RESUMEN
Recent technological advancements have enabled spatially resolved transcriptomic profiling but at a multicellular resolution that is more cost-effective. The task of cell type deconvolution has been introduced to disentangle discrete cell types from such multicellular spots. However, existing benchmark datasets for cell type deconvolution are either generated from simulation or limited in scale, predominantly encompassing data on mice and are not designed for human immuno-oncology. To overcome these limitations and promote comprehensive investigation of cell type deconvolution for human immuno-oncology, we introduce a large-scale spatial transcriptomic deconvolution benchmark dataset named SpatialCTD, encompassing 1.8 million cells and 12,900 pseudo spots from the human tumor microenvironment across the lung, kidney, and liver. In addition, SpatialCTD provides more realistic reference than those generated from single-cell RNA sequencing (scRNA-seq) data for most reference-based deconvolution methods. To utilize the location-aware SpatialCTD reference, we propose a graph neural network-based deconvolution method (i.e., GNNDeconvolver). Extensive experiments show that GNNDeconvolver often outperforms existing state-of-the-art methods by a substantial margin, without requiring scRNA-seq data. To enable comprehensive evaluations of spatial transcriptomics data from flexible protocols, we provide an online tool capable of converting spatial transcriptomic data from various platforms (e.g., 10× Visium, MERFISH, and sci-Space) into pseudo spots, featuring adjustable spot size. The SpatialCTD dataset and GNNDeconvolver implementation are available at https://github.com/OmicsML/SpatialCTD, and the online converter tool can be accessed at https://omicsml.github.io/SpatialCTD/.
RESUMEN
Primary thyroid squamous cell carcinoma is extremely rare. We report a case of primary thyroid squamous cell carcinoma diagnosed using 18F-FDG PET/CT. The patient presented with left axillary lymphadenopathy as the initial symptom. Fine-needle aspiration of the axillary lymph nodes indicated metastatic squamous cell carcinoma. To identify the primary tumor, the patient underwent an 18F-FDG PET/CT scan, which revealed a mass in the thyroid and multiple enlarged lymph nodes with abnormal FDG uptake. Pathological examination of the axillary lymph nodes and thyroid biopsy confirmed the diagnosis of primary thyroid squamous cell carcinoma with lymph node metastasis.
RESUMEN
Interfacial solar evaporation (ISE) holds considerable promise to solve fresh water shortage, but it is challenging to achieve high evaporation rate (Reva) and fresh water yield in close system. Here, we report design and preparation of MOF-based solar evaporators with hierarchical microporous/nanobridged/nanogranular structures for rapid ISE and fresh water collection in close system. The evaporators are fabricated by growing silicone nanofilaments with variable length as nanobridges on a microporous silicone sponge followed by grafting with polydopamine nanoparticles and Cu-MOF nanocrystals. Integration of the unique structure and excellent photothermal composites endows the evaporators with high Reva of 3.5-20 wt% brines (3.60-2.90 kg m-2 h-1 in open system and 2.38-1.44 kg m-2 h-1 in close system) under simulated 1 sun, high Reva under natural sunlight, excellent salt resistance and high fresh water yield, which surpass most state-of-the-art evaporators. Moreover, when combined with a superhydrophilic cover, the evaporators show much higher average Reva of real seawater, remarkable fresh water yield and excellent long-term stability over one month continuous ISE under natural sunlight. The findings here will promote the development of advanced evaporators via microstructure engineering and their real-world ISE applications.
