SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids.

SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages' role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.

Microneedle Patch for Transdermal Sequential Delivery of KGF-2 and aFGF to Enhance Burn Wound Therapy.

Severe burn wounds usually destroy key cells' functions of the skin resulting in delayed re-epithelization and wound regeneration. Promoting key cells' activities is crucial for burn wound repair. It is well known that keratinocyte growth factor-2 (KGF-2) participates in the proliferation and morphogenesis of epithelial cells while acidic fibroblast growth factor (aFGF) is a key mediator for fibroblast and endothelial cell growth and differentiation. However, thick eschar and the harsh environment of a burn wound often decrease the delivery efficiency of fibroblast growth factor (FGF) to the wound site. Therefore, herein a novel microneedle patch for sequential transdermal delivery of KGF-2 and aFGF is fabricated to enhance burn wound therapy. aFGF is first loaded in the nanoparticle (NPaFGF) and then encapsulated NPaFGF with KGF-2 in the microneedle patch (KGF-2/NPaFGF@MN). The result shows that KGF-2/NPaFGF@MN can successfully get across the eschar and sequentially release KGF-2 and aFGF. Additional data demonstrated that KGF-2/NPaFGF@MN achieved a quicker wound closure rate with reduced necrotic tissues, faster re-epithelialization, enhanced collagen deposition, and increased neo-vascularization. Further evidence suggests that improved wound healing is regulated by significantly elevated expressions of hypoxia-inducible factor-1 alpha (HIF-1ɑ) and heat shock protein 90 (Hsp90) in burn wounds. All these data proved that KGF-2/NPaFGF@MN is an effective treatment for wound healing of burns.

Spatiotemporal Utilization of Latent Heat in Erythritol-based Phase Change Materials as Solar Thermal Fuels.

Solar thermal fuels (STFs) have been particularly concerned as sustainable future energy due to their impressive ability to store solar energy in chemical bonds and controllably release thermal energy. However, currently studied STFs mainly focus on molecule-based materials with high photochemical activity, toxicity, and compromised features, which greatly restricts their applications in practical scenarios of solar energy utilization. Herein, we present a novel erythritol-based composite phase change material (PCM) as a new type of STFs with an outstanding capability to store solar energy as latent heat in its stable supercooling state and release thermal energy as needed. This composite PCM with stored thermal energy can be maintained stably at room temperature and subsequently release latent heat as high as 224.9 J/g during the crystallization process triggered by thermal stimuli. Remarkably, solar energy can be converted into latent heat stored in the composite PCM over months. Through mechanical stimulations, the released latent heat can increase the temperature of the composite up to 91 °C. This work presents a new concept of using spatiotemporal storage and release of latent heat in PCMs for solar energy utilization, making it a potential candidate as STFs for developing future clean energy techniques.

Fluorescence detecting glycopeptide antibiotics via a dynamic molecular switch.

BACKGROUND: Glycopeptide antibiotics (GPAs) represented by vancomycin (VAN) are clinically used as a first-line treatment for serious infections caused by Gram-positive pathogens. The use and dosing methods of GPAs are rigorously managed for safety considerations, which calls for fast and accurate quantification approaches. RESULT: A new sort of fluorescent probes for GPAs has been proposed, each of which was integrated by a fluorescein-based reporter and a GPAs' recognition peptide D-alanyl-D-alanine (D-Ala-D-Ala). These probes work as dynamic molecular switches, which mainly exist as non-fluorescent spirolactam forms in the absence of GPAs. GPAs binding with the dipeptide regulates the dynamic balance between fluorescence OFF lactam form and fluorescence ON ring-opened form, rendering these probes capable of GPAs detecting. The most promising one P1 exhibits excellent sensitivity and selectivity towards GPAs detection. SIGNIFICANCE: Different to previous developments, P1 consists of a single fluorophore without the need of a fluorescence-quenching group or a secondary dye, which is the smallest fluorescent probe for GPAs up to now. P1 realizes direct VAN quantification from complex biological samples including real serums, dispensing with additional drug extraction. More interestingly, both P1 and P6 can distinguish GPAs with different peptide backbones, which has not been achieved previously.

PD-L1 regulates inflammatory programs of macrophages from human pluripotent stem cells.

