Artemvulactone E isolated from Artemisia vulgaris L. ameliorates lipopolysaccharide-induced inflammation in both RAW264.7 and zebrafish model.

Introduction: Natural plants are valuable resources for exploring new bioactive compounds. Artemisia vulgaris L. is a traditional Chinese medicinal herb that has been historically used for treating multiple diseases. Active compounds isolated and extracted from A. vulgaris L. typically possess immunomodulatory and anti-inflammatory properties. Artemvulactone E (AE) is a new sesquiterpene lactone isolated and extracted from A. vulgaris L. with unclear biological activities. Methods: The immunoregulatory effects of AE on macrophages were assessed by ELISA, RT-qPCR, immunofluorescence, and western blot assay. The effect of AE on lipopolysaccharide (LPS) -relates signaling pathways was examined by western blot assay. In zebrafish models, the larvae were yolk-microinjected with LPS to establish inflammation model and the effect of AE was evaluated by determining the survival rate, heart rate, yolk sac edema size, neutrophils and macrophages infiltration of zebrafish. The interaction between AE and Toll-like receptor 4 (TLR4) was examined by molecular docking and dynamic stimulation. Results: AE reduced the expression and secretion of pro-inflammatory cytokines (TNF-α and IL-6), inflammatory mediators iNOS and COX-2, as well as decreases the production of intracellular NO and ROS in LPS-stimulated macrophages. In addition, AE exerted its anti-inflammatory effect synergistically by inhibiting MAPK/JAK/STAT3-NF-κB signaling pathways. Furthermore, AE enhanced the survival rate and attenuated inflammatory response in zebrafish embryos treated with LPS. Finally, the molecular dynamics results indicate that AE forms stable complexes with LPS receptor TLR4 through the Ser127 residue, thus completely impairing the subsequent activation of MAPK-NF-κB signaling. Conclusion: AE exhibits notable anti-inflammatory activity and represents as a potential agent for treating inflammation-associated diseases.

CircRNA as an Achilles heel of cancer: characterization, biomarker and therapeutic modalities.

Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs characterized by their lack of 5' caps and 3' poly(A) tails. These molecules have garnered substantial attention from the scientific community. A wide range of circRNA types has been found to be expressed in various tissues of the human body, exhibiting unique characteristics such as high abundance, remarkable stability, and tissue-specific expression patterns. These attributes, along with their detectability in liquid biopsy samples such as plasma, position circRNAs an ideal choice as cancer diagnostic and prognostic biomarkers. Additionally, several studies have reported that the functions of circRNAs are associated with tumor proliferation, metastasis, and drug resistance. They achieve this through various mechanisms, including modulation of parental gene expression, regulation of gene transcription, acting as microRNA (miRNA) sponges, and encoding functional proteins. In recent years, a large number of studies have focused on synthesizing circRNAs in vitro and delivering them to tumor tissue to exert its effects in inhibit tumor progression. Herein, we briefly discuss the biogenesis, characteristics, functions, and detection of circRNAs, emphasizing their clinical potential as biomarkers for cancer diagnosis and prognosis. We also provide an overview the recent techniques for synthesizing circRNAs and delivery strategies, and outline the application of engineered circRNAs in clinical cancer therapy.

Antisense oligonucleotides enhance SLC20A2 expression and suppress brain calcification in a humanized mouse model.

Primary familial brain calcification (PFBC) is a genetic neurological disease, yet no effective treatment is currently available. Here, we identified five novel intronic variants in SLC20A2 gene from six PFBC families. Three of these variants increased aberrant SLC20A2 pre-mRNA splicing by altering the binding affinity of splicing machineries to newly characterized cryptic exons, ultimately causing premature termination of SLC20A2 translation. Inhibiting the cryptic-exon incorporation with splice-switching ASOs increased the expression levels of functional SLC20A2 in cells carrying SLC20A2 mutations. Moreover, by knocking in a humanized SLC20A2 intron 2 sequence carrying a PFBC-associated intronic variant, the SLC20A2-KI mice exhibited increased inorganic phosphate (Pi) levels in cerebrospinal fluid (CSF) and progressive brain calcification. Intracerebroventricular administration of ASOs to these SLC20A2-KI mice reduced CSF Pi levels and suppressed brain calcification. Together, our findings expand the genetic etiology of PFBC and demonstrate ASO-mediated splice modulation as a potential therapy for PFBC patients with SLC20A2 haploinsufficiency.

