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Itch is a somatosensory sensation to remove potential harmful stimulation with a scratching desire, which could be divided into mechanical and chemical itch according to diverse stimuli, such as wool fiber and insect biting. It has been reported that neuropeptide Y (NPY) neurons, a population of spinal inhibitory interneurons, could gate the transmission of mechanical itch, with no effect on chemical itch. In our study, we verified that chemogenetic activation of NPY neurons could inhibit the mechanical itch as well as the chemical itch, which also attenuated the alloknesis phenomenon in the chronic dry skin model. Afterwards, intrathecal administration of NPY1R agonist, [Leu31, Pro34]-NPY (LP-NPY), showed the similar inhibition effect on mechanical itch, chemical itch and alloknesis as chemo-activation of NPY neurons. Whereas, intrathecal administration of NPY1R antagonist BIBO 3304 enhanced mechanical itch and reversed the alloknesis phenomenon inhibited by LP-NPY treatment. Moreover, selectively knocking down NPY1R by intrathecal injection of Npy1r siRNA enhanced mechanical and chemical itch behavior as well. These results indicate that NPY neurons in spinal cord regulate mechanical and chemical itch, and alloknesis in dry skin model through NPY1 receptors.
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Neuropeptídeo Y , Receptores de Neuropeptídeo Y , Animais , Prurido/induzido quimicamente , Transdução de Sinais , Medula EspinalRESUMO
Strain-controlled criticality governs the elasticity of jamming and fiber networks. While the upper critical dimension of jamming is believed to be d_{u}=2, non-mean-field exponents are observed in numerical studies of 2D and 3D fiber networks. The origins of this remains unclear. In this study we propose a minimal mean-field model for strain-controlled criticality of fiber networks. We then extend this to a phenomenological field theory, in which non-mean-field behavior emerges as a result of the disorder in the network structure. We predict that the upper critical dimension for such systems is d_{u}=4 using a Gaussian approximation. Moreover, we identify an order parameter for the phase transition, which has been lacking for fiber networks to date.
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Spinal cord malignant melanotic schwannoma (MMNST) is a rare central nervous system tumor that originates from the spinal cord or spinal myelin sheath cells and can produce melanin. This type of tumor is usually highly aggressive and malignant, with a poor prognosis. The clinical manifestations of spinal cord MMNST are mainly pain, paresthesia, muscle weakness, muscle atrophy, etc., and symptoms of spinal cord compression, such as intestinal and bladder dysfunction, paraplegia, etc. Early detection of tumor lesions can facilitate tumor removal, improve patients' quality of life, and prolong patients' survival. In this case report, a 27-year-old young woman was diagnosed with MMNST of the cervical spinal cord due to weakness of her limbs in our hospital, and underwent surgical resection. The patient's limbs returned to normal after surgery. It is worth mentioning that the patient visited our hospital 7 months ago for "right upper limb pain for 3 days" and was diagnosed with a cervical spine space-occupying lesion at the same position this time, but the pathology report was "hemosiderosis". The patient's limbs returned to normal after surgery. It is worth mentioning that the patient visited our hospital 7 months ago for "right upper limb pain for 3 days" and was diagnosed with a cervical spine space-occupying lesion at the same position this time, but the pathology report was "hemosiderosis". This case report aims to raise awareness of the problem of spinal cord MMNST and contribute to greater knowledge of this rare tumor. This case report aims to raise awareness of the problem of spinal cord MMNST and contribute to greater knowledge of this rare tumor.
