A miRNA-7704/IL2RB/AKT feedback loop regulates tumorigenesis and chemoresistance in ovarian cancer.

Ovarian cancer is one of the most common gynecological tumors worldwide. Despite the availability of multiple treatments for ovarian cancer, its resistance to chemotherapy remains a significant challenge. miRNAs play crucial roles in the initiation and progression of cancer by affecting processes such as differentiation, proliferation, and chemoresistance. According to microarray and qPCR analyses, miR-7704 is significantly downregulated in cisplatin-resistant cells compared to parental cells. In this study, we found that miR-7704 inhibited the proliferation and promoted cisplatin sensitivity of ovarian cancer cells in vitro and in vivo. Moreover, ectopic expression of miR-7704 had the same effect as IL2RB knockdown. Further mechanistic studies revealed that miR-7704 played an inhibitory role by regulating IL2RB expression to inactivate the AKT signaling pathway. Furthermore, IL2RB reversed the miR-7704 mediated resistance to cisplatin in ovarian cancer. Based on these findings, miR-7704 and IL2RB show the potential as novel therapeutic targets for ovarian cancer.

Systematic evaluation of multiple NGS platforms for structural variants detection.

Structural variations (SV) are critical genome changes affecting human diseases. Although many hybridization-based methods exist, evaluating SVs through next-generation sequencing (NGS) data is still necessary for broader research exploration. Here, we comprehensively compared the performance of 16 SV callers and multiple NGS platforms using NA12878 whole genome sequencing (WGS) datasets. The results indicated that several SV callers performed well relatively, such as Manta, GRIDSS, LUMPY, TARDIS, FermiKit, and Wham. Meanwhile, all NGS platforms have a similar performance using a single software. Additionally, we found that the source of undetected SVs was mostly from long reads datasets, therefore, the more appropriate strategy for accurate SV detection will be an integration of long and shorter reads in the future. At present, in the period of NGS as a mainstream method in bioinformatics, our study would provide helpful and comprehensive guidelines for specific categories of SV research.

PagJAZ5 regulates cambium activity through coordinately modulating cytokinin concentration and signaling in poplar.

Wood is resulted from the radial growth paced by the division and differentiation of vascular cambium cells in woody plants, and phytohormones play important roles in cambium activity. Here, we identified that PagJAZ5, a key negative regulator of jasmonate (JA) signaling, plays important roles in enhancing cambium cell division and differentiation by mediating cytokinin signaling in poplar 84K (Populus alba × Populus glandulosa). PagJAZ5 is preferentially expressed in developing phloem and cambium, weakly in developing xylem cells. Overexpression (OE) of PagJAZ5m (insensitive to JA) increased cambium activity and xylem differentiation, while jaz mutants showed opposite results. Transcriptome analyses revealed that cytokinin oxidase/dehydrogenase (CKXs) and type-A response regulators (RRs) were downregulated in PagJAZ5m OE plants. The bioactive cytokinins were significantly increased in PagJAZ5m overexpressing plants and decreased in jaz5 mutants, compared with that in 84K plants. The PagJAZ5 directly interact with PagMYC2a/b and PagWOX4b. Further, we found that the PagRR5 is regulated by PagMYC2a and PagWOX4b and involved in the regulation of xylem development. Our results showed that PagJAZ5 can increase cambium activity and promote xylem differentiation through modulating cytokinin level and type-A RR during wood formation in poplar.

Kinetics of hydrogen absorption/desorption in the Zr-2.5Nb alloy.

The Zr-2.5Nb alloy is a typical pressure tube material in heavy water nuclear reactors, and an increase of hydrogen isotope content in the alloy during service can pose major safety risks; hot vacuum extraction-mass spectrometry is an efficient method for evaluating hydrogen isotope concentrations in the Zr-2.5Nb alloy. This work investigates the kinetics and thermodynamic properties of deuterium (D) absorption and desorption of the Zr-2.5Nb alloy using the constant volume adsorption method and the hot vacuum extraction method. In addition to the previously reported volume contraction model, it was observed that at 600 °C and above, the reaction between D2 and Zr-2.5Nb is dominated by diffusion, while the reaction is predominantly influenced by surface adsorption and dissociation below 600 °C. Phase transition sequence of Zr-2.5Nb deuterides during non-isothermal desorption was established using quantitatively calibrated thermal desorption spectra combined with the phase transition process of deuteride decomposition. These results can provide important references for optimizing the process parameters of the hot vacuum extraction-mass spectrometry method.

