Tape-assisted fabrication method for constructing PDMS membrane-containing culture devices with cyclic radial stretching stimulation.

Advanced in vitro culture systems have emerged as alternatives to animal testing and traditional cell culture methods in biomedical research. Polydimethylsiloxane (PDMS) is frequently used in creating sophisticated culture devices owing to its elastomeric properties, which allow mechanical stretching to simulate physiological movements in cell experiments. We introduce a straightforward method that uses three types of commercial tape-generic, magic and masking-to fabricate PDMS membranes with microscale thicknesses (47.2 µm for generic, 58.1 µm for magic and 89.37 µm for masking) in these devices. These membranes are shaped as the bases of culture wells and can perform cyclic radial movements controlled via a vacuum system. In experiments with A549 cells under three mechanical stimulation conditions, we analysed transcriptional regulators responsive to external mechanical stimuli. Results indicated increased nuclear yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) activity in both confluent and densely packed cells under cyclically mechanical strains (Pearson's coefficient (PC) of 0.59 in confluent and 0.24 in dense cells) compared with static (PC = 0.47 in confluent and 0.13 in dense) and stretched conditions (PC = 0.55 in confluent and 0.20 in dense). This technique offers laboratories without microfabrication capabilities a viable option for exploring cellular behaviour under dynamic mechanical stimulation using PDMS membrane-equipped devices.

Survival Analysis and Prognostic Factors After Endonasal Resection of Advanced Olfactory Neuroblastomas: A Single Institution Experience.

OBJECTIVES: To explore the prognostic factors in patients with advanced olfactory neuroblastoma (ONB) underwent endoscopic surgery. MATERIALS AND METHODS: Retrospective medical records were reviewed of patients with pathologically proven ONB who underwent endoscopic surgical resection. Clinicopathological characteristics including patient demographics, treatment, complications, follow-up, and outcomes were analyzed. Kaplan-Meier overall survival (OS) and disease-free survival (DFS) curves were plotted. Univariate and multivariate Cox regression models were used to determine prognostic factors. RESULTS: Eighty-five patients with Kadish stage C ONB were examined. According to the various staging systems used, most patients harbored modified Kadish stage C (78.8%). Twenty-six patients (30.6%) underwent bony skull base resection, 11 (12.9%) underwent dura resection, and 24 (28.2%) underwent additional intracranial resection that included the olfactory bulb and duct. Median follow-up was 39 months. Five-year OS and DFS rates were 83.7% and 74.9%, respectively. Five-year OS was 100% in patients treated with bony skull base resection and 77.5% in those who were not (P = .052). Dura resection did not improve OS. Multivariate Cox regression analysis identified perioperative complications (P = .009), gross total resection (P = .004), orbital invasion (P = .014), postoperative radiotherapy (P = .030), and bony skull base resection (P = .019) as independent prognostic predictors. CONCLUSION: For patients with advanced ONB, endoscopic surgery in conjunction with radiotherapy and chemotherapy is effective and safe. Dura resection should be performed with caution in selected patients to balance survival and complications. Postoperative radiotherapy is important to improve OS and DFS.

Inference of forensic body fluids/tissues based on mitochondrial DNA copy number: a preliminary study.

The inference of body fluids and tissues is critical in reconstructing crime scenes and inferring criminal behaviors. Nevertheless, present methods are incompatible with conventional DNA genotyping, and additional testing might result in excessive consumption of forensic scene materials. This study aims to investigate the feasibility of distinguishing common body fluids/tissues through the difference in mitochondrial DNA copy number (mtDNAcn). Four types of body fluids/tissues were analyzed in this study - hair, saliva, semen, and skeletal muscle. MtDNAcn was estimated by dividing the read counts of mitochondrial DNA to that of nuclear DNA (RRmt/nu). Results indicated that there were significant differences in RRmt/nu between different body fluids/tissues. Specifically, hair samples exhibited the highest RRmt/nu (log10RRmt/nu: 4.3 ± 0.28), while semen samples showed the lowest RRmt/nu (log10RRmt/nu: -0.1 ± 0.28). RRmt/nu values for DNA samples without extraction were notably higher (approximately 2.9 times) than those obtained after extraction. However, no significant difference in RRmt/nu was observed between various age and gender groups. Hierarchical clustering and Kmeans clustering analyses showed that body fluids/tissues of the same type clustered closely to each other and could be inferred with high accuracy. In conclusion, this study demonstrated that the simultaneous detection of nuclear and mitochondrial DNA made it possible to perform conventional DNA analyses and body fluid/tissue inference at the same time, thus killing two birds with one stone. Furthermore, mtDNAcn has the potential to serve as a novel and promising biomarker for the identification of body fluids/tissues.

