High-nuclearity Luminescent Lanthanide Nanocages for Tumor Drug Delivery.

There is an unmet need for easy-to-visualize drug carriers that can deliver therapeutic cargoes deep into solid tumors. Herein, we report the preparation of ultrasmall luminescent imine-based lanthanide nanocages, Eu60 and Tb60 (collectively Ln60 ), designed to encapsulate anticancer chemotherapeutics for tumor therapy. The as-prepared nanocages possess large cavities suitable for the encapsulation of doxorubicin (DOX), yielding DOX@Ln60 nanocages with diameters around 5 nm. DOX@Ln60 are efficiently internalized by breast cancer cells, allowing the cells to be visualized via the intrinsic luminescent property of Ln(III). Once internalized, the acidic intracellular microenvironment promotes imine bond cleavage and the release of the loaded DOX. DOX@Ln60 inhibits DNA replication and triggers tumor cell apoptosis. In a murine triple negative breast cancer (TNBC) model, DOX@Ln60 was found to inhibit tumor growth with negligible side effects on normal tissues. It proved more effective than various controls, including DOX and Ln60 . The present nanocages thus point the way to the development of precise nanomedicines for tumor imaging and therapy.

In-memory analog solution of compressed sensing recovery in one step.

Modern analog computing, by gaining momentum from nonvolatile resistive memory devices, deals with matrix computations. In-memory analog computing has been demonstrated for solving some basic but ordinary matrix problems in one step. Among the more complicated matrix problems, compressed sensing (CS) is a prominent example, whose recovery algorithms feature high-order matrix operations and hardware-unfriendly nonlinear functions. In light of the local competitive algorithm (LCA), here, we present a closed-loop, continuous-time resistive memory circuit for solving CS recovery in one step. Recovery of one-dimensional (1D) sparse signal and 2D compressive images has been experimentally demonstrated, showing elapsed times around few microseconds and normalized mean squared errors of 10-2. The LCA circuit is one or two orders of magnitude faster than conventional digital approaches. It also substantially outperforms other (electronic or exotically photonic) analog CS recovery methods in terms of speed, energy, and fidelity, thus representing a highly promising technology for real-time CS applications.

SiamPKHT: Hyperspectral Siamese Tracking Based on Pyramid Shuffle Attention and Knowledge Distillation.

Hyperspectral images provide a wealth of spectral and spatial information, offering significant advantages for the purpose of tracking objects. However, Siamese trackers are unable to fully exploit spectral features due to the limited number of hyperspectral videos. The high-dimensional nature of hyperspectral images complicates the model training process. In order to address the aforementioned issues, this article proposes a hyperspectral object tracking (HOT) algorithm callled SiamPKHT, which leverages the SiamCAR model by incorporating pyramid shuffle attention (PSA) and knowledge distillation (KD). First, the PSA module employs pyramid convolutions to extract multiscale features. In addition, shuffle attention is adopted to capture relationships between different channels and spatial positions, thereby obtaining good features with a stronger classification performance. Second, KD is introduced under the guidance of a pre-trained RGB tracking model, which deals with the problem of overfitting in HOT. Experiments using HOT2022 data indicate that the designed SiamPKHT achieves better performance compared to the baseline method (SiamCAR) and other state-of-the-art HOT algorithms. It also achieves real-time requirements at 43 frames per second.

Genome assembly and annotation of the Brown-Spotted Pit viper Protobothrops mucrosquamatus.

The Brown-Spotted Pit viper (Protobothrops mucrosquamatus), also known as the Chinese habu, is a widespread and highly venomous snake distributed from Northeastern India to Eastern China. Genomics research can contribute to our understanding of venom components and natural selection in vipers. Here, we collected, sequenced and assembled the genome of a male P. mucrosquamatus individual from China. We generated a highly continuous reference genome, with a length of 1.53 Gb and 41.18% of repeat elements content. Using this genome, we identified 24,799 genes, 97.97% of which could be annotated. We verified the validity of our genome assembly and annotation process by generating a phylogenetic tree based on the nuclear genome single-copy genes of six other reptile species. The results of our research will contribute to future studies on Protobothrops biology and the genetic basis of snake venom.