Neurotrophic keratitis caused by lightning injury: a case report.

BACKGROUND: This study aimed to report a case of neurotrophic keratitis caused by lightning. CASE PRESENTATION: A 38-year-old man was hit by lightning and suffered eye injury. He eventually developed neurotrophic keratitis. RESULTS: The patient's injury history and burn site were analyzed, and it was judged that lightning directly damaged his cornea, eventually resulting in neurotrophic keratitis. Fortunately, the patient's vision improved after treatment. CONCLUSION: Lightning can cause eye damage, and the clinical manifestations are diverse. Lightning currents cause corneal nerve loss, resulting in neurotrophic keratitis. To maintain corneal integrity and prevent disease progression, early assessment and appropriate treatment are necessary.

Direct Fabrication of Sub-10 nm Nanopores in WO3 Nanosheets Using Single Swift Heavy Ions.

Extending the fabrication methodology of solid-state nanopores in a wide range of materials is significant in the fields of single molecule detection, nanofluidic devices, and nanofiltration membranes. Here, we demonstrate a new method to directly fabricate size- and density-controllable sub-10 nm nanopores in WO3 nanosheets using single swift heavy ions (SHIs) without any chemical etching process. By selecting ions of different electronic energy losses (Se), nanopores with sizes from 1.8 to 7.4 nm can be created in WO3 nanosheets. The creation efficiency of nanopores achieves ∼100% for Se > 20 keV/nm, and there exists a critical thickness below which nanopores can be created. Combined with molecular dynamics simulations, we propose that the viscosity and surface tension of the transient molten phase caused by SHIs are the key factors for the formation of nanopores. This method paves a way to fabricate solid-state nanopores in materials with a low viscosity and surface tension.

PAS-7 is Superior to APAIS for Assessing Preoperative Anxiety in the Chinese Population.

PURPOSE: The purpose of this study was to analyze the reliability and validity of the Perioperative Anxiety Scale-7 (PAS-7), which was created by Chinese medical professionals, by using the State-Trait Anxiety Scale (STAI-S) as the standard for the diagnosis of preoperative anxiety, and to compare whether there is a difference between the PAS-7 and the Amsterdam Preoperative Anxiety and Information Scale (APAIS) in the diagnosis of preoperative anxiety in the Chinese population. DESIGN: This study was an observational study. METHODS: The PAS-7, APAIS, and STAI-S were all completed the day before surgery. The internal consistency test was used to evaluate the scale's reliability, and exploratory factor analysis and confirmatory factor analysis were used to assess the scale's construct validity. Pearson correlation was used to analyze the correlation between PAS-7 and STAI-S, and APAIS. The area under the receiver operating characteristic (ROC) curve was used to compare the diagnostic value of PAS-7 and APAIS. FINDINGS: The PAS-7 Cronbach's α coefficient was 0.804. The indicators of the overall fitting coefficient were within the acceptable range. PAS-7 scores correlated well with STAI-S and APAIS scores (P < .01). The area under the ROC curve of PAS-7 was 0.808 (0.752-0.856), and the area under the ROC curve of APAIS was 0.674 (0.611-0.733). The difference between areas was 0.133 (0.0612-0.206), P < .001, and the diagnostic value of PAS-7 was higher than that of APAIS. CONCLUSIONS: The PAS-7 scale has high reliability and validity and can be used to assess preoperative anxiety in patients undergoing elective surgery. PAS-7 is superior to APAIS for assessing preoperative anxiety in the Chinese population.

Organic-Inorganic Hybrid Cuprous-Based Metal Halides with Unique Two-Dimensional Crystal Structure for White Light-Emitting Diodes.

