Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 4.283
Filter
Add more filters

Publication year range
1.
Proc Natl Acad Sci U S A ; 121(30): e2403460121, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39008666

ABSTRACT

Autonomous nanorobots represent an advanced tool for precision therapy to improve therapeutic efficacy. However, current nanorobotic designs primarily rely on inorganic materials with compromised biocompatibility and limited biological functions. Here, we introduce enzyme-powered bacterial outer membrane vesicle (OMV) nanorobots. The immobilized urease on the OMV membrane catalyzes the decomposition of bioavailable urea, generating effective propulsion for nanorobots. This OMV nanorobot preserves the unique features of OMVs, including intrinsic biocompatibility, immunogenicity, versatile surface bioengineering for desired biofunctionalities, capability of cargo loading and protection. We present OMV-based nanorobots designed for effective tumor therapy by leveraging the membrane properties of OMVs. These involve surface bioengineering of robotic body with cell-penetrating peptide for tumor targeting and penetration, which is further enhanced by active propulsion of nanorobots. Additionally, OMV nanorobots can effectively safeguard the loaded gene silencing tool, small interfering RNA (siRNA), from enzymatic degradation. Through systematic in vitro and in vivo studies using a rodent model, we demonstrate that these OMV nanorobots substantially enhanced siRNA delivery and immune stimulation, resulting in the utmost effectiveness in tumor suppression when juxtaposed with static groups, particularly evident in the orthotopic bladder tumor model. This OMV nanorobot opens an inspiring avenue to design advanced medical robots with expanded versatility and adaptability, broadening their operation scope in practical biomedical domains.


Subject(s)
Bacterial Outer Membrane , Animals , Humans , Bacterial Outer Membrane/metabolism , Mice , Robotics/methods , Urease/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism
2.
Proc Natl Acad Sci U S A ; 121(20): e2320674121, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38684007

ABSTRACT

Identifying and protecting hotspots of endemism and species richness is crucial for mitigating the global biodiversity crisis. However, our understanding of spatial diversity patterns is far from complete, which severely limits our ability to conserve biodiversity hotspots. Here, we report a comprehensive analysis of amphibian species diversity in China, one of the most species-rich countries on Earth. Our study combines 20 y of field surveys with new molecular analyses of 521 described species and also identifies 100 potential cryptic species. We identify 10 hotspots of amphibian diversity in China, each with exceptional species richness and endemism and with exceptional phylogenetic diversity and phylogenetic endemism (based on a new time-calibrated, species-level phylogeny for Chinese amphibians). These 10 hotspots encompass 59.6% of China's described amphibian species, 49.0% of cryptic species, and 55.6% of species endemic to China. Only four of these 10 hotspots correspond to previously recognized biodiversity hotspots. The six new hotspots include the Nanling Mountains and other mountain ranges in South China. Among the 186 species in the six new hotspots, only 9.7% are well covered by protected areas and most (88.2%) are exposed to high human impacts. Five of the six new hotspots are under very high human pressure and are in urgent need of protection. We also find that patterns of richness in cryptic species are significantly related to those in described species but are not identical.


Subject(s)
Amphibians , Biodiversity , Phylogeny , Animals , Amphibians/classification , China , Conservation of Natural Resources
3.
Mol Cell ; 70(2): 340-357.e8, 2018 04 19.
Article in English | MEDLINE | ID: mdl-29628309

ABSTRACT

Whereas the actions of enhancers in gene transcriptional regulation are well established, roles of JmjC-domain-containing proteins in mediating enhancer activation remain poorly understood. Here, we report that recruitment of the JmjC-domain-containing protein 6 (JMJD6) to estrogen receptor alpha (ERα)-bound active enhancers is required for RNA polymerase II recruitment and enhancer RNA production on enhancers, resulting in transcriptional pause release of cognate estrogen target genes. JMJD6 is found to interact with MED12 in the mediator complex to regulate its recruitment. Unexpectedly, JMJD6 is necessary for MED12 to interact with CARM1, which methylates MED12 at multiple arginine sites and regulates its chromatin binding. Consistent with its role in transcriptional activation, JMJD6 is required for estrogen/ERα-induced breast cancer cell growth and tumorigenesis. Our data have uncovered a critical regulator of estrogen/ERα-induced enhancer coding gene activation and breast cancer cell potency, providing a potential therapeutic target of ER-positive breast cancers.


