Intellectual disabilities are genetically heterogeneous and can be associated with congenital anomalies. Using whole-exome sequencing (WES), we identified five different de novo missense variants in ...the protein phosphatase-1 catalytic subunit beta (
PPP1CB
) gene in eight unrelated individuals who share an overlapping phenotype of dysmorphic features, macrocephaly, developmental delay or intellectual disability (ID), congenital heart disease, short stature, and skeletal and connective tissue abnormalities. Protein phosphatase-1 (PP1) is a serine/threonine-specific protein phosphatase involved in the dephosphorylation of a variety of proteins. The
PPP1CB
gene encodes a PP1 subunit that regulates the level of protein phosphorylation. All five altered amino acids we observed are highly conserved among the PP1 subunit family, and all are predicted to disrupt PP1 subunit binding and impair dephosphorylation. Our data suggest that our heterozygous de novo
PPP1CB
pathogenic variants are associated with syndromic intellectual disability.
Women with Turner Syndrome (TS) have a variety of medical needs throughout their lives; however, the peripubertal years are particularly challenging. From a medical perspective, the burden of care ...increases during this time due to growth optimization strategies, frequent health screenings, and puberty induction. Psychologically, girls begin to comprehend the long-term implications of the condition, including their diminished fertility potential. Unfortunately, clear guidelines for how to best approach this stage have not been established. It remains to be determined what is the best age to begin treatment; the best compound, dose, or protocol to induce puberty; how, when or what to discuss regarding fertility and potential fertility preservation options; and how to support them to accept their differences and empower them to take an active role in their care. Given the complexity of this life stage, a multidisciplinary treatment team that includes experts in endocrinology, gynecology, and psychology is optimal.
Abstract
De
novo
variants in
DDX
3X
account for 1–3% of unexplained intellectual disability (
ID
) cases and are amongst the most common causes of
ID
especially in females. Forty‐seven patients (44 ...females, 3 males) have been described. We identified 31 additional individuals carrying 29 unique
DDX
3X
variants, including 30 postnatal individuals with complex clinical presentations of developmental delay or
ID
, and one fetus with abnormal ultrasound findings. Rare or novel phenotypes observed include respiratory problems, congenital heart disease, skeletal muscle mitochondrial
DNA
depletion, and late‐onset neurologic decline. Our findings expand the spectrum of
DNA
variants and phenotypes associated with
DDX
3X
disorders.
Tissue‐engineered scaffolds have been extensively explored for treating bone defects; however, slow and insufficient vascularization throughout the scaffolds remains a key challenge for further ...application. Herein, a versatile microfluidic 3D printing strategy to fabricate black phosphorus (BP) incorporated fibrous scaffolds with photothermal responsive channels for improving vascularization and bone regeneration is proposed. The thermal channeled scaffolds display reversible shrinkage and swelling behavior controlled by near‐infrared irradiation, which facilitates the penetration of suspended cells into the scaffold channels and promotes the prevascularization. Furthermore, the embedded BP nanosheets exhibit intrinsic properties for in situ biomineralization and improve in vitro cell proliferation and osteogenic differentiation. Following transplantation in vivo, these channels also promote host vessel infiltration deep into the scaffolds and effectively accelerate the healing process of bone defects. Thus, it is believed that these near‐infrared responsive channeled scaffolds are promising candidates for tissue/vascular ingrowth in diverse tissue engineering applications.
A photothermal responsive scaffold with biomimetic enrichment channels is fabricated via a coaxial microfluidic 3D printing strategy. The incorporation of black phosphorus nanosheets endows the poly(N‐isopropylacrylamide) based channels with repeatable shrinkage/swelling performance controlled by near‐infrared irradiation, which facilitate vessel/tissue ingrowth into the scaffolds and accelerates bone regeneration in rat cranial defects.
