Mis-expression of GATA6 re-programs cell fate during early hematopoiesis.

The traditional view of hematopoiesis is that myeloid cells derive from a common myeloid progenitor (CMP), whereas all lymphoid cell populations, including B, T, and natural killer (NK) cells and possibly plasmacytoid dendritic cells (pDCs), arise from a common lymphoid progenitor (CLP). In Max41 transgenic mice, nearly all B cells seem to be diverted into the granulocyte lineage. Here, we show that these mice have an excess of myeloid progenitors, but their CLP compartment is ablated, and they have few pDCs. Nevertheless, T cell and NK cell development proceeds relatively normally. These hematopoietic abnormalities result from aberrant expression of Gata6 due to serendipitous insertion of the transgene enhancer (Eµ) in its proximity. Gata6 mis-expression in Max41 transgenic progenitors promoted the gene-regulatory networks that drive myelopoiesis through increasing expression of key transcription factors, including PU.1 and C/EBPa. Thus, mis-expression of a single key regulator like GATA6 can dramatically re-program multiple aspects of hematopoiesis.

Unraveling the diversity and functions of tissue-resident plasma cells.

Antibody-secreting plasma cells (PCs) are generated in secondary lymphoid organs but are reported to reside in an emerging range of anatomical sites. Analysis of the transcriptome of different tissue-resident (Tr)PC populations revealed that they each have their own transcriptional signature indicative of functional adaptation to the host tissue environment. In contrast to expectation, all TrPCs were extremely long-lived, regardless of their organ of residence, with longevity influenced by intrinsic factors like the immunoglobulin isotype. Analysis at single-cell resolution revealed that the bone marrow is unique in housing a compendium of PCs generated all over the body that retain aspects of the transcriptional program indicative of their tissue of origin. This study reveals that extreme longevity is an intrinsic property of TrPCs whose transcriptome is imprinted by signals received both at the site of induction and within the tissue of residence.

Achieving Molecular-Level Selective Detection of Volatile Organic Compounds through a Strong Coupling Effect of Ultrathin Nanosheets and Au Nanoparticles.

The high density of surface active sites, high efficiency of interfacial carrier transport, and molecular diffusion path determine the efficiency of the electrochemical sensors. The ultrathin structures have atomic-level thickness, carrier migration and heat diffusion are limited in the two-dimensional plane, resulting in excellent conductivity and high carrier concentration. A one-step chemical method is applied to synthesize defect-rich Au-SnO2 in an ultrathin nanosheet form (thickness of 2-3 nm). The strong interaction between Au and SnO2 via the Au-O-Sn bonding and the catalytic effect of Au can prolong the service life via decreasing the optimal operating temperature (55 °C) and promote the Au-SnO2 sensor to exclusively detect formaldehyde at the ppb level (300 ppb). The experimental findings along with theoretical study reveal that Au nanoparticles have a different effect on the competitive adsorption and chemical reaction over the surface of the Au-SnO2 with formaldehyde and other interfering VOC gases, such as methanol, ethanol, and acetone. This study provides mechanistic insights into the correlation between operating temperature and the performance of the Au-SnO2 chemiresistive sensor. This work allows the development of highly efficient and stable electrochemical sensors to detect VOC gases at room temperature in the future.

Multi-functional MXene quantum dots enhance the quality of perovskite polycrystalline films and charge transport for solar cells.

Recently, two-dimensional (2D) transition metal carbides/nitrides (MXenes) find applications in perovskite solar cells (PSCs), due to their high conductivity, tunable electronic structures, and rich surface chemistry, etc. However, the integration of 2D MXenes into PSCs is limited by their large lateral sizes and relatively-small surface volume ratios, and the roles of MXenes in PSCs are still ambiguous. In this paper, zero-dimensional (0D) MXene quantum dots (MQDs) with an average size of 2.7 nm are obtained through clipping step by step combining a chemical etching and a hydrothermal reaction, which display rich terminals (i.e., -F, -OH, -O) and unique optical properties. The 0D MQDs incorporated into SnO2 electron transport layers (ETLs) of PSCs exhibit multifunction: 1) increasing the electrical conductivity of SnO2, 2) promoting better alignments of energy band positions at the perovskite/ETL interface, 3) improving the film quality of atop polycrystalline perovskite. Particularly, the MQDs not only tightly bond with the Sn atom for decreasing the defects of SnO2, but also interact with the Pb2+ of perovskite. As a result, the defect density of PSCs is significantly decreased from 5.21 × 1021 to 6.4 × 1020 cm-3, leading to enhanced charge transport and reduced nonradiative recombination. Furthermore, the power conversion efficiency (PCE) of PSCs is substantially improved from 17.44% to 21.63% using the MQDs-SnO2 hybrid ETL compared with the SnO2 ETL. Besides, the stability of the MQDs-SnO2-based PSC is greatly enhanced, with only ～4% degradation of the initial PCE after storage in ambient condition (25 °C, RH: 30-40%) for 1128 h, as compared to that of the reference device with a rapid degradation of ～60% of initial PCE after 460 h. And MQDs-SnO2-based PSC also presents higher thermal stability than SnO2-based device with continuous heating for 248 h at 85 °C. The unique MQDs exhibited in this work might also find other exciting applications such as light-emitting diodes, photodetectors, and fluorescent probes.