Subject(s)
Breast Neoplasms/enzymology , Cell Proliferation , Estrogen Receptor alpha/metabolism , Jumonji Domain-Containing Histone Demethylases/metabolism , Mediator Complex/metabolism , Protein-Arginine N-Methyltransferases/metabolism , Transcriptional Activation , Animals , Binding Sites , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Estradiol/pharmacology , Estrogen Receptor alpha/agonists , Estrogen Receptor alpha/genetics , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , HEK293 Cells , Humans , Jumonji Domain-Containing Histone Demethylases/genetics , MCF-7 Cells , Mediator Complex/genetics , Mice, Inbred BALB C , Mice, Nude , Protein Binding , Protein Transport , Protein-Arginine N-Methyltransferases/genetics , Signal Transduction , Transcriptional Activation/drug effects
4.
Plant J ; 119(2): 879-894, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38923085

ABSTRACT

Cotton is a globally cultivated crop, producing 87% of the natural fiber used in the global textile industry. The pigment glands, unique to cotton and its relatives, serve as a defense structure against pests and pathogens. However, the molecular mechanism underlying gland formation and the specific role of pigment glands in cotton's pest defense are still not well understood. In this study, we cloned a gland-related transcription factor GhHAM and generated the GhHAM knockout mutant using CRISPR/Cas9. Phenotypic observations, transcriptome analysis, and promoter-binding experiments revealed that GhHAM binds to the promoter of GoPGF, regulating pigment gland formation in cotton's multiple organs via the GoPGF-GhJUB1 module. The knockout of GhHAM significantly reduced gossypol production and increased cotton's susceptibility to pests in the field. Feeding assays demonstrated that more than 80% of the cotton bollworm larvae preferred ghham over the wild type. Furthermore, the ghham mutants displayed shorter cell length and decreased gibberellins (GA) production in the stem. Exogenous application of GA3 restored stem cell elongation but not gland formation, thereby indicating that GhHAM controls gland morphogenesis independently of GA. Our study sheds light on the functional differentiation of HAM proteins among plant species, highlights the significant role of pigment glands in influencing pest feeding preference, and provides a theoretical basis for breeding pest-resistant cotton varieties to address the challenges posed by frequent outbreaks of pests.


Subject(s)
Gene Expression Regulation, Plant , Gossypium , Plant Proteins , Gossypium/genetics , Gossypium/parasitology , Gossypium/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Animals , Gibberellins/metabolism , Gossypol/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Disease Resistance/genetics , Plant Diseases/parasitology , Plant Diseases/immunology , Moths/physiology , Larva/growth & development
5.
FASEB J ; 38(4): e23469, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38358361

ABSTRACT

The adenopituitary secretes follicle-stimulating hormone (FSH), which plays a crucial role in regulating the growth, development, and reproductive functions of organisms. Investigating the process of FSH synthesis and secretion can offer valuable insights into potential areas of focus for reproductive research. Epidermal growth factor (EGF) is a significant paracrine/autocrine factor within the body, and studies have demonstrated its ability to stimulate FSH secretion in animals. However, the precise mechanisms that regulate this action are still poorly understood. In this research, in vivo and in vitro experiments showed that the activation of epidermal growth factor receptor (EGFR) by EGF induces the upregulation of miR-27b-3p and that miR-27b-3p targets and inhibits Foxo1 mRNA expression, resulting in increased FSH synthesis and secretion. In summary, this study elucidates the precise molecular mechanism through which EGF governs the synthesis and secretion of FSH via the EGFR/miR-27b-3p/FOXO1 pathway.


Subject(s)
Epidermal Growth Factor , MicroRNAs , Animals , Rats , Biological Transport , ErbB Receptors/genetics , Follicle Stimulating Hormone , MicroRNAs/genetics
6.
Chem Rev ; 123(8): 5049-5138, 2023 04 26.
Article in English | MEDLINE | ID: mdl-36971504

ABSTRACT

Wearable sensors hold great potential in empowering personalized health monitoring, predictive analytics, and timely intervention toward personalized healthcare. Advances in flexible electronics, materials science, and electrochemistry have spurred the development of wearable sweat sensors that enable the continuous and noninvasive screening of analytes indicative of health status. Existing major challenges in wearable sensors include: improving the sweat extraction and sweat sensing capabilities, improving the form factor of the wearable device for minimal discomfort and reliable measurements when worn, and understanding the clinical value of sweat analytes toward biomarker discovery. This review provides a comprehensive review of wearable sweat sensors and outlines state-of-the-art technologies and research that strive to bridge these gaps. The physiology of sweat, materials, biosensing mechanisms and advances, and approaches for sweat induction and sampling are introduced. Additionally, design considerations for the system-level development of wearable sweat sensing devices, spanning from strategies for prolonged sweat extraction to efficient powering of wearables, are discussed. Furthermore, the applications, data analytics, commercialization efforts, challenges, and prospects of wearable sweat sensors for precision medicine are discussed.


