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A new strategy for thiochromen‐4‐one synthesis that relies on the denitrative formal [5+1] cycloaddition of 1‐(2‐nitrophenyl)‐2‐yn‐1‐ones with thioacetamide is described. Achieved under reaction conditions that did not require transition metal catalysis, nor the exclusion of air or moisture, the reaction is suggested to involve exploiting the propensity of thioacetamide to undergo hydrolysis under basic conditions. This is follows by addition of the ensuing sulfide anion to the 1,3‐alkynone and a nucleophilic aromatic substitution and denitrative rearomatization cascade to give the S‐heterocyclic product in yields of 41–99 %. [ABSTRACT FROM AUTHOR]

Primary membranous nephropathy (PMN) is one of the leading causes of end‐stage renal disease, and the most frequent cause of massive proteinuria in nondiabetic adults, resulting in fatal complications. However, the underlying pathomechanisms of PMN remain largely unclear. Here, single‐cell RNA sequencing is employed to analyze kidney biopsies from eleven PMN patients and seven healthy subjects. Profiling 44 060 cells from patients allowed us to characterize the cellular composition and cell‐type‐specific gene expression in the PMN kidney. The complement‐induced BMP2/pSMAD1/COL4 pathway is identified as the pathogenic pathway in podocytes, bridging two key events, i.e., complement system activation and glomerular basement membrane thickening in PMN. Augmented infiltration and activation of myeloid leukocytes and B lymphocytes are found, profiling delicate crosstalk of immune cells in PMN kidneys. Overall, these results provide valuable insights into the roles of podocytes and immune cells in PMN, and comprehensive resources toward the complete understanding of PMN pathophysiology. [ABSTRACT FROM AUTHOR]

Global patterns in soil microbiomes are driven by non‐linear environmental thresholds. Fertilization is known to shape the soil microbiome of terrestrial ecosystems worldwide. Yet, whether fertilization influences global thresholds in soil microbiomes remains virtually unknown. Here, utilizing optimized machine learning models with Shapley additive explanations on a dataset of 10,907 soil samples from 24 countries, we discovered that the microbial community response to fertilization is highly dependent on environmental contexts. Furthermore, the interactions among nitrogen (N) addition, pH, and mean annual temperature contribute to non‐linear patterns in soil bacterial diversity. Specifically, we observed positive responses within a soil pH range of 5.2–6.6, with the influence of higher temperature (>15°C) on bacterial diversity being positive within this pH range but reversed in more acidic or alkaline soils. Additionally, we revealed the threshold effect of soil organic carbon and total nitrogen, demonstrating how temperature and N addition amount interacted with microbial communities within specific edaphic concentration ranges. Our findings underscore how complex environmental interactions control soil bacterial diversity under fertilization. [ABSTRACT FROM AUTHOR]

Pressed 1,3,5‐triamino‐2,4,6‐trinitrobenzene (TATB)‐based polymer‐bonded explosive (PBX) exhibits significant anisotropic and irreversible expansion characteristics during temperature cycling, resulting in both safety and service issues. The anisotropic and irreversible expansion properties of PBX have shown to be closely related to the microstructures, including explosive crystals, binders, micro voids, el. Fiber Bragg grating (FBG) technology has advantages of high reliability, accuracy, and sensitivity, which is more conducive to real‐time capture of the changes in strain throughout the temperature cycling. In this study, temperature cycling strain monitoring experiments of PBX pressed under different thermal–mechanical coupling loading conditions were studied using FBG technology. The effect of the pressing parameters on the anisotropic and irreversible expansion characteristics of the PBX's during temperature cycling was measured and analyzed, taking into account potential microstructural factors such as crystal orientation, binders, and porosity. The results indicated that the strain on the side and top of PBX cylinders were distributed with increasing strain in the direction of higher density. The strain stratification was significant during the high‐temperature stage of temperature cycling and was not obvious during the low‐temperature stage. The degree of strain stratification decreased with an increase in temperature cycling cycles and increased with higher pressing temperatures. The anisotropic expansion of PBX cylinders increased with an increase in temperature during cycling and decreased with a reduction in temperature. The axial expansion degree of PBX cylinders pressed under different compression conditions in the later cycles of temperature cycling is consistent with the different crystal orientations intensity inside them. [ABSTRACT FROM AUTHOR]