Delivery-First Strategy Followed by Endovascular Repair to Treat Pregnant Woman With Acute Complicated Type B Aortic Dissection.

Objective: Aortic dissection, a rare but serious condition, requires timely diagnosis and treatment. Case report: A case report involving a 33-year-old female with Stanford type B aortic dissection at 32 + 3 weeks gestational age highlights the importance of being alert to the symptoms and signs of this condition, particularly in patients with hypertension or a history of connective tissue disorders. The case report suggests a delivery first strategy followed by TEVAR procedure as the preferred approach for managing aortic dissection in pregnancy. This approach can alleviate pressure on the aorta, reduce the risk of rupture, and provide time for stabilization and preparation for the TEVAR procedure. Conclusion: The case report emphasizes the criticality of recognizing and treating aortic dissection in pregnant patients promptly, given its potential life-threatening impact on both mother and fetus.

A Highly Stable, Multifunctional Janus Dressing for Treating Infected Wounds.

The limited and unstable absorption of excess exudate is a major challenge during the healing of infected wounds. In this study, a highly stable, multifunctional Janus dressing with unidirectional exudate transfer capacity is fabricated based on a single poly(lactide caprolactone) (PLCL). The success of this method relies on an acid hydrolysis reaction that transforms PLCL fibers from hydrophobic to hydrophilic in situ. The resulting interfacial affinity between the hydrophilic/phobic PLCL fibers endows the Janus structure with excellent unidirectional liquid transfer and high structural stability against repeated stretching, bending, and twisting. Various other functions, including wound status detection, antibacterial, antioxidant, and anti-inflammatory properties, are also integrated into the dressing by incorporating phenol red and epigallocatechin gallate. An in vivo methicillin-resistant Staphylococcus aureus-infected wound model confirms that the Janus dressing, with the capability to remove exudate from the infected site, not only facilitates epithelialization and collagen deposition, but also ensures low inflammation and high angiogenesis, thus reaching an ideal closure rate up to 98.4% on day 14. The simple structure, multiple functions, and easy fabrication of the dressing may offer a promising strategy for treating chronic wounds, rooted in the challenges of bacterial infection, excessive exudate, and persistent inflammation.

Associations amongst dynamic knee stiffness during gait, quadriceps stiffness, and the incidence of knee osteoarthritis over 24 months: a cohort study with a mediation analysis.

BACKGROUND: Decreased strength and increased stiffness of the quadriceps have been associated with a higher risk of developing knee osteoarthritis (OA) in elders. Dynamic joint stiffness (DJS) represents collective resistance from active and passive knee structures for dynamic knee motions. Elevated sagittal knee DJS has been associated with worsening of cartilage loss in knee OA patients. Altered quadriceps properties may affect DJS, which could be a mediator for associations between quadriceps properties and knee OA. Hence, this study aimed to examine whether DJS and quadriceps properties would be associated with the development of clinical knee OA over 24 months, and to explore the mediation role of DJS in associations between quadriceps properties and knee OA. METHODS: This was a prospective cohort study with 162 healthy community-dwelling elders. Gait analysis was conducted to compute DJS during the loading response phase. Quadriceps strength and stiffness were evaluated using a Cybex dynamometer and shear-wave ultrasound elastography, respectively. Knee OA was defined based on clinical criteria 24 months later. Logistic regression with generalized estimating equations was used to examine the association between quadriceps properties and DJS and incident knee OA. Mediation analysis was performed to explore the mediation role of DJS in associations between quadriceps properties and the incidence of knee OA. RESULTS: A total of 125 participants (65.6 ± 4.0 years, 58.4% females) completed the 24-month follow-up, with 36 out of 250 knees identified as clinical knee OA. Higher DJS (OR = 1.86, 95%CI: 1.33-2.62), lower quadriceps strength (1.85, 1.05-3.23), and greater quadriceps stiffness (1.56, 1.10-2.21) were significantly associated with a higher risk of clinical knee OA. Mediation analysis showed that the DJS was not a significant mediator for the associations between quadriceps properties and knee OA. CONCLUSIONS: Higher sagittal knee dynamic joint stiffness, lower quadriceps strength, and greater quadriceps stiffness are potential risk factors for developing clinical knee OA in asymptomatic elders. Associations between quadriceps properties and knee OA may not be mediated by dynamic joint stiffness. Interventions for reducing increased passive properties of the quadriceps and knee joint stiffness may be beneficial for maintaining healthy knees in the aging population.