Subject(s)
Biosensing Techniques , Skin , Wearable Electronic Devices , Electronics , Monitoring, Physiologic , Precision Medicine , Sweat
7.
Cereb Cortex ; 34(1)2024 01 14.
Article in English | MEDLINE | ID: mdl-37943770

ABSTRACT

Empathic function, which is primarily manifested by facial imitation, is believed to play a pivotal role in interpersonal emotion regulation for mood reinstatement. To explore this association and its neural substrates, we performed a questionnaire survey (study l) to identify the relationship between empathy and interpersonal emotion regulation; and a task-mode fMRI study (study 2) to explore how facial imitation, as a fundamental component of empathic processes, promotes the interpersonal emotion regulation effect. Study 1 showed that affective empathy was positively correlated with interpersonal emotion regulation. Study 2 showed smaller negative emotions in facial imitation interpersonal emotion regulation (subjects imitated experimenter's smile while followed the interpersonal emotion regulation guidance) than in normal interpersonal emotion regulation (subjects followed the interpersonal emotion regulation guidance) and Watch conditions. Mirror neural system (e.g. inferior frontal gyrus and inferior parietal lobe) and empathy network exhibited greater activations in facial imitation interpersonal emotion regulation compared with normal interpersonal emotion regulation condition. Moreover, facial imitation interpersonal emotion regulation compared with normal interpersonal emotion regulation exhibited increased functional coupling from mirror neural system to empathic and affective networks during interpersonal emotion regulation. Furthermore, the connectivity of the right orbital inferior frontal gyrus-rolandic operculum lobe mediated the association between the accuracy of facial imitation and the interpersonal emotion regulation effect. These results show that the interpersonal emotion regulation effect can be enhanced by the target's facial imitation through increased functional coupling from mirror neural system to empathic and affective neural networks.


Subject(s)
Emotional Regulation , Humans , Brain Mapping/methods , Imitative Behavior/physiology , Magnetic Resonance Imaging/methods , Empathy , Functional Neuroimaging , Emotions/physiology , Facial Expression
8.
Cereb Cortex ; 34(13): 30-39, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38696599

ABSTRACT

The amygdala undergoes a period of overgrowth in the first year of life, resulting in enlarged volume by 12 months in infants later diagnosed with ASD. The overgrowth of the amygdala may have functional consequences during infancy. We investigated whether amygdala connectivity differs in 12-month-olds at high likelihood (HL) for ASD (defined by having an older sibling with autism), compared to those at low likelihood (LL). We examined seed-based connectivity of left and right amygdalae, hypothesizing that the HL and LL groups would differ in amygdala connectivity, especially with the visual cortex, based on our prior reports demonstrating that components of visual circuitry develop atypically and are linked to genetic liability for autism. We found that HL infants exhibited weaker connectivity between the right amygdala and the left visual cortex, as well as between the left amygdala and the right anterior cingulate, with evidence that these patterns occur in distinct subgroups of the HL sample. Amygdala connectivity strength with the visual cortex was related to motor and communication abilities among HL infants. Findings indicate that aberrant functional connectivity between the amygdala and visual regions is apparent in infants with genetic liability for ASD and may have implications for early differences in adaptive behaviors.


