lead to a greater degree of scarring and malignant transformation. OBJECTIVE: This study aims to analyze the demographic characteristics, clinicopathological features, treatment response, and outcomes of patients diagnosed with either anogenital or extragenital lichen sclerosus who received hydroxychloroquine therapy. METHODS: A retrospective analysis was conducted involving 70 patients diagnosed with lichen sclerosus who underwent treatment with hydroxychloroquine at our institution between 2018 and 2023. RESULTS: Among the cohort, 67 patients were female, and 3 were male. Extragenital lichen sclerosus was diagnosed in 23 patients, with 16 exhibiting concomitant morphea overlap. Itching was the predominant clinical presentation (67%). A notable proportion of patients (36%) had a connective tissue disorder, prompting hydroxychloroquine therapy. Among the 30 patients treated solely for lichen sclerosus, 21 demonstrated response and 9 had no response. From a broader comparison of response to hydroxychloroquine, the overall anogenital response rate was 84.6% as opposed to 50% in extragenital lichen sclerosus. The median time to initial response was 4 months. Adverse effects, predominantly mild, were observed in 10 (14.3%) patients. LIMITATION: This study is constrained by its retrospective nature and reliance on data from a single center, resulting in a limited sample size. CONCLUSION: Hydroxychloroquine demonstrates promise as a therapeutic option for anogenital lichen sclerosus because of its favorable response rates and low incidence of adverse effects. However, further investigations, including larger-scale or prospective studies, are imperative to ascertain its definitive efficacy.
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Despite evidence to the contrary, many people believe in learning styles (LS)-the idea that students learn best in their preferred modality, such as visual, auditory, or kinesthetic. However, the impact of this belief on instructional decisions remains unclear. Therefore, this study investigated how belief in the neuromyth impacts instructional choices and why educators choose an LS lesson plan or an alternative. We found that educators' beliefs about LS indeed predicted their instructional choice, but that other factors influenced their decisions as well. Three themes encapsulate educators' justifications for their lesson plan choices: beliefs about LS, practical considerations, and student learning and motivation. These findings suggest that for many educators, implementing an LS lesson provides an opportunity to integrate diverse teaching strategies that address multiple educational priorities. Although many prior studies have replicated the prevalence of the myth, this is one of the first to explore the reasons that LS is attractive to educators. Attempts to dispel the LS neuromyth could leverage the reasons educators find LS appealing to provide alternative research-backed approaches to meet their goals. Future research should examine the extent to which beliefs in the LS neuromyth are translated into instructional practices within classroom lessons and explore potential differences across grade levels.
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We investigate the ocular dimensions and shape by using Lenstar900 (LS900), A-scan ultrasonography, and Magnetic Resonance Imaging (MRI) in highly myopic Macaca fascicularis. The ocular dimensions data of LS900, A-scan ultrasonography and MRI was assessed from 8 eyes (4 adult male cynomolgus macaque) with extremely high myopia (≤-1000DS) and compared by means of coefficients of concordance and 95% limits of agreement. Multiple regression analysis was performed to explore the associations between ocular biometry, volume, refraction and inter-instrument discrepancies. Test-retest reliability of three measurements of ocular parameters at two time points was almost equal (intraclass correlation = 0.831 to 1.000). The parallel-forms reliability of three measurements was strong for vitreous chamber depth (VCD) (coefficient of concordance = 0.919 to 0.981), moderate for axial length (AL) (coefficient of concordance = 0.486 to 0.981), and weak for anterior chamber depth (ACD) (coefficient of concordance = 0.267 to 0.621) and lens thickness (LT) (coefficient of concordance = 0.035 to 0.631). The LS900 and MRI systematically underestimated the ACD and LT comparing to A-scan ultrasonography (P < 0.05). Notably, the average AL on LS900 displayed a significant correlation with those on MRI (r = 0.978, P < 0.001) and A-scan ultrasonography (r = 0.990, P < 0.001). Almost 4/5 eyeballs were prolate. The mean eyeball volume positively correlated with AL (r = 0.782, P = 0.022), the width (r = 0.945, P = 0.000), and the length (r = 0.782, P = 0.022) of eyeball, while negatively correlated with SER (r = -0.901, P = 0.000). In conclusion, there was a high inter-instrument concordance for VCD with LS900, A-scan ultrasonography and MRI, while ACD and LT were underestimated with LS900 compared to A-scan ultrasonography, and the LS900 and A-scan ultrasonography could reliably measure the AL. MRI further revealed an equatorial globe shape in extremely myopic non-human primates.