RESUMEN
In recent years, sodium-ion batteries (SIBs) have gained a foothold in specific applications related to lithium-ion batteries, thanks to continuous breakthroughs and innovations in materials by researchers. Commercial graphite anodes suffer from small interlayer spacing (0.334 nm), limited specific capacity (200 mAh g-1), and low discharge voltage (<0.1 V), making them inefficient for high-performance operation in SIBs. Hence, the current research focus is on seeking negative electrode materials that are compatible with the operation of SIBs. Many studies have been reported on the modification of transition metal selenides as anodes in SIBs, mainly targeting the issue of poor cycling life attributed to the volume expansion of the material during sodium-ion extraction and insertion processes. However, the intrinsic electronic structure of transition metal selenides also influences electron transport and sodium-ion diffusion. Therefore, modulating their electronic structure can fundamentally improve the electron affinity of transition metal selenides, thereby enhancing their rate performance in SIBs. This work provides a comprehensive review of recent strategies focusing on the modulation of electronic structures and the construction of heterogeneous structures for transition metal selenides. These strategies effectively enhance their performance metrics as electrodes in SIBs, including fast charging, stability, and first-cycle coulombic efficiency, thereby facilitating the development of high-performance SIBs.
Asunto(s)
Anticuerpos Monoclonales , Oftalmopatía de Graves , Humanos , Administración Intravenosa , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/administración & dosificación , Oftalmopatía de Graves/tratamiento farmacológico , Oftalmopatía de Graves/inmunología , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
HYPOTHESIS: Hydrophilic cationic drugs such as mitoxantrone hydrochloride (MTO) pose a significant delivery challenge to the development of nanodrug systems. Herein, we report the use of a hydrophobic ion-pairing strategy to enhance the nano-assembly of MTO. EXPERIMENTS: We employed biocompatible sodium cholesteryl sulfate (SCS) as a modification module to form stable ion pairs with MTO, which balanced the intermolecular forces and facilitated nano-assembly. PEGylated MTO-SCS nanoassemblies (pMS NAs) were prepared via nanoprecipitation. We systematically evaluated the effect of the ratio of the drug module (MTO) to the modification module (SCS) on the nanoassemblies. FINDINGS: The increased lipophilicity of MTO-SCS ion pair could significantly improve the encapsulation efficiency (â¼97 %) and cellular uptake efficiency of MTO. The pMS NAs showed prolonged blood circulation, maintained the same level of tumor antiproliferative activity, and exhibited reduced toxicity compared with the free MTO solution. It is noteworthy that the stability, cellular uptake, cytotoxicity, and in vivo pharmacokinetic behavior of the pMS NAs increased in proportion to the molar ratio of SCS to MTO. This study presents a self-assembly strategy mediated by ion pairing to overcome the challenges commonly associated with the poor assembly ability of hydrophilic cationic drugs.
Asunto(s)
Antineoplásicos , Ésteres del Colesterol , Interacciones Hidrofóbicas e Hidrofílicas , Mitoxantrona , Mitoxantrona/química , Mitoxantrona/farmacología , Mitoxantrona/farmacocinética , Humanos , Animales , Ésteres del Colesterol/química , Antineoplásicos/química , Antineoplásicos/farmacología , Ratones , Proliferación Celular/efectos de los fármacos , Cationes/química , Supervivencia Celular/efectos de los fármacos , Tamaño de la Partícula , Nanopartículas/química , Propiedades de Superficie , Portadores de Fármacos/química , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral , Polietilenglicoles/químicaRESUMEN
BACKGROUND: Like the coronavirus disease 2019, the hepatitis B virus is also wreaking havoc worldwide, which has infected over 2 billion people globally. Using an experimental animal model, our previous research observed that the hepatitis B virus genes integrated into human spermatozoa can replicate and express after being transmitted to embryos. However, as of now, this phenomenon has not been confirmed in clinical data from patients. OBJECTIVES: To explore the integration of the hepatitis B virus into patients' sperm genome and its potential clinical risks. MATERIALS AND METHODS: Forty-eight patients with chronic hepatitis B virus infection were categorized into two groups: Test Group-1 comprised 23 patients without integration of hepatitis B virus DNA within the sperm genome. Test Group-2 comprised 25 patients with integration of hepatitis B virus DNA within the sperm genome. Forty-eight healthy male donors were included as control. The standard semen parameter analysis, real-time polymerase chain reaction, quantitative real-time polymerase chain reaction, sperm chromatin structure assay, fluorescence in situ hybridization, and immunofluorescence assays were utilized. RESULTS: The difference in the median copy number of hepatitis B virus DNA per mL of sera between Test Group-1 and Group-2 was not statistically significant. In Test Group-2, the integration rate of hepatitis B virus DNA was 0.109%, which showed a significant correlation with the median copy number of hepatitis B virus DNA in motile spermatozoa (1.18 × 103 /mL). Abnormal semen parameters were found in almost all these 25 patients. The integrated hepatitis B virus S, C, X, and P genes were detected to be introduced into sperm-derived embryos through fertilization and retained their function in replication, transcription, and translation. CONCLUSION: Our findings suggest that hepatitis B virus infection can lead to sperm quality deterioration and reduced fertilization capacity. Furthermore, viral integration causes instability in the sperm genome, increasing the potential risk of termination, miscarriage, and stillbirth. This study identified an unconventional mode of hepatitis B virus transmission through genes rather than virions. The presence of viral sequences in the embryonic genome poses a risk of liver inflammation and cancer.