Subject(s)
Amygdala , Magnetic Resonance Imaging , Visual Cortex , Humans , Amygdala/diagnostic imaging , Amygdala/physiopathology , Male , Female , Infant , Visual Cortex/diagnostic imaging , Visual Cortex/physiopathology , Visual Cortex/growth & development , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Autistic Disorder/genetics , Autistic Disorder/physiopathology , Autistic Disorder/diagnostic imaging , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/physiopathology , Autism Spectrum Disorder/diagnostic imaging , Genetic Predisposition to Disease/genetics
9.
Proc Natl Acad Sci U S A ; 119(46): e2212406119, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-36346846

ABSTRACT

Defense against ultraviolet (UV) radiation exposure is essential for survival, especially in high-elevation species. Although some specific genes involved in UV response have been reported, the full view of UV defense mechanisms remains largely unexplored. Herein, we used integrated approaches to analyze UV responses in the highest-elevation frog, Nanorana parkeri. We show less damage and more efficient antioxidant activity in skin of this frog than those of its lower-elevation relatives after UV exposure. We also reveal genes related to UV defense and a corresponding temporal expression pattern in N. parkeri. Genomic and metabolomic analysis along with large-scale transcriptomic profiling revealed a time-dependent coordinated defense mechanism in N. parkeri. We also identified several microRNAs that play important regulatory roles, especially in decreasing the expression levels of cell cycle genes. Moreover, multiple defense genes (i.e., TYR for melanogenesis) exhibit positive selection with function-enhancing substitutions. Thus, both expression shifts and gene mutations contribute to UV adaptation in N. parkeri. Our work demonstrates a genetic framework for evolution of UV defense in a natural environment.


Subject(s)
Anura , Ultraviolet Rays , Animals , Anura/genetics , Skin , Gene Expression Profiling , Antioxidants
10.
BMC Biol ; 22(1): 70, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38519936

ABSTRACT

BACKGROUND: Eriophyoid mites (Eriophyoidea) are among the largest groups in the Acariformes; they are strictly phytophagous. The higher-level phylogeny of eriophyoid mites, however, remains unresolved due to the limited number of available morphological characters-some of them are homoplastic. Nevertheless, the eriophyoid mites sequenced to date showed highly variable mitochondrial (mt) gene orders, which could potentially be useful for resolving the higher-level phylogenetic relationships. RESULTS: Here, we sequenced and compared the complete mt genomes of 153 eriophyoid mite species, which showed 54 patterns of rearranged mt gene orders relative to that of the hypothetical ancestor of arthropods. The shared derived mt gene clusters support the monophyly of eriophyoid mites (Eriophyoidea) as a whole and the monophylies of six clades within Eriophyoidea. These monophyletic groups and their relationships were largely supported in the phylogenetic trees inferred from mt genome sequences as well. Our molecular dating results showed that Eriophyoidea originated in the Triassic and diversified in the Cretaceous, coinciding with the diversification of angiosperms. CONCLUSIONS: This study reveals multiple molecular synapomorphies (i.e. shared derived mt gene clusters) at different levels (i.e. family, subfamily or tribe level) from the complete mt genomes of 153 eriophyoid mite species. We demonstrated the use of derived mt gene clusters in unveiling the higher-level phylogeny of eriophyoid mites, and underlines the origin of these mites and their co-diversification with angiosperms.


Subject(s)
Genome, Mitochondrial , Magnoliopsida , Mites , Animals , Phylogeny , Mites/genetics , Genes, Mitochondrial , Multigene Family , Magnoliopsida/genetics
11.
Chem Soc Rev ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38985007

ABSTRACT

The rapid advancements in nucleic acid-based electrochemical sensors for implantable and wearable applications have marked a significant leap forward in the domain of personal healthcare over the last decade. This technology promises to revolutionize personalized healthcare by facilitating the early diagnosis of diseases, monitoring of disease progression, and tailoring of individual treatment plans. This review navigates through the latest developments in this field, focusing on the strategies for nucleic acid sensing that enable real-time and continuous biomarker analysis directly in various biofluids, such as blood, interstitial fluid, sweat, and saliva. The review delves into various nucleic acid sensing strategies, emphasizing the innovative designs of biorecognition elements and signal transduction mechanisms that enable implantable and wearable applications. Special perspective is given to enhance nucleic acid-based sensor selectivity and sensitivity, which are crucial for the accurate detection of low-level biomarkers. The integration of such sensors into implantable and wearable platforms, including microneedle arrays and flexible electronic systems, actualizes their use in on-body devices for health monitoring. We also tackle the technical challenges encountered in the development of these sensors, such as ensuring long-term stability, managing the complexity of biofluid dynamics, and fulfilling the need for real-time, continuous, and reagentless detection. In conclusion, the review highlights the importance of these sensors in the future of medical engineering, offering insights into design considerations and future research directions to overcome existing limitations and fully realize the potential of nucleic acid-based electrochemical sensors for healthcare applications.