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Neurilemoma , Neoplasias da Medula Espinal , Humanos , Feminino , Adulto , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/cirurgia , Neoplasias da Medula Espinal/diagnóstico , Neurilemoma/patologia , Neurilemoma/diagnóstico , Neurilemoma/cirurgia , Medula Cervical/patologia , Medula Cervical/diagnóstico por imagem , Vértebras Cervicais/patologia , Vértebras Cervicais/cirurgiaRESUMO
BACKGROUND: Sedentary behavior (SB) is deeply ingrained in the daily lives of community-dwelling older adults with type 2 diabetes mellitus (T2DM). However, the specific underlying mechanisms of the determinants associated with SB remain elusive. We aimed to explore the determinants of SB based on the behavior change wheel framework as well as a literature review. METHODS: This cross-sectional study recruited 489 community-dwelling older adults with T2DM in Jinan City, Shandong Province, China. Convenience sampling was used to select participants from relevant communities. This study used the Measure of Older Adults' Sedentary Time-T2DM, the Abbreviated-Neighborhood Environment Walkability Scale, the Social Support Rating Scale, the Lubben Social Network Scale 6, the Subjective Social Norms Questionnaire for Sedentary Behavior, the Functional Activities Questionnaire, the Numerical Rating Scale, the Short Physical Performance Battery, and the Montreal Cognitive Assessment Text to assess the levels of and the determinants of SB. Descriptive statistical analysis and path analysis were conducted to analyze and interpret the data. RESULTS: Pain, cognitive function, social isolation, and social support had direct and indirect effects on SB in community-dwelling older adults with T2DM (total effects: ß = 0.426, ß = -0.171, ß = -0.209, and ß = -0.128, respectively), and physical function, walking environment, and social function had direct effects on patients' SB (total effects: ß = -0.180, ß = -0.163, and ß = 0.127, respectively). All the above pathways were statistically significant (P < 0.05). The path analysis showed that the model had acceptable fit indices: RMSEA = 0.014, χ 2/df = 1.100, GFI = 0.999, AGFI = 0.980, NFI = 0.997, RFI = 0.954, IFI = 1.000, TLI = 0.996, CFI = 1.000. CONCLUSION: Capability (physical function, pain, and cognitive function), opportunity (social isolation, walking environment, and social support), and motivation (social function) were effective predictors of SB in community-dwelling older adults with T2DM. Deeper knowledge regarding these associations may help healthcare providers design targeted intervention strategies to decrease levels of SB in this specific population.
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Diabetes Mellitus Tipo 2 , Vida Independente , Comportamento Sedentário , Humanos , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/epidemiologia , Idoso , Masculino , Feminino , Estudos Transversais , Vida Independente/psicologia , Apoio Social , China/epidemiologia , Pessoa de Meia-Idade , Isolamento Social/psicologia , Inquéritos e Questionários , Idoso de 80 Anos ou maisRESUMO
An upconversion fluorescence sensing platform was developed with upconversion nanoparticles (UCNPs) as energy donors and gold nanoparticles (AuNPs) as energy acceptors, based on the FRET principle. They were used for quantitative detection of uranyl ions (UO22+) by amplifying the signal of the hybrid chain reaction (HCR). When UO22+ are introduced, the FRET between AuNPs and UCNPs can be modulated through a HCR in the presence of high concentrations of sodium chloride. This platform provides exceptional sensitivity, with a detection limit as low as 68 pM for UO22+ recognition. We have successfully validated the reliability of this method by analyzing authentic water samples, achieving satisfactory recoveries (89.00%-112.50%) that are comparable to those of ICP-MS. These results indicate that the developed sensing platform has the capability to identify trace UO22+ in complex environmental samples.
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The European-centered genome-wide association studies of schizophrenia (SCZ) may not be well applied to non-European populations. We analyzed 1,592 reported SCZ-associated genes using the public genome data and found an overall higher Asian-European differentiation on the SCZ-associated variants than at the genome-wide level. Notable examples included 15 missense variants, a regulatory variant SLC5A10-rs1624825, and a damaging variant TSPAN18-rs1001292. Independent local adaptations in recent 25,000 years, after the Asian-European divergence, could have contributed to such genetic differentiation, as were identified at a missense mutation LTN1-rs57646126-A in Asians, and a non-risk allele ZSWIM6-rs72761442-G in Europeans. Altai-Neanderthal-derived alleles may have opposite effects on SCZ susceptibility between ancestries. Furthermore, adaptive introgression was detected on the non-risk haplotype at 1q21.2 in Europeans, while in Asians it was observed on the SCZ risk haplotype at 3p21.31 which is also potentially ultra-violet protective. This study emphasizes the importance of including more representative Asian samples in future SCZ studies.
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Materials exhibiting a significant shift current response could potentially outperform conventional solar cell materials. The myriad of factors governing shift-current response, however, poses significant challenges in finding such strong shift-current materials. Here we propose a general design principle that exploits inter-orbital mixing to excite virtual multiband transitions in materials with multiple flat bands to achieve an enhanced shift current response. We further relate this design principle to maximizing Wannier function spread as expressed through the formalism of quantum geometry. We demonstrate the viability of our design using a 1D stacked Rice-Mele model. Furthermore, we consider a concrete material realization - alternating angle twisted multilayer graphene (TMG) - a natural platform to experimentally realize such an effect. We identify a set of twist angles at which the shift current response is maximized via virtual transitions for each multilayer graphene and highlight the importance of TMG as a promising material to achieve an enhanced shift current response at terahertz frequencies. Our proposed mechanism also applies to other 2D systems and can serve as a guiding principle for designing multiband systems that exhibit an enhanced shift current response.