Impact of transforming karst mountainous forests into urban parks on plant diversity patterns.

The conversion of urban montane forest resources into urban parks requires careful assessment to understand its impacts on plant diversity over time. This study aims to enhance urban biodiversity conservation strategies by analyzing how habitat type and park age affect woody plant diversity. We surveyed woody plant species in 60 sample plots across two different habitats (remnant forest vs. artificial green space) within three mountain parks in Guiyang, China, established at different times. The alpha diversity of saplings/seedlings was significantly higher in remnant forests than in artificial green spaces. Artificial green spaces exhibited more homogenous woody plant composition compared with remnant forests. Newer parks showed greater variation in plant composition between the two habitats than older parks. Indicative species in remnant forests were predominantly native, whereas those in artificial green spaces were mainly ornamental species. The transformation of karst mountainous forests into urban parks leads to the homogenization of woody plant composition and impedes the regeneration of saplings/seedlings. Therefore, it is crucial to manage these conversions carefully and strive to preserve as many native species as possible to support urban plant diversity conservation.

An essential role of the E3 ubiquitin ligase RNF126 in ensuring meiosis I completion during spermatogenesis.

INTRODUCTION: Homologous recombination repair during meiosis is essential for the exchange of genetic information between sister chromosomes, underpinning spermatogenesis and, consequently, fertility. The disruption of this process can lead to infertility, highlighting the importance of identifying the molecular actors involved. OBJECTIVES: This study aims to elucidate the role of the E3 ubiquitin ligase Rnf126 in spermatogenesis and its impact on fertility, particularly through its involvement in meiotic homologous recombination repair. METHODS: We used heterozygous and homozygous Rnf126 deletion models in mouse testes to examine the consequences on testicular health, sperm count, and the process of spermatogenesis. Additionally, we explored the association between RNF126 gene missense variants and nonobstructive male infertility in patients, with a focus on their functional impact on the protein's ubiquitin ligase activity. RESULTS: Rnf126 deletion led to testicular atrophy, disrupted seminiferous tubule structure, reduced sperm count, and spermatogenesis arrest at meiotic prophase I. Furthermore, male mice exhibited impaired homologous recombination repair and increased apoptosis within the seminiferous tubules. We identified four missense variants of the RNF126 (V68M, R241H, E261A, D253N) associated with male infertility. Specifically, the E261A and D253N variants, located in the RING domain, directly compromised the E3 ubiquitin ligase activity of RNF126. CONCLUSION: Our findings demonstrate the pivotal role of RNF126 in maintaining spermatogenesis and fertility, offering insights into the molecular mechanisms underlying male infertility. The identified RNF126 variants present novel targets for diagnostic and therapeutic strategies in treating nonobstructive male infertility.

Will AMPK be a potential therapeutic target for hepatocellular carcinoma?

Cancer is the disease that poses the greatest threat to human health today. Among them, hepatocellular carcinoma (HCC) is particularly prominent due to its high recurrence rate and extremely low five-year postoperative survival rate. In addition to surgical treatment, radiotherapy, chemotherapy, and immunotherapy are the main methods for treating HCC. Due to the natural drug resistance of chemoradiotherapy and targeted drugs, satisfactory results have not been achieved in terms of therapeutic efficacy and cost. AMP-Activated Protein Kinase (AMPK) is a serine/threonine protein kinase. It mainly coordinates the metabolism and transformation of energy between cells, which maintaining a balance between energy supply and demand. The processes of cell growth, proliferation, autophagy, and survival all involve various reaction of cells to energy changes. The regulatory role of AMPK in cellular energy metabolism plays an important role in the occurrence, development, treatment, and prognosis of HCC. Here, we reviewed the latest progress on the regulatory role of AMPK in the occurrence and development of HCC. Firstly, the molecular structure and activation mechanism of AMPK were introduced. Secondly, the emerging regulator related to AMPK and tumors were elaborated. Next, the multitasking roles of AMPK in the occurrence and development mechanism of HCC were discussed separately. Finally, the translational implications and the challenges of AMPK-targeted therapies for HCC treatment were elaborated. In summary, these pieces of information suggest that AMPK can serve as a promising specific therapeutic target for the treatment of HCC.