Aims: The extent of perihematomal edema following intracerebral hemorrhage (ICH) significantly impacts patient prognosis, and disruption of the blood–brain barrier (BBB) exacerbates perihematomal edema. However, the role of peripheral IL‐10 in mitigating BBB disruption through pathways that link peripheral and central nervous system signals remains poorly understood. Methods: Recombinant IL‐10 was administered to ICH model mice via caudal vein injection, an IL‐10‐inhibiting adeno‐associated virus and an IL‐10 receptor knockout plasmid were delivered intraventricularly, and neurobehavioral deficits, perihematomal edema, BBB disruption, and the expression of JAK1 and STAT3 were evaluated. Results: Our study demonstrated that the peripheral cytokine IL‐10 mitigated BBB breakdown, perihematomal edema, and neurobehavioral deficits after ICH and that IL‐10 deficiency reversed these effects, likely through the IL‐10R/JAK1/STAT3 signaling pathway. Conclusions: Peripheral IL‐10 has the potential to reduce BBB damage and perihematomal edema following ICH and improve patient prognosis. [ABSTRACT FROM AUTHOR]

Background: Left ventricular global function index (LVGFI) integrates LV volumetric and functional parameters. In patients with end‐stage renal disease (ESRD), cardiac injury manifests as LV hypertrophy and dysfunction. However, the prognostic value of LVGFI in this population remains unclear. Purpose: To investigate the association of LVGFI with major adverse cardiac events (MACE) in patients with ESRD. Study Type: Prospective. Population: One hundred fifty‐eight ESRD patients (mean age: 54.1 ± 14.4 years; 105 male) on maintenance dialysis. Filed Strength/Sequence: 3.0 T, balanced steady‐state free precession (bSSFP) cine and modified Look‐Locker inversion recovery (MOLLI) sequences. Assessment: LV volumetric and functional parameters were determined from bSSFP images. LVGFI was calculated as the ratio of stroke volume to global volume and native T1 was determined from MOLLI T1 maps. MACE was recorded on follow up. Models were developed to predict MACE from conventional risk factors combined with LVGFI, GLS, native T1, and LV mass index (LVMI), respectively. Subgroup analyses were further performed in participants with LVEF above median. Statistical Tests: Cox proportional hazard regression and log‐rank test were used to investigate the association between LVGFI and MACE. The predictive models were evaluated and compared using Harrell's C‐statistics and DeLong tests. A P value <0.05 was considered statistically significant. Results: Thirty‐four MACE occurred during the median follow‐up period of 26 months. The hazard of MACE increased by 114% for each 10% decrease in LVGFI in univariable analysis. The predictive model consisting of LVGFI (C‐statistic: 0.724) had significantly better predictive performance than the others (all P < 0.001). These results were consistent in patients (N = 79) with LVEF > median (63.54%). Data Conclusion: LVGFI is a novel marker for MACE risk stratification in patients with ESRD and was better able to predict MACE than native T1 mapping and GLS. Evidence Level: 2 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Tailoring of organometallics structure toward desirable properties continues to be both fascinating and challenging in the field of materials science. Herein, a novel ferrocene derivative with long straight‐chain alkane mono‐substituent is synthesized and used as multifunctional organometallic additive in the base oil. This ferrocene‐based organometallic compound (MFc) is synthesized via the Friedel‐Crafts acylation of ferrocene with myristyl chloride, followed by reduction with sodium borohydride. The chemical structure, crystallizability, surface morphology, and the thermal properties of the as‐synthesized compound are systematically characterized. As the iron‐containing standard substance, the MFc was preferable dissolve in lubricating oil with the iron element content as high as 2*105 ppm. Resultantly, the MFc/oil solutions exhibited excellent stability even after high‐speed centrifugal treatment, long‐term storage up to 3 months, and ultra‐low temperature treatment at −40°C for 24 h. Moreover, the MFc as a functional lubricant additive could reduce the average wear scar diameter, wear volume, and coefficient of friction with 40%, 73%, and 18%, respectively, as compared to the corresponding pure base oil. This synthetic strategy provides a novel perspective for the design of functional organometallics, and the as‐synthesized novel ferrocene derivative may find a wide range of advanced potential applications in analytical chemistry, tribology, and interfacial science. [ABSTRACT FROM AUTHOR]