Ternary cuprous (Cu+)-based metal halides, represented by cesium copper iodide (e.g., CsCu2I3 and Cs3Cu2I5), are garnering increasing interest for light-emitting applications owing to their intrinsically high photoluminescence quantum yield and direct bandgap. Toward electrically driven light-emitting diodes (LEDs), it is highly desirable for the light emitters to have a high structural dimensionality as it may favor efficient electrical injection. However, unlike lead-based halide perovskites whose light-emitting units can be facilely arranged in three-dimensional (3D) ways, to date, nearly all ternary Cu+-based metal halides crystallize into 0D or 1D networks of Cu-X (X = Cl, Br, I) polyhedra, whereas 3D and even 2D structures remain mostly uncharted. Here, by employing a fluorinated organic cation, we report a new kind of ternary Cu+-based metal halides, (DFPD)CuX2 (DFPD+ = 4,4-difluoropiperidinium), which exhibits unique 2D layered crystal structure. Theoretical calculations reveal a highly dispersive conduction band of (DFPD)CuBr2, which is beneficial for charge carrier injection. It is also of particular significance to find that the 2D (DFPD)CuBr2 crystals show appealing properties, including improved ambient stability and an efficient warm white-light emission, making it a promising candidate for single-component lighting and display applications.

Effects of plaque characteristics and artery hemodynamics on the residual stenosis after carotid artery stenting.

OBJECTIVE: Carotid artery stenting (CAS) has become an alternative strategy to carotid endarterectomy for carotid artery stenosis. Residual stenosis was an independent risk factor for restenosis, with the latter affecting the long-term outcomes of CAS. This multicenter study aimed to evaluate the echogenicity of plaques and hemodynamic alteration by color duplex ultrasound (CDU) examination and investigate their effects on the residual stenosis after CAS. METHODS: From June 2018 to June 2020, 454 patients (386 males and 68 females) with a mean age of 67.2 ± 7.9 years, who underwent CAS from 11 advanced stroke centers in China were enrolled. One week before recanalization, CDU was used to evaluate the responsible plaques, including the morphology (regular or irregular), echogenicity of the plaques (iso-, hypo-, or hyperechoic) and calcification characteristics (without calcification, superficial calcification, inner calcification, and basal calcification). One week after CAS, the alteration of diameter and hemodynamic parameters were evaluated by CDU, and the occurrence and degree of residual stenosis were determined. In addition, magnetic resonance imaging was performed before and during the 30-day postprocedural period to identify new ischemic cerebral lesions. RESULTS: The rate of composite complications, including cerebral hemorrhage, symptomatic new ischemic cerebral lesions, and death after CAS, was 1.54% (7/454 cases). The rate of residual stenosis after CAS was 16.3% (74/454 cases). After CAS, both the diameter and peak systolic velocity (PSV) improved in the preprocedural 50% to 69% and 70% to 99% stenosis groups (P < .05). Compared with the groups without residual stenosis and with <50% residual stenosis, the PSV of all three segments of stent in the 50% to 69% residual stenosis group were the highest, and the difference in the midsegment of stent PSV was the largest (P < .05). Logistic regression analysis showed that preprocedural severe (70% to 99%) stenosis (odds ratio [OR], 9.421; P = .032), hyperechoic plaques (OR, 3.060; P = .006) and plaques with basal calcification (OR, 1.885; P = .049) were independent risk factors for residual stenosis after CAS. CONCLUSIONS: Patients with hyperechoic and calcified plaques of the carotid stenosis are at a high risk of residual stenosis after CAS. CDU is an optimal, simple and noninvasive imaging method to evaluate plaque echogenicity and hemodynamic alterations during the perioperative period of CAS, which can help surgeons to select the optimal strategies and prevent the occurrence of residual stenosis.

The roles of different microRNAs in the regulation of cholesterol in viral hepatitis.