12.
BMC Genomics ; 25(1): 456, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730418

ABSTRACT

In this study, we investigated the codon bias of twelve mitochondrial core protein coding genes (PCGs) in eight Pleurotus strains, two of which are from the same species. The results revealed that the codons of all Pleurotus strains had a preference for ending in A/T. Furthermore, the correlation between codon base compositions and codon adaptation index (CAI), codon bias index (CBI) and frequency of optimal codons (FOP) indices was also detected, implying the influence of base composition on codon bias. The two P. ostreatus species were found to have differences in various base bias indicators. The average effective number of codons (ENC) of mitochondrial core PCGs of Pleurotus was found to be less than 35, indicating strong codon preference of mitochondrial core PCGs of Pleurotus. The neutrality plot analysis and PR2-Bias plot analysis further suggested that natural selection plays an important role in Pleurotus codon bias. Additionally, six to ten optimal codons (ΔRSCU > 0.08 and RSCU > 1) were identified in eight Pleurotus strains, with UGU and ACU being the most widely used optimal codons in Pleurotus. Finally, based on the combined mitochondrial sequence and RSCU value, the genetic relationship between different Pleurotus strains was deduced, showing large variations between them. This research has improved our understanding of synonymous codon usage characteristics and evolution of this important fungal group.


Subject(s)
Codon Usage , Genome, Mitochondrial , Pleurotus , Pleurotus/genetics , Codon/genetics , Base Composition , Species Specificity , Selection, Genetic , Evolution, Molecular , Genetic Variation
13.
Anal Chem ; 96(19): 7487-7496, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38695134

ABSTRACT

Cinchona alkaloid derivatives as Brønsted base catalysts have attracted considerable attention in the field of asymmetric catalysis. However, their potential application as chiral solvating agents has not been described. In this research, we investigated the use of the Cinchona alkaloid dimer, namely, (DHQ)2PHAL, as a chiral solvating agent for discerning various mandelic acid derivatives through 1H NMR spectroscopy. The addition of catalytic amounts of DMAP facilitated this process. Our experimental results demonstrate that dimeric (DHQ)2PHAL exhibits remarkable chiral discrimination properties regarding the diagnostic split protons of 1H NMR signals (including 24 examples, up to 0.321 ppm). Furthermore, it serves as an excellent chiral discriminating agent and provides good resolution for racemic chiral phosphoric acid as determined by 31P NMR spectroscopy. The quality of enantiodifferentiation has also been evaluated by means of the parameter "resolution (Rs)". Significantly, this class of CSAs based on (alkaloid)2linker systems with an azaaromatic linker can be directly employed, which is commercially available in an enantiopure form at very low cost and exhibits promising potential in determining the enantiopurity of α-hydroxy acids by chemoselective and biocatalytic reactions.

14.
Biochem Biophys Res Commun ; 706: 149744, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38479244

ABSTRACT

Acute kidney injury (AKI) is a common clinical disease with a high incidence and mortality rate. It typically arises from hemodynamic alterations, sepsis, contrast agents, and toxic drugs, instigating a series of events that culminate in tissue and renal damage. This sequence of processes often leads to acute renal impairment, prompting the initiation of a repair response. Cellular senescence is an irreversible arrest of the cell cycle. Studies have shown that renal cellular senescence is closely associated with AKI through several mechanisms, including the promotion of oxidative stress and inflammatory response, telomere shortening, and the down-regulation of klotho expression. Exploring the role of cellular senescence in AKI provides innovative therapeutic ideas for both the prevention and treatment of AKI. Furthermore, it has been observed that targeted removal of senescent cells in vivo can efficiently postpone senescence, resulting in an enhanced prognosis for diseases associated with senescence. This article explores the effects of common anti-senescence drugs senolytics and senostatic and lifestyle interventions on renal diseases, and mentions the rapid development of mesenchymal stem cells (MSCs). These studies have taken senescence-related research to a new level. Overall, this article comprehensively summarizes the studies on cellular senescence in AKI, aiming is to elucidate the relationship between cellular senescence and AKI, and explore treatment strategies to improve the prognosis of AKI.