The genome assembly and annotation of the Chinese cobra, Naja atra.

In China, 65 types of venomous snakes exist, with the Chinese Cobra Naja atra being prominent and a major cause of snakebites in humans. Furthermore, N. atra is a protected animal in some areas, as it has been listed as vulnerable by the International Union for Conservation of Nature. Recently, due to the medical value of snake venoms, venomics has experienced growing research interest. In particular, genomic resources are crucial for understanding the molecular mechanisms of venom production. Here, we report a highly continuous genome assembly of N. atra, based on a snake sample from Huangshan, Anhui, China. The size of this genome is 1.67 Gb, while its repeat content constitutes 37.8% of the genome. A total of 26,432 functional genes were annotated. This data provides an essential resource for studying venom production in N. atra. It may also provide guidance for the protection of this species.

The genome assembly and annotation of the Oriental rat snake Ptyas mucosa.

The Oriental rat snake Ptyas mucosa is a common non-venomous snake of the colubrid family, spanning most of South and Southeast Asia. P. mucosa is widely bred for its uses in traditional medicine, scientific research, and handicrafts. Therefore, genome resources of P. mucosa could play an important role in the efficacy of traditional medicine and the analysis of the living environment of this species. Here, we present a highly continuous P. mucosa genome with a size of 1.74 Gb. Its scaffold N50 length is 9.57 Mb, and the maximal scaffold length is 78.3 Mb. Its CG content is 37.9%, and its gene integrity reaches 86.6%. Assembled using long-reads, the total length of the repeat sequences in the genome reaches 735 Mb, and its repeat content is 42.19%. Finally, 24,869 functional genes were annotated in this genome. This study may assist in understanding P. mucosa and supporting medicinal research.

Nitric oxide-dependent immunosuppressive function of thymus-derived mesenchymal stromal/stem cells.

BACKGROUND: The thymus is required for T cell development and the formation of the adaptive immunity. Stromal cells, which include thymic epithelial cells (TECs) and mesenchymal stromal cells (MSCs), are essential for thymic function. However, the immunomodulatory function of thymus-derived MSCs (T-MSCs) has not been fully explored. METHODS: MSCs were isolated from mouse thymus and their general characteristics including surface markers and multi-differentiation potential were characterized. The immunomodulatory function of T-MSCs stimulated by IFN-γ and TNF-α was evaluated in vitro and in vivo. Furthermore, the spatial distribution of MSCs in the thymus was interrogated by using tdTomato-flox mice corssed to various MSC lineage Cre recombinase lines. RESULTS: A subset of T-MSCs express Nestin, and are mainly distributed in the thymic medulla region and cortical-medulla junction, but not in the capsule. The Nestin-positive T-MSCs exhibit typical immunophenotypic characteristics and differentiation potential. Additionally, when stimulated with IFN-γ and TNF-α, they can inhibit activated T lymphocytes as efficiently as BM-MSCs, and this function is dependent on the production of nitric oxide (NO). Additionally, the T-MSCs exhibit a remarkable therapeutic efficacy in acute liver injury and inflammatory bowel disease (IBD). CONCLUSIONS: Nestin-positive MSCs are mainly distributed in medulla and cortical-medulla junction in thymus and possess immunosuppressive ability upon stimulation by inflammatory cytokines. The findings have implications in understanding the physiological function of MSCs in thymus.

Genome assembly and annotation of the Sharp-nosed Pit Viper Deinagkistrodon acutus based on next-generation sequencing data.

The study of the currently known >3,000 species of snakes can provide valuable insights into the evolution of their genomes. Deinagkistrodon acutus, also known as Sharp-nosed Pit Viper, one hundred-pacer viper or five-pacer viper, is a venomous snake with significant economic, medicinal and scientific importance. Widely distributed in southeastern China and South-East Asia, D. acutus has been primarily studied for its venom. Here, we employed next-generation sequencing to assemble and annotate a highly continuous genome of D. acutus. The genome size is 1.46 Gb; its scaffold N50 length is 6.21 Mb, the repeat content is 42.81%, and 24,402 functional genes were annotated. This study helps to further understand and utilize D. acutus and its venom at the genetic level.