Effectiveness of colonoscopy, immune fecal occult blood testing, and risk-graded screening strategies in colorectal cancer screening.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors, and early screening is crucial to improving the survival rate of patients. The combination of colonoscopy and immune fecal occult blood detection has garnered significant attention as a novel method for CRC screening. Colonoscopy and fecal occult blood tests, when combined, can improve screening accuracy and early detection rates, thereby facilitating early intervention and treatment. However, certain risks and costs accompany it, making the establishment of a risk classification model crucial for accurate classification and management of screened subjects. AIM: To evaluate the feasibility and effectiveness of colonoscopy, immune fecal occult blood test (FIT), and risk-graded screening strategies in CRC screening. METHODS: Based on the randomized controlled trial of CRC screening in the population conducted by our hospital May 2020 to May 2023, participants who met the requirements were randomly assigned to a colonoscopy group, an FIT group, or a graded screening group at a ratio of 1:2:2 (after risk assessment, the high-risk group received colonoscopy, the low-risk group received an FIT test, and the FIT-positive group received colonoscopy). The three groups received CRC screening with different protocols, among which the colonoscopy group only received baseline screening, and the FIT group and the graded screening group received annual follow-up screening based on baseline screening. The primary outcome was the detection rate of advanced tumors, including CRC and advanced adenoma. The population participation rate, advanced tumor detection rate, and colonoscopy load of the three screening programs were compared. RESULTS: A total of 19373 subjects who met the inclusion and exclusion criteria were enrolled, including 8082 males (41.7%) and 11291 females (58.3%). The mean age was 60.05 ± 6.5 years. Among them, 3883 patients were enrolled in the colonoscopy group, 7793 in the FIT group, and 7697 in the graded screening group. Two rounds of follow-up screening were completed in the FIT group and the graded screening group. The graded screening group (89.2%) and the colonoscopy group (42.3%) had the lowest overall screening participation rates, while the FIT group had the highest (99.3%). The results of the intentional analysis showed that the detection rate of advanced tumors in the colonoscopy group was greater than that of the FIT group [2.76% vs 2.17%, odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.01-1.65, P = 0.037]. There was no significant difference in the detection rate of advanced tumors between the colonoscopy group and the graded screening group (2.76% vs 2.35%, OR = 1.9, 95%CI: 0.93-1.51, P = 0.156), as well as between the graded screening group and the FIT group (2.35% vs 2.17%, OR = 1.09%, 95%CI: 0.88-1.34, P = 0.440). The number of colonoscopy examinations required for each patient with advanced tumors was used as an index to evaluate the colonoscopy load during population screening. The graded screening group had the highest colonoscopy load (15.4 times), followed by the colonoscopy group (10.2 times), and the FIT group had the lowest (7.8 times). CONCLUSION: A hierarchical screening strategy based on CRC risk assessment is feasible for screening for CRC in the population. It can be used as an effective supplement to traditional colonoscopy and FIT screening programs.

Clinicopathological characteristics and prognosis of uterine sarcoma: a 10-year retrospective single-center study in China.