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In recent years, the significant impact of lactate in the tumor microenvironment has been greatly documented. Acting not only as an energy substance in tumor metabolism, lactate is also an imperative signaling molecule. It plays key roles in metabolic remodeling, protein lactylation, immunosuppression, drug resistance, epigenetics and tumor metastasis, which has a tight relation with cancer patients' poor prognosis. This review illustrates the roles lactate plays in different aspects of tumor progression and drug resistance. From the comprehensive effects that lactate has on tumor metabolism and tumor immunity, the therapeutic targets related to it are expected to bring new hope for cancer therapy.
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Resistencia a Medicamentos Antineoplásicos , Ácido Láctico , Neoplasias , Microambiente Tumoral , Humanos , Relevância Clínica , Ácido Láctico/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/genética , Neoplasias/tratamento farmacológico , Transdução de SinaisRESUMO
AIM: This work aimed to investigate the role of M1 intestinal macrophages-derived exosomes (M1-Exo) in colitis and its mechanism. METHODS: M1 polarization of intestinal macrophages was induced in vitro, and their exosomes were extracted and identified. Thereafter, the DSS-induced colitis mouse model was built. Each mouse was given intraperitoneal injection of exosomes, and then mouse weight and DAI were dynamically monitored. In addition, the levels of cytokines were detected by ELISA. After treatment with the TLR4 inhibitor Resatorvid, the effects of M1 macrophages-derived exosomes were observed. Besides, the mouse intestinal epithelial cells were cultured in vitro for observing function of M1-Exo. RESULTS: M1-exo aggravated the colitis and tissue inflammation in mice, activated the TLR4 signal, and destroyed the mucosal barrier. But M0 macrophages-derived exosomes (M0-Exo) did not have the above effects. Resatorvid treatment antagonized the roles of M1-exo. Moreover, as confirmed by cellular experiments in vitro, M1-exo destroyed mucosal barrier. CONCLUSION: M1-exo serve as the pro-inflammatory mediator, which can promote mouse colitis progression by activating TLR4 signal.
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Colite , Exossomos , Sulfonamidas , Animais , Camundongos , Receptor 4 Toll-Like , Colite/induzido quimicamente , MacrófagosRESUMO
The Qinghai-Tibet Plateau faces dramatic global change, which can greatly affect its plant growth, biomass accumulation, and carbon cycling. However, it is still unclear how belowground plant biomass, which is the major part of vegetation biomass on the plateau, changes with different environmental factors, impeding accurate prediction of ecosystem carbon cycling under future global change scenarios. To reveal the patterns of belowground biomass and root:shoot ratio with environmental factors in different vegetation types on the Qinghai-Tibet Plateau, we synthesized data for 158 sites from 167 publications, including 585 and 379 observations for above- and below-ground biomass, respectively. Data on temperature, precipitation, soil nitrogen content, evapotranspiration and solar radiation were collected from open databases. The results showed that precipitation, rather than temperature, was closely associated with other environmental factors including soil N and solar radiation. Also, both above- and below-ground biomass significantly increased with annual precipitation and its related environmental factors, while elevation-related coldness only slightly decreased aboveground biomass. In addition, the positive effect of precipitation on belowground biomass is more obvious in higher elevations (colder areas). As a result, root:shoot ratio significantly increased with precipitation in colder areas but not in warmer areas. Finally, the positive relationship between biomass and precipitation was stronger for dryer steppes than for wetter meadows and shrublands. Our findings indicate that precipitation, as well as the associated nitrogen availability and solar radiation, together are more important drivers than temperature for ecosystem productivity and biomass allocation on the Qinghai-Tibet Plateau. Given the heterogeneous trend of precipitation change on the plateau, productivity response to global change can be highly variable across different regions and vegetation types, which can consequently impact soil carbon dynamics and regional carbon cycling.