Characterization of the Heat Shock Transcription Factor Family in Medicago sativa L. and Its Potential Roles in Response to Abiotic Stresses.

Heat shock transcription factors (HSFs) are important regulatory factors in plant stress responses to various biotic and abiotic stresses and play important roles in growth and development. The HSF gene family has been systematically identified and analyzed in many plants but it is not in the tetraploid alfalfa genome. We detected 104 HSF genes (MsHSFs) in the tetraploid alfalfa genome ("Xinjiangdaye" reference genome) and classified them into three subgroups: 68 in HSFA, 35 in HSFB and 1 in HSFC subgroups. Basic bioinformatics analysis, including genome location, protein sequence length, protein molecular weight and conserved motif identification, was conducted. Gene expression analysis revealed tissue-specific expression for 13 MsHSFs and tissue-wide expression for 28 MsHSFs. Based on transcriptomic data analysis, 21, 11 and 27 MsHSFs responded to drought stress, cold stress and salt stress, respectively, with seven responding to all three. According to RT-PCR, MsHSF27/33 expression gradually increased with cold, salt and drought stress condition duration; MsHSF6 expression increased over time under salt and drought stress conditions but decreased under cold stress. Our results provide key information for further functional analysis of MsHSFs and for genetic improvement of stress resistance in alfalfa.

IL4I1-catalyzed tryptophan metabolites mediate the anti-inflammatory function of cytokine-primed human muscle stem cells.

Muscle stem cells (MuSCs) have been demonstrated to exert impressive therapeutic efficacy in disease settings through orchestrating inflammatory microenvironments. Nevertheless, the mechanisms underlying the immunoregulatory property of MuSCs remain largely uncharacterized. Here, we showed that interleukin-4-induced-1 (IL4I1), an essential enzyme that catalyzes indole metabolism in humans, was highly expressed in human MuSCs exposed to IFN-γ and TNF-α. Functionally, the MuSCs were found to inhibit the infiltration of neutrophils into sites of inflammation in a IL4I1-dependent manner and thus ameliorate acute lung injury in mice. Mechanistically, the indole metabolites, including indole-3-pyruvic acid (I3P) and indole-3-aldehyde (I3A), produced by IL4I1, acted as ligands to activate aryl hydrocarbon receptor (AHR), leading to augmented expression of TNF-stimulated gene 6 (TSG-6) in inflammatory cytokine-primed MuSCs. Furthermore, I3P administration alone suppressed neutrophil infiltration into damaged lungs. I3P could also reduce the level of reactive oxygen species in neutrophils. Therefore, our study has uncovered a novel mechanism by which MuSCs acquire their immunoregulatory property and may help to develop or optimize MuSC-based therapies for inflammatory diseases.

Steerable artificial magnetic bacteria with target delivery ability of calcium carbonate for soil improvement.

