Restoration of HMGCS2-mediated ketogenesis alleviates tacrolimus-induced hepatic lipid metabolism disorder.

Tacrolimus, one of the macrolide calcineurin inhibitors, is the most frequently used immunosuppressant after transplantation. Long-term administration of tacrolimus leads to dyslipidemia and affects liver lipid metabolism. In this study, we investigated the mode of action and underlying mechanisms of this adverse reaction. Mice were administered tacrolimus (2.5 mg·kg-1·d-1, i.g.) for 10 weeks, then euthanized; the blood samples and liver tissues were collected for analyses. We showed that tacrolimus administration induced significant dyslipidemia and lipid deposition in mouse liver. Dyslipidemia was also observed in heart or kidney transplantation patients treated with tacrolimus. We demonstrated that tacrolimus did not directly induce de novo synthesis of fatty acids, but markedly decreased fatty acid oxidation (FAO) in AML12 cells. Furthermore, we showed that tacrolimus dramatically decreased the expression of HMGCS2, the rate-limiting enzyme of ketogenesis, with decreased ketogenesis in AML12 cells, which was responsible for lipid deposition in normal hepatocytes. Moreover, we revealed that tacrolimus inhibited forkhead box protein O1 (FoxO1) nuclear translocation by promoting FKBP51-FoxO1 complex formation, thus reducing FoxO1 binding to the HMGCS2 promoter and its transcription ability in AML12 cells. The loss of HMGCS2 induced by tacrolimus caused decreased ketogenesis and increased acetyl-CoA accumulation, which promoted mitochondrial protein acetylation, thereby resulting in FAO function inhibition. Liver-specific HMGCS2 overexpression via tail intravenous injection of AAV8-TBG-HMGCS2 construct reversed tacrolimus-induced mitochondrial protein acetylation and FAO inhibition, thus removing the lipid deposition in hepatocytes. Collectively, this study demonstrates a novel mechanism of liver lipid deposition and hyperlipidemia induced by long-term administration of tacrolimus, resulted from the loss of HMGCS2-mediated ketogenesis and subsequent FAO inhibition, providing an alternative target for reversing tacrolimus-induced adverse reaction.

Factors affecting long-term myopic regression after corneal refractive surgery for civilian pilots in southwest China.

BACKGROUND: The purpose of this study was to analyze myopic regression after corneal refractive surgery (CRS) in civilian pilots and to explore the factors that may cause long-term myopic regression. METHODS: We included civilian pilots who had undergone CRS to correct their myopia and who had at least 5 years of follow-up. We collected retrospective data and completed eye examinations and a questionnaire to assess their eye habits. RESULTS: A total of 236 eyes were evaluated in this study. 211 eyes had Intrastromal ablations (167 eyes had laser in situ keratomileusis, LASIK, 44 eyes had small incision lenticule extraction, SMILE) and 25 eyes had subepithelial ablations (15 eyes had laser epithelial keratomileusis, LASEK and 10 eyes had photorefractive keratectomy, PRK). The mean preoperative spherical equivalent (SE) was - 2.92 ± 1.11 D (range from - 1.00 to -5.00 D). A total of 56 eyes (23.6%) suffered from myopic regression after CRS. Comparisons of individual and eye characteristics between the regression and non-regression groups revealed statistically significant differences in age, cumulative flight time, postoperative SE (at 6 months and current), uncorrected visual acuity (UCVA), accommodative amplitude (AA), positive relative accommodation (PRA), postoperative period, types of CRS and eye habits. Generalized propensity score weighting (GPSW) was used to balance the distribution of covariates among different age levels, types of CRS, cumulative flying time, postoperative period and continuous near-work time. The results of GPS weighted logistic regression demonstrated that the associations between age and myopic regression, types of CRS and myopic regression, continuous near-work time and myopic regression were significant. Cumulative flying time and myopic regression, postoperative period and myopic regression were no significant. Specifically, the odds ratio (OR) for age was 1.151 (P = 0.022), and the OR for type of CRS was 2.769 (P < 0.001). The OR for continuous near-work time was 0.635 with a P value of 0.038. CONCLUSIONS: This is the first report to analyze myopic regression after CRS in civilian pilots. Our study found that for each year increase in age, the risk of civilian pilots experiencing myopic regression was increased. Intrastromal ablations had a lower risk of long-term myopia regression than subepithelial ablations. There is a higher risk of myopic progression with continuous near-work time > 45 min and poor accommodative function may be related factors in this specific population.