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Ecossistema , Solo , Biomassa , Tibet , Temperatura , Carbono , Nitrogênio/análise , PradariaRESUMO
PURPOSE: Cystatin SA (CST2) belongs to the superfamily of cysteine protease inhibitors. Emerging research indicates that CST2 is often dysregulated across various cancers. Its role and molecular mechanisms in gastric cancer remain underexplored. This study aims to explore the expression and function of CST2 in gastric cancer. METHODS: CST2 expression was analyzed and validated through Western blot. CST2 overexpression was induced by lentivirus in GC cells, and the correlation between CST2 expression levels and downstream signaling pathways was assessed. In addition, multiple assays, including cell proliferation, colony formation, wound-healing, and transwell migration/invasion, were considered to ascertain the influence of CST2 overexpression on gastric cancer. The cell cycle and apoptosis were detected by flow cytometry. RESULTS: CST2 expression at the protein level was decreased to be reduced in both gastric cancer tissues and cell lines, and CST2 expression attenuate gastric cancer growth, an effect restricted to gastric cancer cells and absent in gastric epithelial GES-1 cells. Furthermore, CST2 was demonstrated to improve chemosensitivity to Oxaliplatin in gastric cancer cells through the PI3K/AKT signaling pathway. CONCLUSION: These findings indicate that CST2 is downregulated at the protein level in gastric cancer tissues and cell lines. Additionally, CST2 was found to attenuate the growth of gastric cancer cells and to enhance sensitivity to Oxaliplatin through the PI3K/AKT signaling pathway, specific to gastric cancer cell lines. CST2 may serve as a tumor suppressor gene increasing sensitivity to Oxaliplatin in gastric cancer.
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Proliferação de Células , Oxaliplatina , Cistatinas Salivares , Neoplasias Gástricas , Humanos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Oxaliplatina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Cistatinas Salivares/metabolismo , Cistatinas Salivares/genética , Transdução de Sinais/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genéticaRESUMO
The ongoing reduction in transistor sizes drives advancements in information technology. However, as transistors shrink to the nanometer scale, surface and edge states begin to constrain their performance. 2D semiconductors like transition metal dichalcogenides (TMDs) have dangling-bond-free surfaces, hence achieving minimal surface states. Nonetheless, edge state disorder still limits the performance of width-scaled 2D transistors. This work demonstrates a facile edge passivation method to enhance the electrical properties of monolayer WSe2 nanoribbons, by combining scanning transmission electron microscopy, optical spectroscopy, and field-effect transistor (FET) transport measurements. Monolayer WSe2 nanoribbons are passivated with amorphous WOxSey at the edges, which is achieved using nanolithography and a controlled remote O2 plasma process. The same nanoribbons, with and without edge passivation are sequentially fabricated and measured. The passivated-edge nanoribbon FETs exhibit 10 ± 6 times higher field-effect mobility than the open-edge nanoribbon FETs, which are characterized with dangling bonds at the edges. WOxSey edge passivation minimizes edge disorder and enhances the material quality of WSe2 nanoribbons. Owing to its simplicity and effectiveness, oxidation-based edge passivation could become a turnkey manufacturing solution for TMD nanoribbons in beyond-silicon electronics and optoelectronics.
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Traditionally, many researchers have supported a uniformitarian view whereby all languages are of roughly equal complexity, facilitated by internal trade-offs between complexity at different levels, such as morphology and syntax. The extent to which the speakers' societies influence the trade-offs has not been well studied. In this paper, we focus on morphology and syntax, and report significant correlations between specific linguistic and societal features, in particular those relating to exoteric (open) vs. esoteric (close-knit) society types, characterizable in terms of population size, mobility, communication across distances, etc. We conduct an exhaustive quantitative analysis drawing upon WALS, D-Place, Ethnologue and Glottolog, finding some support for our hypothesis that languages spoken by exoteric societies tend towards more complex syntaxes, while languages spoken by esoteric societies tend towards more complex morphologies.
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Idioma , Linguística , Humanos , Comunicação , PesquisadoresRESUMO
Endangered species generally have small populations with low genetic diversity and a high genetic load. Thuja sutchuenensis is an endangered conifer endemic to southwestern China. It was once considered extinct in the wild, but in 1999 was rediscovered. However, little is known about its genetic load. We collected 67 individuals from five wild, isolated T. sutchuenensis populations, and used 636,151 SNPs to analyze the level of genetic diversity and genetic load in T. sutchuenensis to delineate the conservation units of T. sutchuenensis, based on whole transcriptome sequencing data, as well as target capture sequencing data. We found that populations of T. sutchuenensis could be divided into three groups. These groups had low levels genetic diversity and were moderately genetically differentiated. Our findings also indicate that T. sutchuenensis suffered two severe bottlenecks around the Last Glaciation Period and Last Glacial Maximum. Among Thuja species, T. sutchuenensis presented the lowest genetic load and hence might have purged deleterious mutations efficiently through purifying selection. However, distribution of fitness effects analysis indicated a high extinction risk for T. sutchuenensis. Multiple lines of evidence identified three management units for T. sutchuenensis. Although T. sutchuenensis possesses a low genetic load, low genetic diversity, suboptimal fitness, and anthropogenic pressures all present an extinction risk for this rare conifer. This might also hold true for many endangered plant species in the mountains all over the world.
