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This paper studies the heterogeneous responses of firms to monetary policy shocks and the possible adverse effect of expansionary monetary policy on resource reallocation. Using Chinese firm‐level data, we find that when expansionary monetary shock hits the economy, less productive firms are more responsive than productive firms in terms of resource accumulation. We identify two mechanisms for this effect. First, less productive firms accumulate net worth more slowly. They have higher leverage ratio and are more sensitive to monetary policy changes (the intensive margin). Second, monetary expansion relaxes borrowing constraints, which enables unproductive firms to survive. The congestion effect prevents resources from allocating to more productive firms. Our finding is robust even if we use private firm subsamples or avoid the massive fiscal stimulus in China around 2009. We provide a simple model of firm dynamics to capture these effects. [ABSTRACT FROM AUTHOR]

Allogeneic grafts are vulnerable to the attack launched by host alloreactive T cells, which accounts primarily for allograft failure in the clinic. Conventional pharmacological intervention mainly involves broad‐acting, nonspecific immunosuppressants that provide limited protection over the graft and may cause deleterious side effects due to insufficient allospecificity. Here, core–shell structured nanoparticles co‐loaded with allogeneic antigen (Ag) and immunosuppressive agent Tacrolimus (Ag@FK506‐NPs) are constructed. Dendritic cells (DCs) pulsed with Ag@FK506‐NPs present alloantigenic epitopes on the cell surface as a bait to capture specific T cells, especially CD8+ T cells, for intercellular FK506 transfer and alloreactive T‐cell deletion. Meanwhile, DCs are maintained in an immature tolerogenic state that induces the functional inactivation of recruited T cells. Compared with free FK506, the adoptive transfer of low immunosuppressant dose (25 000‐fold lower) of Ag@FK506‐NPs pulsed DCs is enough to yield a superior antirejection effect in a major histocompatibility complex‐mismatched murine skin transplant model. Of note, due to the cell–cell communication conferred selective T‐cell suppression, the recipient mouse is able to respond to the subsequent stimulation of an irrelevant Ag, indicating that off‐target toxicity is bypassed. Overall, this work may address some of the limitations of current allograft therapeutics. [ABSTRACT FROM AUTHOR]

Ferroptosis, featuring an iron‐dependent peroxidation of lipids, is a novel form of programmed cell death that may hold great potential in cancer therapy. Our study found that palmitic acid (PA) inhibited colon cancer cell viability in vitro and in vivo, in conjunction with an accumulation of reactive oxygen species and lipid peroxidation. The ferroptosis inhibitor Ferrostatin‐1 but not Z‐VAD‐FMK (a pan‐caspase inhibitor), Necrostatin‐1 (a potent necroptosis inhibitor), or CQ (a potent inhibitor of autophagy), rescued the cell death phenotype induced by PA. Subsequently, we verified that PA induces ferroptotic cell death through excess iron as cell death was inhibited by iron chelator deferiprone (DFP), while it was exacerbated by a supplement of ferric ammonium citrate. Mechanistically, PA affects intracellular iron content by inducing endoplasmic reticulum (ER) stress leading to ER calcium release and regulating transferrin (TF) transport through increasing cytosolic calcium levels. Furthermore, we observed that cells with high expression of CD36 were more vulnerable to PA‐induced ferroptosis. Altogether, our findings reveal that PA engages in anti‐cancer properties by activating ER stress/ER calcium release/TF‐dependent ferroptosis, and PA might serve as a compound to activate ferroptosis in colon cancer cells with high CD36 expression. [ABSTRACT FROM AUTHOR]

