Highly Stable Neutral Corrole Radical: Amphoteric Aromatic-Antiaromatic Switching and Efficient Photothermal Conversion.

The preparation of novel stable radical systems that survive and may be manipulated under harsh conditions is essential for their practical applications, such as energy storage and conversion materials. Here, we present a facile synthesis of an electrically neutral benzo-fused nickel corrole radical that shows remarkable photo- and thermal stability. The carbon-based organic radical character was confirmed using electron spin resonance and spin population analyses. This radical may be reversibly converted to its aromatic or antiaromatic ion via a one-electron redox process, as indicated by nuclear magnetic resonance chemical shifts and theoretical calculations. Notably, the antiaromatic state is stable, showing intense ring currents with complex pathways. The spectroscopic characteristics and calculated molecular orbitals of the corrole radical exhibit a combination of aromatic and antiaromatic features. On the basis of the aromatic light-harvesting property and antiaromatic emission-free character, the corrole radical exhibits highly robust, efficient photothermal energy conversion in water after encapsulation within nanoparticles, with the unpaired spin simultaneously retained. These results provide a fundamental understanding of the relationship between the (anti)aromaticity and photophysical properties of a porphyrinoid radical and a promising platform for the design of radical-based functional materials.

Clonal expansion of hepatic progenitor cells and differentiation into hepatocyte-like cells.

Hepatic progenitor cells (HPCs) in adult liver are promising for treatment of liver diseases. A biliary-derived HPC population in adult mice has been characterized by co-expression of stem cell marker Sry (sex determining region Y)-box 9 (SOX9) and biliary marker cytokeratin 7 (CK7). However, isolation of these HPCs in adult healthy liver without any selection procedures remains a big challenge in this field. Here, by establishing a simple and efficient method to isolate and expand the CK7+ SOX9+ HPCs in vitro as clones, we acquired a stable and largely scalable cell source. The CK7+ SOX9+ progenitor cells were then further induced to differentiate into hepatocyte-like cells with expression of mature hepatocyte markers albumin (Alb) and hepatocyte nuclear factor 4 alpha (HNF4α), both in vitro and in vivo in the presence of hepatocyte growth factor (HGF) and fibroblast growth factor 9 (FGF9). Furthermore, we found that the HPCs are highly responsive to transforming growth factor-beta (TGF-ß) signals. Collectively, we identified and harvested a CK7+ SOX9+ progenitor cell population from adult mouse liver by a simple and efficient approach. The exploration of this HPC population offers an alternative strategy of generating hepatocyte-like cells for cell-based therapies of acute and chronic liver disorders.

Synergistic meso-ß regulation of porphyrins: squeezing the band gap into the near-infrared I/II region.

The development of novel near-infrared (NIR) materials with extremely small energy gaps and high stability is highly desirable in bioimaging and phototherapy. Here we report an effective strategy for narrowing the energy gaps of porphyrins by synergistic regulation of meso/ß substituents. The novel NIR absorbing/emitting meso-alkynyl naphthoporphyrins (Zn-TNP and Pt-TNP) are synthesized via the retro-Diels-Alder reaction. X-ray crystallography analysis confirms the highly distorted structures of the complexes. Both compounds exhibit intense Q bands around 800 nm, while Zn-TNP shows deep NIR fluorescence at 847 nm. Pt-TNP displays NIR-II room temperature phosphorescence peaking at 1106 nm with an extremely large Stokes shift of 314 nm, which are the longest wavelengths observed among the reported platinum porphyrinoids. Furthermore, Pt-TNP shows remarkable photostability and a notable capacity for synchronous singlet oxygen and heat generation under NIR light irradiation, demonstrating potential in combined photodynamic/photothermal therapy. A theoretical analysis reveals the progressive lifting of the HOMO by the ß-fused benzene ring, the decrease of the LUMO upon meso-alkynyl substitution, and energy-releasing pathways varying with metal ions. This dual regulation approach demonstrates great promise in designing innovative multifunctional NIR porphyrin materials.

Postvaccination serosurveillance of foot-and-mouth disease through virus-neutralizing and nonstructural protein antibody tests on pig farms in Taiwan: 2009-2020.

The use of virus-neutralizing (VN) and nonstructural protein (NSP) antibody tests in a serosurveillance program for foot-and-mouth disease (FMD) can identify pig herds that are adequately vaccinated, with a high percentage of pigs with VN positive antibody titers; these tests can also help identify pigs with NSP-positivity that have previously been or are currently infected even in vaccinated herds. To identify infected herds and manage infection, the combination of VN and NSP antibody tests was used in Taiwan's serosurveillance program implemented simultaneously with the compulsory FMD vaccination program. The result was the eradication of FMD: Taiwan was recognized by the World Organization for Animal Health as an FMD-free country without vaccination in 2020. Evaluation of the compulsory vaccination program incorporated in the FMD control program in Taiwan revealed that the vaccine quality was satisfactory and the vaccination program was effective during the period of compulsory vaccination (2010-2017). Sound immunological coverage was achieved, with 89.1% of pigs having VN antibody titers exceeding 1:16 in 2016. This level of immunological coverage would be expected to substantially reduce or prevent FMD transmission, which was borne out by the results of the NSP tests. We identified farms having positive NSP reactors (very low annual prevalence) before the cessation of FMD vaccination in July 2018; however, detailed serological and clinical investigations of pigs of all ages in suspect herds demonstrated that no farms were harboring infected animals after the second half of 2013. Thus, the results revealed no evidence of FMD circulation in the field, and Taiwan regained FMD-free status.