Analysis of spatial variation of street landscape greening and influencing factors: an example from Fuzhou city, China.

Urban street greening is an important part of urban green infrastructure, and Green View Index (GVI) is widely used to assess urban street quality and ecosystem service value as an important indicator to quantify the perception of green street landscape from a pedestrian perspective. However, the distribution of street greenery is imbalanced. Therefore, to explore the differences in street greening levels within urban cities, we crawled streetscape data using the Internet to assess the spatial distribution patterns of urban street GVI using deep learning and spatial autocorrelation, and combined 11 surrounding environmental features with multi-source geographic data to further analyze the key factors influencing the spatial variation of block GVI using ordinary least squares, geographically weighted regression (GWR) models, and multi-scale geographically weighted regression (MGWR) models. The results show that the mean value of GVI in Fuzhou city is low (23.08%), with large differences among neighborhoods and a significant spatial autocorrelation. Among the regression models, MGWR has the best fit with an R2 of 0.702, where the variables of NDVI, house price, accessibility of water bodies and parks, and the proportion of built-up land have a greater impact on GVI, and the factors do not have the same spatial effect size. The results can provide a scientific basis for promoting green visual equity in different blocks.

Thermal ablation of hepatic hemangioma: A multi-center experience with long-term outcomes.

BACKGROUND: Thermal ablation, currently used extensively for liver tumors, also has been applied. successfully to hepatic hemangioma; however, it is still considered experimental because previous studies have comprised small sample sizes with short follow-up periods. PURPOSE: We aimed to investigate the effectiveness, safety, and long-term outcomes of thermal ablation for hepatic hemangioma. MATERIALS AND METHODS: From October 2011 to February 2021, the data of 357 patients with 378 hepatic hemangiomas treated by thermal ablation at six hospitals were analyzed in this retrospective study. The technical success, safety, and long-term follow-up results were analyzed. RESULTS: A total of 252 patients (mean age, 49.2 ± 10.5 years) with 273 subcapsular hemangiomas underwent laparoscopic thermal ablation, whereas 105 patients with 105 hemangiomas located in the liver parenchyma underwent CT-guided percutaneous ablation. Of the 378 hepatic hemangiomas (5.0-21.2 cm), 369 lesions were subjected to one session of ablation, while 9 lesions were subjected to two sessions of ablation. Technical success was achieved in 100.0% of cases. Complete ablation was achieved in 361 of 378 hemangiomas (95.5%), while 17 hemangiomas (4.5%) were incompletely ablated, showing subtle enhancement at the peripheral rim. The major complication rate was 2.0% (7/357). The median follow-up period was 67 months (range, 12-124 months). Of the 224 patients with hemangioma-related symptoms, 216 demonstrated complete disappearance of symptoms (96.4%), while 8 were ameliorated (3.6%). Ablated lesion shrinkage was progressive, and 11.4% of hemangiomas almost completely disappeared over time (P < 0.01). CONCLUSION: With a reasonable ablation strategy and comprehensive treatment measurements, thermal ablation could be a safe, feasible, and effective treatment option for hepatic hemangioma.

Analytical method for calculating internal stray radiation from an IR spectrometer based on the view factor.

Optomechanical components such as the lens barrels and frames of IR spectrometers produce strong internal stray radiation, which reduces the instrument's SNR and dynamic range. An IR internal stray radiation calculation method based on an analytical model of the view factor is proposed. The mathematical model of the view factor calculation method of typical optomechanical components is established. For any IR optical systems, the internal stray radiation can be quickly and accurately calculated by adjusting the coordinate systems in the calculation method. Based on the proposed method, the internal stray radiation of a double-pass long-wave IR spectrometer was calculated. The calculation results are consistent with the simulation results. The RMS value of the relative error between the calculated value and the simulated value is around 11%. To verify the proposed method, an experiment was conducted to test the internal stray radiation of the long-wave IR spectrometer. The internal stray radiation test results agree with the calculated and simulated results, and the relative error between the test results and the calculation results is within 9%.