Radiation resistance is the leading cause of radiotherapy failure in patients with cancer. Enhanced DNA damage repair is the main reason for cancer cells to develop resistance to radiation. Autophagy has been widely reported to be linked to increased genome stability and radiation resistance. Mitochondria are highly involved in the cell response to radiotherapy. However, the autophagy subtype mitophagy has not been studied in terms of genome stability. We have previously demonstrated that mitochondrial dysfunction is the cause of radiation resistance in tumour cells. In the present study, we found that SIRT3 was highly expressed in colorectal cancer cells with mitochondrial dysfunction, leading to PINK1/Parkin‐mediated mitophagy. Excessive activation of mitophagy enhanced DNA damage repair, therefore promoting the resistance of tumour cells to radiation. Mechanistically, mitophagy resulted in decreased RING1b expression, which led to a reduction in the ubiquitination of histone H2A at K119, thereby enhancing the repair of DNA damage caused by radiation. Additionally, high expression of SIRT3 was related to a poor tumour regression grade in rectal cancer patients treated with neoadjuvant radiotherapy. These findings suggest that restoring mitochondrial function could be an effective method for increasing the radiosensitivity of patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Magnaporthe oryzae (M. oryzae) is a devastating pathogenic fungal disease that has a serious threat to the global rice security. Recently, an in‐depth study of the pathogenic mechanism and developmental process of M. oryzae became a primary model in the study of host–fungal pathogen interactions. Here, we have identified a gene MoJMJD3 (MGG_02032, accession XM_003708733) encoding the JumonjiC (JmjC) domain through bioinformatics analysis in M. oryzae. The ΔMojmjd3 deletion mutants showed defects in early appressorium formation and fungal virulence during pathogenesis. At 4 h after inoculation, the early appressorium formation of ΔMojmjd3 was decreased when compared with that of the wild‐type P131. Analysis of intracellular localization of MoJMJD3 with RFP fluorescence observation showed that MoJMJD3 was mainly localized in the cytoplasm of the conidia, appressoria, hyphae, and infective hyphae. Furthermore, by spray inoculation analysis, the ΔMojmjd3deletion mutants reduced virulence on the leaves of rice. These data suggest that MoJMJD3 plays important roles in fungal virulence during pathogenesis in M. oryzae. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by flora disequilibrium and mucosal immunity disorder. Here, we report that salidroside effectively restricts experimental colitis from two aspects of intestinal macrophage pyroptosis and dysbacteriosis‐derived colonic Th17/Treg imbalance. In innate immunity, the upregulated TREM1 and pyroptosis‐related proteins in inflamed colons were inhibited by salidroside administration and further experiments in vitro showed that salidroside suppressed LPS/ATP‐induced bone marrow‐derived macrophages (BMDMs) pyroptosis evident by the decline of LDH and IL‐1β release as well as the protein level of NLRP3, caspase‐1, and GSDMD p30. Moreover, the TREM1 inhibitor weakened the effect of salidroside on BMDMs pyroptosis, whereas salidroside still could downregulate TREM1 when NLRP3 was inhibited. In adaptive immunity, salidroside improved the gut microflora diversity and Th17/Treg ratio in DSS‐induced mice, especially promoting the abundance of Firmicutes. Clearance of the gut flora blocked the benefit of salidroside on colonic inflammation and Th17/Treg adaptive immunity, but transplanting salidroside‐treated foecal bacterium into flora‐depleted wild mice reproduced the resistance of salidroside to gut inflammation. Taken together, our data demonstrated that salidroside protected experimental colitis via skewing macrophage pyroptosis and Th17/Treg balance, indicating its potential effect on UC and other immune disorders. [ABSTRACT FROM AUTHOR]

Primarily responsible for the biogenesis and metabolism of biomolecules, endoplasmic reticulum (ER) and mitochondria are gradually becoming the targets of therapeutic modulation, whose physiological activities and pathological manifestations determine the functional capacity and even the survival of cells. Drug delivery systems with specific physicochemical properties (passive targeting), or modified by small molecular compounds, polypeptides, and biomembranes demonstrating tropism for ER and mitochondria (active targeting) are able to reduce the nonselective accumulation of drugs, enhancing efficacy while reducing side effects. Lipid nanoparticles feature high biocompatibility, diverse cargo loading, and flexible structure modification, which are frequently used for subcellular organelle‐targeted delivery of therapeutics. However, there is still a lack of systematic understanding of lipid nanoparticle‐based ER and mitochondria targeting. Herein, we review the pathological significance of drug selectively delivered to the ER and mitochondria. We also summarize the molecular basis and application prospects of lipid nanoparticle‐based ER and mitochondria targeting strategies, which may provide guidance for the prevention and treatment of associated diseases and disorders. This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseBiology‐Inspired Nanomaterials > Lipid‐Based StructuresNanotechnology Approaches to Biology > Nanoscale Systems in BiologyDiagnostic Tools > In Vivo Nanodiagnostics and Imaging [ABSTRACT FROM AUTHOR]