RESUMEN
Prodrug nanoassemblies are emerging as a novel drug delivery system for chemotherapy, comprising four fundamental modules: a drug module, a modification module, a response module, and a surface functionalization module. Among these modules, surface functionalization is an essential process to enhance the biocompatibility and stability of the nanoassemblies. Here, we selected mitoxantrone (MTO) as the drug module and DSPE-PEG2K as surface functionalization module to develop MTO prodrug nanoassemblies. We systematically evaluated the effect of surface functionalization module ratios (10%, 20%, 40%, and 60% of prodrug, WDSPE-mPEG2000/Wprodrug) on the prodrug nanoassemblies. The results indicated that 40% NPs significantly improved the self-assembly stability and cellular uptake of prodrug nanoassemblies. Compared with MTO solution, 40% NPs showed better tumor specificity and pharmacokinetics, resulting in potent antitumor activity with a good safety profile. These findings highlighted the pivotal role of the surface functionalization module in regulating the performance of mitoxantrone prodrug nanoassemblies for cancer treatment.
Asunto(s)
Antineoplásicos , Nanopartículas , Profármacos , Mitoxantrona , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodosRESUMEN
DANCE is the first standard, generic, and extensible benchmark platform for accessing and evaluating computational methods across the spectrum of benchmark datasets for numerous single-cell analysis tasks. Currently, DANCE supports 3 modules and 8 popular tasks with 32 state-of-art methods on 21 benchmark datasets. People can easily reproduce the results of supported algorithms across major benchmark datasets via minimal efforts, such as using only one command line. In addition, DANCE provides an ecosystem of deep learning architectures and tools for researchers to facilitate their own model development. DANCE is an open-source Python package that welcomes all kinds of contributions.
Asunto(s)
Benchmarking , Aprendizaje Profundo , Humanos , Algoritmos , Biblioteca de Genes , Análisis de la Célula IndividualRESUMEN
Dimeric prodrug nanoassemblies (DPNAs) stand out as promising strategies for improving the efficiency and safety of chemotherapeutic drugs. The success of trisulfide bonds (-SSS-) in DPNAs makes polysulfide bonds a worthwhile focus. Here, we explore the comprehensive role of tetrasulfide bonds (-SSSS-) in constructing superior DPNAs. Compared to trisulfide and disulfide bonds, tetrasulfide bonds endow DPNAs with superlative self-assembly stability, prolonged blood circulation, and high tumor accumulation. Notably, the ultra-high reduction responsivity of tetrasulfide bonds make DPNAs a highly selective "tumor bomb" that can be ignited by endogenous reducing agents in tumor cells. Furthermore, we present an "add fuel to the flames" strategy to intensify the reductive stress at tumor sites by replenishing exogenous reducing agents, making considerable progress in selective tumor inhibition. This work elucidates the crucial role of tetrasulfide bonds in establishing intelligent DPNAs, alongside the combination methodology, propelling DPNAs to new heights in potent cancer therapy.