The microbial-induced carbonate precipitation (MICP) has acquired significant attention due to its immense potential in sustainable engineering applications, particularly in soil improvement. However, the precise control of microbial-induced calcium carbonate precipitation remains a formidable challenge in engineering practices, owing to the uncertain movement paths of bacteria and the nonuniform distribution of soil pores. Taking inspiration from targeted therapy in medicine, this paper presents novel research on the development and validation of magnetically responsive bacteria. These bacteria demonstrate the ability to target calcium carbonate precipitation in a microfluidic chip, thereby promoting an environmentally friendly and ecologically sustainable biomineralization paradigm. The study focuses on investigating the migration of magnetite nanoparticles (MNPs) in aqueous solutions and enhancing the stability of MNP culture liquids. A specially designed microfluidic chip is utilized to simulate natural sand particles and their pores, while an external magnetic field is applied to precisely control the movement path of the artificial magnetic bacteria, enabling targeted precipitation of calcium carbonate at the micron-scale. Verification of the engineered artificial magnetic bacteria and their ability to induce calcium carbonate precipitation is conducted through SEM-EDS analysis, microfluidic chip observations, and the application of the K-means algorithm and ImageJ software to analyze calcium carbonate formation. The influence of the concentration of magnetic nanoparticles on the calcium carbonate production rate was also studied. The results confirm the potential of the artificial magnetic bacteria for future engineering applications. KEY POINTS: • Sporosarcina pasteurii is first time successfully engineered into artificial magnetic bacteria. • The artificial magnetic bacteria show excellent performance of targeted transportation and directional deposition of CaCO3 in microfluidic chip. • The emergence of artificial magnetic bacteria promotes paradigm shift of next generation environmentally friendly biomineralization.

Whole exome sequencing reveals novel variants associated with diminished ovarian reserve in young women.

Background: Diminished ovarian reserve is one of the most important causes of female infertility. In the etiology study of DOR, besides age, it is known that chromosomal abnormality, radiotherapy, chemotherapy and ovarian surgery can result in DOR. For young women without obvious risk factors, gene mutation should be considered as a possible cause. However, the specific molecular mechanism of DOR has not been fully elucidated. Methods: In order to explore the pathogenic variants related to DOR, twenty young women under 35 years old affected by DOR without definite factors damaging ovarian reserve were recruited as the research subjects, and five women with normal ovarian reserve were recruited as the control group. Whole exome sequencing was applied as the genomics research tool. Results: As a result, we obtained a set of mutated genes that may be related to DOR, where the missense variant on GPR84 was selected for further study. It is found that GPR84Y370H variant promotes the expression of proinflammatory cytokines (TNF-α, IL12B, IL-1ß) and chemokines (CCL2, CCL5), as well as the activation of NF-κB signaling pathway. Conclusion: In conclusion, GPR84Y370H variant was identified though analysis for WES results of 20 DOR patients. The deleterious variant of GPR84 could be the potential molecular mechanism of non-age-related pathological DOR through its role in promoting inflammation. The findings of this study can be used as a preliminary research basis for the development of early molecular diagnosis and treatment target selection of DOR.

COMMD3-Mediated Endosomal Trafficking of HER2 Inhibits the Progression of Ovarian Carcinoma.

The dysregulated endocytic traffic of oncogenic receptors, such as the EGFR family especially HER2, contributes to the uncontrolled activation of the downstream oncogenic signaling and progression of various carcinomas, including 90% of ovarian carcinoma. However, the key regulators in the intracellular trafficking of HER2 and their impacts for cancer progression remain largely unknown. In this study, through a genome-wide CRISPR/Cas9 screening for key genes affecting the peritoneal disseminated metastasis of ovarian carcinoma, we identified a member of COMMD family, that is, COMMD3, as a key regulator in the endosomal trafficking of HER2. In the patients with high-grade serous ovarian carcinoma (HGSOC), the expression of COMMD3 is dramatically decreased in the peritoneal disseminated ovarian carcinoma cells comparing with that in the primary ovarian carcinoma cells. COMMD3 greatly inhibits the proliferation, migration, and epithelial-mesenchymal transition (EMT) of HGSOC cells, and dramatically suppresses the tumor growth, the formation of malignant ascites, and the peritoneal dissemination of cancer cells in the orthotopic murine model of HGSOC. Further transcriptome analysis reveals that silencing COMMD3 boosts the activation of HER2 downstream signaling. As a component in the Retriever-associated COMMD/CCDC22/CCDC93 complex responsible for the recognition and recycling of membrane receptors, COMMD3 physically interacts with HER2 for directing it to the slow recycling pathway, leading to the attenuated downstream tumor-promoting signaling. IMPLICATIONS: Collectively, this study reveals a novel HER2 inactivation mechanism with a high value for the clinic diagnosis of new ovarian carcinoma types and the design of new therapeutic strategy.