Programmed death ligand 1 (PD-L1) serves as a pivotal immune checkpoint in both the innate and adaptive immune systems. PD-L1 is expressed in macrophages in response to IFNγ. We examined whether PD-L1 might regulate macrophage development. We established PD-L1 KO (CD274 -/- ) human pluripotent stem cells and differentiated them into macrophages and observed a 60% reduction in CD11B+CD45+ macrophages in CD274 -/- ; this was orthogonally verified, with the PD-L1 inhibitor BMS-1166 reducing macrophages to the same fold. Single-cell RNA sequencing further confirmed the down-regulation of the macrophage-defining transcription factors SPI1 and MAFB Furthermore, CD274 -/- macrophages reduced the level of inflammatory signals such as NF-κB and TNF, and chemokine secretion of the CXCL and CCL families. Anti-inflammatory TGF-ß was up-regulated. Finally, we identified that CD274 -/- macrophages significantly down-regulated interferon-stimulated genes despite the presence of IFNγ in the differentiation media. These data suggest that PD-L1 regulates inflammatory programs of macrophages from human pluripotent stem cells.

City-level population projection for China under different pathways from 2010 to 2100.

Cities play a fundamental role in policy decision-making processes, necessitating the availability of city-level population projections to better understand future population dynamics and facilitate research across various domains, including urban planning, shrinking cities, GHG emission projections, GDP projections, disaster risk mitigation, and public health risk assessment. However, the current absence of city-level population projections for China is a significant gap in knowledge. Moreover, aggregating grid-level projections to the city level introduces substantial errors of approximately 30%, leading to discrepancies with actual population trends. The unique circumstances of China, characterized by comprehensive poverty reduction, compulsory education policies, and carbon neutrality goals, render scenarios like SSP4(Shared Socioeconomic Pathways) and SSP5 less applicable. To address the aforementioned limitations, this study made three key enhancements, which significantly refines and augments our previous investigation. Firstly, we refined the model, incorporating granular demographic data at the city level. Secondly, we redesigned the migration module to consider both regional and city-level population attractiveness. Lastly, we explored diverse fertility and migration scenarios.

HPV16 infection promotes the malignant transformation of the esophagus and progression of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) may be correlated with HPV infection, and the mechanism underlying the ESCC formation induced by HPV16 infection remains elusive. Here, we overexpressed HPV16 E6 and E7 and coordinated the overexpression of these two genes in EPC2 and ESCC cells. We found that E7 and coordinated expression of E6 and E7 promoted the proliferation of EPC2 cells, and upregulation of shh was responsible for cell proliferation since the use of vismodegib led to the failure of organoid formation. Meanwhile, overexpression of E6 and E7 in ESCC cells promoted cell proliferation, migration, and invasion in vitro. Importantly, E6 and E7 coordinately increased the capability of tumor growth in nude mice, while vismodegib slowed the growth of tumors in NCG mice. Moreover, a series of genes and proteins changed in cell lines after overexpression of the E6 and E7 genes, the potential biological processes and pathways were systematically analyzed using a bioinformatics assay. Together, these findings suggest that the activation of the hedgehog pathway induced by HPV16 infection may initially transform basal cells in the esophagus and promote following malignant processes in ESCC cells. The application of hedgehog inhibitors may represent a therapeutic avenue for ESCC treatment.

Targeting the SOX2/CDP protein complex with a peptide suppresses the malignant progression of esophageal squamous cell carcinoma.

Emerging evidence indicates that SOX2 is an oncogene for esophageal squamous cell carcinoma (ESCC). However, direct targeting of SOX2 is not feasible given that this transcription factor plays important roles in the maintenance of tissues such as the brain. Here, we identified CDP (Homeobox protein cut-like 1 or CASP) as a unique SOX2 binding partner enriched in ESCC with Duolink proximity ligation assay, bimolecular fluorescence complementation (BiFc) and immunoprecipitation. We then screened a peptide aptamer library using BiFc and immunoprecipitation and identified several peptide aptamers, including P58, that blocked the CDP/SOX2 interaction, leading to the inhibition of ESCC progress in vitro and in vivo. Upon administration, synthetic peptide P58, containing the YGRKKRRQRRR cell-penetrating peptide and the fluorophore TAMRA, also blocked the growth and metastasis of ESCC in both mice and zebrafish. Therefore, targeting the SOX2 binding partner CDP with peptide P58 offers an alternative avenue to treat ESCC with increased SOX2 levels.

Pressure-induced disorder and nanosizing inhibits superconductivity in In2Te3.

The generation of disorder often gives rise to profound and irreversible physical phenomena. Here, we explore the influence of disorder on the superconducting properties of In2Te3through comprehensive high-pressure investigations. Building upon previous findings, we investigated the progressive suppression of superconductivity in In2Te3during the depressurization process: the increased disorder that ultimately leads to the complete disappearance of the superconducting state. Simultaneously, our high-pressure x-ray diffraction analysis reveals an irreversible structural phase transition. Furthermore, microstructure analysis using transmission electron microscopy clearly demonstrates both grain refinement and a substantial enhancement of disorder. These findings not only provide valuable insights into the mechanism by which disorder suppresses superconductivity, but also offer guidance for future advancements in the fabrication of atmospheric-pressure superconductors.