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Longitud Axial del Ojo , Biometría , Macaca fascicularis , Imagen por Resonancia Magnética , Ultrasonografía , Animales , Masculino , Imagen por Resonancia Magnética/métodos , Ultrasonografía/métodos , Longitud Axial del Ojo/diagnóstico por imagen , Longitud Axial del Ojo/patología , Reproducibilidad de los Resultados , Imagenología Tridimensional , Refracción Ocular/fisiología , Modelos Animales de Enfermedad , Miopía Degenerativa/diagnóstico por imagen , Cámara Anterior/diagnóstico por imagen , Cámara Anterior/patología , Miopía/diagnóstico por imagen , Miopía/fisiopatología , Ojo/diagnóstico por imagenRESUMEN
A significant proportion of the world's population suffers from insomnia, a disorder characterized by complications in initiating and maintaining sleep. Many medications used to treat insomnia target the γ-aminobutyric acid (GABA) neurotransmitter system. However, these substances, such as benzodiazepines, induce significant adverse consequences, including dependence and memory impairment, after prolonged use. Thus, current studies are aimed at developing therapeutic hypnotics derived from natural sources that may cause less severe side effects. Heukharang is a variety of lettuce from Korea that was discovered to contain sleep-promoting compounds. Therefore, we investigated the potential effects of sub-chronic administration of Heukharang extract (FSD-LS) on sleep behavior (pentobarbital-induced sleeping test), brain wave activity and sleep architecture (electroencephalography), and physiological behavior (open-field test and rota-rod) in mice, along with radioligand binding assays (GABAA, adenosine A1 and A2A receptors). We found that FSD-LS prolonged the total sleep duration and reduced the onset time of sleep, and enhanced delta wave power and non-rapid eye movement (NREM) sleep duration, all indicating persistent sleep-enhancing effects. FSD-LS lacked adverse effects on the spontaneous locomotor activity and motor coordination of mice, unlike diazepam. Pharmacological blocking using caffeine and bicuculline supported the possible involvement of adenosine receptors in the sleep-promoting effects of FSD-LS, with partial contribution from GABA receptor activity. Overall, our study recommends FSD-LS as a potential source for the development of sleep-aiding therapeutics.
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This study was carried out to investigate the continuous aqueous pretreatment of sugarcane bagasse (SCB) through twin-screw extrusion for a new integrated full valorization, where the solid residue (extrudate) was used for the production of bio-based materials by thermocompression and the filtrate for the production of high-value-added molecules. Two configurations, with and without a filtration module, were tested and the influence of the SCB composition and structure on the properties of the materials were determined. The impact of the liquid-to-solid (L/S) ratio was studied (0.65-6.00) in relation to the material properties and the biomolecule extraction yield in the filtrate (with the filtration configuration). An L/S ratio of at least 1.25 was required to obtain a liquid filtrate, and increasing the L/S ratio to 2 increased the extraction yield to 11.5 g/kg of the inlet SCB. The extrudate obtained without filtration yielded materials with properties equivalent to those obtained with filtration for L/S ratios of at least 1.25. Since the molecule extraction process was limited, a configuration without filtration would make it possible to reduce water consumption in the process while obtaining high material properties. Under the filtration configuration, an L/S ratio of 2 was the best tradeoff between water consumption, extraction yield, and the material properties, which included 1485 kg/m3 density, 6.2 GPa flexural modulus, 51.2 MPa flexural strength, and a water absorption (WA) and thickness swelling (TS) of 37% and 44%, respectively, after 24 h of water immersion. The aqueous pretreatment by twin-screw extrusion allowed for the overall valorization of SCB, resulting in materials with significantly improved properties compared to those obtained with raw SCB due to fiber deconstruction.