BACKGROUND: Uterine sarcoma is a rare and heterogeneous gynecological malignancy characterized by aggressive progression and poor prognosis. The current study aimed to investigate the relationship between clinicopathological characteristics and the prognosis of uterine sarcoma in Chinese patients. METHODS: In this single-center retrospective study, we reviewed the medical records of 75 patients with histologically verified uterine sarcoma treated at the First Affiliated Hospital of Xi'an Jiaotong University between 2011 and 2020. Information on clinical characteristics, treatments, pathology and survival was collected. Progression-free survival (PFS) and overall survival (OS) were visualized in Kaplan-Meier curves. Prognostic factors were identified using the log-rank test for univariate analysis and Cox-proportional hazards regression models for multivariate analysis. RESULTS: The histopathological types included 36 endometrial stromal sarcomas (ESS,48%), 33 leiomyosarcomas (LMS,44%) and 6 adenosarcomas (8%). The mean age at diagnosis was 50.2 ± 10.7 years. Stage I and low-grade accounted for the majority. There were 26 recurrences and 25 deaths at the last follow-up. The mean PFS and OS were 89.41 (95% CI: 76.07-102.75) and 94.03 (95% CI: 81.67-106.38) months, respectively. Univariate analysis showed that > 50 years, post-menopause, advanced stage, ≥ 1/2 myometrial invasion, lymphovascular space invasion and high grade were associated with shorter survival (P < 0.05). Color Doppler flow imaging positive signals were associated with shorter PFS in the LMS group (P = 0.046). The ESS group had longer PFS than that of the LMS group (99.56 vs. 76.05 months, P = 0.043). The multivariate analysis showed that post-menopause and advanced stage were independent risk factors of both PFS and OS in the total cohort and LMS group. In the ESS group, diagnosis age > 50 years and high-grade were independent risk factors of PFS, while high-grade and lymphovascular space invasion were independent risk factors of OS. CONCLUSION: In Chinese patients with uterine sarcoma, post-menopause and advanced stage were associated with a significantly poorer prognosis. The prognosis of ESS was better than that of LMS. Color Doppler flow imaging positive signals of the tumor helped to identify LMS, which needs to be further tested in a larger sample in the future.

Efficacy of dupilumab in the treatment of severe vulvar pruritus associated with lichen sclerosus et atrophicus: a case report.

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory skin lesion with an undefined cause. It is more commonly found in the genital area, particularly in adolescents, premenopausal women and postmenopausal women. LSA is difficult to treat and often recurs. The primary treatment for LSA involves the administration of potent topical corticosteroids. Dupilumab is increasingly being used for the treatment of itching in non-atopic dermatitis patients but there are few reports on its use for the treatment of LSA. Here, we present a case of LSA in a 61-year-old woman with extensive vulvar itching. Over four months of dupilumab therapy, significant therapeutic effects were observed, including vulvar skin thinning and pruritus relief without adverse reactions.

Vision-related quality of life after unilateral occipital stroke.

BACKGROUND/OBJECTIVES: Stroke damage to the primary visual cortex induces large, homonymous visual field defects that impair daily living. Here, we asked if vision-related quality of life (VR-QoL) is impacted by time since stroke. SUBJECTS/METHODS: We conducted a retrospective meta-analysis of 95 occipital stroke patients (female/male = 26/69, 27-78 years old, 0.5-373.5 months poststroke) in whom VR-QoL was estimated using the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ) and its 10-item neuro-ophthalmic supplement (Neuro10). Visual deficit severity was represented by the perimetric mean deviation (PMD) calculated from 24-2 Humphrey visual fields. Data were compared with published cohorts of visually intact controls. The relationship between VR-QoL and time poststroke was assessed across participants, adjusting for deficit severity and age with a multiple linear regression analysis. RESULTS: Occipital stroke patients had significantly lower NEI-VFQ and Neuro10 composite scores than controls. All subscale scores describing specific aspects of visual ability and functioning were impaired except for ocular pain and general health, which did not differ significantly from controls. Surprisingly, visual deficit severity was not correlated with either composite score, both of which increased with time poststroke, even when adjusting for PMD and age. CONCLUSIONS: VR-QoL appears to improve with time postoccipital stroke, irrespective of visual deficit size or patient age at insult. This may reflect the natural development of compensatory strategies and lifestyle adjustments. Thus, future studies examining the impact of rehabilitation on daily living in this patient population should consider the possibility that their VR-QoL may change gradually over time, even without therapeutic intervention.

Research Progress on the Correlation of Atopic Dermatitis with Gut Microbiota.

Atopic dermatitis (AD) is a common skin disease, the pathogenesis of which has not been fully elucidated. The gut microbiota is the largest micro-ecosystem in the human body that affects the immune system and skin barrier function. Recent studies have shown that in addition to the environmental factors, skin barrier, genetic factors and immune response, gut microbiota disturbance may also cause AD. This review described the correlation of AD with gut microbiota and existing research status of AD treatment via targeting gut microbiota.

A colorimetric/electrochemical microfluidic biosensor using target-triggered DNA hydrogels for organophosphorus detection.