CIS controls the functional polarization of GM-CSF-derived macrophages.

The cytokine granulocyte-macrophage-colony stimulating factor (GM-CSF) possesses the capacity to differentiate monocytes into macrophages (MØs) with opposing functions, namely, proinflammatory M1-like MØs and immunosuppressive M2-like MØs. Despite the importance of these opposing biological outcomes, the intrinsic mechanism that regulates the functional polarization of MØs under GM-CSF signaling remains elusive. Here, we showed that GM-CSF-induced MØ polarization resulted in the expression of cytokine-inducible SH2-containing protein (CIS) and that CIS deficiency skewed the differentiation of monocytes toward immunosuppressive M2-like MØs. CIS deficiency resulted in hyperactivation of the JAK-STAT5 signaling pathway, consequently promoting downregulation of the transcription factor Interferon Regulatory Factor 8 (IRF8). Loss- and gain-of-function approaches highlighted IRF8 as a critical regulator of the M1-like polarization program. In vivo, CIS deficiency induced the differentiation of M2-like macrophages, which promoted strong Th2 immune responses characterized by the development of severe experimental asthma. Collectively, our results reveal a CIS-modulated mechanism that clarifies the opposing actions of GM-CSF in MØ differentiation and uncovers the role of GM-CSF in controlling allergic inflammation.

3D Interconnected Honeycomb-Like Multifunctional Catalyst for Zn-Air Batteries.

Developing high-performance and low-cost electrocatalysts is key to achieve the clean-energy target. Herein, a dual regulation method is proposed to prepare a 3D honeycomb-like carbon-based catalyst with stable Fe/Co co-dopants. Fe atoms are highly dispersed and fixed to the polymer microsphere, followed by a high-temperature decomposition, for the generation of carbon-based catalyst with a honeycomb-like structure. The as-prepared catalyst contains a large number of Fe/Co nanoparticles (Fe/Co NPs), providing the excellent catalytic activity and durability in oxygen reduction reaction, oxygen evolution reaction and hydrogen evolution reaction. The Zn-air battery assembled by the as-prepared catalyst as air cathode shows a good charge and discharge capacity, and it exhibits an ultra-long service life by maintaining a stable charge and discharge platform for a 311-h cycle. Further X-ray absorption fine structure characterization and density functional theory calculation confirms that the Fe doping optimizes the intermediate adsorption process and electron transfer of Co.

Correlation between Carotid Stenosis Degree and Blood Pressure Variability in Patients with Carotid Stenosis.

