Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in psoriasis.

Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.

Buffalo yogurt fermented with commercial starter and Lactobacillus plantarum originating from breast milk lowered blood pressure in pregnant hypertensive rats.

Nutritional therapy, which may have advantages over medication, is being investigated as a novel treatment for pregnancy-induced hypertension. Several studies have shown that probiotic yogurt supplementation during pregnancy has beneficial effects on maternal and fetal health. In this study, fermented buffalo milk was produced with yogurt culture and Lactobacillus plantarum B, a probiotic isolated from healthy breast milk with high angiotensin-converting enzyme inhibitory activity. The fermentation conditions under which the angiotensin-converting enzyme (ACE) inhibitory activity reached 84.51% were optimized by the response surface method as follows: 2 × 106 cfu/mL of L. plantarum B, yogurt culture 2.5 × 105 cfu/mL, and 8 h at 37°C. The distribution of ACE inhibitory peptides from fermented buffalo milk and fermented cow milk were further analyzed by liquid chromatography-mass spectrometry. By searching according to the structural features of ACE inhibitory peptides, 29 and 11 peptides containing ACE inhibitory peptide features were found in fermented buffalo milk and fermented cow milk, respectively. To investigate the in vivo antihypertensive activity of fermented buffalo milk, 18 pregnant rats were divided into 3 groups (n = 6 in each group) and administered 10 mL of normal saline, yogurt (20 mg/kg), or labetalol hydrochloride (4 mg/kg) daily from the beginning of pregnancy to parturition. To induce hypertension, methyl nitrosoarginine (125 mg/kg) was injected subcutaneously every day from d 15 of pregnancy to the day of delivery. Blood pressure was not significantly changed in the yogurt and labetalol groups after induction of hypertension and was lower compared with the normal saline group, but there was no difference between the yogurt and labetalol groups. This implied that the buffalo yogurt had a preventive and antihypertensive effect in the pregnancy-induced hypertensive rat model. Further studies to determine the mechanism of action, as well as a randomized control trial, are warranted.

A Fully Amorphous, Dynamic Cross-Linked Polymer Electrolyte for Lithium-Sulfur Batteries Operating at Subzero-Temperatures.

Solid-state lithium-sulfur batteries have shown prospects as safe, high-energy electrochemical storage technology for powering regional electrified transportation. Owing to limited ion mobility in crystalline polymer electrolytes, the battery is incapable of operating at subzero temperature. Addition of liquid plasticizer into the polymer electrolyte improves the Li-ion conductivity yet sacrifices the mechanical strength and interfacial stability with both electrodes. In this work, we showed that by introducing a spherical hyperbranched solid polymer plasticizer into a Li+ -conductive linear polymer matrix, an integrated dynamic cross-linked polymer network was built to maintain fully amorphous in a wide temperature range down to subzero. A quasi-solid polymer electrolyte with a solid mass content >90 % was prepared from the cross-linked polymer network, and demonstrated fast Li+ conduction at a low temperature, high mechanical strength, and stable interfacial chemistry. As a result, solid-state lithium-sulfur batteries employing the new electrolyte delivered high reversible capacity and long cycle life at 25 °C, 0 °C and -10 °C to serve energy storage at complex environmental conditions.

Photon color conversion enhancement of colloidal quantum dots inserted into a subsurface laterally-extended GaN nano-porous structure in an InGaN/GaN quantum-well template.

To improve the color conversion performance, we study the nanoscale-cavity effects on the emission efficiency of a colloidal quantum dot (QD) and the Förster resonance energy transfer (FRET) from quantum well (QW) into QD in a GaN porous structure (PS). For this study, we insert green-emitting QD (GQD) and red-emitting QD (RQD) into the fabricated PSs in a GaN template and a blue-emitting QW template, and investigate the behaviors of the photoluminescence (PL) decay times and the intensity ratios of blue, green, and red lights. In the PS samples fabricated on the GaN template, we observe the efficiency enhancements of QD emission and the FRET from GQD into RQD, when compared with the samples of surface QDs, which is attributed to the nanoscale-cavity effect. In the PS samples fabricated on the QW template, the FRET from QW into QD is also enhanced. The enhanced FRET and QD emission efficiencies in a PS result in an improved color conversion performance. Because of the anisotropic PS in the sample surface plane, the polarization dependencies of QD emission and FRET are observed.