Hernandonine-mediated autophagic cell death in hepatocellular carcinoma: Interplay of p53 and YAP signaling pathways.

Hepatocellular carcinoma (HCC), the primary form of liver cancer, is the third leading cause of cancer-related death globally. Hernandonine is a natural alkaloid derived from Hernandia nymphaeifolia that has been shown to exert various biological functions. In a previous study, hernandonine was shown to suppress the proliferation of several solid tumor cell lines without affecting normal human cell lines. However, little is known about the effect of hernandonine on HCC. Therefore, this study aimed to investigate the effect and mechanism of hernandonine on HCC in relation to autophagy. We found that hernandonine inhibited HCC cell growth in vitro and in vivo. In addition, hernandonine elicited autophagic cell death and DNA damage in HCC cells. RNA-seq analysis revealed that hernandonine upregulated p53 and Hippo signaling pathway-related genes in HCC cells. Small RNA interference of p53 resulted in hernandonine-induced autophagic cell death attenuation. However, inhibition of YAP sensitized HCC cells to hernandonine by increasing the autophagy induction. This is the first study to illustrate the complex involvement of p53 and YAP in the hernandonine-induced autophagic cell death in human HCC cells. Our findings provide novel evidence for the potential of hernandonine as a therapeutic agent for HCC treatment.

Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis.

Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.

Application of cord blood-derived platelet-rich plasma in the treatment of diseases.

Platelet-rich plasma (PRP), a blood product containing high concentrations of platelets, has been increasingly used for the treatment of a number of diseases because of its anti-inflammatory and regenerative properties. PRP is generally obtained from the patient's own peripheral blood when used in clinical applications, but allogeneic PRP extracted from umbilical cord blood has also attracted attention due to its unique advantages. The main purpose of this narrative review was to summarize the research and clinical application of cord blood-derived PRP (CB-PRP) in the treatment of diseases up to April 2024. This review also discusses the differences between CB-PRP and autologous PRP (A-PRP). A thorough search of PubMed® and Clinicaltrials.gov identified 13 articles and four clinical trials. To date, CB-PRP has been primarily studied in the fields of orthopaedics, dermatology, neurology, obstetrics/gynaecology and ophthalmology. This is likely to be because this research is relatively novel. Considering the differences between the characteristics of A-PRP and CB-PRP, it is thought that CB-PRP might hold more promise for broader applications in the future.

Screening of Secretory Proteins Linking Major Depressive Disorder with Heart Failure Based on Comprehensive Bioinformatics Analysis and Machine Learning.