Mitochondria-ER contact mediated by MFN2-SERCA2 interaction supports CD8+ T cell metabolic fitness and function in tumors.

Metabolic fitness of T cells is essential for their vitality, which is largely dependent on the behavior of the mitochondria. The nature of mitochondrial behavior in tumor-infiltrating T cells remains poorly understood. In this study, we show that mitofusin-2 (MFN2) expression is positively correlated with the prognosis of multiple cancers. Genetic ablation of Mfn2 in CD8+ T cells dampens mitochondrial metabolism and function and promotes tumor progression. In tumor-infiltrating CD8+ T cells, MFN2 enhances mitochondria-endoplasmic reticulum (ER) contact by interacting with ER-embedded Ca2+-ATPase SERCA2, facilitating the mitochondrial Ca2+ influx required for efficient mitochondrial metabolism. MFN2 stimulates the ER Ca2+ retrieval activity of SERCA2, thereby preventing excessive mitochondrial Ca2+ accumulation and apoptosis. Elevating mitochondria-ER contact by increasing MFN2 in CD8+ T cells improves the efficacy of cancer immunotherapy. Thus, we reveal a tethering-and-buffering mechanism of organelle cross-talk that regulates the metabolic fitness of tumor-infiltrating CD8+ T cells and highlights the therapeutic potential of enhancing MFN2 expression to optimize T cell function.

De novo creation of popcorn-like fragrant foxtail millet.

Popcorn aroma is a valuable flavor quality in cereals, but, despite more than ten thousand years of millet domestication, millet lacks traits that confer this desirable aroma. Here, we developed a popcorn-scented millet, providing an important resource for future breeding.

Regulating Magnetic Relaxations of Cyano-Bridged {DyIII MoV } Systems by Tuning the N-Sites in ß-Diketone Ligands.

Cyano-bridged 4d-4f molecular nanomagnets have re-called increasing research interests in molecular magnetism since they offer more possibilities in achieving novel nanomagnets with versatile structures and magnetic interactions. In this work, four ß-diketone ligands bearing different substitution N-sites were designed and synthesized, namely 1-(2-pyridyl)-3-(3-pyridyl)-1,3-propanedione (HL1 ), 1,3-Bis (3-pyridyl)-1,3-propanedione (HL2 ), 1-(4-pyridyl)-3-(3-pyridyl)-1,3-propanedione (HL3 ), and 1,3-Bis (4-pyridyl)-1,3-propanedione (HL4 ), to tune the magnetic relaxation behaviors of cyano-bridged {DyIII MoV } systems. By reacting with DyCl3 ⋅ 6H2 O and K4 Mo(CN)8 ⋅ 2H2 O, four cyano-bridged complexes, namely {[Dy[MoV (CN)8 ](HL1 )2 (H2 O)3 ]} ⋅ 6H2 O (1), {[Dy[MoV (CN)8 ](HL2 )(H2 O)3 (CH3 OH)]}2 ⋅ 2CH3 OH ⋅ 3H2 O (2), {[Dy[MoV (CN)8 ](HL3 )(H2 O)2 (CH3 OH)] ⋅ H2 O}n (3), and {[Dy[MoV (CN)8 ](HL4 )2 (H2 O)3 ]} ⋅ 2H2 O⋅CH3 OH (4) were obtained. Structural analyses revealed that 1 and 4 are binuclear complexes, 2 has a tetragonal structure, and 3 exhibits a stair-like polymer chain structure. The DyIII ions in all complexes have eight-coordinated configurations with the coordination spheres DyO7 N1 for 1 and 4, DyO6 N2 for 2, and DyO5 N3 for 3. Magnetic measurements indicate that 1 is a zero-field single-molecule magnet (SMM) and complexes 2-4 are field-induced SMMs, with complex 4 featuring a two-step relaxation process. The magnetic characterizations and ab initio calculations revealed that changing the N-sites in the ß-diketone ligands can effectively alter the structures and magnetic properties of cyano-bridged 4d-4f nanomagnets by adjusting the coordination environments of the DyIII centers.

A high spatial resolution dataset of China's biomass resource potential.

Assessing biomass resource potential is essential for China's ambitious goals of carbon neutrality, rural revitalization, and poverty eradication. To fill the data gap of high spatial resolution biomass resources in China, this study estimates the biomass resource potential for all types of lignocellulosic biomass feedstock at 1 km resolution in 2018, including 9 types of agricultural residues, 11 types of forestry residues, and 5 types of energy crops. By combining the statistical accounting method and the GIS-based method, this study develops a transparent and comprehensive assessment framework, which is in accordance with the principle of food security, forest land and pasture protection, and biodiversity protection. In the end, we organize and store the data in different formats (GeoTIFF, NetCDF, and Excel) for GIS users, integrated modelers, and policymakers. The reliability of this high spatial resolution dataset has been proved by comparing the aggregated data at the subnational and national levels with the existing literature. This dataset has numerous potential uses and is a crucial input to many bioenergy-related studies.