Background: Carotid artery stenosis is one of the most serious diseases that endanger human health in contemporary times. It is a frequently occurring and common disease of the middle-aged and elderly people. Its incidence is increasing year by year, bringing a heavy economic burden to society and families. Whether there is a relationship between the degree of carotid artery stenosis and blood pressure variability is less studied. Aims: To investigate the correlation between the degree of carotid stenosis and blood pressure variability in patients with carotid stenosis. Materials and Methods: A total of 200 patients with carotid artery stenosis who were treated in our hospital from January 2017 to January 2020 were selected as the subjects of prospective study and were divided into mild stenosis according to the degree of carotid stenosis (carotid artery stenosis rate was 0-50%), moderate stenosis (carotid artery stenosis rate was between 50% and 70%), severe stenosis (carotid artery stenosis rate≧70%), and the control group with 50 cases each. The correlations between the hemodynamics, the degree of carotid artery stenosis, and blood pressure variability in patients with carotid artery stenosis were analyzed. Results: The levels of 24hSSD, 24hDSD, dSSD, dDSD, and nSSD in the mild stenosis group and moderate stenosis group were significantly higher than those in the control group. In the stenosis group, the levels of 24hSSD, 24hDSD, dSSD, dDSD, and nSSD in the severe stenosis group were significantly higher than those in the moderate stenosis group, with statistical significance (P < 0.05). The levels of PSV, EDV, and MV in the mild stenosis group and moderate stenosis group were lower than those in the control group, while the PI and RI indexes were higher than those in the control group. PI and RI levels were significantly higher than those in the mild stenosis group and moderate stenosis group (P < 0.05). Logistic analysis showed that EDV (P = 0.001, OR = 2.245, 95%CI = 1.638 ~ 3.078), SSD (P = 0.014, OR = 0.725, 95%CI = 0.528 ~ 0.996), and PSV (P = 0.001, OR = 1.970, 95%CI = 1.300 ~ 2.990) were closely related to the degree of carotid artery stenosis. Conclusion: Hemodynamics and blood pressure variability are related to the severity of carotid stenosis, which provides a reference and basis for clinical treatment of carotid stenosis.

Anchoring Platinum Clusters onto Oxygen Vacancy-Modified In2O3 for Ultraefficient, Low-Temperature, Highly Sensitive, and Stable Detection of Formaldehyde.

To avoid carcinogenicity, formaldehyde gas, currently being only detected at higher operating temperatures, should be selectively detected in time with ppb concentration sensitivity in a room-temperature indoor environment. This is achieved in this work through introducing oxygen vacancies and Pt clusters on the surface of In2O3 to reduce the optimal operating temperature from 120 to 40 °C. Previous studies have shown that only water participates in the competitive adsorption on the sensor surface. Here, we experimentally confirm that the adsorbed water on the fabricated sensor surface is consumed via a chemical reaction due to the strong interaction between the oxygen vacancies and Pt clusters. Therefore, the long-term stability of formaldehyde gas detection is improved. The results of theoretical calculations in this work reveal that the excellent formaldehyde gas detection of Pt/In2O3-x originates from the electron enrichment due to the surface oxygen vacancies and the molecular adsorption and activation ability of Pt clusters on the surface. The developed Pt/In2O3-x sensor has potential use in the ultraefficient, low-temperature, highly sensitive, and stable detection of indoor formaldehyde at an operating temperature as low as room temperature.

Ti3C2Tx MXene Nanoflakes Embedded with Copper Indium Selenide Nanoparticles for Desalination and Water Purification through High-Efficiency Solar-Driven Membrane Evaporation.

Solar-driven interface evaporation recently emerges as one of the most promising methods for seawater desalination and wastewater purification, mainly due to its low energy consumption. However, there still exist special issues in the present material system based on conventional noble metals or two-dimensional (2D) nanomaterials etc., such as high costs, low light-to-heat conversion efficiencies, and unideal channels for water transport. Herein, a composite photothermal membrane based on Ti3C2Tx MXene nanoflakes/copper indium selenide (CIS) nanoparticles is reported for highly efficient solar-driven interface evaporation toward water treatment applications. Results indicate that the introduction of CIS improves the spatial accessibility of the membrane by increasing the interlayer spacings and wettability of MXene nanoflakes and enhances light absorption capability as well as reduces reflection for the photothermal membrane. Simultaneously, utilization of the MXene/CIS composite membrane improves the efficiency of light-to-heat conversion probably due to formation of a Schottky junction between MXene and CIS. The highest water evaporation rate of 1.434 kgm-2 h-1 and a maximum water evaporation efficiency of 90.04% as well as a considerable cost-effectiveness of 62.35 g h-1/$ are achieved by using the MXene/CIS composite membrane for solar interface evaporation, which also exhibits excellent durability and light intensity adaptability. In addition, the composite photothermal membrane shows excellent impurity removal ability, e.g., >98% for salt ions, >99.8% for heavy metal ions, and ∼100% for dyes molecules. This work paves a promising avenue for the practical application of MXene in the field of water treatment.

Liver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia.