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Severe intrauterine adhesions (IUAs) have a great negative impact on women's psychological and reproductive health. It remains a significant challenge to prevent postoperative IUAs ...because of the complications of various clinical preventive measures and incompatibility of uterine cavity morphology. Herein, we present a new drug-loadedporous scaffold based on a microfluidic droplet template, which combines the characteristics of the artificial biocompatible material GelMA and the natural polysaccharide material Na-alginate. By changing the containers that collect the microfluidic droplets, the porous scaffold conforming to the shape of the uterine cavity could be obtained. The porous structure, mechanical property, and flexibility impart the scaffold with compressibility and send it to the uterus through the vagina. In addition, the external–internal connected open structures could load and control the release of drugs to repair the damaged region continuously in vivo. To verify the antiadhesion and repair of drug-loaded porous scaffolds, we tested the system in the rat model of IUAs, and it was demonstrated that the system had the ability to improve neovascularization, cellularize the damaged tissue, and repair the endometrium. These features provide the drug-loaded porous scaffolds with new options for the improvement of postoperative IUAs.
Intrauterine adhesions are caused by various causes of damage to the endometrial basal layer, thus leading to part or entire adhesions in the cervical or uterine cavity. Clinically, various preventive measures reach the barrier effect through the physical barrier, which are difficult to further promote the repair of the damaged endometrium, and most of them have apparent side effects. This study aims to prepare compressible and biodegradable three-dimensional porous drug-loading biological scaffolds. GelMA and Na-alginate have desirable biocompatibility. The interconnect porous scaffolds, which were prepared through the combination of biomaterials and single emulsion microfluidics, not only have compressibility but also provide space for drug delivery and release. This system can further promote the repair of the endometrium while preventing adhesion.
Micromotors have exhibited great potential in multidisciplinary nanotechnology, environmental science, and especially biomedical engineering due to their advantages of controllable motion, long ...lifetime, and high biocompatibility. Marvelous efforts focusing on endowing micromotors with novel characteristics and functionalities to promote their applications in biomedical engineering have been taken in recent years. Here, inspired by the flagellar motion of Escherichia coli, we present helical micromotors as dynamic cell microcarriers using simple microfluidic spinning technology. The morphologies of micromotors can be easily tailored because of the highly controllable and feasible fabrication process including microfluidic generation and manual dicing. Benefiting from the biocompatibility of the materials, the resultant helical micromotors could be ideal cell microcarriers that are suitable for cell seeding and further cultivation; the magnetic nanoparticle encapsulation imparts the helical micromotors with kinetic characteristics in response to mobile magnetic fields. Thus, the helical micromotors could be applied as dynamic cell culture blocks and further assembled to complex geometrical structures. The constructed structures out of cell-seeded micromotors could find practical potential in biomedical applications as the stack-shaped assembly embedded in the hydrogel may be used for tissue repairing and the tube-shaped assembly due to its resemblance to vascular structures in the microchannel for organ-on-a-chip study or blood vessel regeneration. These features manifest the possibility to broaden the biomedical application scope for micromotors.
The organ-on-a-chip platform based on inverse opal scaffolds is proposed for tumor spheroids formation and dynamic drug resistance investigation. The tumor models with varying degrees of ...drug-resistant phenotypes are realized by simply gradient injection of hepatoma parental and resistant cells into the microfluidic chip. This organ-on-a-chip platform will provide new ideas for constructing 3D tumor models for drug resistance research.
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•The organ-on-a-chip is constructed for dynamic tumor drug resistance study.•This chip is established by integrating inverse opal scaffold with microfluidic chip.•The inverse opal scaffold is prepared by droplet microfluidics.