Progression of hepatocellular carcinoma after radiofrequency ablation: Current status of research.

Hepatocellular carcinoma (HCC) remains an important disease for health care systems in view of its high morbidity, mortality, and increasing incidence worldwide. Radiofrequency ablation (RFA) is preferred to surgery as a local treatment for HCC because it is safer, less traumatic, less painful, better tolerated, causes fewer adverse reactions, and allows more rapid postoperative recovery. The biggest shortcoming of RFA when used to treat HCC is the high incidence of residual tumor, which is often attributed to the vascular thermal deposition effect, the wide infiltration zone of peripheral venules, and the distance between satellite foci and the main focus of the cancer. Recurrence and progression of the residual tumor is the most important determinant of the prognosis. Therefore, it is important to be aware of the risk of recurrence and to improve the efficacy of RFA. This review summarizes the relevant literature and the possible mechanisms involved in progression of HCC after RFA. Current studies have demonstrated that multimodal treatments which RFA combined with other anti-cancer approaches can prevent progression of HCC after RFA.

Anatomic resection versus radiofrequency ablation with an ablative margin ≥ 1.0 cm for solitary small hepatocellular carcinoma measuring ≤ 3 cm: Comparison of long-term outcomes using propensity score matching analysis.

PURPOSE: To compare the long-term outcomes of anatomic resection (AR) and radiofrequency ablation (RFA) with an ablative margin (AM) of ≥ 1.0 cm as first-line treatment for solitary hepatocellular carcinoma measuring ≤ 3 cm. METHODS: Two hundred and fifty-one patients who underwent AR (n = 156) or RFA (ablative margin ≥ 1.0 cm, n = 95) at any of 6 tertiary hospitals from 2009 to 2018 were enrolled. Propensity score matched analysis (PSM) were used to compare overall survival (OS), recurrence-free survival (RFS), and perioperative outcomes. Univariate and multivariate analyses were performed to identify prognostic factors associated with RFS and OS. RESULTS: PSM created 67 patient-pairs. After 96 months of follow-up, RFA with an ablative margin ≥ 1.0 cm and AR showed comparable 1-year, 3-year, 5-year, and 8-year OS rates before (P = 0.580) and after (P = 0.640) PSM. However, RFS was better at 1, 3, 5, and 8 years after AR before (P = 0.0036) and after (P = 0.017) PSM. The operation time and postoperative hospital stay were significantly longer in the AR group than in the RFA group before and after PSM (P < 0.05). Multivariate analysis identified age and type of treatment to be independent prognostic factors for RFS and age and hepatitis C to be associated with OS. CONCLUSIONS: Long-term OS was not significantly different between AR and RFA with an AM ≥ 1.0 cm in patients with a solitary hepatocellular carcinoma measuring ≤ 3 cm; but, RFS appeared to be better after AR than after RFA. However, RFA was associated with fewer perioperative complications and a shorter postoperative hospital stay.

Phenylene segments of zigzag carbon nanotubes synthesized by metal-mediated dimerization.

Well-studied cycloparaphenylenes (CPPs) correspond to the simplest segments of armchair CNTs, whereas the corresponding macrocyclic oligophenylene strip of zigzag CNTs is still missing. Herein, we present two series of conjugated macrocycles (CM2PP and CN2PP) containing two meta-phenylene or 2,7-naphthylene units facing each other in the strip. CM2PP and CN2PP can be regarded as the shortest cyclic primitive segments of zigzag CNTs. They were synthesized by gold-mediated dimerization and unambiguously characterized. They adopted the tubular structures and can further pack into one-dimensional supramolecular nanotubes. In particular, the supramolecular nanotube of CM2P4P mimics the CNT(9, 0) structure. Structural analysis and theoretical calculation accounted for the reduced ring strain in CM2PPs and CN2PPs. CM2PPs and CN2PPs exhibited a large optical extinction coefficient and high photoluminescence quantum yield. CN2P8P can accommodate fullerene C60, forming a Saturn-like C60@CN2P8P complex, a mimic structure of zigzag CNT peapods.

Comprehensive design analysis and verification of space-based short-wave infrared coded spectrometer via curved prism dispersion.