BACKGROUND: Major depressive disorder (MDD) plays a crucial role in the occurrence of heart failure (HF). This investigation was undertaken to explore the possible mechanism of MDD's involvement in HF pathogenesis and identify candidate biomarkers for the diagnosis of MDD with HF. METHODS: GWAS data for MDD and HF were collected, and Mendelian randomization (MR) analysis was performed to investigate the causal relationship between MDD and HF. Differential expression analysis (DEA) and WGCNA were used to detect HF key genes and MDD-associated secretory proteins. Protein-protein interaction (PPI), functional enrichment, and cMAP analysis were used to reveal potential mechanisms and drugs for MDD-related HF. Then, four machine learning (ML) algorithms (including GLM, RF, SVM, and XGB) were used to screen candidate biomarkers, construct diagnostic nomograms, and predict MDD-related HF. Furthermore, the MCPcounter algorithm was used to explore immune cell infiltration in HF, and MR analysis was performed to explore the causal effect of immunophenotypes on HF. Finally, the validation of the association of MDD with reduced left ventricular ejection fraction (LVEF) and the performance assessment of diagnostic biomarkers was accomplished based on animal models mimicking MDD. RESULTS: The MR analysis showed that the MDD was linked to an increased risk of HF (OR = 1.129, p < 0.001). DEA combined with WGCNA and secretory protein gene set identified 315 HF key genes and 332 MDD-associated secretory proteins, respectively. Through PPI and MCODE analysis, 78 genes were pinpointed as MDD-related pathogenic genes for HF. The enrichment analysis revealed that these genes were predominantly enriched in immune and inflammatory regulation. Through four ML algorithms, two hub genes (ISLR/SFRP4) were identified as candidate HF biomarkers, and a nomogram was developed. ROC analysis showed that the AUC of the nomogram was higher than 0.90 in both the HF combined dataset and two external cohorts. In addition, an immune cell infiltration analysis revealed the immune dysregulation in HF, with ISLR/SFRP4 displaying notable associations with the infiltration of B cells, CD8 T cells, and fibroblasts. More importantly, animal experiments showed that the expression levels of ISLR (r = -0.653, p < 0.001) and SFRP4 (r = -0.476, p = 0.008) were significantly negatively correlated with LVEF. CONCLUSIONS: The MR analysis indicated that MDD is a risk factor for HF at the genetic level. Bioinformatics analysis and the ML results suggest that ISLR and SFRP4 have the potential to serve as diagnostic biomarkers for HF. Animal experiments showed a negative correlation between the serum levels of ISLR/SFRP4 and LVEF, emphasizing the need for additional clinical studies to elucidate their diagnostic value.

Formation and culture of cell spheroids by using magnetic nanostructures resembling a crown of thorns.

In contrast to traditional two-dimensional cell-culture conditions, three-dimensional (3D) cell-culture models closely mimic complexin vivoconditions. However, constructing 3D cell culture models still faces challenges. In this paper, by using micro/nano fabrication method, including lithography, deposition, etching, and lift-off, we designed magnetic nanostructures resembling a crown of thorns. This magnetic crown of thorns (MCT) nanostructure enables the isolation of cells that have endocytosed magnetic particles. To assess the utility of this nanostructure, we used high-flux acquisition of Jurkat cells, an acute-leukemia cell line exhibiting the native phenotype, as an example. The novel structure enabled Jurkat cells to form spheroids within just 30 min by leveraging mild magnetic forces to bring together endocytosed magnetic particles. The size, volume, and arrangement of these spheroids were precisely regulated by the dimensions of the MCT nanostructure and the array configuration. The resulting magnetic cell clusters were uniform in size and reached saturation after 1400 s. Notably, these cell clusters could be easily separated from the MCT nanostructure through enzymatic digestion while maintaining their integrity. These clusters displayed a strong proliferation rate and survival capabilities, lasting for an impressive 96 h. Compared with existing 3D cell-culture models, the approach presented in this study offers the advantage of rapid formation of uniform spheroids that can mimicin vivomicroenvironments. These findings underscore the high potential of the MCT in cell-culture models and magnetic tissue enginerring.

Amorphous P-CoOX Promotes the Formation of Hypervalent Ni Species in NiFe LDHs by Amorphous/Crystalline Interfaces for Excellent Catalytic Performance of Oxygen Evolution Reaction.