Subject(s)
Acute Kidney Injury , Mesenchymal Stem Cells , Humans , Acute Kidney Injury/metabolism , Cellular Senescence , Kidney/metabolism , Mesenchymal Stem Cells/metabolism , Oxidative Stress
15.
BMC Plant Biol ; 24(1): 318, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38654190

ABSTRACT

BACKGROUND: Class III peroxidases (PODs) perform crucial functions in various developmental processes and responses to biotic and abiotic stresses. However, their roles in wheat seed dormancy (SD) and germination remain elusive. RESULTS: Here, we identified a wheat class III POD gene, named TaPer12-3A, based on transcriptome data and expression analysis. TaPer12-3A showed decreasing and increasing expression trends with SD acquisition and release, respectively. It was highly expressed in wheat seeds and localized in the endoplasmic reticulum and cytoplasm. Germination tests were performed using the transgenic Arabidopsis and rice lines as well as wheat mutant mutagenized with ethyl methane sulfonate (EMS) in Jing 411 (J411) background. These results indicated that TaPer12-3A negatively regulated SD and positively mediated germination. Further studies showed that TaPer12-3A maintained H2O2 homeostasis by scavenging excess H2O2 and participated in the biosynthesis and catabolism pathways of gibberellic acid and abscisic acid to regulate SD and germination. CONCLUSION: These findings not only provide new insights for future functional analysis of TaPer12-3A in regulating wheat SD and germination but also provide a target gene for breeding wheat varieties with high pre-harvest sprouting resistance by gene editing technology.


Subject(s)
Germination , Plant Dormancy , Triticum , Triticum/genetics , Triticum/enzymology , Triticum/physiology , Plant Dormancy/genetics , Germination/genetics , Seeds/genetics , Seeds/growth & development , Seeds/physiology , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Hydrogen Peroxide/metabolism , Gibberellins/metabolism , Arabidopsis/genetics , Arabidopsis/physiology , Peroxidases/genetics , Peroxidases/metabolism , Plants, Genetically Modified , Abscisic Acid/metabolism , Genes, Plant
16.
Mol Genet Genomics ; 299(1): 66, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980418

ABSTRACT

PIK3CA-related overgrowth spectrum (PROS) is an umbrella term to describe a diverse range of developmental disorders. Research to date has predominantly emerged from Europe and North America, resulting in a notable scarcity of studies focusing on East Asian populations. Currently, the prevalence and distribution of PIK3CA variants across various genetic loci and their correlation with distinct phenotypes in East Asian populations remain unclear. This study aims to elucidate the phenotype-genotype correlations of PROS in East Asian populations. We presented the phenotypes and genotypes of 82 Chinese patients. Among our cohort, 67 individuals carried PIK3CA variants, including missense, frameshift, and splice variants. Six patients presented with both PIK3CA and an additional variant. Seven PIK3CA-negative patients exhibited overlapping PROS manifestations with variants in GNAQ, AKT1, PTEN, MAP3K3, GNA11, or KRAS. An integrative review of the literature pertaining to East Asian populations revealed that specific variants are uniquely associated with certain PROS phenotypes. Some rare variants were exclusively identified in cases of megalencephaly and diffuse capillary malformation with overgrowth. Non-hotspot variants with undefined oncogenicity were more common in CNS phenotypes. Diseases with vascular malformation were more likely to have variants in the helical domain, whereas phenotypes involving adipose/muscle overgrowth without vascular abnormalities predominantly presented variants in the C2 domain. Our findings underscore the unique phenotype-genotype patterns within the East Asian PROS population, highlighting the necessity for an expanded cohort to further elucidate these correlations. Such endeavors would significantly facilitate the development of PI3Kα selective inhibitors tailored for the East Asian population in the future.


Subject(s)
Asian People , Class I Phosphatidylinositol 3-Kinases , Genotype , Phenotype , Humans , Class I Phosphatidylinositol 3-Kinases/genetics , Female , Male , Child , Child, Preschool , Asian People/genetics , Genetic Association Studies , Infant , Growth Disorders/genetics , Growth Disorders/pathology , Adolescent , Mutation , Asia, Eastern , East Asian People
17.
Small ; 20(28): e2310777, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38299481