The spaceborne dispersive spectrometer is widely used in environmental, resource, and ocean observations. The coded spectrometer has higher energy advantages than the dispersion spectrometer, so it has great application prospects. In the current study, we developed an off-axis short-wave infrared coded optical system (SICOS) based on curved prism dispersion, and we further explored the design and optimization of the SICOS structure. Finite element analyses of a space-based short-wave infrared coded spectrometer based on curved prism dispersion (SSICS-CPD), including static simulation, modal analysis, sinusoidal vibration mechanical analysis, and random vibration mechanical analysis, were carried out. Simulation results showed that the SICOS support structure had excellent mechanical and thermal stability. As off-axis optical systems cannot meet the requirements of optical position accuracy through centering processing, a point source microscope and three-coordinate measuring machines were employed to complete the high-precision and rapid assembly of the SSICS-CPD. In addition, verification tests of surface shape error, stress relief, random vibration, and optical design parameters were carried out to validate the high stability and imaging performance of the SSICS-CPD. Results showed that the average modulation transfer function in the full field was 0.43 at 16.67 lp/mm, the spectral smile was <0.2 pixels, and the spectral keystone was <0.1 pixels. The design, analysis, assembly, and verification of the SSICS-CPD provide a useful reference for the development of other spaceborne prism dispersion spectrometers.

Nanographene with Multiple Embedded Heptagons: Cascade Radical Photocyclization.

Although heptagons are widely found in graphenic materials, the precise synthesis of nanocarbons containing heptagons remains a challenge, especially for the nanocarbons containing multiple-heptagons. Herein, we show that photo-induced radical cyclization (PIRC) can be used to synthesize multi-heptagon-embedded nanocarbons. Notably, a nanographene containing six heptagons (1) was obtained via a six-fold cascade PIRC reaction. The structure of 1 was clearly validated and showed a Monkey-saddle-shaped conformation. Experimental bond analysis and theoretical calculations indicated that the heptagons in 1 were non-aromatic, whereas the peripheral rings were highly aromatic. Compared to planar nanographene with the same number of π electrons, 1 had a similar optical gap due to a compromise between the decreased conjugation in the wrapped structure and enhanced electronic delocalization at the rim. Electrochemical studies showed that 1 had low-lying oxidation potentials, which was attributed to the nitrogen-doping.

Overexpression of SgGH3.1 from Fine-Stem Stylo (Stylosanthes guianensis var. intermedia) Enhances Chilling and Cold Tolerance in Arabidopsis thaliana.

Stylosanthes (stylo) species are commercially significant tropical and subtropical forage and pasture legumes that are vulnerable to chilling and frost. However, little is known about the molecular mechanisms behind stylos' responses to low temperature stress. Gretchen-Hagen 3 (GH3) proteins have been extensively investigated in many plant species for their roles in auxin homeostasis and abiotic stress responses, but none have been reported in stylos. SgGH3.1, a cold-responsive gene identified in a whole transcriptome profiling study of fine-stem stylo (S. guianensis var. intermedia) was further investigated for its involvement in cold stress tolerance. SgGH3.1 shared a high percentage of identity with 14 leguminous GH3 proteins, ranging from 79% to 93%. Phylogenetic analysis classified SgGH3.1 into Group Ⅱ of GH3 family, which have been proven to involve with auxins conjugation. Expression profiling revealed that SgGH3.1 responded rapidly to cold stress in stylo leaves. Overexpression of SgGH3.1 in Arabidopsis thaliana altered sensitivity to exogenous IAA, up-regulated transcription of AtCBF1-3 genes, activated physiological responses against cold stress, and enhanced chilling and cold tolerances. This is the first report of a GH3 gene in stylos, which not only validated its function in IAA homeostasis and cold responses, but also gave insight into breeding of cold-tolerant stylos.

Confined Thermolysis for Oriented N-Doped Carbon Supported Pd toward Stable Catalytic and Energy Storage Applications.