Total Synthesis of (+)-Haperforin G.

(+)-Haperforin G was synthesized in 20 steps from commercially available starting materials. A Co-catalyzed intramolecular Pauson-Khand reaction was used for stereoselective construction of cyclopentanone bearing an all-carbon quaternary stereogenic center at the bridge-head position. Light-initiated photocatalysis was used for convergent and asymmetric cross-coupling of the unstabilized C(sp3) radical with an enone. The developed chemistry paves the way to the synthesis of structurally diverse analogs of haperforin G (6).

Evolutionary Changes in Pathology and Our Understanding of Disease.

The history of pathology involves human dissections, autopsies, microscopy, as well as the development of histopathological, immunohistochemical, and molecular techniques. Through these methods, our understanding of anatomy and disease improved, and models of pathogenesis were gradually refined over time. This review discusses key milestones in the development of pathology as a branch of medical science, from ancient civilizations to the modern day.

Noncoordinating Flame-Retardant Functional Electrolyte Solvents for Rechargeable Lithium-Ion Batteries.

In Li-ion batteries, functional cosolvents could significantly improve the specific performance of the electrolyte, for example, the flame retardancy. In case the cosolvent shows strong Li+-coordinating ability, it could adversely influence the electrochemical Li+-intercalation reaction of the electrode. In this work, a noncoordinating functional cosolvent was proposed to enrich the functionality of the electrolyte while avoiding interference with the Li storage process. Hexafluorocyclotriphosphazene, an efficient flame-retardant agent with proper physicochemical properties, was chosen as a cosolvent for preparing functional electrolytes. The nonpolar phosphazene molecules with low electron-donating ability do not coordinate with Li+ and thus are excluded from the primary solvation sheath. In graphite-anode-based Li-ion batteries, the phosphazene molecules do not cointercalate with Li+ into the graphite lattice during the charging process, which helps to maintain integral anode structure and interface and contributes to stable cycling. The noncoordinating cosolvent was also applied to other types of electrode materials and batteries, paving a new way for high-performance electrochemical energy storage systems with customizable functions.

Nanoscale-cavity enhancement of color conversion with colloidal quantum dots embedded in the surface nano-holes of a blue-emitting light-emitting diode.

Although the method of inserting colloidal quantum dots (QDs) into deep nano-holes fabricated on the top surface of a light-emitting diode (LED) has been widely used for producing effective Förster resonance energy transfer (FRET) from the LED quantum wells (QWs) into the QDs to enhance the color conversion efficiency, an important mechanism for enhancing energy transfer in such an LED structure was overlooked. This mechanism, namely, the nanoscale-cavity effect, represents a near-field Purcell effect and plays a crucially important role in enhancing the color conversion efficiency. Here, we demonstrate the results of LED performance, time-resolved photoluminescence (TRPL), and numerical simulation to elucidate the nanoscale-cavity effect on color conversion by inserting a photoresist solution of red-emitting QDs into the nano-holes fabricated on a blue-emitting QW LED. Based on the TRPL study of the inserted QDs in a nano-hole structure fabricated on an un-doped GaN template of no QW, it is found that the emission efficiency of the inserted QDs is significantly increased due to the nanoscale-cavity effect. From the simulation study, it is confirmed that this effect can also increase the FRET efficiency, particularly for those radiating dipoles in the QWs oriented perpendicular to the sidewalls of the nano-holes. In the nanoscale-cavity effect, the enhanced near field distribution inside a nano-hole excited by a light emitter modifies its own radiation behavior through the Purcell effect such that its far-field emission becomes stronger.

Eosinophilic angiocentric fibrosis and immunoglobulin 4-related disease revisited.

Eosinophilic angiocentric fibrosis (EAF) has been postulated to lie on the spectrum of IgG4-related disease (IgG4-RD) in a study reported in 2011. However, the aetiology of EAF remains controversial, despite increasing literature reporting IgG4-RD targeted investigations in those studies. This review aims to formally evaluate the relationship between EAF and IgG4-RD using the latest 2019 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification scheme for IgG4-RD. A literature search was performed on the PubMed database for all studies describing patients diagnosed with EAF. Additionally, two EAF cases were retrospectively identified from our institution and presented. The demographics, clinical presentation, histological and serological data of each patient were analysed. A total of 20 cases were evaluated, including 18 patients from 14 articles in the English literature and two cases from our institution. Six of 20 (30%) patients with EAF met the criteria for IgG4-RD with the 2019 ACR/EULAR classification scheme. This represents the first attempt at formally evaluating the relationship between EAF and IgG4-RD using a validated set of classification criteria. Using the currently available data, a small proportion of patients with EAF met the criteria for IgG4-RD. However, various limitations of this study suggest that further efforts at disease characterization of EAF may be required.