Water electrolysis has become an attractive hydrogen production method. Oxygen evolution reaction (OER) is a bottleneck of water splitting as its four-electron transfer procedure presents sluggish reaction kinetics. Designing composite catalysts with high performance for efficient OER still remains a huge challenge. Here, the P-doped cobalt oxide/NiFe layered double hydroxides (P-CoOX/NiFe LDHs) composite catalysts with amorphous/crystalline interfaces are successfully prepared for OER by hydrothermal-electrodeposition combined method. The results of electrochemical characterizations, operando Raman spectra, and DFT theoretical calculations have demonstrated the electrons in the P-CoOX/NiFe LDHs heterointerfaces are easily transferred from Ni2+ to Co3+ because that the amorphous configuration of P-CoOX can well induce Ni-O-Co orbital coupling. The electron transfer of Ni2+ to the surrounding Fe3+ and Co3+ will lead to the unoccupied eg orbitals of Ni3+ that can promote water dissociation and accelerate *OOH migration to improve OER catalytic performance. The optimized P-CoOX/NiFe LDHs exhibit superior catalytic performance for OER with a very low overpotential of 265 mV at 300 mA cm-2 and excellent long-term stability of 500 h with almost no attenuation at 100 mA cm-2. This work will provide a new method to design high-performance NiFe LDHs-based catalysts for OER.

Shared genetics and causal association between plasma levels of SARS-CoV-2 entry receptor ACE2 and Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the highest risk of COVID-19 infection, hospitalization, and mortality. However, it remains largely unclear about the link between AD and COVID-19 outcomes. ACE2 is an entry receptor for SARS-CoV-2. Circulating ACE2 is a novel biomarker of death and associated with COVID-19 outcomes. METHODS: Here, we explored the shared genetics and causal association between AD and plasma ACE2 levels using large-scale genome-wide association study, gene expression, expression quantitative trait loci, and high-throughput plasma proteomic profiling datasets. RESULTS: We found a significant causal effect of genetically increased circulating ACE2 on increased risk of AD. Cross-trait association analysis identified 19 shared genetic variants, and three variants rs3104412, rs2395166, and rs3135344 at chromosome 6p21.32 were associated with COVID-19 infection, hospitalization, and severity. We mapped 19 variants to 117 genes, which were significantly upregulated in lung, spleen, and small intestine, downregulated in brain tissues, and involved in immune system, immune disease, and infectious disease pathways. The plasma proteins corresponding to LST1, AGER, TNXB, and APOC1 were predominantly associated with COVID-19 infection, ventilation, and death. CONCLUSION: Together, our findings suggest the shared genetics and causal association between AD and plasma ACE2 levels, which may partially explain the link between AD and COVID-19.

Promoting Polysulfide Redox Reactions through Electronic Spin Manipulation.

Catalytic additives able to accelerate the lithium-sulfur redox reaction are a key component of sulfur cathodes in lithium-sulfur batteries (LSBs). Their design focuses on optimizing the charge distribution within the energy spectra, which involves refinement of the distribution and occupancy of the electronic density of states. Herein, beyond charge distribution, we explore the role of the electronic spin configuration on the polysulfide adsorption properties and catalytic activity of the additive. We showcase the importance of this electronic parameter by generating spin polarization through a defect engineering approach based on the introduction of Co vacancies on the surface of CoSe nanosheets. We show vacancies change the electron spin state distribution, increasing the number of unpaired electrons with aligned spins. This local electronic rearrangement enhances the polysulfide adsorption, reducing the activation energy of the Li-S redox reactions. As a result, more uniform nucleation and growth of Li2S and an accelerated liquid-solid conversion in LSB cathodes are obtained. These translate into LSB cathodes exhibiting capacities up to 1089 mA h g-1 at 1 C with 0.017% average capacity loss after 1500 cycles, and up to 5.2 mA h cm-2, with 0.16% decay per cycle after 200 cycles in high sulfur loading cells.

Pulsed Laser-Bleaching Semiconductor and Photodetector.