Cholesterol plays a significant role in stabilizing lipid or membrane rafts, which are specific cellular membrane structures. Cholesterol is involved in numerous cellular processes, including regulating virus entry into the host cell. Multiple viruses have been shown to rely on cholesterol for virus entry and/or morphogenesis. Research indicates that reprogramming of the host's lipid metabolism is associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in the progression to severe liver disease for viruses that cause chronic hepatitis. Moreover, knowing the precise mode of viral interaction with target cells sheds light on viral pathogenesis and aids in the development of vaccines and therapeutic targets. As a result, the area of cholesterol-lowering therapy is quickly evolving and has many novel antiviral targets and medications. It has been shown that microRNAs (miRNAs) either directly or indirectly target the viral genome, preventing viral replication. Moreover, miRNAs have recently been shown to be strong post-transcriptional regulators of the genes involved in lipid metabolism, particularly those involved in cholesterol homeostasis. As important regulators of lipid homeostasis in several viral infections, miRNAs have recently come to light. In addition, multiple studies demonstrated that during viral infection, miRNAs modulate several enzymes in the mevalonate/cholesterol pathway. As cholesterol metabolism is essential to the life cycle of viral hepatitis and other viruses, a sophisticated understanding of miRNA regulation may contribute to the development of a novel anti-HCV treatment. The mechanisms underlying the effectiveness of miRNAs as cholesterol regulators against viral hepatitis are explored in this review. Video Abstract.

Acidaminococcus homini s sp. nov., Amedibacillus hominis sp. nov., Lientehia hominis gen. nov. sp. nov., Merdimmobilis hominis gen. nov. sp. nov., and Paraeggerthella hominis sp. nov., isolated from human faeces.

The human gastrointestinal tract is inhabited by various microorganisms, including thousands of bacterial taxa that have yet to be cultured and characterized. In this report, we describe the isolation, cultivation, genotypic and phenotypic characterization and taxonomy of five novel anaerobic bacterial strains that were recovered during the massive cultivation and isolation of gut microbes from human faecal samples. On the basis of the polyphasic taxonomic results, we propose two novel genera and five novel species. They are Acidaminococcus hominis sp. nov. (type strain NSJ-142T=CGMCC 1.17903T=KCTC 25346T), Amedibacillus hominis sp. nov. (type strain NSJ-176T=CGMCC 1.17933T=KCTC 25355T), Lientehia hominis gen. nov. sp. nov. (type strain NSJ-141T=CGMCC 1.17902T=KCTC 25345T), Merdimmobilis hominis gen. nov. sp. nov. (type strain NSJ-153T=CGMCC 1.17915T=KCTC 25350T) and Paraeggerthella hominis sp. nov. (type strain NSJ-152T=CGMCC 1.17914T=KCTC 25349T).

Childhood environment and adulthood food addiction: Testing the multiple mediations of life history strategies and attitudes toward self.

Food addiction is associated with both physical and mental health conditions, such as obesity and depression, and is considered a public health problem. Based on life history (LH) theory, this study aimed to test the association between unpredictable childhood environment and food addiction in adulthood and to examine LH strategies and attitudes toward self as psychological mediators of this association. A random sample of 1010 adults, aged from 18 to 88 years (44.8% male; Mage = 38.52, SDage = 14.53), voluntarily participated in an anonymous telephone survey conducted in Macao, China. The results of a path analysis showed the significant and positive direct effect of childhood unpredictability on food addiction and its negative association with slow LH strategy, which in turn was negatively correlated with food addiction. In addition, slow LH strategy and self-judgment, rather than self-kindness, acted as serial mediators in the association between childhood unpredictability and food addiction. These findings support the applicability of LH theory to understanding food addiction, as well as pointing to the potential risk effect of self-judgment for food addiction in adulthood. Self-judgment reduction may be a potential supplementary approach for future food addiction intervention.

Synthesis, molecular docking, and binding Gibbs free energy calculation of ß-nitrostyrene derivatives: Potential inhibitors of SARS-CoV-2 3CL protease.