Developing efficient and inexpensive oxygen evolution reaction (OER) electrocatalysts is crucial to address the ever‐increasing energy crisis and environment pollution. In this work, bimetallic nickel‐iron carbonate hydroxide arrays were strongly grown on a conductive carbon cloth (NiFeCH/CC) through a facile one‐step hydrothermal method, which were used as oxygen evolution reaction (OER) electrocatalysts. Ni0.8Fe0.2CH/CC requires overpotential of just 246 mV at 10 mA cm−2, Tafel slope of 43 mV dec−1, and charge transfer resistance of 3.1 Ω for OER in 1 M KOH. The catalyst also shows excellent durability by a long‐term operation for 10 h. A post‐OER study of Ni0.8Fe0.2CH/CC reveals that the NiFeOOH species form on the surface during OER and the carbonate ions still intercalate between the cationic layers. Benefiting from a three‐dimensional structure and Fe doping strategy, the performance of Ni0.8Fe0.2CH/CC has been improved. This work provides an effective strategy to design efficient OER electrocatalysts in alkaline media. [ABSTRACT FROM AUTHOR]

This paper examines the impact of foreign entry deregulation in China on the export price and quality of manufacturing firms through input–output linkage. We create a unique dataset describing the extent of regulatory control over foreign entry across approximately 900 industries covering all primary, manufacturing and services sectors. Results suggest foreign entry deregulation encourages firms to improve product quality and increase export prices. Deregulation in the manufacturing sectors has more impact on downstream export price and quality, compared with services sectors. Moreover, firms having larger imported inputs benefit more from foreign entry deregulation. These effects are robust to alternative specifications. [ABSTRACT FROM AUTHOR]

Background: The number of cancer patients with diabetes mellitus (DM) is steadily rising. Little is known about the nutritional status of this population. This study characterized the nutritional status and survival of cancer patients with diabetes compared with those without diabetes. Methods: A total of 8247 cancer patients were prospectively enrolled from 72 hospitals in China and followed until August 2019. A global estimation of the nutritional status was performed for each participant using standardized tools. The outcomes were cancer‐specific survival (CSS) and overall survival (OS). Results: The incidence of diabetes was 7.6% in the whole population. In comparison with the non‐DM group, the DM group had greater body weight, but a similar fat‐free mass, a lower handgrip strength and a decreased Karnofsky performance score. A higher proportion of patients with diabetes were overweight/obese as indicated by BMI. The percentage of patients who were at risk of malnutrition (evaluated by PG‐SGA) was higher in the DM group (score ≥ 4, 56.7% vs 52.9%). Patients with DM showed a worse CSS (4‐year CSS, 62% vs 73%) and OS (4‐year OS 39% vs 52%). Diabetes was associated with an increased risk of both cancer‐specific (hazard ratio (HR) = 1.282, 95% confidence interval (CI) 1.070‐1.536) and overall (HR = 1.206, 95% CI 1.040‐1.399) mortality. Conclusions: Cancer patients with diabetes had a larger body mass but lower muscle strength, poorer performance status and higher incidence of malnourishment. Diabetes was associated with compromised survival. Tailored nutritional intervention is necessary for this subpopulation of patients. [ABSTRACT FROM AUTHOR]

The development of gene delivery has attracted increasing attention, especially when the introduction and application of the CRISPR/Cas9 gene editing system appears promising for gene therapy. However, ensuring biosafety and high gene editing efficiency at the same time poses a great challenge for its in vivo applications. Herein, a pardaxin peptide (PAR)‐modified cationic liposome (PAR‐Lipo) is developed. The results are indicative that significantly enhanced gene editing efficiency can be obtained through the mediation of PAR‐Lipos compared to non‐Lipos (non‐PAR‐modified liposomes) and Lipofectamine 2000, owing to its protection toward carried nucleotide by the prevention of lysosomal capture, prolongation of retention time in cells through the accumulation in the endoplasmic reticulum (ER), and more importantly, facilitation of the nuclear access via an ER‐nucleus route. Accumulation of PAR‐Lipos in the ER may improve the binding of Cas9 and sgRNA, thus further contributing to the eventually enhanced gene editing efficiency. Given their high biosafety, PAR‐Lipos are used to mediate the knockout of the oncogene CDC6 in vivo, which results in significant tumor growth inhibition. This work may provide a useful reference for enhancing the delivery of gene editing systems, thus improving the potential for their future clinical applications. [ABSTRACT FROM AUTHOR]

