Iron-Catalyzed C(sp3)-C(sp3) Coupling to Construct Quaternary Carbon Centers.

The construction of quaternary carbon centers via C-C coupling protocols remains challenging. The coupling of tertiary C(sp3) with secondary or tertiary C(sp3) counterparts has been hindered by pronounced steric clashes and many side reactions. Herein, we have successfully developed a type of bisphosphine ligand iron complex-catalyzed coupling reactions of tertiary alkyl halides with secondary alkyl zinc reagents and efficiently realized the coupling reaction between tertiary C(sp3) and secondary C(sp3) with high selectivity for the initial instance, which provided an efficient method for the construction of quaternary carbon centers with high steric hindrance. The combination of an iron catalyst and directing group of the substrate makes the great challenging transformation possible.

Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine.

BACKGROUND AND PURPOSE: In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression. METHOD: C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR. RESULTS: This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression. CONCLUSION: Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.

Sex-specific scaling of leaf phosphorus vs. nitrogen under unequal reproductive requirements in Eurya japonica, a dioecious plant.

PREMISE: Previous work searching for sexual dimorphism has largely relied on the comparison of trait mean vectors between sexes in dioecious plants. Whether trait scaling (i.e., the ratio of proportional changes in covarying traits) differs between sexes, along with its functional significance, remains unclear. METHODS: We measured 10 vegetative traits pertaining to carbon, water, and nutrient economics across 337 individuals (157 males and 180 females) of the diocious species Eurya japonica during the fruiting season in eastern China. Piecewise structural equation modeling was employed to reveal the scaling relationships of multiple interacting traits, and multivariate analysis of (co)variance was conducted to test for intersexual differences. RESULTS: There was no sexual dimorphism in terms of trait mean vectors across the 10 vegetative traits in E. japonica. Moreover, most relationships for covarying trait pairs (17 out of 19) exhibited common scaling slopes between sexes. However, the scaling slopes for leaf phosphorus (P) vs. nitrogen (N) differed between sexes, with 5.6- and 3.0-fold increases of P coinciding with a 10-fold increase of N in male and female plants, respectively. CONCLUSIONS: The lower ratio of proportional changes in P vs. N for females likely reflects stronger P limitation for their vegetative growth, as they require greater P investments in fruiting. Therefore, P vs. N scaling can be a key avenue allowing for sex-specific strategic optimization under unequal reproductive requirements. This study uncovers a hidden aspect of secondary sex character in dioecious plants, and highlights the use of trait scaling to understand sex-defined economic strategies.

Liver-specific FGFR4 knockdown in mice on an HFD increases bile acid synthesis and improves hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with increased risk in patients with metabolic syndrome. There are no FDA-approved treatments, but FXR agonists have shown promising results in clinical studies for NAFLD management. In addition to FXR, fibroblast growth factor receptor FGFR4 is a key mediator of hepatic bile acid synthesis. Using N-acetylgalactosamine-conjugated siRNA, we knocked down FGFR4 specifically in the liver of mice on chow or high-fat diet and in mouse primary hepatocytes to determine the role of FGFR4 in metabolic processes and hepatic steatosis. Liver-specific FGFR4 silencing increased bile acid production and lowered serum cholesterol. Additionally, we found that high-fat diet-induced liver steatosis and insulin resistance improved following FGFR4 knockdown. These improvements were associated with activation of the FXR-FGF15 axis in intestinal cells, but not in hepatocytes. We conclude that targeting FGFR4 in the liver to activate the intestinal FXR-FGF15 axis may be a promising strategy for the treatment of NAFLD and metabolic dysfunction.

Baccaramiones A-D, Four Highly Oxygenated and Rearranged Trinorditerpenoids from Baccaurea ramiflora.

Baccaramiones A-D (1-4), four highly oxygenated and rearranged trinorditerpenoids, were isolated from Baccaurea ramiflora. Compound 1 is a 1(10 → 5)-abeo-15,16,17-trinor-ent-abietane featuring a unique 5/6/6 spirocyclic scaffold, and 2-4 are the first example of a novel 20(10 → 5)-abeo-15,16,17-trinor-ent-abietane skeleton. Their structures were established by spectroscopic analysis, X-ray crystallography, and electronic circular dichroism calculations. A plausible biosynthetic pathway for 1-4 was proposed. Interestingly, compounds 3 and 4 exhibited significant immunosuppressive activities against concanavalin A-induced T cell proliferation and lipopolysaccharide-induced B cell proliferation in vitro.