The outbreak of novel coronavirus disease 2019 (COVID-19), caused by the novel coronavirus (SARS-CoV-2), has had a significant impact on human health and the economic development. SARS-CoV-2 3CL protease (3CLpro) is highly conserved and plays a key role in mediating the transcription of virus replication. It is an ideal target for the design and screening of anti-coronavirus drugs. In this work, seven ß-nitrostyrene derivatives were synthesized by Henry reaction and ß-dehydration reaction, and their inhibitory effects on SARS-CoV-2 3CL protease were identified by enzyme activity inhibition assay in vitro. Among them, 4-nitro-ß-nitrostyrene (compound a) showed the lowest IC50 values of 0.7297 µM. To investigate the key groups that determine the activity of ß-nitrostyrene derivatives and their interaction mode with the receptor, the molecular docking using the CDOCKER protocol in Discovery Studio 2016 was performed. The results showed that the hydrogen bonds between ß-NO2 and receptor GLY-143 and the π-π stacking between the aryl ring of the ligand and the imidazole ring of receptor HIS-41 significantly contributed to the ligand activity. Furthermore, the ligand-receptor absolute binding Gibbs free energies were calculated using the Binding Affinity Tool (BAT.py) to verify its correlation with the activity of ß-nitrostyrene 3CLpro inhibitors as a scoring function. The higher correlation(r2=0.6) indicates that the absolute binding Gibbs free energy based on molecular dynamics can be used to predict the activity of new ß-nitrostyrene 3CLpro inhibitors. These results provide valuable insights for the functional group-based design, structure optimization and the discovery of high accuracy activity prediction means of anti-COVID-19 lead compounds.

Molecular Dynamics Study of the Effect of Charge and Glycosyl on Superoxide Anion Distribution near Lipid Membrane.

To examine the effects of membrane charge, the electrolyte species and glycosyl on the distribution of negatively charged radical of superoxide anion (·O2-) around the cell membrane, different phospholipid bilayer systems containing ·O2- radicals, different electrolytes and phospholipid bilayers were constructed through Charmm-GUI and Amber16. These systems were equilibrated with molecular dynamics by using Gromacs 5.0.2 to analyze the statistical behaviors of ·O2- near the lipid membrane under different conditions. It was found that in the presence of potassium rather than sodium, the negative charge of the phospholipid membrane is more likely to rarefy the superoxide anion distribution near the membrane surface. Further, the presence of glycosyl significantly reduced the density of ·O2- near the phospholipid bilayer by 78.3% compared with that of the neutral lipid membrane, which may have a significant contribution to reducing the lipid peroxidation from decreasing the ·O2- density near the membrane.

Vasculoprotective Potential of Baicalein in Angiotensin II-Infused Abdominal Aortic Aneurysms through Inhibiting Inflammation and Oxidative Stress.

Aortic wall inflammation, abnormal oxidative stress and progressive degradation of extracellular matrix proteins are the main characteristics of abdominal aortic aneurysms (AAAs). The nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome dysregulation plays a crucial role in aortic damage and disease progression. The first aim of this study was to examine the effect of baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one) on AAA formation in apolipoprotein E-deficient (ApoE-/-) mice. The second aim was to define whether baicalein attenuates aberrant vascular smooth muscle cell (VSMC) proliferation and inflammation in VSMC culture. For male ApoE-/- mice, a clinically relevant AAA model was randomly divided into four groups: saline infusion, baicalein intraperitoneal injection, Angiotensin II (Ang II) infusion and Ang II + baicalein. Twenty-seven days of treatment with baicalein markedly decreased Ang II-infused AAA incidence and aortic diameter, reduced collagen-fiber formation, preserved elastic structure and density and prevented smooth muscle cell contractile protein degradation. Baicalein inhibited rat VSMC proliferation and migration following the stimulation of VSMC cultures with Ang II while blocking the Ang II-inducible cell cycle progression from G0/G1 to the S phase in the synchronized cells. Cal-520 AM staining showed that baicalein decreased cellular calcium in Ang II-induced VSMCs; furthermore, a Western blot assay indicated that baicalein inhibited the expression of PCNA and significantly lowered levels of phospho-Akt and phospho-ERK, along with an increase in baicalein concentration in Ang II-induced VSMCs. Immunofluorescence staining showed that baicalein pretreatment reduced NF-κB nuclear translocation in Ang II-induced VSMCs and furthered the protein expressions of NLRP3 while ASC and caspase-1 were suppressed in a dose-dependent manner. Baicalein pretreatment upregulated Nrf2/HO-1 signaling in Ang II-induced VSMCs. Thus, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining showed that its reactive oxygen species (ROS) production decreased, along with the baicalein pretreatment. Our overall results indicate that baicalein could have therapeutic potential in preventing aneurysm development.

PagERF81 regulates lignin biosynthesis and xylem cell differentiation in poplar.