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Stereotaxic injection of a specific brain region constitutes a fundamental experimental technique in basic neuroscience. Researchers commonly base their choice of stereotaxic injection parameters on mouse brain atlases or published materials that employed various populations/ages of mice and different stereotaxic equipment, necessitating further validation of the stereotaxic coordinate parameters. The efficacy of calcium imaging, chemogenetic, and optogenetic manipulations relies on the precise expression of reporter genes within the region of interest, often requiring several weeks of effort. Thus, it is a time-consuming task if the coordinates of the target brain region are not verified in advance. Using an appropriate dye instead of a virus and implementing cryosectioning, researchers can observe the injection site immediately following dye administration. This facilitates timely adjustments to coordinate parameters in cases where discrepancies exist between the actual injection site and the theoretical position. Such adjustments significantly enhance the accuracy of viral expression within the target region in subsequent experiments.
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Técnicas Estereotáxicas , Animais , Camundongos , Crioultramicrotomia/métodos , Encéfalo/metabolismoRESUMO
Gasdermin E (GSDME) has recently been identified as a critical executioner to mediate pyroptosis. While epidermal keratinocytes can initiate GSDME-mediated pyroptosis, the role of keratinocyte GSDME in psoriatic dermatitis remains poorly characterized. Through analysis of GEO datasets, we found elevated GSDME levels in psoriatic lesional skin. Additionally, GSDME levels correlated with both psoriasis severity and response to biologics treatments. Single-cell RNA sequencing (scRNA-seq) from a GEO dataset revealed GSDME upregulation in keratinocytes of psoriasis patients. In the imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model, both full-length and cleaved forms of caspase-3 and GSDME were elevated in the epidermis. Abnormal proliferation and differentiation of keratinocytes and dermatitis were attenuated in Gsdme-/- mice and keratinocyte-specific Gsdme conditional knockout mice after IMQ stimulation. Exposure of keratinocytes to mixed cytokines (M5), mimicking psoriatic conditions, led to GSDME cleavage. Moreover, the interaction between GSDME-FL and p65 or c-jun was significantly increased after M5 stimulation. GSDME knockdown inhibited nuclear translocation of p65 and c-jun and decreased upregulation of psoriatic inflammatory mediators such as IL1ß, CCL20, CXCL1, CXCL8, S100A8, and S100A9 in M5-challenged keratinocytes. In conclusion, GSDME in keratinocytes contributes to the pathogenesis and progression of psoriasis, potentially in a pyroptosis-independent manner by interacting and promoting translocation of p65 and c-jun. These findings suggest that keratinocyte GSDME could serve as a potential therapeutic target for psoriasis treatment.
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Dermatite , Gasderminas , Psoríase , Animais , Humanos , Camundongos , Dermatite/metabolismo , Dermatite/patologia , Gasderminas/metabolismo , Imiquimode/efeitos adversos , Inflamação/patologia , Queratinócitos/patologia , Psoríase/metabolismo , Psoríase/patologia , Fator de Transcrição RelA/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismoRESUMO
Proteins are inherently dynamic, and their conformational ensembles are functionally important in biology. Large-scale motions may govern protein structure-function relationship, and numerous transient but stable conformations of intrinsically disordered proteins (IDPs) can play a crucial role in biological function. Investigating conformational ensembles to understand regulations and disease-related aggregations of IDPs is challenging both experimentally and computationally. In this paper first an unsupervised deep learning-based model, termed Internal Coordinate Net (ICoN), is developed that learns the physical principles of conformational changes from molecular dynamics (MD) simulation data. Second, interpolating data points in the learned latent space are selected that rapidly identify novel synthetic conformations with sophisticated and large-scale sidechains and backbone arrangements. Third, with the highly dynamic amyloid-ß1-42 (Aß42) monomer, our deep learning model provided a comprehensive sampling of Aß42's conformational landscape. Analysis of these synthetic conformations revealed conformational clusters that can be used to rationalize experimental findings. Additionally, the method can identify novel conformations with important interactions in atomistic details that are not included in the training data. New synthetic conformations showed distinct sidechain rearrangements that are probed by our EPR and amino acid substitution studies. The proposed approach is highly transferable and can be used for any available data for training. The work also demonstrated the ability for deep learning to utilize learned natural atomistic motions in protein conformation sampling.