A nano-innate immune system activator for cancer therapy in a 4T1 tumor-bearing mouse model.

BACKGROUND: Harnessing the immune system to fight cancer has led to prominent clinical successes. Strategies to stimulate innate immune effectors are attracting considerable interest in cancer therapy. Here, through conjugating multivalent Fc fragments onto the surface of mesoporous silica nanoparticles (MSN), we developed a nanoparticle-based innate immune system activator (NISA) for breast cancer immunotherapy. METHODS: NISA was prepared through conjugating mouse IgG3 Fc to MSN surface. Then, long-chain PEG5000, which was used to shield Fc to confer nanoparticle colloidal stability, was linked to the MSN surface via matrix metalloprotease-2 (MMP-2)-cleavable peptide (GPLGIAGQC). The activation of multiple components of innate immune system, including complement and the innate cells (macrophages and dendritic cells) and the associated anticancer effect were investigated. RESULTS: Fc fragments of NISA can be exposed through hydrolysis of long-chain PEG5000 by highly expressed MMP-2 in tumor microenvironment. Then, effective stimulation and activation of multiple components of innate immune system, including complement, macrophages, and dendritic cells were obtained, leading to efficient antitumor effect in 4T1 breast cancer cells and orthotopic breast tumor model in mice. CONCLUSIONS: The antitumor potency conferred by NISA highlights the significance of stimulating multiple innate immune elements in cancer immunotherapy.

Rejection of Acellular Porcine Corneal Stroma Transplantation During Coronavirus Disease 2019 Pandemic.

ABSTRACT: To report 2 successfully managed cases of graft rejection with acellular porcine corneal stroma (APCS) transplantation in patients with fungal corneal ulcer. Two patients were diagnosed with fungal corneal ulcer and received APCS transplantation. Graft rejection developed due to the lost follow-up during the period of coronavirus disease 2019 outbreak. Amniotic membranes transplantation and cauterization of neovascularization was performed, respectively. The graft failure resolved successfully after the procedure. To the best of our knowledge, amniotic membranes transplantation and cauterization of new vessels are the firstly reported in treating APCS graft failure. Amniotic membranes transplantation or cauterization of neovascularization appear to be a safe and costeffective method for treating graft failure.

Whole-Genome Sequence of Diaporthe citri Isolate NFHF-8-4, the Causal Agent of Citrus Melanose.

Diaporthe species are the causal agents of melanose, stem-end rot, and gummosis diseases of citrus. D. citri is the predominant species on different citrus varieties. These diseases exceedingly reduce quality and marketability of fresh fruits. Melanose on fruits especially causes massive economic losses. The infection mechanisms of D. citri are still unclear and the genome sequence of D. citri has not been released. In order to systemically explore the interaction between citrus and D. citri, we sequenced the whole-genome of D. citri NFHF-8-4, which was isolated from a sample with melanose in Jiangxi Province. The NFHF-8-4 genome sequence will provide valuable information for studying the development process, infection process, and resistance to fungicides mechanisms in D. citri.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Linking intraspecific trait variability and spatial patterns of subtropical trees.

The importance of intraspecific trait variability (ITV) to the spatial distribution of individual species is unclear. We hypothesized that intraspecific trait dispersions underlying niche processes deviate more from null model expectations, by reducing their spread (range and variance), kurtosis, and standard deviation of near-neighbor distance, for species with aggregated than those with random distributions. The link between species' spatial distributions and ITV patterns was examined using an individual tree-based trait data set, in which specific leaf area, mean leaf area, leaf dry matter content, and diameter at breast height were measured for 18,773 stems of 45 species in a 4.84 ha mapped subtropical forest plot in China. The nearest-neighbor distance analysis showed that, of 45 species, 14 species were distributed in random and 31 species were distributed in aggregation, while no species was distributed in uniform in the plot. The dispersions of all studied traits in species with an aggregated distribution on average deviated more strongly from the null expectation than those in species with a random distribution and that the extent of deviation was negatively associated with the degree of spatial randomness across species. Our results indicate that niche processes are primarily responsible for the spatial structure of species with aggregated distributions, while stochastic processes drive those with random distributions. Our results highlight the fundamental role of ITV in shaping spatial patterns of co-existing species.