Lignin is a major component of plant cell walls and is essential for plant growth and development. Lignin biosynthesis is controlled by a hierarchical regulatory network involving multiple transcription factors. In this study, we showed that the gene encoding an APETALA 2/ethylene-responsive element binding factor (AP2/ERF) transcription factor, PagERF81, from poplar 84 K (Populus alba × P. glandulosa) is highly expressed in expanding secondary xylem cells. Two independent homozygous Pagerf81 mutant lines created by gene editing, produced significantly more but smaller vessel cells and longer fiber cells with more lignin in cell walls, while PagERF81 overexpression lines had less lignin, compared to non-transgenic controls. Transcriptome and reverse transcription quantitative PCR data revealed that multiple lignin biosynthesis genes including Cinnamoyl CoA reductase 1 (PagCCR1), Cinnamyl alcohol dehydrogenase 6 (PagCAD6), and 4-Coumarate-CoA ligase-like 9 (Pag4CLL9) were up-regulated in Pagerf81 mutants, but down-regulated in PagERF81 overexpression lines. In addition, a transient transactivation assay revealed that PagERF81 repressed the transcription of these three genes. Furthermore, yeast one hybrid and electrophoretic mobility shift assays showed that PagERF81 directly bound to a GCC sequence in the PagCCR1 promoter. No known vessel or fiber cell differentiation related genes were differentially expressed, so the smaller vessel cells and longer fiber cells observed in the Pagerf81 lines might be caused by abnormal lignin deposition in the secondary cell walls. This study provides insight into the regulation of lignin biosynthesis, and a molecular tool to engineer wood with high lignin content, which would contribute to the lignin-related chemical industry and carbon sequestration.

Using Pgst-4::GFP-transformed Caenorhabditis elegans for drinking water quality monitoring.

Biological effect-based monitoring is essential for predicting or alerting to a possible deterioration in drinking water quality. In the present study, a reporter gene assay based on oxidative stress-mediated Pgst-4::GFP induction in the Caenorhabditis elegans strain VP596 (VP596 assay) was assessed for its applicability in evaluating drinking water safety and quality. This assay was used to measure the oxidative stress response in VP596 worms exposed to six ubiquitous components (As3+, Al3+, F-, NO3--N, CHCl3, and residual chlorine) in drinking water, eight mixtures of these six components designed through orthogonal design, ninety-six unconcentrated water samples from source to tap water in two supply systems, and organic extracts (OEs) of twenty-five selected water samples. Pgst-4::GFP fluorescence was not induced by Al3+, F-, NO3--N, and CHCl3, and was significantly enhanced by As3+ and residual chlorine only at concentrations higher than their respective drinking water guideline levels. Pgst-4::GFP induction was not detected in any of the six-component mixtures. Induction of Pgst-4::GFP was observed in 9.4% (3/32) of the source water samples but not in the drinking water samples. However, a notable induction effect was revealed in the three OEs of drinking water, with a relative enrichment factor of 200. These results suggest that the VP596 assay has limited utility for screening drinking water safety by testing unconcentrated water samples; however, it offers a supplemental in vivo tool for prioritizing water samples for an enhanced quality assessment, monitoring pollutant removal performance by drinking water treatment plants, and evaluating water quality in water supplies.

Excitation Wavelength-Dependent Fluorescence of a Lanthanide Organic Metal Halide Cluster for Anti-Counterfeiting Applications.

The achievement of significant photoluminescence (PL) in lanthanide ions (Ln3+ ) has primarily relied on host sensitization, where energy is transferred from the excited host material to the Ln3+ ions. However, this luminous mechanism involves only one optical antenna, namely the host material, which limits the accessibility of excitation wavelength-dependent (Ex-De) PL. Consequently, the wider application of Ln3+ ions in light-emitting devices is hindered. In this study, we present an organic-inorganic compound, (DMA)4 LnCl7 (DMA+ =[CH3 NH2 CH3 ]+ , Ln3+ =Ce3+ , Tb3+ ), which serves as an independent host lattice material for efficient Ex-De emission by doping it with trivalent antimony (Sb3+ ). The pristine (DMA)4 LnCl7 compounds exhibit high luminescence, maintaining the characteristic sharp emission bands of Ln3+ and demonstrating a high PL quantum yield of 90-100 %. Upon Sb3+ doping, the compound exhibits noticeable Ex-De emission with switchable colors. Through a detailed spectral study, we observe that the prominent energy transfer process observed in traditional host-sensitized systems is absent in these materials. Instead, they exhibit two independent emission centers from Ln3+ and Sb3+ , each displaying distinct features in luminous color and radiative lifetime. These findings open up new possibilities for designing Ex-De emitters based on Ln3+ ions.