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Supramolecular hydrogels are typically assembled through weak non-covalent interactions, posing a significant challenge in achieving ultra strength. Developing a higher strength based on molecular/nanoscale engineering concepts is a potential improvement strategy. Herein, a super-tough supramolecular hydrogel is assembled by gradually diffusing lignosulfonate sodium (LS) into a polyvinyl alcohol (PVA) solution. Both simulations and analytical results indicate that the assembly and subsequent enhancement of the crosslinked network are primarily attributed to LS-induced formation and gradual densification of strong crystalline domains within the hydrogel. The optimized hydrogel exhibits impressive mechanical properties with tensile strength of ≈20 MPa, Young's modulus of ≈14 MPa, and toughness of ≈50 MJ mâ»3, making it the strongest lignin-PVA/polymer hydrogel known so far. Moreover, LS provides the supramolecular hydrogel with excellent low-temperature stability (<-60 °C), antibacterial, and UV-blocking capability (≈100%). Interestingly, the diffusion ability of LS is demonstrated for self-restructuring damaged supramolecular hydrogel, achieving 3D patterning on hydrogel surfaces, and enhancing the local strength of the freeze-thaw PVA hydrogel. The goal is to foster a versatile hydrogel platform by combining eco-friendly LS with biocompatible PVA, paving the way for innovation and interdisciplinarity in biomedicine, engineering materials, and forestry science.
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Clear cell carcinoma (CCC) of the diaphragm is rare, with an origin that is reported to be associated with malignant transformation of extraperitoneal endometriosis. Lynch syndrome (LS) is an autosomal dominant hereditary cancer syndrome caused by germline pathogenic variants in one of the DNA mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2. Women with LS have a significantly increased lifetime risk of endometrial and ovarian cancer. CCC is a common histology of endometriosis- and LS-associated malignancy. The present study describes the case of a 51-year-old woman with an intra-abdominal mass found during a routine physical examination. The patient had undergone total hysterectomy and bilateral adnexectomy for atypical endometrial hyperplasia (AEH) and ovarian endometriosis, respectively, 3 years previously. Enhanced computed tomography showed a mass on the surface of the liver. Laparoscopic examination of the abdominal cavity revealed a tumor on the underside of the right diaphragm, which was then surgically excised. Pathological examination of the excised tumor, along with immunohistochemistry, led to a diagnosis of CCC. Since LS was suspected due to the genetic family history of the patient, microsatellite instability analysis was performed on the diaphragmatic tumor, and the results were positive. Immunohistochemistry was performed for MMR proteins in AEH and CCC cells, both of which revealed loss of MSH2 and MSH6 expression. Following detailed genetic counseling, genetic testing of MMR genes was performed, revealing a germline pathogenic variant in MSH2 (c.1000C>T, p.Gln344*), thus confirming the diagnosis of LS. To the best of our knowledge, this is the first case report of concurrent diaphragmatic CCC and LS. Patients with LS and endometriosis are at risk of developing ovarian cancer or intra-abdominal malignant tumors. In addition, immunohistochemistry screening for MMR proteins should be considered in patients with AEH and a family history of LS-related cancer, to enable early clinical intervention in cases of endometrial cancer.
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Background: Concerns over the security of laparoscopic radical operation for gallbladder cancer (GBC) persist. This systematic review and meta-analysis attempted to compare the safety and efficacy of laparoscopic surgery (LS) versus open surgery (OS) in the treatment of GBC. Methods: The PubMed, EMBASE, and Web of Science were searched from inception to July 18, 2022. Literature search, quality assessment, and data extraction were completed independently and in duplicate. Effect-size estimates expressed as weighted mean difference (WMD) or odds ratio (OR) with 95% confidence interval (CI) were derived under the random-effects model. Results: A total of 27 independent studies including 2,868 participants were meta-analyzed. Significance was noted for intraoperative blood loss (WMD: -117.194, 95% CI: -170.188 to 64.201, P<0.001), harvested lymph nodes (WMD: -1.023, 95% CI: -1.776 to -0.269, P=0.008), postoperative hospital stay (WMD: -3.555, 95% CI: -4.509 to -2.601, P<0.001), postoperative morbidity (OR: 0.596, 95% CI: 0.407 to 0.871, P=0.008), overall survival rate at 2-year (OR: 1.524, 95% CI: 1.143 to 2.031, P=0.004), T2 survival at 1-year (OR: 1.799, 95% CI: 1.777 to 2.749, P<0.01) and 2-year (OR: 2.026, 95% CI: 1.392 to 2.949, P<0.001), as well as T3 survival at 1-year (OR: 2.669, 95% CI: 1.564 to 4.555, P<0.001) and 2-year (OR: 2.300, 95% CI: 1.308 to 4.046, P=0.004). Subgroup analyses revealed that ethnicity, incidental GBC, sample size, and follow-up period were possible sources of heterogeneity. There was a low probability of publication bias for all outcomes except postoperative morbidity. Conclusions: Our findings indicated that LS statistically had better 2-year survival rates, less intraoperative bleeding, shorter hospitalization times, and lower rates of complications than OS. However, the superiority and even the safety of LS still remain an open question due to the impact of incidental GBC, unaccounted heterogeneity, publication bias, lymph node dissection, and port-site metastasis.