Electrostatic Potential Determined Magnetic Dynamics Observed in Two Mononuclear ß-Diketone Dysprosium(III) Single-Molecule Magnets.

Two ß-diketone mononuclear Dy(III) compounds, formulated as Dy(BTFA)3(H2O)2 (1) and Dy(BTFA)3(bpy) (2) (BTFA = 3-benzoyl-1,1,1-trifluoroacetone, bpy = 2,2'-bipyridine), were prepared. Compound 1 can be identified to transform to 2 in the attendance of bpy coligand, when the local geometry symmetry of eight-coordinated Dy(III) ion changes from a dodecahedron (D2d) in 1 to a square antiprism (D4d) in 2. Fine-tuning structure aroused by auxiliary ligand has dramatical impact on magnetic properties of compounds 1 and 2. Magnetic investigations demonstrate that both 1 and 2 display dynamic magnetic relaxation of single-molecule magnets (SMMs) behavior with different effective barriers (ΔE/kB) of 93.09 K for 1 under zero direct-current (DC) field as well as 296.50 K for 1 and 151.01 K for 2 under 1200 Oe DC field, respectively. As noticed, compound 1 possesses higher effective barrier than 2, despite 1 exhibiting a lower geometrical symmetry of the Dy(III) ion. Ab initio studies reveal that the Kramers doublet ground state is predominantly axial with the gz tensors of two compounds matching the Ising-limit factor of 20 anticipated for the pure MJ = ±15/2 state. Electrostatic analysis confirms the uniaxial anisotropy directions, highlighting that the proper electrostatic distribution of the coordination sphere around Ln(III) center is the critical factor to improve the magnetic anisotropy and determine the dynamic behaviors of SMMs.

Crystal structure of a copper-transporting PIB-type ATPase.

Heavy-metal homeostasis and detoxification is crucial for cell viability. P-type ATPases of the class IB (PIB) are essential in these processes, actively extruding heavy metals from the cytoplasm of cells. Here we present the structure of a PIB-ATPase, a Legionella pneumophila CopA Cu(+)-ATPase, in a copper-free form, as determined by X-ray crystallography at 3.2 Å resolution. The structure indicates a three-stage copper transport pathway involving several conserved residues. A PIB-specific transmembrane helix kinks at a double-glycine motif displaying an amphipathic helix that lines a putative copper entry point at the intracellular interface. Comparisons to Ca(2+)-ATPase suggest an ATPase-coupled copper release mechanism from the binding sites in the membrane via an extracellular exit site. The structure also provides a framework to analyse missense mutations in the human ATP7A and ATP7B proteins associated with Menkes' and Wilson's diseases.

Eu-MOFs with 2-(4-carboxyphenyl)imidazo[4,5-f]-1,10-phenanthroline and ditopic carboxylates as coligands: synthesis, structure, high thermostability, and luminescence properties.

Hydrothermal reactions of europium(III) salt with 2-(4-carboxyphenyl)imidazo[4,5-f]-1,10-phenanthroline and dicarboxylic acid as coligands-benzene-1,4-dicarboxylic acid, 4,4'-biphenyldicarboxylic acid, 2,5-dibromoterephthalic acid, and naphthalene-1,4-dicarboxylic acid-lead to four europium fluorescent materials (1-4). Structural analyses reveal that 1-4 have binuclear 3D metal-organic frameworks with different channels, void volumes, and conjugated structures tuned by ditopic carboxylates. There are no latticed and coordinated water molecules occurring in 1-3, while the free water molecules fill in 1D channels of 4. 4' was readily obtained via water removal of 4. Thermal analyses of all compounds show the high thermal stability of the main framework up to 450 °C. Optical studies indicate that 1-4 and 4' show the characteristic red luminescence emission of the Eu(III) ion in the visible regions at room temperature. On the basis of emission spectra, their luminescence lifetimes were determined. In particular, compound 4' shows a longer lifetime (τ = 0.942 ms) and significantly enhanced quantum yield (39%) compared with those of 1 (11%, 0.770 ms), 2 (4%, 0.414 ms), 3 (18%, 0.807 ms), and 4 (26%, 0.858 ms).