Carbon-based nanomaterials have been widely utilized in catalysis and energy-related fields due to their fascinating properties. However, the controllable synthesis of porous carbon with refined morphology is still a formidable challenge due to inevitable aggregation/fusion of resulted carbon particles during the high-temperature synthetic process. Herein, a hierarchically oriented carbon-structured (fiber-like) composite is fabricated by simultaneously taking advantage of a confined pyrolysis strategy and disparate bond environments within metal-organic frameworks (MOFs). In the resultant composite, the oriented carbon provides a fast mass (molecule/ion/electron) transfer efficiency; the doping-N atoms can anchor or act as active sites; the mesoporous SiO2 (mSiO2 ) shell not only effectively prevents the derived carbon or active metal nanoparticles (NPs) from aggregation or leaching, but also acts as a "polysulfide reservoir" in the Li-S batteries to suppress the "shuttle" effect. Benefiting from these advantages, the synthesized composite Pd@NDHPC@mSiO2 (NDHPC means N-doped hierarchically porous carbon) exhibits extremely high catalytic activity and stability toward the one-pot Knoevenagel condensation-hydrogenation reaction. Furthermore, the oriented NDHPC@mSiO2 manifests a boosted capacity and cycling stability in Li-S batteries compared to the counterpart that directly pyrolyzes without silica protection. This report provides an effective strategy of fabricating hierarchically oriented carbon composites for catalysis and energy storage applications.

SgRVE6, a LHY-CCA1-Like Transcription Factor From Fine-Stem Stylo, Upregulates NB-LRR Gene Expression and Enhances Cold Tolerance in Tobacco.

Stylosanthes species are economically important tropical and subtropical forage legumes which are generally vulnerable to chilling and frost. Fine-stem stylo (S. guianensis var. intermedia) has the most superior cold tolerance among all stylo species. A REVEILLE (RVE) gene, SgRVE6, was cloned from fine-stem stylo. Bioinformatic analysis suggests that SgRVE6 encodes a transcription factor of 292 amino acid residues, which belongs to the LATE ELONGATED HYPOCOTYL/CIRCADIAN CLOCK ASSOCIATED 1-LIKE (LCL) subgroup of RVE family and contains a SHAQKYF-class MYB domain and a LCL domain. SgRVE6 is universally expressed in root, stem and leaf tissues of fine-stem stylo and is rapidly up-regulated in all tested tissues under cold stress. Over-expressing SgRVE6 affects expression of 21 circadian clock genes, up-regulates expression of 6 nucleotide binding domain leucine-rich repeats (NB-LRR) encoding genes associated with tobacco cold tolerance, improves physiological responses to low temperature, and endows the transgenic tobaccos with higher tolerance to cold stress. This is the first time a study investigates the biological function of RVE6 in cold responses of plant species.

Inhibition of orf virus replication in goat skin fibroblast cells by the HSPA1B protein, as demonstrated by iTRAQ-based quantitative proteome analysis.

Orf virus (ORFV) infects sheep and goat tissues, resulting in severe proliferative lesions. To analyze cellular protein expression in ORFV-infected goat skin fibroblast (GSF) cells, we used two-dimensional liquid chromatography-tandem mass spectrometry coupled with isobaric tags for relative and absolute quantification (iTRAQ). The proteomics approach was used along with quantitative reverse transcription polymerase chain reaction (RT-qPCR) to detect differentially expressed proteins in ORFV-infected GSF cells and mock-infected GSF cells. A total of 282 differentially expressed proteins were identified. It was found that 222 host proteins were upregulated and 60 were downregulated following viral infection. We confirmed that these proteins were differentially expressed and found that heat shock 70-kDa protein 1B (HSPA1B) was differentially expressed and localized in the cytoplasm. It was also noted that HSPA1B caused inhibition of viral proliferation, in the middle and late stages of viral infection. The differentially expressed proteins were associated with the biological processes of viral binding, cell structure, signal transduction, cell adhesion, and cell proliferation.

Tetra-benzothiadiazole-based [12]Cycloparaphenylene with Bright Emission and Its Supramolecular Assembly.

The radial conjugated π-system of cycloparaphenylenes (CPPs) makes them intriguing fluorophores and unique supramolecular hosts. However, the bright photoluminescence (PL) of CPPs was limited to the blue light and the supramolecular assembly behavior of large CPPs was rarely investigated. Here we present the synthesis of tetra-benzothiadiazole-based [12]cycloparaphenylene (TB[12]CPP), which exhibits a lime to orange PL with an excellent quantum yield up to 82 % in solution. The PL quantum yield of TB[12]CPP can be further improved to 98 % in polymer matrix. Benefiting from its enlarged size, TB[12]CPP can accommodate a fullerene derivative or concave-convex complexes of fullerene and buckybowl through the combined π-π and C-H⋅⋅⋅π interactions. The latter demonstrates the first case of a ternary supramolecule of CPPs.