Quantifying the potential of morphological parameters for human dental identification: part 2-selecting the strongest identifiers in mandibular permanent teeth.

The current study aimed to select the best dental morphological identifiers for human identification. Sixty-two panoramic radiographs were collected retrospectively, in which six measurements were performed on all seven mandibular left permanent teeth: tooth length (TL), crown length (CL), root length (RL), crown width (CW), cervical width (CEJW), and root width (RW). Nine length-width ratios were then calculated using these measurements. Three groups of statistics were considered: (1) inter-observer reliability quantified by intra-class correlation (ICC); (2) mean "potential set"; and (3) Spearman correlation. A step-by-step cascade was then established based on selected parameters. In a univariate approach, the following parameters were the best identifiers: TL/CW for tooth 36 (ICC 0.82; mean potential set 13.7%), TL/CEJW for tooth 35 (ICC 0.87; mean potential set 15.2%), and TL/RW for tooth 32 (ICC 0.89; mean potential set 16.0%). The correlations between these three parameters ranged from 0.24 to 0.47. In a multivariate approach, the following parameters had the best identifying capacity: all parameters combined for tooth 31 (mean potential set 8.1%), for tooth 35 (mean potential set 11.9%), and for tooth 32 (mean potential set 16.3%). In conclusion, a single ratio in a specific tooth narrows down the potential set of matches, but the mean potential set remains relatively large. Combining all ratios of a single specific tooth increases the certainty of the match. In particular, tooth 31 was the strongest identifier.

ROS-mediated time-varying cytotoxic effects on Phaeodactylum tricornutum under the stress of commercial naphthenic acids.

The aquatic toxicity and ecological risks of naphthenic acids (NAs) in marine environments have attracted an increasing amount of attention. However, there remains a lack of methodologies for the long-term risk assessment of NAs on marine ecosystems after high acid crude oil spill accidents. In this study, using the model microalgae Phaeodactylum tricornutum as the target object, the time-effect manner under NAs stress is investigated for a continuous 24-144 h. We found that: 1) NAs caused photosynthetic damage and persistent oxidative stress that slowed the growth rate and limited the maximum growth of P. tricornutum population within 24 h to 144 h of exposure, especially under the high concentration treatment; 2) Within 144 h, NAs can cause oxidative stress to P. tricornutum. The damage to cell membrane and radical oxidative species (ROS) accumulation of P. tricornutum were observed as obvious time-effect; 3) Under NAs stress, the two types of cell death (accidental cell death and regulated cell death) of P. tricornutum cell mediated by ROS played different roles in the population growth inhibition of P. tricornutum. Moreover, regulated cell death of the P. tricornutum cell was accompanied by PS externalization, DNA fragment and the G2/M phase stagnation acted as an adaptive regulatory mechanism under NAs stress. This explained the dose-time-effects of NAs on the population growth of P. tricornutum. Overall, the results suggested that NAs have a lasting effect on marine phytoplankton populations, and long-term risk assessments are required after high acid crude oil spill accidents. This is the first attempt to identify the different types of death at the cellular level to explain the time-effect toxicity at the population level of marine microalgae when exposed to NAs. This research will provide a new approach to facilitate further risk assessments for NAs and related contaminants in marine ecosystems.

Enhancement of the Modulation Response of Quantum-Dot-Based Down-Converted Light through Surface Plasmon Coupling.