[Lipoprotein lipase and diabetic cardiomyopathy].

Lipoprotein lipase (LPL) hydrolyzes plasma triglyceride-rich lipoproteins into free fatty acids (FFA) to provide energy for cardiac tissue. During diabetes, cardiac energy supply is insufficient due to defected utilization of glucose. As a compensation of cardiac energy supply, FFAs are released through the hydrolysis of very low density lipoprotein (VLDL) and chylomicrons (CM) due to activation of LPL activity. In diabetic patients, activated LPL activity and elevated FFAs result in the intracellular accumulation of reactive oxygen species and lipids in myocardium and potentially induce the diabetic cardiomyopathy (DCM). The present review summarizes the regulatory mechanisms of myocardial LPL and the pathogenesis of DCM induced by LPL and provides novel therapeutic targets and pathways for DCM.

Cobalt-based Polymerized Porphyrinic Network for Visible-light-driven CO2 Reduction.

Visible-light-driven conversion of carbon dioxide to valuable compounds and fuels is an important but challenging task due to the inherent stability of the CO2 molecules. Herein, we report a series of cobalt-based polymerized porphyrinic network (PPN) photocatalysts for CO2 reduction with high activity. The introduction of organic groups results in the addition of more conjugated electrons to the networks, thereby altering the molecular orbital levels within the networks. This integration of functional groups effectively adjusts the levels of the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO). The PPN(Co)-NO2 exhibits outstanding performance, with a CO evolution rate of 12 268 µmol/g/h and 85.8% selectivity, surpassing most similar photocatalyst systems. The performance of PPN(Co)-NO2 is also excellent in terms of apparent quantum yield (AQY) for CO production (5.7% at 420 nm). Density functional theory (DFT) calculations, time-resolved photoluminescence (TRPL), and electrochemical tests reveal that the introduction of methyl and nitro groups leads to a narrower energy gap, facilitating a faster charge transfer. The coupling reaction in this study enables the formation of stable C-C bonds, enhancing the structural regulation, active site diversity, and stability of the catalysts for photocatalytic CO2 reduction. This work offers a facile strategy to develop reliable catalysts for efficient CO2 conversion.

Age-related changes in meningeal lymphatic function are closely associated with vascular endothelial growth factor-C expression.

Meningeal lymphatic vessels (MLVs) have crucial roles in removing metabolic waste and toxic proteins from the brain and transporting them to the periphery. Aged mice show impaired meningeal lymphatic function. Nevertheless, as the disease progresses, and significant pathological changes manifest in the brain, treating the condition becomes increasingly challenging. Therefore, investigating the alterations in the structure and function of MLVs in the early stages of aging is critical for preventing age-related central nervous system degenerative diseases. We detected the structure and function of MLVs in young, middle-aged, and aged mice. Middle-aged mice, compared with young and aged mice, showed enhanced meningeal lymphatic function along with MLV expansion and performed better in the Y maze test. Moreover, age-related changes in meningeal lymphatic function were closely associated with vascular endothelial growth factor-C (VEGF-C) expression in the brain cortex. Our data suggested that the cerebral cortex may serve as a target for VEGF-C supplementation to ameliorate meningeal lymphatic dysfunction, thus providing a new strategy for preventing age-related central nervous system diseases.

Primary malignant melanoma of the esophagus combined with squamous cell carcinoma: A case report.