The roles of the SOX2 protein in the development of esophagus and esophageal squamous cell carcinoma, and pharmacological target for therapy.

SOX2 is a transcription factor belonging to the SOX gene family, whose activity has been associated with the maintenance of the stemness and self-renewal of embryonic stem cells (ESCs), as well as the induction of differentiated cells into induced pluripotent stem cells (iPSCs). Moreover, accumulating studies have shown that SOX2 is amplified in various cancers, notably in esophageal squamous cell carcinoma (ESCC). In addition, SOX2 expression is linked to multiple malignant processes, including proliferation, migration, invasion, and drug resistance. Taken together, targeting SOX2 might shed light on novel approaches for cancer therapy. In this review, we aim to summarize the current knowledge regarding SOX2 in the development of esophagus and ESCC. We also highlight several therapeutic strategies for targeting SOX2 in different cancer types, which can provide new tools to treat cancers possessing abnormal levels of SOX2 protein.

Microstructural changes of cartilage and subchondral bone in a guinea pig model of early- and middle-stage patellofemoral arthritis.

OBJECTIVE: Patellofemoral arthritis is a common type of knee osteoarthritis and a prime cause of anterior knee pain and disability. Most of the existing research on knee osteoarthritis focuses on tibial-femoral arthritis, while studies on patellofemoral arthritis are relatively rare. This study aims to observe changes in osteochondral and subchondral bone structure over time in the patella and femoral trochlea in an animal model of spontaneous patellofemoral arthritis. METHODS: A total of 24 1-, 3- or 5-month-old healthy female Hartley guinea pigs were used for experiments. No intervention was applied, and the mechanical pain threshold was assessed prior to euthanasia. Bilateral knee joints were collected in the animals at the different ages, and the patellofemoral joints were taken to evaluate the bone microstructure of patellofemoral articular cartilage and subchondral bone by macroscopy, histopathology and micro-computed tomography (micro-CT). RESULTS: There was a significant difference in the severity of femoral trochlea injury assessed by the Macro score between 5- and 1-month-old groups (P<0.01), as well as in patellar cartilage damage (P<0.05). The mechanical pain threshold of lower extremities in each group was statistically different between different age groups (P<0.05). The OARSI articular cartilage histopathological scores, including patella and femoral trochlea, were significantly different among 1-, 3- and 5-month-old groups. The 5-month-old group exhibited statistically lower values of bone volume/trabecular volume, trabecular number and trabecular thickness in the femoral subchondral bone and evidently higher structure model index than the 1-month-old group. CONCLUSIONS: This study demonstrated that 3- to 5-month-old female Hartley guinea pigs can develop early-to-mid-stage spontaneous patellofemoral arthritis that causes significant cartilage degeneration and loss of subchondral bone. In addition, the bone microarchitecture of the femur is more severely degraded.

Constructing spin crossover-fluorescence bifunctional iron(II) complexes based on tetraphenyl ethylene-decorated AIEgens.

Investigating spin crossover (SCO)-fluorescence bifunctional materials and establishing their structure-function relationships are attractive topics in chemistry and materials science. However, it remains challenging to preserve the fluorescence and SCO properties simultaneously in aggregated solid states. Herein, we design an (E)-2,6-bis(1H-pyrazol-1-yl)-4-(4-(1,2,2-triphenylvinyl)styryl)pyridine (tpe-bpp) ligand, which contains coordinated SCO and fluorescence units of an aggregation-induced emission luminogen (AIEgen). The coordination of the tpe-bpp ligand with different FeII salts generated three mononuclear complexes: [Fe(tpe-bpp)2](ClO4)2·5.75CH2Cl2 (1), [Fe(tpe-bpp)2](ClO4)2·CH2Cl2·3CH3OH (2) and [Fe(tpe-bpp)2](BF4)2·CH2Cl2·3CH3OH (3). Single-crystal X-ray diffraction studies showed that they shared a similar [Fe(tpe-bpp)2]2+ complex cation. Their counterions and co-crystallized solvents were different. Magnetic measurements revealed that 1, 2, and 3 exhibited a complete SCO behavior with the transition temperatures T1/2 of 375, 260, and 248 K, respectively. Fluorescence measurements confirmed the existence of the AIE property for both the tpe-bpp ligand and Fe(II) complexes. A monotonic decrease of the photoluminescence (PL) intensity upon increasing the temperature was behavior observed for all three complexes.