Oxidized Low-Density Lipoprotein (Ox-LDL)-Triggered Double-Lock Probe for Spatiotemporal Lipoprotein Oxidation and Atherosclerotic Plaque Imaging.

Low-density lipoprotein (LDL), especially oxidative modified LDL (Ox-LDL), is the key risk factor for plaque accumulation and the development of cardiovascular disease. Herein, a highly specific Ox-LDL-triggered fluorogenic-colorimetric probe Pro-P1 is developed for visualizing the oxidation and aggregation progress of lipoproteins and plaque. A series of green fluorescent protein chromophores with modified donor-acceptor structures, containing carbazole as an electron donor and various substituents including pyridine-vinyl (P1), phenol-vinyl (P2), N, N-dimethylaniline-vinyl (P3), and thiophene-vinyl (P4), have been synthesized and evaluated. Emission spectroscopy and theoretical calculations of P1-P4 indicate that P1 shows enhanced green fluorescence (λem = 560 nm) by inhibiting its twisted intramolecular charge transfer in the presence of Ox-LDL. This feature allows the selection of P1 as a sensitive probe to directly visualize ferroptosis and Cu2+ -mediated LDL oxidative aggregation via in situ formation of fluorophore-bound Ox-LDL in living cells. The red-emissive probe Pro-P1 (λem = 660 nm) is prepared via borate protection of P1, which can be cleaved into P1 under high expression of HOCl and Ox-LDL condition at the lesion site, resulting in enhanced green emission. The plaque area and size with clear boundaries can be delineated by colorimetric fluorescence imaging and fluorescence lifetime imaging with precise differentiation.

Prevalence and risk factors for Salmonella spp. contamination of slaughtered chickens in Taiwan.

The present study was designed to estimate the prevalence of Salmonella contamination in Taiwanese broilers at slaughter and to identify risk factors associated with the presence of Salmonella in processed batches of broilers. Carcass rinse samples from 362 batches of broilers were collected from 45 chicken abattoirs in Taiwan between February 2013 and November 2014. Univariate analyses and multivariable logistic regression analyses were conducted to identify putative risk factors for contamination. Salmonella was detected in 32.6 % (95 % CI: 30.4-34.8) of individual broilers and 56.4 % (95 % CI: 51.1-61.5) of the sampled batches. The multivariable logistic regression model identified season (July to November) (OR = 1.95; 95 % CI: 1.2-3.2) as increasing the risk of infection. Abattoirs in the southern region (Taichung and Kaohsiung) (OR = 0.45; 95 % CI: 0.3-0.8); batches scalded for > 90 s (OR = 0.2; 95 % CI: 0.1-0.3) and batches of commercial white broilers (BR) (OR = 0.21; 95 % CI: 0.1-0.4) all had a decreased risk of contamination compared to abattoirs from the northern region, scalding < 90 s and Taiwan native chickens (TNC), respectively. This study highlights the influence of environmental conditions and poultry breed on the risk of Salmonella contamination of chickens during slaughter.

Application of autologous SOX9+ airway basal cells in patients with bronchiectasis.

INTRODUCTION: Bronchiectasis is a common condition and a leading cause of respiratory morbidity and mortality. The treatment method for bronchiectasis is mainly symptomatic treatment or surgery; however, this condition is extremely prone to recurrence. OBJECTIVES: To preliminarily evaluate the safety and efficacy of applying SOX9+ autologous airway basal cells (BCs) in patients with bronchiectasis. METHODS: SOX9+ BCs were isolated from microscale tissue of a grade 3-5 bronchus by bronchoscopic brushing and expanded in vitro for approximately 4 weeks. Subsequently, the autologous SOX9+ BCs were transplanted into the diseased bronchus to treat patients with bronchiectasis. RESULTS: The forced expiratory volume in1 second (FEV1)%, forced vital capacity (FVC)%, total lung capacity (TLC)%, residual volume (RV)% and RV/TLC ratio of predicted value in patients with bronchiectasis were improved at 4, 12, 24 and 48 weeks after cell transplantation, although the differences were not statistically significant (P > .05). Chest CT scans showed that the lesions in the pulmonary segment had not progressed at 4, 12 and 24 weeks after transplantation. No patients died during the follow-up. At 4, 12 and 24 weeks after transplantation, routine blood tests, liver function tests, renal function tests and myocardial enzymatic indexes were normal (P > .05). CONCLUSION: Transplantation of autologous SOX9+ BCs has positive effects and is safe for patients with bronchiectasis.