Asunto(s)
Profármacos , Profármacos/farmacología , Profármacos/uso terapéutico , Profármacos/química , Sustancias Reductoras , Línea Celular TumoralRESUMEN
Solar-driven interfacial evaporation (SIE) is very promising to solve the issue of fresh water shortage, however, poor salt resistance severely hinders long-term stable SIE and fresh water collection. Here, we report design of superhydrophilic solar evaporators for long-term stable desalination, fresh water collection and salt collection by vertical salt deposition. The evaporators are prepared by sequentially deposition of silicone nanofilaments, polypyrrole and Au nanoparticles on a polyester fabric composed of microfibers. The evaporators feature excellent photothermal effect and ultrafast water transport, due to their unique micro-/nanostructure and superhydrophilicity. As a result, during SIE the salt gradually deposits vertically rather than occupies larger area on the evaporators. Consequently, long-term stable SIE with high evaporation rates of 2.4-2.1â kg m-2 h-1 for 3.5-20â wt % brine in continuous 10â h is achieved under 1â sun illumination. Meanwhile, the loosely deposited salt can be easily collected, realizing zero brine discharge. Moreover, scalable preparation of the evaporator is achieved, which exhibits efficient collection of high quality fresh water (10.08â kg m-2 in 8â h) via SIE desalination under weak natural sunlight (0.46~0.66â sun). This strategy sheds a new light on the design of high-performance solar evaporators and their real-world fresh water collection.
RESUMEN
We present the Empathy for Pain Stimuli System (EPSS): a large-scale database of stimuli for studying people's empathy for pain. The EPSS comprises five sub-databases. First, the Empathy for Limb Pain Picture Database (EPSS-Limb) provides 68 painful and 68 non-painful limb pictures, exhibiting people's limbs in painful and non-painful situations, respectively. Second, the Empathy for Face Pain Picture Database (EPSS-Face) provides 80 painful and 80 non-painful pictures of people's faces being penetrated by a syringe or touched by a Q-tip. Third, the Empathy for Voice Pain Database (EPSS-Voice) provides 30 painful and 30 non-painful voices exhibiting either short vocal cries of pain or neutral interjections. Fourth, the Empathy for Action Pain Video Database (EPSS-Action_Video) provides 239 painful and 239 non-painful videos of whole-body actions. Finally, the Empathy for Action Pain Picture Database (EPSS-Action_Picture) provides 239 painful and 239 non-painful pictures of whole-body actions. To validate the stimuli in the EPSS, participants evaluated the stimuli using four different scales, rating pain intensity, affective valence, arousal, and dominance. The EPSS is available to download for free at https://osf.io/muyah/?view_only=33ecf6c574cc4e2bbbaee775b299c6c1 .
Asunto(s)
Empatía , Dolor , Humanos , Estimulación Luminosa , Dolor/psicología , Nivel de Alerta , TactoRESUMEN
When hematopoietic cells are overwhelmed with ionizing radiation (IR) DNA damage, the alternative non-homologous end-joining (aNHEJ) repair pathway is activated to repair stressed replication forks. While aNHEJ can rescue cells overwhelmed with DNA damage, it can also mediate chromosomal deletions and fusions, which can cause mis-segregation in mitosis and resultant aneuploidy. We previously reported that a hematopoietic microRNA, miR-223-3p, normally represses aNHEJ. We found that miR-223-/- mice have increased survival of hematopoietic stem and progenitor cells (HSPCs) after sublethal IR. However, this came at the cost of significantly more genomic aberrancies, with miR-223-/- hematopoietic progenitors having increased metaphase aberrancies, including chromothripsis, and increased sequence abnormalities, especially deletions, which is consistent with aNHEJ. These data imply that when an HSPC is faced with substantial DNA damage, it may trade genomic damage for its own survival by choosing the aNHEJ repair pathway, and this choice is regulated in part by miR-223-3p.