ABSTRACT

Quasi-solid state thermocells hold immense potential for harnessing untapped low-grade heat and converting it into electricity via the thermogalvanic effect. However, integrated N-type thermocells face limitations in thermoelectric performance due to the rare N-type systems and the poor electroactivity of the electrode interfaces. Herein, a low-cost, high-power N-type quasi-solid state thermocell employing PVA-CuSO4-Cu is presented, which is enhanced by synergistic engineering of an anisotropic network and hierarchical electrodes. The anisotropic polymer network, combined with the salting-out effect, yields impressive mechanical properties that exceed those of most N-type quasi-solid state thermocells. Furthermore, through the synergistic construction of aligned ion transport pathways in the anisotropic thermocell and optimization of the electroactive interface between electrodes and thermocell, a remarkable enhancement of 1500% in output power density (compared to pristine thermocell), reaching 0.51 mW m-2 at ∆T = 5 °C. It is believed that this cost-effective N-type thermocell, enhanced by the synergistic anisotropic network and hierarchical electrodes, paves the way for effective energy harvesting from diverse heat sources and promises to reshape sustainable energy utilization.

18.
Small ; 20(29): e2400158, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38415969

ABSTRACT

Noble metallic aerogels with the self-supported hierarchical structure and remarkable activity are promising for methanol fuel cells, but are limited by the severe poisoning and degradation of active sites during electrocatalysis. Herein, the highly stable electrocatalyst of N-doped carbon dots-PtNi (NCDs-PtNi) aerogels is proposed by confining NCDs with alloyed PtNi for methanol oxidation and oxygen reduction reactions. Comprehensive electrocatalytic measurements and theoretical investigations suggest the improvement in structure stability and regulation in electronic structure for better electrocatalytic durability when confining NCDs with PtNi aerogels. Notably, the NCDs-PtNi aerogels perform 12-fold higher activity than that of Pt/C and maintain 52% of their initial activity after 5000 cycles toward acidic methanol oxidation. The enhanced stability and activity of NCDs-PtNi aerogels are also evident for oxygen reduction reactions in different electrolytes. These results highlight the effectiveness of stabilizing metallic aerogels with NCDs, offering a feasible pathway to develop robust electrocatalysts for fuel cells.

19.
Small ; : e2401031, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38970556

ABSTRACT

1D fiber devices, known for their exceptional flexibility and seamless integration capabilities, often face trade-offs between desired wearable application characteristics and actual performance. In this study, a multilayer device composed of carbon nanotube (CNT), transition metal carbides/nitrides (MXenes), and cotton fibers, fabricated using a dry spinning method is presented, which significantly enhances both strain sensing and supercapacitor functionality. This core-shell fiber design achieves a record-high sensitivity (GF ≈ 4500) and maintains robust durability under various environmental conditions. Furthermore, the design approach markedly influences capacitance, correlating with the percentage of active material used. Through systematic optimization, the fiber device exhibited a capacitance 26-fold greater than that of a standard neat CNT fiber, emphasizing the crucial role of innovative design and high active material loading in improving device performance.

20.
Small ; : e2311606, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38497093

ABSTRACT

Novel 2D materials with low-symmetry structures exhibit great potential applications in developing monolithic polarization-sensitive photodetectors with small volume. However, owing to the fact that at least half of them presented a small anisotropic factor of ≈2, comprehensive performance of present polarization-sensitive photodetectors based on 2D materials is still lower than the practical application requirements. Herein, a self-driven photodetector with high polarization sensitivity using a broken-gap ReSe2 /SnSe2 van der Waals heterojunction (vdWH) is demonstrated. Anisotropic ratio of the photocurrent (Imax /Imin ) could reach 12.26 (635 nm, 179 mW cm-2 ). Furthermore, after a facile combination of the ReSe2 /SnSe2 device with multilayer graphene (MLG), Imax /Imin of the MLG/ReSe2 /SnSe2 can be further increased up to13.27, which is 4 times more than that of pristine ReSe2 photodetector (3.1) and other 2D material photodetectors even at a bias voltage. Additionally, benefitting from the synergistic effect of unilateral depletion and photoinduced tunneling mechanism, the MLG/ReSe2 /SnSe2 device exhibits a fast response speed (752/928 µs) and an ultrahigh light on/off ratio (105 ). More importantly, MLG/ReSe2 /SnSe2 device exhibits excellent potential applications in polarized imaging and polarization-coded optical communication with quaternary logic state without any power supply. This work provides a novel feasible avenue for constructing next-generation smart polarization-sensitive photodetector with low energy consumption.

SELECTION OF CITATIONS
SEARCH DETAIL