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Autophagy participates in the regulation of ferroptosis. Among numerous autophagy-related genes (ATGs), ATG5 plays a pivotal role in ferroptosis. However, how ATG5-mediated ferroptosis functions in UVB-induced skin inflammation is still unclear. In this study, we unveil that the core ferroptosis inhibitor GPX4 is significantly decreased in human skin tissue exposed to sunlight. We report that ATG5 deletion in mouse keratinocytes strongly protects against UVB-induced keratinocyte ferroptosis and skin inflammation. Mechanistically, ATG5 promotes the autophagy-dependent degradation of GPX4 in UVB-exposed keratinocytes, which leads to UVB-induced keratinocyte ferroptosis. Furthermore, we find that IFN-γ secreted by ferroptotic keratinocytes facilitates the M1 polarization of macrophages, which results in the exacerbation of UVB-induced skin inflammation. Together, our data indicate that ATG5 exacerbates UVB-induced keratinocyte ferroptosis in the epidermis, which subsequently gives rise to the secretion of IFN-γ and M1 polarization. Our study provides novel evidence that targeting ATG5 may serve as a potential therapeutic strategy for the amelioration of UVB-caused skin damage.
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Proteína 5 Relacionada à Autofagia , Ferroptose , Interferon gama , Queratinócitos , Macrófagos , Raios Ultravioleta , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Queratinócitos/citologia , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Animais , Camundongos , Interferon gama/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos da radiação , Macrófagos/citologia , Humanos , Pele/efeitos da radiação , Pele/metabolismo , Pele/patologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Autofagia/efeitos da radiação , Inflamação/metabolismo , Inflamação/patologiaRESUMO
In this study, lead(II) sulphide (PbS) nanoparticles of varying particle sizes were synthesized using the hot injection method, employing 1-octadecene (ODE) as a coordinating ligand in conjunction with oleylamine (OAm). This synthesis approach was compared with the preparation of hexagonal-shaped nanoparticles through the ligand of 1-Dodecanethiol (DT), resulting in DT-capped PbS nanoparticles. The prepared nanoparticles were characterized using multiple techniques including photoluminescence (PL), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR). The condensation reaction of DT ligands led to various nanoparticles within the range of 34.87 nm to 35.87 nm across different synthesis temperatures (120 °C, 150 °C, 180 °C, 210 °C, and 240 °C). The PbS with DT ligands exhibited a highly crystalline and superhydrophilic structure. Interestingly, near-infrared (NIR)-PL analysis revealed peaks at 1100 nm, representing the lowest-energy excitonic absorption peak of PbS nanoparticles for both ligands. This suggests their potential utility in various applications, including IR photoreactors, as well as in the development of non-toxic nanoparticles for potential applications in in vivo bioimaging.
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Proteins are inherently dynamic, and their conformational ensembles are functionally important in biology. Large-scale motions may govern protein structure-function relationship, and numerous transient but stable conformations of intrinsically disordered proteins (IDPs) can play a crucial role in biological function. Investigating conformational ensembles to understand regulations and disease-related aggregations of IDPs is challenging both experimentally and computationally. In this paper we first introduced an unsupervised deep learning-based model, termed Internal Coordinate Net (ICoN), which learns the physical principles of conformational changes from molecular dynamics (MD) simulation data. Second, we selected interpolating data points in the learned latent space that rapidly identify novel synthetic conformations with sophisticated and large-scale sidechains and backbone arrangements. Third, with the highly dynamic amyloid-ß 1-42 (Aß42) monomer, our deep learning model provided a comprehensive sampling of Aß42's conformational landscape. Analysis of these synthetic conformations revealed conformational clusters that can be used to rationalize experimental findings. Additionally, the method can identify novel conformations with important interactions in atomistic details that are not included in the training data. New synthetic conformations showed distinct sidechain rearrangements that are probed by our EPR and amino acid substitution studies. This approach is highly transferable and can be used for any available data for training. The work also demonstrated the ability for deep learning to utilize learned natural atomistic motions in protein conformation sampling.