Molecular Dynamics Simulation of Entangled Melts at High Rates: Identifying Entanglement Lockup Mechanism Leading to True Strain Hardening.

In the present work, molecular dynamics simulations are carried out based on the bead-spring model to indicate how the entanglement lockup manifests in the late stage of fast Rouse-Weissnberg number (WiR >>1) uniaxial melt stretching of entangled polymer melts. At high strains, distinct features show up to reveal the emergence of an increasingly tightened entanglement network. Chain tension can build up, peaking at the middle of the chain, to a level for chain scission, through accumulated interchain interactions, as if there is a tug-of-war ongoing for each load-bearing chain. Thanks to the interchain uncrossability, network junctions form by the pairing of two or more hairpins. It is hypothesized that the interchain entanglement at junctions can lockup through prevailing twist-like interchain couplings as long as WiR > 9. In this limit, a significant fraction of chains act like cyclic chains to form a network held by interchain uncrossability, and appreciable chain tension emerges.

Nanoconfined Crystallization in Poly(lactic acid) (PLA) and Poly(ethylene terephthalate) (PET) Induced by Various Forms of Premelt-Deformation.

The processing-structure-property relationship using poly(lactic acid) (PLA) and poly(ethylene terephthalate) (PET) is explored. Specifically, both pre-extension and preshear of amorphous PLA and PET above their glass transition temperatures Tg , carried out in the affine deformation limit, can induce a specific type of cold crystallization during annealing, i.e., nanoconfined crystallization (NCC) where crystal sizes are limited to a nanoscopic scale in all dimensions so as to render the processed PLA and PET optically transparent. The new polymer structure after premelt deformation can show considerably enhanced mechanical properties. For example, premelt stretching produces geometric condensation of the chain network. This structural alternation can profoundly change the mechanical characteristics, e.g., turning brittle PLA ductile. In contrast, after preshear of amorphous PLA above Tg , the NCC containing PLA remains brittle, showing the importance to have geometric condensation from processing. Both AFM imaging and SAXS measurements are performed to verify that premelt deformation of PLA and PET indeed results in NCC from annealing that permits the strain-induced cold crystallization to take place on the length scale of the mesh size of the deformed chain network.

UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis.

Up-frameshift 1 (UPF1), as the most critical factor in nonsense-mediated messenger RNA (mRNA) decay (NMD), regulates tumor-associated molecular pathways in many cancers. However, the role of UPF1 in lung adenocarcinoma (LUAD) amino acid metabolism remains largely unknown. In this study, we found that UPF1 was significantly correlated with a portion of amino acid metabolic pathways in LUAD by integrating bioinformatics and metabolomics. We further confirmed that UPF1 knockdown inhibited activating transcription factor 4 (ATF4) and Ser51 phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), the core proteins in amino acid metabolism reprogramming. In addition, UPF1 promotes cell proliferation by increasing the amino-acid levels of LUAD cells, which depends on the function of ATF4. Clinically, UPF1 mRNA expression is abnormal in LUAD tissues, and higher expression of UPF1 and ATF4 was significantly correlated with poor overall survival (OS) in LUAD patients. Our findings reveal that UPF1 is a potential regulator of tumor-associated amino acid metabolism and may be a therapeutic target for LUAD.

Spatiotemporal Variations of Carbon Emissions and Their Driving Factors in the Yellow River Basin.