Abstract: Shenkang injection is a traditional Chinese formula with good curative effect on chronic renal failure. In this paper, a novel, rapid and sensitive ultra‐high‐performance liquid chromatography coupled with Q Exactive hybrid quadrupole Orbitrap high‐resolution accurate mass spectrometry was developed and validated for simultaneous determination of seven bioactive constituents of Shenkang injection in rat plasma and tissues after intravenous administration. Acetonitrile was used as a protein precipitation agent in biological samples disposal with carbamazepine as internal standard. The chromatographic separation was carried out on a C18 column with a gradient mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). The MS analysis was performed in the full‐scan positive and negative ion mode. The lower limits of quantification for the seven analytes in rat plasma and tissues were 0.1–10 ng/mL. The validated method was successfully applied to tissue distribution and pharmacokinetic studies of Shenkang injection after intravenous administration. The results of the tissue distribution study showed that the high concentrations of seven constituents were primarily in the kidney tract. This is the first report of the application of Q‐Orbitrap with full‐scan mass spectrometry in tissue distribution and pharmacokinetic studies of Shenkang injection. [ABSTRACT FROM AUTHOR]

Abstract: Objects: This study aimed to report a novel point mutation associated with juvenile amyotrophic lateral sclerosis (JALS) in a Chinese Han family. Methods: Detailed clinical assessment was applied to two patients, including proband (II‐2) and his mother (I‐2). Next‐generation sequencing (NGS), also known as high‐throughput sequencing in whole exon sequence, was performed in the proband to reach the target region. Sanger sequencing was also used to detect DNA sequence variants of the proband and other three members of his family. Results: The proband (II‐2) and his mother (I‐2) were successfully diagnosed according to the clinical manifestations and physical examination. A novel point mutation c.1157T > C in the exon 10 of the SETX gene was identified in II‐2 and I‐2, resulting in a substitution of methionine (ATG) to threonine (ACG). However, we ultimately did not find the same variant in the other two normal members of his family in addition to 100 unrelated normal subjects. Conclusion: We presented a novel probably pathogenic missense mutation in exon 10 of SETX gene in a Chinese Han family with JALS. [ABSTRACT FROM AUTHOR]

Abstract: Objects: To capture point mutations and short insertions/deletions in 49 previously reported genes associated with Parkinson's disease (PD) in a Chinese pedigree with early‐onset Parkinson's disease (EOPD)‐affected individuals. Methods: Clinical examinations and genomic analysis were performed on 21 subjects belonging to three generations of a Chinese family. Target region capture and high‐throughput sequencing were used for screening 49 genes, which were previously reported to be associated with PD. The direct Sanger sequencing method in all subjects further verified the abnormal DNA fragments in the PARK2 gene. Results: Four family members, including a mother (I‐1) and her three children (II‐2, II‐3, and II‐7), were diagnosed with PD by clinical manifestations and/or PET/CT imaging analyses. Novel compound heterozygous mutations, consisting of a fragment deletion in exon 1 to 2 (EX 1‐2 del) and a splicing point mutation c.619‐1 (G > C) in the 6th intron of the PARK2 gene, were identified in II‐2, II‐3, and II‐7. Individual EX 1‐2 del or c.619‐1 (G > C) mutations were detected in I‐1 and the third generation (III‐2, 3, 5, 10, and 11).Other mutations were not detected in the 49 known PD‐associated genes. Conclusion: Novel compound heterozygous mutations were identified in a Chinese pedigree and might represent a cause of familial EOPD with autosomal dominant inheritance. [ABSTRACT FROM AUTHOR]

Maleic anhydride was grafted onto a polyacrylonitrile (PAN) membrane surface via ultraviolet irradiation. Then, hyperbranched polyester, with varying numbers of hydroxyl end-groups (H20, H30, and H40), was grafted onto the PAN membrane surface by the reaction of hydroxyl groups with anhydride groups of maleic anhydride. The modified membranes were characterized by scanning electron microscopy, static water contact angle, and attenuated total reflectance-Fourier transform infrared spectroscopy measurements. The modified membranes showed a higher water flux and better antifouling properties than pristine PAN membranes, and their hydrophilicity was significantly improved. Membrane biocompatibility was characterized by platelet adhesion, and the results indicate that the modified membranes exhibited good biocompatibility. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A novel zwitterionic surfactant N-dodecyl aspartic acid was synthesized with dodecylamine, maleic acid anhydride and sodium hydroxide in ethanol-water as the solvent. The chemical structure of N-dodecyl aspartic acid was characterized by IR, H NMR and MS. The surface properties of the surfactant were studied by measuring the equilibrium surface tensions of the dilute aqueous solutions. The synthesized surfactant can reduce the surface tension of water to 29-32 mN m at temperatures of 298-313 K, the surface activity reaches its highest under mild pH conditions. The water hardness has almost no effect on foam power and foam stability of the surfactant at lower and middle water hardnesses. [ABSTRACT FROM AUTHOR]