Organophosphorus compounds are widely distributed and highly toxic to the environment and living organisms. The current detection of organophosphorus compounds is based on a single-mode method, which makes it challenging to achieve good portability, accuracy, and sensitivity simultaneously. This study designed a multifunctional microfluidic chip to develop a dual-mode biosensor employing a DNA hydrogel as a carrier and aptamers as recognition probes for the colorimetric/electrochemical detection of malathion, an organophosphorus compound. The biosensor balanced portability and stability by combining a microfluidic chip and target-triggered DNA hydrogel-sensing technologies. Moreover, the biosensor based on target-triggered DNA hydrogel modified microfluidic developed in this study exhibited a dual-mode response to malathion, providing both colorimetric and electrochemical signals. The colorimetric mode enables rapid visualization and qualitative detection and, when combined with a smartphone, allows on-site quantitative analysis with a detection limit of 56 nM. The electrochemical mode offers a broad linear range (0.01-3000 µM) and high sensitivity (a limit of detection of 5 nM). The two modes could validate each other and improve the accuracy of detection. The colorimetric/electrochemical dual-mode biosensor based on target-triggered DNA hydrogel modified microfluidic chip offers a portable, simple, accurate, and sensitive strategy for detecting harmful environmental and food substances.

Controversy between biopsy and risk in children with proteinuria: is there a paradigm war?

BACKGROUND: Proteinuria is a prevalent symptom of pediatric nephrology, while kidney biopsy remains the gold standard for kidney tissue analysis, and it is currently controversial. We report the rare case that the mutation in the AMN gene was considered to cause chronically isolated proteinuria and also suggest that renal biopsy should be chosen with caution in children with chronic isolated non-nephrotic levels of proteinuria and that genetic testing may be feasible for the early precise diagnosis. CASE PRESENTATION: A 35-month-old boy presented with excessive urine foaming for more than half a month; his proteinuria was considered non-nephrotic range and urine protein electrophoresis was suggestive of mixed proteinuria; other than that, the investigations are non-specific. Given the child's chronic isolated proteinuria and good renal function, we chose to refine the genetic test rather than a renal biopsy; a compound heterozygous variant was found in the AMN gene of this child which was caused by a point mutation in the father, and a partial chromosomal deletion in the mother. CONCLUSIONS: Cubilin(encoded by CUBN), amnionless(encoded by AMN), and megalin form a multiligand receptor complex; CUBN or AMN gene variants have been implicated as a hereditary cause of megaloblastic anemia, proteinuria, and neurological impairment. In the past few decades, chronic isolated proteinuria caused by CUBN gene variants is benign, non-progressive, and has normal renal function. However, the child is the first reported case of isolated proteinuria of AMN gene mutation, indicating that the earlier diagnostic genetic sequencing in an otherwise well, not nephrotic proteinuria child may be a convenient, cost-effective, and harmless option, challenging the traditional paradigm.

Effect of Bile Acids Supplementation in Fatty Liver Hemorrhagic Syndrome, Production Performance, Physiological and Quality Characteristics of Laying Hen Eggs.