The Yellow River Basin (YRB) is a significant area of economic development and ecological protection in China. Scientifically clarifying the spatiotemporal patterns of carbon emissions and their driving factors is of great significance. Using the methods of spatial autocorrelation analysis, hot-spot analysis, and a geodetector, the analysis framework of spatiotemporal differentiation and the driving factors of carbon emissions in the YRB was constructed in this paper from three aspects: natural environment, social economy, and regional policy. Three main results were found: (1) The carbon emissions in the YRB increased gradually from 2000 to 2020, and the growth rates of carbon emissions in the different river reaches were upper reaches > middle reaches > lower reaches. (2) Carbon emissions have an obvious spatial clustering character from 2000-2020, when hot spots were concentrated in the transition area from the Inner Mongolia Plateau to the Loess Plateau. The cold spots of carbon emissions tended to be concentrated in the junction area of Qinghai, Gansu, and Shaanxi. (3) From 2000 to 2020, the driving factors of spatial differentiation of carbon emissions in the YRB and its different reaches tended to be diversified, so the impacts of socioeconomic factors increased, while the impacts of natural environmental factors decreased. The influence of the interactions of each driving factor showed double factor enhancement and nonlinear enhancement. This study will provide a scientific reference for green and low-carbon development, emphasizing the need to pay more attention to environmental protection, develop the green economy vigorously, and promote the economic cycle, so as to achieve green development and reduce carbon emissions.

Advances in chitosan-based wound dressings: Modifications, fabrications, applications and prospects.

In the field of medical research, the development of safe and effective wound dressings is a continuous goal. Chitosan (CS) is highly sought after because of its unique biocompatibility, biodegradability, antibacterial, and healing-promoting properties. The CS molecule has a significant number of active amino and hydroxyl groups; thus, making substitutions and creating derivatives with varied biochemical properties are relatively straightforward processes. This review addresses the range of functions performed by CS and its derivatives in wound care, such as haemostasis, antibacterial, antioxidant, and wound healing. Furthermore, it summarises the various types of CS-based dressings, their performance features and applications. Finally, the future directions of CS-based dressings are proposed.

Conversion of coal into N-doped porous carbon for high-performance SO2 adsorption.

The large-scale burning of coal has led to increasingly serious SO2 environmental pollution problems. The SO2 adsorption and removal technology based on porous carbons has the advantages of less water consumption, no secondary pollution, recycling of pollutants, and renewable utilization of adsorbents, in contrast to the wet desulfurization process. In this work, we developed a series of N-doped coal-based porous carbons (NCPCs) by calcining a mixture of anthracite, MgO, KOH and carbamide at 800 °C. Among them, the NCPC-2 sample achieves a high N-doped amount of 1.29 at%, and suitable pores with a specific surface area of 1370 m2 g-1 and pore volume of 0.62 cm3 g-1. This N-doped porous carbon exhibits excellent SO2 adsorption capacity as high as 115 mg g-1, which is 3.47 times that of commercial coal-based activated carbon, and 2 times that of NCPC-0 without N-doping. Theoretical calculations show that the active adsorption sites of SO2 are located at the edges and gaps of carbon materials, and surface N doping enhances the adsorption affinity of carbon materials for SO2. In addition, the NCPCs prepared in this work are rich in raw materials and cheap, which meets the needs of industrial production, having excellent SO2 adsorption capacity.

Ti(IV)-MOF with Specific Facet-Ag Nanoparticle Composites for Enhancing the Photocatalytic Activity and Selectivity of CO2 Reduction.

Metal nanoparticles deposited in the photocatalyst not only can serve as a cocatalyst but also can act as a light harvester to extend the light absorption, resulting from the surface plasmon resonance (SPR). In this study, we deposited silver nanoparticles (Ag NPs) onto NH2-MIL-125(Ti) with exposed specific facets and achieved effectively improved activity and selectivity for photocatalytic CO2 reduction. Loading Ag NPs on the exposed {111} facets of NH2-MIL-125(Ti) generates a highly effective composite catalyst for the photoreduction of CO2, resulting in the maximal CO and CH4 yields of 26.7 and 63.3 µmol g-1 h-1, respectively, which are 2.2- and 16.2-fold those of the NH2-MIL-125(Ti) exposing {111} facets, and a CH4 selectivity of 90.5%. Incorporation of Ag NPs not only optimizes the electronic structure of the photocatalyst but also suppresses the recombination of photogenerated electron-hole pairs. This study provides an exciting example for creating and understanding metal-decorated facet-dependent effects on metal-organic frameworks (MOFs) for photocatalytic reactions.