BACKGROUND: Primary malignant melanoma of the esophagus is a rare malignant tumor of the esophagus, and its combination with squamous cell carcinoma is also rare. Here, we report the diagnosis and treatment of a case of primary esophageal malignant melanoma combined with squamous cell carcinoma. CASE SUMMARY: A middle-aged man underwent gastroscopy for dysphagia. Gastroscopy revealed multiple bulging esophageal lesions, and after pathologic and immunohistochemical analyses, the patient was finally diagnosed with "malignant melanoma with squamous cell carcinoma". This patient received comprehensive treatment. After one year of follow-up, the patient was in good condition, and the esophageal lesions seen on gastroscopy were controlled, but unfortunately, liver metastasis occurred. CONCLUSION: When multiple esophageal lesions are present, the possibility of multiple pathological sources should be considered. This patient was diagnosed with primary esophageal malignant melanoma combined with squamous cell carcinoma.

Acute acquired concomitant esotropia with congenital paralytic strabismus: A case report.

BACKGROUND: An unusual case of acute acquired concomitant esotropia (AACE) with congenital paralytic strabismus in the right eye is reported. CASE SUMMARY: A 23-year-old woman presented with complaints of binocular diplopia and esotropia of the right eye lasting 4 years and head tilt to the left since 1 year after birth. The Bielschowsky head tilt test showed right hypertropia on a right head tilt. She did not report any other intracranial pathology. A diagnosis of AACE and right congenital paralytic strabismus was made. Then, she underwent medial rectus muscle recession and lateral rectus muscle resection combined with inferior oblique muscle myectomy in the right eye. One day after surgery, the patient reported that she had no diplopia at either distance or near fixation and was found to be orthophoric in the primary position; furthermore, her head posture immediately and markedly improved. CONCLUSION: In future clinical work, in cases of AACE combined with other types of strabismus, we can perform conventional single surgery for both at the same time, and the two types of strabismus can be solved simultaneously.

Retraction notice to "Betulinic acid downregulates expression of oxidative stress-induced lipoprotein lipase via PKC/ERK/c-Fos pathways in RAW264.7 macrophages" [Biochimie 119C (2015) 192-203].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Concerns raised by Dr. Sander Kersten in PubPeer pointed out that Figs. 6.1B and 6.2B of this paper were different figures but the legends and Western blots were identical; the quantification was also seen to be different between the two figures. Shortly afterwards, the authors asked to publish a corrigendum for part B of Fig. 6.1, including images of western blots and associated bar plots. Subsequently, the journal conducted an investigation and found evidence that there had been improper manipulation and duplication of images in Fig. 2 E, 6.2 B, 5 A and and 6.2 D, as shown by the reuse of several western blot bands with approximately 180° rotation in each case. After raising the complaint with the authors, the corresponding author agreed that the paper should be retracted. The authors apologise to the readers of the journal.

Biosynthetic pathway of prescription bergenin from Bergenia purpurascens and Ardisia japonica.

Bergenin is a typical carbon glycoside and the primary active ingredient in antitussive drugs widely prescribed for central cough inhibition in China. The bergenin extraction industry relies on the medicinal plant species Bergenia purpurascens and Ardisia japonica as their resources. However, the bergenin biosynthetic pathway in plants remains elusive. In this study, we functionally characterized a shikimate dehydrogenase (SDH), two O-methyltransferases (OMTs), and a C-glycosyltransferase (CGT) involved in bergenin synthesis through bioinformatics analysis, heterologous expression, and enzymatic characterization. We found that BpSDH2 catalyzes the two-step dehydrogenation process of shikimic acid to form gallic acid (GA). BpOMT1 and AjOMT1 facilitate the methylation reaction at the 4-OH position of GA, resulting in the formation of 4-O-methyl gallic acid (4-O-Me-GA). AjCGT1 transfers a glucose moiety to C-2 to generate 2-Glucosyl-4-O-methyl gallic acid (2-Glucosyl-4-O-Me-GA). Bergenin production ultimately occurs in acidic conditions or via dehydration catalyzed by plant dehydratases following a ring-closure reaction. This study for the first time uncovered the biosynthetic pathway of bergenin, paving the way to rational production of bergenin in cell factories via synthetic biology strategies.

Is endoscopic mucosal ablation a valid option for treating colon polyps?

The present letter to editor is related to endoscopic mucosal ablation (EMA). EMA is safe and effective in the treatment of colonic polyps when endoscopic resection is not possible or available, but the indication of EMA should be determined for a further large number of studies. EMA should be used with caution for larger lesions.