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Background: Auditory brainstem response (ABR) to the level-specific (LS) CE-Chirp has been reported to provide optimum neural synchrony along cochlear partitions, theoretically improving ABR waveform resolution. Despite this promising finding, limited studies have been conducted to contrast the results between LS CE-Chirp and Click stimuli. The current study aimed to compare the results of ABR between the two stimuli (Click and LS CE-Chirp). Method: Sixty-seven normal-hearing infants, both with and without risk factors, aged less than 7 months old, participated in this study. The ABR test was conducted at 70 dBnHL using 33.3 stimulus repetition rates with both Click and LS CE-Chirp stimuli. The signal averaging was stopped at a maximum fixed signal average of 2,500 sweeps. Data were statistically compared between the two stimuli using the Wilcoxon signed-rank test. Results: The waves I and V ABRs elicited by LS CE-Chirp exhibited significantly larger amplitudes than the Click stimulus. However, the amplitude of wave III and absolute latencies were similar in both stimuli at a supra-threshold level. Conclusion: LS CE-Chirp has the advantage of larger amplitudes than the ABR from Click at the supra-threshold level (70 dBnHL) in normal-hearing infants.
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One of the most recent advancements in the field of cataract surgery is optical biometry. With the advent of optical biometry ocular measurements are now simpler, quicker, and more precise. The devices have made intraocular lens (IOL) power calculations easier in difficult situations too, such as in cases with extremes of axial lengths, silicone filled eyes, cataract surgery in post-keratoplasty eyes, post Laser-Assisted in Situ Keratomileusis (LASIK) eyes, etc. The gold standard for IOL power calculation in the present day is by the use of optical biometry devices. The anatomical measurements by these devices are highly precise and because of these measurements and the incorporation of various IOL power calculation formulas the optical biometry devices give the accurate power and the post-operative visual outcome is highly satisfactory among the patients. The growing use of these devices has made cataract the most commonly performed refractive surgical procedure nowadays. In the current scenario, optical biometry has widespread acceptance in almost all countries and has many advantages over ultrasound or immersion biometry. Cataract surgeons can obtain easy and reliable measurements from these devices. Refractive surprises have also decreased considerably with their use. This article will comprehensively review the principles of the various optical biometry devices, the parameters used in each of the devices, the advantages and disadvantages, and add more like what all this article will add.
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Introduction Androgens play a key role in modulating periurethral and preputial vascularity, cavernosal smooth muscle integrity, and penile growth. As a result, low testosterone may adversely affect the severity and outcome of urethral stricture patients. So, to find out the hormonal influence on the clinical outcome of urethral stricture we conducted a prospective longitudinal study at our institute. Methods The study was conducted at the Department of Urology, Institute of Post Graduate Medical Education & Research (IPGMER), Kolkata, India, from February 2023 to September 2023. This study was approved by the Institutional Ethics Committee at IPGMER, Kolkata with the approval number IPGMER/IEC/2023/436. Hormonal levels in patients with diagnosed non-traumatic urethral stricture were compared with patients without stricture. Patients with any overt hormonal abnormality or androgen-secreting tumor were excluded. A morning 10 cc blood sample was collected for testosterone, follicle-stimulating hormone, luteinizing hormone, and thyroid-stimulating hormone. The association of hormonal levels was measured in both groups and compared statistically. Any association of hypogonadism (testosterone <300 ng/dL) with respect to length, severity, and recurrence of urethral stricture was also studied. Results Forty patients with urethral stricture and same number of patients without stricture were included in the study. The mean testosterone level was found to be significantly low in patients with stricture (386 ng/dL vs 660 ng/dL). The age-wise distribution also showed low mean testosterone compared to patients without stricture. The incidence of hypogonadism is also found to be higher in stricture patients (47.5% vs 27.5%). It was also observed low testosterone is more prevalent in pan-anterior stricture (10/40) and long-segment stricture(>2 cm). Patients with stricture were also followed up for 6 months for recurrence of symptoms. Thirteen patients had recurrence. Patients with recurrence had significantly low serum testosterone (272 ng/dL vs 440 ng/dL). Conclusion Our study documented stricture patients with low serum testosterone have poor outcomes. Low testosterone level is strongly associated with longer stricture and increased risk of stricture recurrence.