Pulsed lasers alter the optical properties of semiconductors and affect the photoelectric function of the photodetectors significantly, resulting in transient changes known as bleaching. Bleaching has a profound impact on the control and interference of photodetector applications. Experiments using pump-probe techniques have made significant contributions to understanding ultrafast carrier dynamics. However, there are few theoretical studies to the best of our knowledge. Here, carrier dynamic models for semiconductors and photodetectors are established, respectively, employing the rectified carrier drift-diffusion model. The pulsed laser bleaching effect on seven types of semiconductors and photodetectors from visible to long-wave infrared is demonstrated. Additionally, a continuous bleaching method is provided, and the finite-difference time-domain (FDTD) method is used to solve carrier dynamic theory models. Laser parameters for continuous bleaching of semiconductors and photodetectors are calculated. The proposed bleaching model and achieved laser parameters for continuous bleaching are essential for several applications using semiconductor devices, such as infrared detection, biological imaging, and sensing.

Congruent or conflicting? The interaction between emoji and textual sentence is not that simple!

As a Japanese graphic symbol widely used in the world, Emoji plays an important role in computer mediated communication. Despite its prevalent use, the interaction dynamics between emoji and textual sentences remain inadequately explored. Based on the emotional function of emoji, this study uses the indirect priming method to explore the emotional impact of emoji on subsequent text in computer mediated communication through two progressive behavioral experiments. The results show that: (1) Emoji positioned at the onset of a sentence induce an emotional priming effect; (2) The processing speed is slowest when emoji and text are emotionally conflicting, while in non-conflicting condition, the type of emoji moderates the processing of combined sentences; (3) The emotional influence of emoji plays an auxiliary role, and the valence of textual sentence plays a decisive role in emotional perception.

Comparisons of Various Anthropometric Indices for Incident Hypertension in Military Young Adults: The CHIEF Cohort Study.

AIM: The study aimed to compare the predictive capabilities of the traditional anthropometric indices with the novel anthropometric indices for incident hypertension. BACKGROUND: Some novel anthropometric indices, e.g., the Body Roundness Index (BRI) and A Body Shape Index (ABSI) have been associated with prevalent hypertension. There are a few cohort studies that have examined the association of the novel anthropometric indices with newonset hypertension in young adults. METHODS: This study included 2,448 military male and female young adults, aged 18-39 years, free of hypertension at baseline in Taiwan; they were followed for incidence of hypertension from 2014 till the end of 2020. Blood Pressure (BP) in mmHg was measured twice and averaged to verify hypertension, which was defined as systolic BP ≥130 and/or diastolic BP ≥80 or on antihypertensive medication therapy in each annual health examination. Anthropometric indices included the Body Mass Index (BMI) defined as the weight (kg)/height squared (m2), Waist Girth (WC) in cm, the Waist-to-height Ratio (WHtR), the BRI defined as 364.2 - 365.5 × {1 - [(WC/2π)/(0.5 × height)]2}0.5, as well as ABSI defined as WC/(BMI2/3 × height1/2). Multiple Cox regression analysis and Area Under the Curve (AUC) of the Receiver of Operating Characteristics (ROC) were utilized with adjustments for the baseline potential covariates to determine the association and compare the performance of various indices for incident hypertension. RESULTS: During a median follow-up period of 6.0 years, 920 new-onset hypertension cases (37.6%) developed. Higher BMI, WC, BRI (per each 1-unit increase) and WHtR (per each 0.1- unit increase) were associated with a greater risk of new-onset hypertension [Hazard Ratios (HRs) and 95% confidence intervals: 1.060 (1.035-1.085), 1.021 (1.011-1.030), and 1.178 (1.077-1.288), respectively], whereas there was no association between ABSI and new-onset hypertension. For the ROC, WC was observed with the greatest AUC for incident new-onset hypertension [0.661 (0.638-0.683)], followed by BMI [0.650 (0.628-0.673)], while the ABSI was found with the lowest AUC [0.544 (0.521-0.568)]. CONCLUSION: Most of the anthropometric indices were associated with a higher risk of new-onset hypertension among young adults, except for ABSI. In addition, this study has suggested the traditional indices, such as WC and BMI, to be superior to the latest ones, e.g., BRI and ABSI, for the prediction of new-onset hypertension.