Asunto(s)
MicroARNs , Ratones , Animales , MicroARNs/genética , Daño del ADN , Reparación del ADN por Unión de Extremidades , Radiación Ionizante , Inestabilidad GenómicaRESUMEN
Prolonged exposure to others' suffering can lead to empathy fatigue, especially when individuals struggle to effectively regulate their empathic capacity. Shifting active attention away from emotional components toward cognitive components of others' suffering is an effective strategy for mitigating empathy fatigue. This research investigated how top-down attentional manipulation modulates empathy fatigue in both auditory (Study 1) and visual (Study 2) modalities. Participants completed two tasks in both studies: (i) the attention to cognitive empathy task (A-C task) and (ii) the attention to emotional empathy task (A-E task). Each task included three blocks (Time Block 1, Time Block 2, and Time Block 3) designed to induce empathy fatigue. Study 1 revealed that the A-C task reduced empathy fatigue and N1 amplitudes than the A-E task in Time Block 3, indicating that attention to cognitive empathy might decrease auditory empathy fatigue. Study 2 indicates that the A-C task caused a longer N2 latency than the A-E task, signifying a decelerated emotional empathic response when attention was on cognitive empathy in the visual modality. Overall, prioritizing cognitive empathy seems to conserve mental resources and reduce empathy fatigue. This research documented the relationship between top-down attention and empathy fatigue and the possible neural mechanism.
Asunto(s)
Emociones , Empatía , Humanos , Emociones/fisiologíaRESUMEN
Coastal pollution caused by the importation of agricultural herbicides is one of the main environmental problems that directly affect the coastal primary productivity and even the safety of human seafood. It is urgent to evaluate the ecological risk objectively and explore feasible removal strategies. However, existing studies focus on the runoff distribution and risk assessment of specific herbicides in specific areas, and compared with soil environment, there are few studies on remediation methods for water environment. Therefore, we systematically reviewed the current situation of herbicide pollution in global coastal waters and the dose-response relationships of various herbicides on phytoplankton and higher trophic organisms from the perspective of ecological risks. In addition, we believe that compared with the traditional single physical and chemical remediation methods, biological remediation and its combined technology are the most promising methods for herbicide pollution remediation currently. Therefore, we focus on the application prospects, challenges, and management strategies of new bioremediation systems related to biology, such as constructed wetlands, membrane bioreactor processes, and microbial co-metabolism, in order to provide more advanced methods for reducing herbicide pollution in the water environment.
Asunto(s)
Restauración y Remediación Ambiental , Herbicidas , Contaminantes Químicos del Agua , Humanos , Herbicidas/análisis , Contaminantes Químicos del Agua/análisis , Agricultura , AguaRESUMEN
Homodimeric prodrug nanoassemblies (HDPNs) hold promise for improving the delivery efficiency of chemo-drugs. However, the key challenge lies in designing rational chemical linkers that can simultaneously ensure the chemical stability, self-assembly stability, and site-specific activation of prodrugs. The "in series" increase in sulfur atoms, such as trisulfide bond, can improve the assembly stability of HDPNs to a certain extent, but limits the chemical stability of prodrugs. Herein, trithiocarbonate bond (âSC(S)Sâ), with a stable "satellite-type" distribution of sulfur atoms, is developed via the insertion of a central carbon atom in trisulfide bonds. âSC(S)Sâ bond effectively addresses the existing predicament of HDPNs by improving the chemical and self-assembly stability of homodimeric prodrugs while maintaining the on-demand bioactivation. Furthermore, âSC(S)Sâ bond inhibits antioxidant defense system, leading to up-regulation of the cellular ROS and apoptosis of tumor cells. These improvements of âSC(S)Sâ bond endow the HDPNs with in vivo longevity and tumor specificity, ultimately enhancing the therapeutic outcomes. âSC(S)Sâ bond is, therefore, promising for overcoming the bottleneck of HDPNs for efficient oncological therapy.