Detection of chicken carcasses contaminated with Salmonella enterica serovar in the abattoir environment of Taiwan.

Although a nation-wide microbiological screening program of chicken carcasses after chilling in Taiwanese chicken abattoirs has been undertaken since 2006, little is known regarding the potential sources of the Salmonella during the slaughter process. The present study provides data on the detection and serotypes of Salmonella isolated from broilers during processing and from the environment in six abattoirs in Taiwan. Overall, Salmonella were detected in 156 of 622 samples (25.1%; 95% CI: 21.7-28.7) collected. The prevalence of Salmonella varied between sampling sites with 5.8, 17.6, 31.3 and 35.5% of cloacal swabs, environmental samples prior to processing, environmental samples during processing and carcass rinse fluid, respectively, being positive (χ2 = 51.3, p < 0.0001). A total of 15 serotypes were identified from the 156 Salmonella isolates with S. Albany (41.7%) S. Schwarzengrund (20.5%), S. Kentucky (12.8%) and S. Tennessee (5.1%) being the most commonly isolated serotypes. Characterization of 156 isolates by Pulse Field Gel Electrophoresis (PFGE) identified 50 PFGE types. Typing confirmed the presence of the same PFGE type at multiple stages during processing including plucking, evisceration, chilling and post-chilling. The abattoir environment and intestinal contents of chickens are important sources of Salmonella in broiler chicken abattoirs, with the same PFGE types detected at different stages of processing both before and during slaughtering. It is concluded that Salmonella isolates present in the environment and intestinal contents of processed birds survived in the abattoir environment resulting in subsequent carcass contamination along the processing chain including plucking, evisceration, chilling and post-chilling.

Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection.

Severe pulmonary infection is a major threat to human health accompanied by substantial medical costs, prolonged inpatient requirements, and high mortality rates. New antimicrobial therapeutic strategies are urgently required to address the emergence of antibiotic resistance and persistent bacterial infections. In this study, we show that the constitutive expression of a native antimicrobial peptide LL-37 in transgenic mice aids in clearing Pseudomonas aeruginosa (PAO1), a major pathogen of clinical pulmonary infection. Orthotopic transplantation of adult mouse distal airway stem cells (DASCs), genetically engineered to express LL-37, into injured mouse lung foci enabled large-scale incorporation of cells and long-term release of the host defense peptide, protecting the mice from bacterial pneumonia and hypoxemia. Further, correlates of DASCs in adult humans were isolated, expanded, and genetically engineered to demonstrate successful construction of an anti-infective artificial lung. Together, our stem cell-based gene delivery therapeutic platform proposes a new strategy for addressing recurrent pulmonary infections with future translational opportunities.

Alveolar Differentiation Potency of Human Distal Airway Stem Cells Is Associated with Pulmonary Pathological Conditions.

BACKGROUND: This study is aimed at characterizing the human distal airway stem cells (DASCs) and assessing their therapeutic potential in patients with chronic, degenerative lung diseases. These findings will provide a comprehensive understanding for further clinical applications utilizing autologous airway stem cells as therapeutic intervention in respiratory diseases. METHODS: DASCs were isolated from healthy subjects or patients diagnosed with bronchiectasis, chronic obstructive pulmonary diseases (COPD), or interstitial lung disease (ILD). Differentiation capacity, a key property of the stem cells, was studied using a novel monolayer differentiation system. The differentiated cells were evaluated for alveolar and bronchial cell marker expression, and the quantified expression level of differentiated cells was further examined for their relationship with age and pulmonary function of the subjects. RESULTS AND CONCLUSIONS: Differentiation of DASCs and tracheal stem cells (TSCs) yielded an alveolus-like structure and a tube-shaped structure, respectively, with distinct marker gene expression. Additionally, single-cell-derived clones showed diverse differentiation fates, even if the clones arise from identical or different individuals. More importantly, the alveolar differentiation potency was higher in DASCs derived from patients than from healthy people. The differentiation efficiency of DASCs also correlates with age in patients with bronchiectasis and ILD.

Function and molecular mechanism of acetylation in autophagy regulation.

Protein acetylation emerged as a key regulatory mechanism for many cellular processes. We used genetic analysis of Saccharomyces cerevisiae to identify Esa1 as a histone acetyltransferase required for autophagy. We further identified the autophagy signaling component Atg3 as a substrate for Esa1. Specifically, acetylation of K19 and K48 of Atg3 regulated autophagy by controlling Atg3 and Atg8 interaction and lipidation of Atg8. Starvation induced transient K19-K48 acetylation through spatial and temporal regulation of the localization of acetylase Esa1 and the deacetylase Rpd3 on pre-autophagosomal structures (PASs) and their interaction with Atg3. Attenuation of K19-K48 acetylation was associated with attenuation of autophagy. Increased K19-K48 acetylation after deletion of the deacetylase Rpd3 caused increased autophagy. Thus, protein acetylation contributes to control of autophagy.