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Concrete-filled double steel tubes (CFDSTs) are a load-bearing structure of composite materials. By combining concrete and steel pipes in a nested structure, the performance of the column will be greatly improved. The performance of CFDSTs is closely related to their design. However, existing codes for CFDST design often focus on how to verify the reliability of a design, but specific design parameters cannot be directly provided. As a machine learning technique that can simultaneously learn multiple related tasks, multi-task learning (MTL) has great potential in the structural design of CFDSTs. Based on 227 uniaxial compression cases of CFDSTs collected from the literature, this paper utilized three multi-task models (multi-task Lasso, VSTG, and MLS-SVR) separately to provide multiple parameters for CFDST design. To evaluate the accuracy of models, four statistical indicators were adopted (R2, RMSE, RRMSE, and ρ). The experimental results indicated that there was a non-linear relationship among the parameters of CFDSTs. Nevertheless, MLS-SVR was still able to provide an accurate set of design parameters. The coefficient matrices of two linear models, multi-task Lasso and VSTG, revealed the potential connection among CFDST parameters. The latent-task matrix V in VSTG divided the prediction tasks of inner tube diameter, thickness, strength, and concrete strength into three groups. In addition, the limitations of this study and future work are also summarized. This paper provides new ideas for the design of CFDSTs and the study of related codes.
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Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in the fragment crystallizable region to improve pharmacokinetic profiles. The LS mutation delays antibody clearance by enhancing binding affinity to the neonatal fragment crystallizable receptor found on endothelial cells. To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV. We described serum concentrations of these monoclonal antibodies following intravenous or subcutaneous administration by an open two-compartment disposition, with first-order elimination from the central compartment using non-linear mixed effects pharmacokinetic models. We compared estimated pharmacokinetic parameters using the targeted maximum likelihood estimation method, accounting for participant differences. We observed lower clearance rate, central volume, and peripheral volume of distribution for all LS variants compared to parental monoclonal antibodies. LS monoclonal antibodies showed several improvements in pharmacokinetic parameters, including increases in the elimination half-life by 2.7- to 4.1-fold, the dose-normalized area-under-the-curve by 4.1- to 9.5-fold, and the predicted concentration at 4 weeks post-administration by 3.4- to 7.6-fold. Results suggest a favorable pharmacokinetic profile of LS variants regardless of HIV epitope specificity. Insights support lower dosages and/or less frequent dosing of LS variants to achieve similar levels of antibody exposure in future clinical applications.