Drug resistance continues to be the main limiting factor in the cure of cancer patients. Herein, an organ-on-a-chip platform based on inverse opal scaffold was proposed to generate tumor cell spheroids and study resistance dynamically. The relevant inverse opal scaffold with desired tridimensional porous structure was prepared by negatively replicating the assembled microfluidic droplet template. Benefitting from the ordered and uniform porous structure of the inverse opal scaffolds, hepatoma cells could aggregate in the pores of the scaffold and form large amounts of homogeneous hepatoma cell spheroids. The proposed liver tumor-on-a-chip was established by integrating the inverse opal scaffolds with a well-designed gradient microfluidic chip. The liver tumor models with varying degrees of drug-resistant phenotypes were realized by simply gradient injection of hepatoma parental and resistant cells into the microfluidic chip. Based on the resultant system, we have obtained the dynamic drug resistance performance of different tumor stages and diverse medication periods, which will provide extremely significant preclinical data for drug therapy of tumors. These features make the proposed organ-on-a-chip platform a valuable candidate for preclinical drug resistance evaluation.
Activating mutations in epidermal growth factor receptor (EGFR) have been identified as key predictive biomarkers for the customized treatment with EGFR tyrosine kinase inhibitors (TKIs) in non-small ...cell lung cancer (NSCLC), aiding in improving patient response rates and survival. However, resistance challenges the efficacy of these treatments, with limited understanding of post-resistance therapeutic strategies. A deep understanding of the biology and resistance mechanisms of EGFR-mutant NSCLC is crucial for developing new treatment approaches. This study, through bibliometric analysis, summarizes the trends in research on resistance to EGFR-TKIs.PurposeActivating mutations in epidermal growth factor receptor (EGFR) have been identified as key predictive biomarkers for the customized treatment with EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), aiding in improving patient response rates and survival. However, resistance challenges the efficacy of these treatments, with limited understanding of post-resistance therapeutic strategies. A deep understanding of the biology and resistance mechanisms of EGFR-mutant NSCLC is crucial for developing new treatment approaches. This study, through bibliometric analysis, summarizes the trends in research on resistance to EGFR-TKIs.Research papers on NSCLC with EGFR inhibitor resistance were collected from the Web of Science Core Collection (WoSCC). The analysis utilized bibliometric tools like CiteSpace, VOSviewer, and other platforms for comprehensive analysis and visualization of the outcomes.MethodsResearch papers on NSCLC with EGFR inhibitor resistance were collected from the Web of Science Core Collection (WoSCC). The analysis utilized bibliometric tools like CiteSpace, VOSviewer, and other platforms for comprehensive analysis and visualization of the outcomes.The WoSCC database contains a total of 5866 documents on resistance to EGFR-TKIs treatment, including 4727 articles (93.48%) and 1139 reviews (6.52%), spanning 81 countries and regions, 4792 institutions, with the involvement of 23,594 authors. Since 2016, there has been a significant increase in publications in this field. China has the highest publication output, while the United States has the highest citation count for papers. Harvard University leads in terms of the number of publications. Among the top ten journals with the highest output, Clinical Cancer Research has the highest impact factor at 11.5, with 90% of the journals classified in Q1 or Q2. Rafael Rosell is one of the most influential authors in this field, ranking second in publication volume and fourth in citation count. Research on EGFR-TKIs resistance mainly focuses on genetic testing, resistance mechanisms, and post-resistance treatment strategies.ResultsThe WoSCC database contains a total of 5866 documents on resistance to EGFR-TKIs treatment, including 4727 articles (93.48%) and 1139 reviews (6.52%), spanning 81 countries and regions, 4792 institutions, with the involvement of 23,594 authors. Since 2016, there has been a significant increase in publications in this field. China has the highest publication output, while the United States has the highest citation count for papers. Harvard University leads in terms of the number of publications. Among the top ten journals with the highest output, Clinical Cancer Research has the highest impact factor at 11.5, with 90% of the journals classified in Q1 or Q2. Rafael Rosell is one of the most influential authors in this field, ranking second in publication volume and fourth in citation count. Research on EGFR-TKIs resistance mainly focuses on genetic testing, resistance mechanisms, and post-resistance treatment strategies.This study provides researchers with a reliable basis and guidance for finding authoritative references, understanding research trends, and exploring potential directions.ConclusionThis study provides researchers with a reliable basis and guidance for finding authoritative references, understanding research trends, and exploring potential directions.
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