Highly Luminescent One-Dimensional Organic-Inorganic Hybrid Double-Perovskite-Inspired Materials for Single-Component Warm White-Light-Emitting Diodes.

Double perovskites (DPs) are one of the most promising candidates for developing white light-emitting diodes (WLEDs) owing to their intrinsic broadband emission from self-trapped excitons (STEs). Translation of three-dimensional (3D) DPs to one-dimensional (1D) analogues, which could break the octahedral tolerance factor limit, is so far remaining unexplored. Herein, by employing a fluorinated organic cation, we report a series of highly luminescent 1D DP-inspired materials, (DFPD)2 MI InBr6 (DFPD=4,4-difluoropiperidinium, MI =K+ and Rb+ ). Highly efficient warm-white photoluminescence quantum yield of 92 % is achieved by doping 0.3 % Sb3+ in (DFPD)2 KInBr6 . Furthermore, single-component warm-WLEDs fabricated with (DFPD)2 KInBr6 :Sb yield a luminance of 300 cd/m2 , which is one of the best-performing lead-free metal-halides WLEDs reported so far. Our study expands the scope of In-based metal-halides from 3D to 1D, which exhibit superior optical performances and broad application prospects.

PKCα/ZFP64/CSF1 axis resets the tumor microenvironment and fuels anti-PD1 resistance in hepatocellular carcinoma.

BACKGROUND & AIMS: Despite remarkable advances in treatment, most patients with hepatocellular carcinoma (HCC) respond poorly to anti-programmed cell death 1 (anti-PD1) therapy. A deeper insight into the tolerance mechanism of HCC against this therapy is urgently needed. METHODS: We performed next-generation sequencing, multiplex immunofluorescence, and dual-color immunohistochemistry and constructed an orthotopic HCC xenograft tumor model to identify the key gene associated with anti-PD1 tolerance. A spontaneously tumorigenic transgenic mouse model, an in vitro coculture system, mass cytometry, and multiplex immunofluorescence were used to explore the biological function of zinc finger protein 64 (ZFP64) on tumor progression and immune escape. Molecular and biochemical strategies like RNA-sequencing, chromatin immunoprecipitation-sequencing and mass spectrometry were used to gain insight into the underlying mechanisms of ZFP64. RESULTS: We showed that ZFP64 is frequently upregulated in tumor tissues from patients with anti-PD1-resistant HCC. Elevated ZFP64 drives anti-PD1 resistance by shifting macrophage polarization toward an alternative activation phenotype (M2) and fostering an inhibitory tumor microenvironment. Mechanistically, we primarily demonstrated that protein kinase C alpha (PKCα) directly phosphorylates ZFP64 at S226, leading to its nuclear translocation and the transcriptional activation of macrophage colony-stimulating factor (CSF1). HCC-derived CSF1 transforms macrophages to the M2 phenotype to drive immune escape and anti-PD1 tolerance. Notably, Gö6976, a protein kinase inhibitor, and lenvatinib, a multi-kinase inhibitor, reset the tumor microenvironment and restore sensitivity to anti-PD1 by blocking the PKCα/ZFP64/CSF1 axis. CONCLUSIONS: We propose that the PKCα/ZFP64/CSF1 axis is critical for triggering immune evasion and anti-PD1 tolerance. Inhibiting this axis with Gö6976 or lenvatinib overcomes anti-PD1 resistance in HCC. LAY SUMMARY: Despite remarkable treatment progress, most patients with hepatocellular carcinoma respond poorly to anti-PD1 therapy (a type of immunotherapy). A deeper insight into the tolerance mechanisms to this therapy is urgently needed. Herein, we unravel a previously unexplored mechanism linking tumor progression, macrophage polarization, and anti-PD1 resistance, and offer an attractive novel target for anti-PD1 combination therapy, which may benefit patients with hepatocellular carcinoma.