This study aimed to investigate the effects of bile acids (BAs) supplementation on fatty liver hemorrhagic syndrome (FLHS), production performance, and physiological and quality characteristics of laying hen eggs. Sixty Sanhuang laying hens, aged 28 weeks, were randomly allocated to six dietary treatments over a 4-week period, including the control (CON) group (feeding basal diet), the high-fat diet (HFD)-treated group (basal diet containing 10% soybean oil), and HFD supplemented with 0.01% and 0.02% of chenodeoxycholic acid (CDCA) or hyodeoxycholic acid (HDCA) groups. Production performance, egg quality, liver morphology, serum biochemical indexes, antioxidant capacity, proinflammatory cytokines, and intestinal microbiota were evaluated. The average body weight in 0.01% CDCA was larger than in the HFD group (p < 0.05). Eggshell Thickness in the CON group was greater than in the HFD, 0.01% CDCA, and HDCA groups (p < 0.05). Albumen height in the 0.02% HDCA group was higher than the HFD group (p < 0.05). Eggshell weight in the HFD group was less than the CON group (p < 0.05). Haugh unit (HU) in the HDCA group was larger than the HFD group (p < 0.05). Albumen weight in the 0.02% HDCA group was greater than the CON and HFD groups (p < 0.05). In the HFD group, the levels of triglyceride (TG), total cholesterol (TC), and low-density lipo-protein cholesterol (LDL-C) were surpassing the other groups (p < 0.05). The levels of catalase (CAT) and total superoxide dismutase (T-SOD) in the HFD group was smaller than the other groups (p < 0.05). The level of malondialdehyde (MDA) in the HFD group was higher than in the other groups (p < 0.05). Tumor necrosis factor-α (TNF-α) levels were larger in the HFD group than in the other groups (p < 0.05). The 16S rRNA sequencing analysis indicated significant variations in the relative abundance of specific bacterial populations among the different treatment groups. The treatment and CON groups exhibited a higher presence of bacteria that inhibit host energy absorption or promote intestinal health such as Firmicutes, Bacteroidetes, and Ruminococcus, whereas the HFD group showed an increased prevalence of potentially pathogenic or deleterious bacteria, such as Desulfovibrio spp. In conclusion, the supplementation of BAs in poultry feed has been demonstrated to effectively mitigate the detrimental effects of FLHS in laying hens. This intervention regulates lipid metabolism, bolsters antioxidant defenses, reduces inflammation, and modulates the gut microbiota, offering a novel perspective on the application of BAs in the poultry industry.

Analyzing how SiMiao Wan regulates ferroptosis to prevent RA-ILD using metabolomics and cyberpharmacology.

BACKGROUND: Interstitial lung disease (ILD) is a common complication of rheumatoid arthritis (RA) that plays a significant role in the morbidity and mortality of individuals with this condition. In clinical settings, Si Miao Wan (SMW), a traditional Chinese medicine, is often utilized for the management of RA, as it is believed to possess properties that aid in reducing inflammation, eliminating excess moisture, and alleviating joint pain. PURPOSE: The primary objective of this investigation was to elucidate the potential mechanism of RA-ILD prevention from the perspective of ferroptosis mediated by SMW. METHODS: UPLC-Q-TOF/MS and network pharmacology were employed to forecast the potential targets of SMW for the early prevention of RA-ILD. Following this, HE staining, metabolomics, and RT-PCR were utilized to investigate the mechanism by which SMW prevents RA-ILD at an early stage. RESULTS: Following six weeks of continuous administration of SMW extract at a dosage of 2.16 g/kg/day, it was observed that SMW exhibited early preventive effects against RA-ILD. Metabolomics analysis revealed seven potential biomarkers linked to the pharmacological efficacy of SMW in the early prevention of RA-ILD. Additionally, network pharmacology analysis suggested that SMW may exert its therapeutic effects on RA-ILD by modulating signaling pathways associated with lipid metabolism, atherosclerosis, TNF, and IL-17. Ultimately, through the integration of metabolomics and network pharmacology analysis, along with subsequent verification, it was determined that the early prevention of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) by Shenmai injection (SMW) is associated with the ferroptosis pathway. CONCLUSION: This research offers preliminary insights into the potential mechanism by which traditional Chinese medicine Shen Mai Wan (SMW) may mitigate the early onset of Rheumatoid Arthritis-Interstitial Lung Disease (RA-ILD) via the process of ferroptosis. Furthermore, it establishes a theoretical framework for the development of innovative SMW-based pharmaceuticals for the management of RA-ILD. The signal proteins implicated in this process are anticipated to emerge as crucial targets for the prevention of RA-ILD.

Magnetic materials as adsorbents for the pre-concentration and separation of active ingredients from herbal medicine.

Herbal medicine (HM) is crucial in disease management and contains complex compounds with few active pharmacological ingredients, presenting challenges in quality control of raw materials and formulations. Effective separation, identification, and analysis of active components are vital for HM efficacy. Traditional methods like liquid-liquid extraction and solid-phase extraction are time-consuming and environmentally concerning, with limitations such as sorbent issues, pressure, and clogging. Magnetic solid-phase extraction uses magnetic sorbents for targeted analyte separation and enrichment, offering rapid, pressure-free separation. However, inorganic magnetic particles' aggregation and oxidation, as well as lack of selectivity, have led to the use of various coatings and modifications to enhance specificity and selectivity for complex herbal samples. This review delves into magnetic composites in HM pretreatment, specifically focusing on encapsulated or modified magnetic nanoparticles and materials like silica, ionic liquids, graphene family derivatives, carbon nanotubes, metal-organic frameworks, covalent organic frameworks, and molecularly imprinted polymers.