Targeting focal adhesion kinase (FAK) in cancer therapy: A recent update on inhibitors and PROTAC degraders.

Focal adhesion kinase (FAK) is considered as a pivotal intracellular non-receptor tyrosine kinase, and has garnered significant attention as a promising target for anticancer drug development. As of early 2024, a total of 12 drugs targeting FAK have been approved for clinical or preclinical studies worldwide, including three PROTAC degraders. In recent three years (2021-2023), significant progress has been made in designing targeted FAK anticancer agents, including the development of a novel benzenesulfofurazan type NO-releasing FAK inhibitor and the first-in-class dual-target inhibitors simultaneously targeting FAK and HDACs. Given the pivotal role of FAK in the discovery of anticancer drugs, as well as the notable advancements achieved in FAK inhibitors and PROTAC degraders in recent years, this review is underbaked to present a comprehensive overview of the function and structure of FAK. Additionally, the latest findings on the inhibitors and PROTAC degraders of FAK from the past three years, along with their optimization strategies and anticancer activities, were summarized, which might help to provide novel insights for the development of novel targeted FAK agents with promising anticancer potential and favorable pharmacological profiles.

Novel ectopic expression of zona pellucida 3 glycoprotein in lung cancer promotes tumor growth.

Zona pellucida 3 (ZP3) expression is classically found in the ZP-layer of the oocytes, lately shown in ovarian and prostate cancer. A successful ZP3 ovarian cancer immunotherapy in transgenic mice suggested its use as an attractive therapeutic target. The biological role of ZP3 in cancer growth and progression is still unknown. We found that ~88% of the analyzed adenocarcinoma, squamous and small cell lung carcinomas to express ZP3. Knockout of ZP3 in a ZP3-expressing lung adenocarcinoma cell line, significantly decreased cell viability, proliferation, and migration rates in vitro. Zona pellucida 3 knock out (ZP3-KO) cell tumors inoculated in vivo in immunodeficient non-obese diabetic, severe combined immunodeficient mice showed significant inhibition of tumor growth and mitigation of the malignant phenotype. RNA sequencing revealed the deregulation of cell migration/adhesion signaling pathways in ZP3-KO cells. This novel functional relevance of ZP3 in lung cancer emphasized the suitability of ZP3 as a target in cancer immunotherapy and as a potential cancer biomarker.

Tunning the hydrophobic performance and thermal stability of pectin film by acetic anhydride esterification.

Pectin, a polysaccharide found in plant cell walls, is characterized by a high abundance of hydroxyl groups and carboxylic acid groups, which results in a strong affinity for water and limits its suitability as a film material. This study aimed to modulate the esterification degree of PEC films by adjusting the concentration of acetic anhydride, and assess the impact of acetic anhydride esterification modification on the properties of the resultant PEC films. The results demonstrated successful grafting of acetic anhydride onto the galacturonic acid ring in the PEC molecule through the esterification process. The hydrophobicity, thermal stability, barrier properties, and mechanical properties of the esterified PEC films were investigated. Among the various concentrations tested, the E-PEC-0.25 film exhibited the highest contact angle of 103.46° and tensile strength of 33.44 MPa, showcasing optimal performance. The E-PEC-0.1 film achieved the highest esterification degree of 0.94 and elongation at a break of 21.11 %. It also exhibited the transparency of 11.66 and the lowest water vapor transmission rate of 0.56 g·mm/(m2·h·kpa). Additionally, TGA and DSC tests revealed enhanced thermal stability of the esterification-prepared films. These findings highlight the potential of acetic anhydride tuning as a promising strategy for optimizing pectin film production.