Spatial acid-base-Pd triple-sites of a hierarchical core-shell structure for three-step tandem reaction.

Spatial catalytic acid-base-Pd triple-sites of a hierarchical core-shell structure have been successfully constructed for a three-step reaction, and exhibited excellent catalytic activity and stability. A catalytic mechanism has been systematically studied via single one- and two-step reactions, and possible molecular reactions have been proposed.

Orf Virus VIR Antagonizes p53-Mediated Antiviral Effects to Facilitate Viral Replication.

As a zoonotic disease, ovine contagious pustular dermatitis (Orf) is a serious threat to sheep as well as humans. Orf virus (ORFV) interferon resistance protein (VIR) is the principal virulence protein that encodes a dsRNA-binding protein to inhibit host antiviral response. p53 is one of the key proteins of the host antiviral innate immunity. It not only enhances type I interferon secretion but also induces apoptosis in infected cells, and plays a crucial role in the immune response against various viral infections. However, it remains to be elucidated what role p53 plays in ORFV replication and whether ORFV's own protein VIR regulates p53 expression to promote self-replication. In this study, we showed that p53 has an antiviral effect on ORFV and can inhibit ORFV replication. In addition, ORFV nonstructural protein VIR interacts with p53 and degrades p53, which inhibits p53-mediated positive regulation of downstream antiviral genes. This study provides new insight into the immune evasion mediated by ORFV and identifies VIR as an antagonistic factor for ORFV to evade the antiviral response.

Treatment of Insulinomas by Laparoscopic Radiofrequency Ablation: Case Reports and Literature Review.

Despite its rarity, insulinoma is the most common type of pancreatic endocrine neoplasm, with an occurrence of 1 to 5 per million per year in the population. Surgical resection or enucleation is the first line of curative treatment choice for insulinoma. Eight patients with symptomatic insulinomas treated by radiofrequency ablation have been described since 2009. In the past two years, we treated two patients with symptomatic insulinomas (one in the pancreatic tail and the other in the pancreatic neck) successfully using laparoscopic radiofrequency ablation. Both patients achieved complete elimination without any significant complications. Our study suggests laparoscopic radiofrequency ablation could be developed as a safe and effective alternative treatment to surgery for the patients with insulinomas who refuse or are not eligible for surgery.

Spatially Ordered Arrangement of Multifunctional Sites at Molecule Level in a Single Catalyst for Tandem Synthesis of Cyclic Carbonates.

With fossil energy resources increasingly drying up and gradually causing serious environmental impacts, pursuing a tandem and green synthetic route for a complex and high-value-added compound by using low-cost raw materials has attracted considerable attention. In this regard, the selective and efficient conversion of light olefins with CO2 into high-value-added organic cyclic carbonates (OCCs) is of great significance owing to their high atom economy and absence of the isolation of intermediates. To fulfill this expectation, a multifunctional catalytic system with controllable spatial arrangement of varied catalytic sites and stable texture, in particular, within a single catalyst, is generally needed. Here, by using a stepwise electrostatic interaction strategy, imidazolium-based ILs and Au nanoparticles (NPs) were stepwise immobilized into a sulfonic group grafted MOF to construct a multifunctional single catalyst with a highly ordered arrangement of catalytic sites. The Au NPs and imidazolium cation are separately responsible for the selective epoxidation and cycloaddition reaction. The mesoporous cage within the MOF enriches the substrate molecules and provides a confined catalytic room for the tandem catalysis. More importantly, the highly ordered arrangement of the varied active sites and strong electrostatic attraction interaction result in the intimate contact and effective mass transfer between the catalytic sites, which allow for the highly efficient (>74% yield) and stable (repeatedly usage for at least 8 times) catalytic transformation. The stepwise electrostatic interaction strategy herein provides an absolutely new approach in fabricating the controllable multifunctional catalysts, especially for tandem catalysis.