Background: Itch is the most common symptom of atopic dermatitis (AD) and significantly decreases the quality of life. Skin microbiome is involved in AD pathogenesis, whereas its role in the regulation of itch remains elusive. In this study, we aimed to investigate the effects of skin microbial metabolite propionate on acute and chronic pruritus and to explore the mechanism. Methods: Using various mouse models of itch, the roles of propionate were explored by behavioral tests and histopathology/immunofluorescent analysis. Primary‐cultured dorsal root ganglion neurons and HEK293 cells expressing recombinant human TRP channels were utilized for in vitro calcium imaging/in vivo miniature two‐photon imaging in combination with electrophysiology and molecular docking approaches for investigation of the mechanism. Results: Propionate significantly alleviated itch and alloknesis in various mouse models of pruritus and AD and decreased the density of intraepidermal nerve fibers. Propionate reduced the responsiveness of dorsal root ganglion neurons to pruritogens in vitro, attenuated the hyper‐excitability in sensory neurons in MC903‐induced AD model, and inhibited capsaicin‐evoked hTRPV1 currents (IC50 = 20.08 ± 1.11 μM) via interacting with the vanilloid binding site. Propionate also decreased the secretion of calcitonin gene‐related peptide by nerves in MC903‐induced AD mouse model, which further attenuated itch and skin inflammation. Conclusion: Our study revealed a protective effect of propionate against persistent itch through direct modulation of sensory TRP channels and neuropeptide production in neurons. Regulation of itch via the skin microbiome might be a novel strategy for the treatment of AD. [ABSTRACT FROM AUTHOR]

Acute myeloid leukaemia (AML) is a fatal and refractory haematologic cancer that primarily affects adults. It interferes with bone marrow cell proliferation. Patients have a 5 years survival rate of less than 30% despite the availability of several treatments, including chemotherapy, allogeneic haematopoietic stem cell transplantation (Allo‐HSCT), and receptor antagonist drugs. Allo‐HSCT is the mainstay of acute myeloid leukaemia treatment. Although it does work, there are severe side effects, such as graft‐versus‐host disease (GVHD). In recent years, chimeric antigen receptor (CAR)‐T cell therapies have made significant progress in the treatment of cancer. These engineered T cells can locate and recognize tumour cells in vivo and release a large number of effectors through immune action to effectively kill tumour cells. CAR‐T cells are among the most effective cancer treatments because of this property. CAR‐T cells have demonstrated positive therapeutic results in the treatment of acute myeloid leukaemia, according to numerous clinical investigations. This review highlights recent progress in new targets for AML immunotherapy, and the limitations, and difficulties of CAR‐T therapy for AML. [ABSTRACT FROM AUTHOR]

Hypertensive vascular remodeling is defined as the changes in vascular function and structure induced by persistent hypertension. Maresin‐1 (MaR1), one of metabolites from Omega‐3 fatty acids, has been reported to promote inflammation resolution in several inflammatory diseases. This study aims to investigate the effect of MaR1 on hypertensive vascular remodeling. Here, we found serum MaR1 levels were reduced in hypertensive patients and was negatively correlated with systolic blood pressure (SBP). The treatment of MaR1 reduced the elevation of blood pressure and alleviated vascular remodeling in the angiotensin II (AngII)‐infused mouse model. In addition, MaR1‐treated vascular smooth muscle cells (VSMCs) exhibited reduced excessive proliferation, migration, and phenotype switching, as well as impaired pyroptosis. However, the knockout of the receptor of MaR1, leucine‐rich repeat‐containing G protein‐coupled receptor 6 (LGR6), was seen to aggravate pathological vascular remodeling, which could not be reversed by additional MaR1 treatment. The mechanisms by which MaR1 regulates vascular remodeling through LGR6 involves the Ca2+/calmodulin‐dependent protein kinase II/nuclear factor erythroid 2‐related factor 2/heme oxygenase‐1 signaling pathway. Overall, supplementing MaR1 may be a novel therapeutic strategy for the prevention and treatment of hypertension. [ABSTRACT FROM AUTHOR]