Biliary atresia (BA) is a severe cholangiopathy that leads to liver failure in infants, but its pathogenesis remains to be fully characterized. By single-cell RNA profiling, we observed macrophage hypo-inflammation, Kupffer cell scavenger function defects, cytotoxic T cell expansion, and deficiency of CX3CR1+effector T and natural killer (NK) cells in infants with BA. More importantly, we discovered that hepatic B cell lymphopoiesis did not cease after birth and that tolerance defects contributed to immunoglobulin G (IgG)-autoantibody accumulation in BA. In a rhesus-rotavirus induced BA model, depleting B cells or blocking antigen presentation ameliorated liver damage. In a pilot clinical study, we demonstrated that rituximab was effective in depleting hepatic B cells and restoring the functions of macrophages, Kupffer cells, and T cells to levels comparable to those of control subjects. In summary, our comprehensive immune profiling in infants with BA had educed that B-cell-modifying therapies may alleviate liver pathology.

IL-17 production by tissue-resident MAIT cells is locally induced in children with pneumonia.

Community-acquired pneumonia (CAP) contributes substantially to morbidity and mortality in children under the age of 5 years. In examining bronchoalveolar lavages (BALs) of children with CAP, we found that interleukin-17 (IL-17) production was significantly increased in severe CAP. Immune profiling showed that mucosal-associated invariant T (MAIT) cells from the BALs, but not blood, of CAP patients actively produced IL-17 (MAIT17). Single-cell RNA-sequencing revealed that MAIT17 resided in a BAL-resident PLZFhiCD103+ MAIT subset with high expression of hypoxia-inducible factor 1α (HIF-1α), reflecting the hypoxic state of the inflamed tissue. CAP BALs also contained a T-bet+ MAIT1 subset and a novel DDIT3+ (DNA damage-inducible transcript 3-positive) MAIT subset with low expression of HIF1A. Furthermore, MAIT17 differed from T-helper type 17 (Th17) cells in the expression of genes related to tissue location, innateness, and cytotoxicity. Finally, we showed that BAL monocytes were hyper-inflammatory and elicited differentiation of MAIT17. Thus, tissue-resident MAIT17 cells are induced at the infected respiratory mucosa, likely influenced by inflammatory monocytes, and contribute to IL-17-mediated inflammation during CAP.

TiO2 with exposed (001) facets/Bi4O5Br2 nanosheets heterojunction with enhanced photocatalytic for NO removal.

A TiO2 with exposed (001) facets/Bi4O5Br2 nanosheets heterojunction (TNS/BOB) was fabricated via a hydrothermal and electrostatic self-assembly method. The photocatalytic activity for NO removal was evaluated under simulated solar light irradiation. Through optimizing the content of TNS nanosheets, the photo-oxidative NO removal rate of 15% TNS/BOB was increased by up to 54.3%. This value is much higher than that of the individual components TNS (31.1%) and BOB (37.7%). Through capturing experiments and electron spin resonance (ESR) measurements, the main active species in the photocatalytic process were identified as ·[Formula: see text] and ·OH. Discrete Fourier transform computation results and ESR tests revealed that the photo-induced electrons in TNS should recombine with the holes in BOB, leading to effectively promoted charge separation at the TNS/BOB interface through the Z-type charge transfer. This work showed that with appropriate facet control and heterojunction design TiO2 can be used as an effective visible-light photocatalyst material.

The SIAH2-NRF1 axis spatially regulates tumor microenvironment remodeling for tumor progression.

The interactions between tumor cells with their microenvironments, including hypoxia, acidosis and immune cells, lead to the tumor heterogeneity which promotes tumor progression. Here, we show that SIAH2-NRF1 axis remodels tumor microenvironment through regulating tumor mitochondrial function, tumor-associated macrophages (TAMs) polarization and cell death for tumor maintenance and progression. Mechanistically, low mitochondrial gene expression in breast cancers is associated with a poor clinical outcome. The hypoxia-activated E3 ligase SIAH2 spatially downregulates nuclear-encoded mitochondrial gene expression including pyruvate dehydrogenase beta via degrading NRF1 (Nuclear Respiratory Factor 1) through ubiquitination on lysine 230, resulting in enhanced Warburg effect, metabolic reprogramming and pro-tumor immune response. Dampening NRF1 degradation under hypoxia not only impairs the polarization of TAMs, but also promotes tumor cells to become more susceptible to apoptosis in a FADD-dependent fashion, resulting in secondary necrosis due to the impairment of efferocytosis. These data represent that inhibition of NRF1 degradation is a potential therapeutic strategy against cancer.