Discovery of a Novel and Potent LCK Inhibitor for Leukemia Treatment via Deep Learning and Molecular Docking.

The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger's suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50 of 0.43 nM. Further in vitro bioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivo antileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.

Computer-aided discovery of novel aryl hydrocarbon receptor ligands to regulate CYP1A1 expression in inflammatory macrophages.

The environmental factor aryl hydrocarbon receptor (AhR), a key protein connecting the external environmental signals (e.g., environmental endocrine disruptor TCDD) to internal cellular processes, is involved in the activation of peripheral macrophages and inflammatory response in human body. Thus, there is widespread interest in finding compounds to anti-inflammatory response in macrophages by targeting human AhR. Here, ensemble docking based-virtual screening was first used to screen a library (~200,000 compounds) against human AhR ligand binding domain (LBD) and 25 compounds were identified as potential inhibitors. Then, 9 out of the 25 ligands were found to down-regulate the mRNA expression of CYP1A1 (a downstream gene of AhR signaling) in AhR overexpressing macrophages. The most potent compound AE-411/41415610 was selected for further study and found to reduce both mRNA and protein expressions level of CYP1A1 in mouse peritoneal macrophage. Moreover, protein chip signal pathway analysis indicated that AE-411/41415610 play a role in regulating JAK-STAT and AKT-mTOR pathways. In sum, the discovered hits with novel scaffolds provided a starting point for future design of more effective AhR-targeted lead compounds to regulate CYP1A1 expression of inflammatory peritoneal macrophages.

Effect of Calcination Atmosphere on the Performance of Cu/Al2O3 Catalyst for the Selective Hydrogenation of Furfural to Furfuryl Alcohol.

The selective hydrogenation of the biomass platform molecule furfural (FAL) to produce furfuryl alcohol (FA) is of great significance to alleviate the energy crisis. Cu-based catalysts are the most commonly used catalysts, and their catalytic performance can be optimized by changing the preparation method. This paper emphasized the effect of calcination atmosphere on the performance of a Cu/Al2O3 catalyst for the selective hydrogenation of FAL. The precursor of the Cu/Al2O3 catalyst prepared by the ammonia evaporation method was treated with different calcination atmospheres (N2 and air). On the basis of the combined results from the characterizations using in situ XRD, TEM, N2O titration, H2-TPR and XPS, the Cu/Al2O3 catalyst calcined in the N2 atmosphere was more favorable for the dispersion and reduction of Cu species and the reduction process could produce more Cu+ and Cu0 species, which facilitated the selective hydrogenation of FAL to FA. The experimental results showed that the N2 calcination atmosphere improved the FAL conversion and FA selectivity, and the FAL conversion was further increased after reduction. Cu/Al2O3-N2-R exhibited the outstanding performance, with a high yield of 99.9% of FA after 2 h at 120 °C and an H2 pressure of 1 MPa. This work provides a simple, efficient and economic method to improve the C=O hydrogenation performance of Cu-based catalysts.

Improvement of Surimi Gel from Frozen-Stored Silver Carp.

Silver Carp (SC) is an under-utilized, invasive species in North American river systems. In this study, the synergistic effects of manufactured Microfiber (MMF), Transglutaminase (TG), and chicken skin collagen (CLG)) to enhance surimi gel quality from frozen SC were studied. The gel strength, textural properties, rheological properties, water-holding capacity (WHC), water mobility, microstructure, and protein composition of the gel samples were determined to assess the impact of the additives individually and synergistically. The results suggested that TG had the most pronounced effect on the surimi gel properties by promoting protein cross-linking. Synergistic effects between TG, MMF, and CLG can bring effective gel property enhancement larger than the individual effect of each additive alone. With the established response-surface models, the combination of CLG and MMF can be optimized to produce surimi gels with less TG but comparable in properties to that of the optimal result with high TG usage. The findings of this study provided a technical foundation for making high-quality surimi gel products out of frozen-stored SC with synergistic utilization of additives, which could serve as guidelines for the industrial development of new surimi products.