The excited state properties of thionated 5‐fluorouridine (2′,3′,5′‐tri‐O‐acetyl‐5‐fluoro‐4‐thiouridine; ta5F4TUrd), synthesized with Lawesson's reagent, have been intensively investigated with nanosecond transient absorption spectroscopy, time‐resolved thermal lensing, near‐infrared emission, and quantum chemical calculation. The intrinsic triplet lifetime of ta5F4TUrd was determined to be 4.2±0.7 μs in acetonitrile, and the formation quantum yield of the excited triplet state was as large as 0.79±0.01. The quenching rate constants of the triplet ta5F4TUrd by the dissolved oxygen molecule and by the self‐quenching process were found to be nearly equal to the diffusion‐controlled rate of acetonitrile. The quantum yield of the singlet molecular oxygen produced through energy transfer between the triplet ta5F4TUrd and the dissolved oxygen, ΦΔ, was successfully determined to be 0.61±0.02 under the oxygen‐saturated condition. From the oxygen concentration dependence of the ΦΔ value, the fraction of triplet ta5F4TUrd quenched by dissolved oxygen which gives rise to the 1O2* formation, SΔ, was successfully obtained to be 0.78±0.01, which was the largest among the thionucleobases and the thionucleosides reported so far. This could be due to the lower energy and/or the ππ* character of the triplet state. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low‐density lipoprotein cholesterol (LDL‐C). PCSK9 inhibitors are developed to primarily reduce the cardiovascular risk by lowering LDL‐C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its effects on central nervous system (CNS) diseases have been increasingly identified. Emerging clinical evidence have revealed that PCSK9 may play a significant role in neurocognition, depression, Alzheimer's disease, and stroke. The focus of this review is to elucidate the functions of PCSK9 and highlight the effects of PCSK9 in CNS diseases, with the aim of identifying the potential risks that may arise from low PCSK9 level (variant or inhibitor) in the clinical practice. [ABSTRACT FROM AUTHOR]

Malignant bone tumors are a group of rare malignant tumors and our study aimed to update the recent epidemiologic estimates based on the Surveillance, Epidemiology and End Results database. Patients diagnosed with malignant bone tumors from 2000 to 2019 were included and their characteristics were retrospectively described. The limited‐duration prevalence, annual age‐adjusted incidence and mortality were calculated, and the annual percentage changes were analyzed to quantify the rate change. Finally, observed survival and relative survival rate were illustrated. Subgroup analysis across tumor type, age, gender, tumor Grade, primary tumor site and stage was also performed. As for results, a total of 11 655 eligible patients with malignant bone tumor were selected. Osteosarcoma was the most common tumor type, followed by chondrosarcoma, Ewing sarcoma and chordoma. The estimated limited‐duration prevalence of malignant bone tumors increased from 2000 (0.00069%) to 2018 (0.00749%). Steady age‐adjusted incidence was observed in all patients during the study period while the highest rate occurred in osteosarcoma. Mortality rates differed in subgroups while elder patients (older than 64 years) presented the highest mortality rate compared to other age groups. In all bone tumors, the 10‐year observed survival and relative survival rates were 58.0% and 61.9%, respectively. Chondrosarcoma patients had the best survival outcome, followed by osteosarcoma, Ewing sarcoma, chordoma and other bone tumors. In conclusion, different epidemiologic performance in incidence and mortality was observed across tumor type as well as other demographic and clinicopathological variables, which provide potential suggestion for further adjustment of medical resource. [ABSTRACT FROM AUTHOR]

The excited state properties of thionated 5‐fluorouridine (2′,3′,5′‐tri‐O‐acetyl‐5‐fluoro‐4‐thiouridine; ta5F4TUrd), synthesized with Lawesson's reagent, have been intensively investigated with nanosecond transient absorption spectroscopy, time‐resolved thermal lensing, near‐infrared emission, and quantum chemical calculation. The intrinsic triplet lifetime of ta5F4TUrd was determined to be 4.2±0.7 μs in acetonitrile, and the formation quantum yield of the excited triplet state was as large as 0.79±0.01. The quenching rate constants of the triplet ta5F4TUrd by the dissolved oxygen molecule and by the self‐quenching process were found to be nearly equal to the diffusion‐controlled rate of acetonitrile. The quantum yield of the singlet molecular oxygen produced through energy transfer between the triplet ta5F4TUrd and the dissolved oxygen, ΦΔ, was successfully determined to be 0.61±0.02 under the oxygen‐saturated condition. From the oxygen concentration dependence of the ΦΔ value, the fraction of triplet ta5F4TUrd quenched by dissolved oxygen which gives rise to the 1O2* formation, SΔ, was successfully obtained to be 0.78±0.01, which was the largest among the thionucleobases and the thionucleosides reported so far. This could be due to the lower energy and/or the ππ* character of the triplet state. [ABSTRACT FROM AUTHOR]