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Berberis vulgaris L. (Berberidaceae) is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of the chemopreventive action of the plant's methanolic root extract (BVR) against colon cancer cells. Studies were conducted in human colon adenocarcinoma cell lines (LS180 and HT-29) and control colon epithelial CCD841 CoN cells. According to the MTT assay, after 48 h of cell exposure, the IC50 values were as follows: 4.3, 46.1, and 50.2 µg/mL for the LS180, HT-29, and CCD841 CoN cells, respectively, showing the greater sensitivity of the cancer cells to BVR. The Cell Death Detection ELISAPLUS kit demonstrated that BVR induced programmed cell death only against HT-29 cells. Nuclear double staining revealed the great proapoptotic BVR properties in HT-29 cells and subtle effect in LS180 cells. RT-qPCR with the relative quantification method showed significant changes in the expression of genes related to apoptosis in both the LS180 and HT-29 cells. The genes BCL2L1 (126.86-421.43%), BCL2L2 (240-286.02%), CASP3 (177.19-247.83%), and CASP9 (157.99-243.75%) had a significantly elevated expression, while BCL2 (25-52.03%) had a reduced expression compared to the untreated control. Furthermore, in a panel of antioxidant tests, BVR showed positive effects (63.93 ± 0.01, 122.92 ± 0.01, and 220.29 ± 0.02 mg Trolox equivalents (TE)/g in the DPPHâ¢, ABTSâ¢+, and ORAC assays, respectively). In the lipoxygenase (LOX) inhibition test, BVR revealed 62.60 ± 0.87% of enzyme inhibition. The chemical composition of BVR was determined using a UHPLC-UV-CAD-MS/MS analysis and confirmed the presence of several known alkaloids, including berberine, as well as other alkaloids and two derivatives of hydroxycinnamic acid (ferulic and sinapic acid hexosides). The results are very promising and encourage the use of BVR as a comprehensive chemopreventive agent (anti-inflammatory, antioxidant, and pro-apoptotic) in colorectal cancer, and were widely discussed alongside data from the literature.
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Adenocarcinoma , Apoptosis , Berberis , Neoplasias del Colon , Extractos Vegetales , Raíces de Plantas , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Apoptosis/efectos de los fármacos , Neoplasias del Colon/metabolismo , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Raíces de Plantas/química , Berberis/química , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Células HT29 , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacologíaRESUMEN
The utilization of lignosulfonate (LS) as a naturally derived biopolymer sourced from lignin in soil stabilization has gained significant attention in recent years. Its intermolecular interaction, hydrophobic and hydrophilic effects, adhesive and binding properties, erosion control abilities, compatibility with various soil types, and environmental sustainability make it a promising alternative to traditional soil stabilizers as well as highlighting its importance. By integrating LS into soil stabilization practices, soil properties can be enhanced, and an eco-friendlier approach can be adopted in the construction sector. This comprehensive review paper extensively examines the applications and structure of LS, as well as their efficacy and mechanisms on a micro-level scale. Afterward, it discusses the geotechnical characteristics of LS-treated soils, including consistency characteristics, dispersivity properties and erosion behavior, electrical conductivity, compaction parameters, permeability and hydraulic conductivity, compressibility characteristics, swelling potential, strength and stiffness properties, durability, and cyclic loading response. In general, LS incorporation into the soils could enhance the geotechnical properties. For instance, the Unconfined Compressive Strength (UCS) of fine-grained soils was observed to improve up to 105 %, while in the case of granular soils, the improvement can be as high as 450 %. This review also examines the economic and environmental efficiency, as well as challenges and ways forward related to LS stabilization. This can lead to economic and environmental benefits given the abundance of LS as a plant polymer for cleaner production and owing to its carbon neutrality and renewability.
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This paper investigates numerically the effect of damage evolution on adiabatic shear banding (ASB) formation and its transition to fracture during high-speed blanking of 304 stainless steel sheets. A structural-thermal-damage-coupled finite element (FE) analysis is developed in LS-DYNA considering the modified Johnson-Cook thermo-viscoplastic model for both plasticity flow rule and damage law, while further, a temperature-dependent fracture criterion is implemented by introducing a critical temperature. The modeling approach is initially validated against experimental data regarding the fracture profile and ASB width. Next, FE simulations are conducted to examine the effect of strain rate and temperature dependence on damage law, while the effect of damage coupling is also evaluated, aiming to highlight the connection between thermal and damage softening and attribute them a specific role regarding ASB formation and transition to fracture. Also, the influence of dynamic recrystallization (DRX) softening is studied macroscopically, while further, a parametric analysis of the Taylor-Quinney coefficient is conducted to highlight the effect of plastic work-to-internal heat conversion efficiency on ASB formation. The results revealed that the implementation of damage coupling reacts to reduced ASB width and provides an S-shaped fracture profile, while it also decreases the peak force and results in an earlier fracture. Both findings are enhanced when accounting further for DRX softening and a higher value of the Taylor-Quinney coefficient. Finally, the simulations indicated that thermal softening precedes damage softening, showing that the temperature rise is responsible for ASB initiation, while instead, damage evolution drives ASB propagation and fracture.