Asunto(s)
Antineoplásicos , Nanopartículas , Profármacos , Tionas , Profármacos/farmacología , Profármacos/química , Línea Celular Tumoral , Antineoplásicos/farmacología , Polímeros , Azufre , Nanopartículas/química , Liberación de FármacosRESUMEN
The prodrug-based nanoassemblies offer an alternative to settle the deficiencies of traditional chemotherapy drugs. In this nanosystem, prodrugs typically comprise drug modules, modification modules, and response modules. The response modules are crucial for facilitating the accurate conversion of prodrugs at specific sites. In this work, we opted for differentiated disulfide bonds as response modules to construct docetaxel (DTX) prodrug nanoassemblies. Interestingly, a subtle change in response modules leads to a "U-shaped" conversion rate of DTX-prodrug nanoassemblies. Prodrug nanoassemblies with the least carbon numbers between the disulfide bond and ester bond (PDONα) offered the fastest conversion rate, resulting in powerful treatment outcomes with some unavoidable toxic effects. PDONß, with more carbon numbers, possessed a slow conversion rate and poor antitumor efficacy but good tolerance. With most carbon numbers in PDONγ, it demonstrated a moderate conversion rate and antitumor effect but induced a risk of lethality. Our study explored the function of response modules and highlighted their importance in prodrug development.
Asunto(s)
Antineoplásicos , Nanopartículas , Profármacos , Docetaxel , Profármacos/química , Línea Celular Tumoral , Disulfuros/química , Carbono , Antineoplásicos/farmacología , Nanopartículas/químicaRESUMEN
Trimethylamine N-oxide (TMAO) is widely present in marine animals. However, the characteristics of TMAO content in different classes of marine animals are insufficiently understood. In this study, the TMAO content in 79 marine animals (48 species, 7 classes) collected in the coastal and offshore areas of China during year 2019-2022 was analysed. The results showed that the TMAO content of the total samples varied from 0 to 139.19 mmol kg-1. The TMAO content in the classes Bivalvia, Gastropoda, Polychaeta and Holothuroidea varied from 0.06 ± 0.09 to 0.38 ± 0.63 mmol kg-1, but it varied from 30.20 ± 24.20 to 75.90 ± 38.59 mmol kg-1 in the classes Crustacea, Cephalopoda, and Osteichthyes. The TMAO content in the latter 3 classes was 2-3 orders of magnitude higher than that of the former 4 classes. It was inferred that the significant difference was related to the food sources or physiological metabolic mechanisms of different classes.
Asunto(s)
Peces , Metilaminas , Animales , Metilaminas/análisis , Metilaminas/metabolismo , Peces/metabolismo , ChinaRESUMEN
Solar-driven atmospheric water harvesting technology has the advantage of not being limited by geography and has great potential in solving the freshwater crisis. Here, we first propose a purely natural and degradable superhydrophilic composite macroporous hygroscopic material by applying guar gum (GG) to atmospheric water harvesting. The material consists of GG-cellulose nanofibers (CNFs) as a porous substrate material, limiting the hygroscopic factor lithium chloride (LiCl) in its three-dimensional (3D) network structure, and carbon nanotubes (CNTs) play a photothermal conversion role. The composite material has a high light absorption rate of more than 95%, and the macroporous structure (20-60 µm) allows for rapid adsorption/desorption kinetics. At 35 °C and 90% relative humidity (RH), the moisture absorption capacity is as high as 1.94 g/g. Under 100 mW/cm2 irradiation, the absorbed water is almost completely desorbed within 3 h, and the water harvesting performance is stable in 10 cycles. Moreover, liquid water was successfully collected in an actual outdoor experiment. This work demonstrates the great potential of biomass materials in the field of atmospheric water collection and provides more opportunities for various energy and sustainable applications in the future.
RESUMEN
Superhydrophobic (SH) surfaces have progressed rapidly in fundamental research over the past 20 years, but their practical applications lag far behind. In this perspective, we first present the findings of a survey on the current state of SH surfaces including fundamental research, patenting, and commercialization. On the basis of the survey and our experience, this perspective explores the challenges and strategies for commercialization and widespread practical applications of SH surfaces. The comprehensive performances, preparation methods, and application scenarios of SH surfaces are the major constraints. These challenges should be addressed simultaneously, and the actionable strategies are provided. We then highlight the standard test methods of the comprehensive performances including mechanical stability, impalement resistance, and weather resistance. Last, the prospects of SH surfaces in the future are discussed. We anticipate that SH surfaces may be widely commercialized and used in practical applications around the year 2035 through combination of the suggested strategies and input from both academia and industry.