In this paper, we first elaborate on the effects of surface plasmon (SP) coupling on the modulation responses of the emission of a light-emitting diode (LED) and its down-converted lights through colloidal quantum dots (QDs). The results of our past efforts for this subject are briefly discussed. The discussions lay the foundation for the presentation of the new experimental data of such down-converted lights in this paper. In particular, the enhancement of the modulation bandwidth (MB) of a QD-based converted light through SP coupling is demonstrated. By linking green-emitting QDs (GQDs) and/or red-emitting QDs (RQDs) with synthesized Ag nano-plates via surface modifications and placing them on a blue-emitting LED, the MBs of the converted green and red emissions are significantly increased through the induced SP coupling of the Ag nano-plates. When both GQD and RQD exist and are closely spaced in a sample, the energy transfer processes of emission-reabsorption and Förster resonance energy transfer from GQD into RQD occur, leading to the increase (decrease) in the MB of green (red) light. With SP coupling, the MB of a mixed light is significantly enhanced.

Bioinspired Palladium-Catalyzed Intramolecular C(sp3 )-H Activation for the Collective Synthesis of Proline Natural Products.

Bioinspired palladium-catalyzed intramolecular cyclization of amino acid derivatives containing a vinyl iodide moiety by C-H activation enabled rapid access to a wide range of functionalized proline derivatives with an exocyclic olefin. To demonstrate the practicality of this methodology, the functionalized prolines were used as intermediates for the synthesis of several natural products: lucentamycin A, oxotomaymycin, oxoprothracarcin, and barmumycin.

The role of long non-coding RNAs in drug resistance of cancer.

Long non-coding RNAs (lncRNAs), a class of long RNAs, are longer than 200 nucleotides in length but lack protein-coding capacity. LncRNAs, as critical genomic regulators, are involved in genomic imprinting regulation, histone modification and gene expression regulation as well as tumor initiation and progression. However, it is also found that lncRNAs are associated with drug resistance in several types of cancer. Drug resistance is an important reason for clinical chemotherapy failure, and the molecular mechanism of tumor resistance is complex, which is a process of multi-cause, multi-gene and multi-signal transduction pathway interaction. Then comprehending the mechanisms of chemoresistance will help find ways to control the tumor progression effectively. Therefore, in this review, we will construct lncRNAs /drug resistance interaction network and shed light on the role of lncRNAs in drug resistance.

Do annual and perennial populations of an insect-pollinated plant species differ in mating system?

BACKGROUND AND AIMS: Theory predicts that outcrossing should be more prevalent among perennials than annuals, a pattern confirmed by comparative evidence from diverse angiosperm families. However, intraspecific comparisons between annual and perennial populations are few because such variation is uncommon among flowering plants. Here, we test the hypothesis that perennial populations outcross more than annual populations by investigating Incarvillea sinensis, a wide-ranging insect-pollinated herb native to China. The occurrence of both allopatric and sympatric populations allows us to examine the stability of mating system differences between life histories under varying ecological conditions. METHODS: We estimated outcrossing rates and biparental inbreeding in 16 allopatric and five sympatric populations in which both life histories coexisted using 20 microsatellite loci. In each population we measured height, branch number, corolla size, tube length and herkogamy for ~30 individuals. In a sympatric population, we recorded daily flower number, pollinator visitation and the fruit and seed set of annual and perennial plants. KEY RESULTS: As predicted, outcrossing rates (t) were considerably higher in perennial (mean = 0.76) than annual (mean = 0.09) populations. This difference in mating system was also maintained at sympatric sites where plants grew intermixed. In both allopatric and sympatric populations the degree of herkogamy was consistently larger in outcrossing than selfing plants. Perennials were more branched, with more and larger flowers than in annuals. In a sympatric population, annuals had a significantly higher fruit and seed set than perennials. CONCLUSIONS: Genetically based differences in herkogamy between annuals and perennials appear to play a key role in governing outcrossing rates in populations, regardless of variation in local ecological conditions. The maintenance of mating system and life history trait differentiation between perennial and annual populations of I. sinensis probably results from correlated evolution in response to local environmental conditions.

Paired Electrolysis Enabled Ni-Catalyzed Unconventional Cascade Reductive Thiolation Using Sulfinates.

Herein, we have reported a nickel-catalyzed cascade reductive thiolation of aryl halides with sulfinates driven by paired electrolysis. This protocol uses sulfinates as the sulfur source, and various thioethers could be synthesized under mild conditions. By mechanism exploration, we find that a cascade chemical step is allowed on the electrode interface and could alter the reaction pathway in paired electrolysis, whose findings could help the discovery of novel cascade reactions with unique reactivity.

Total Synthesis of (+)-Haperforin G.

A concise chemical synthesis of (+)-haperforin G in 20 steps from commercially available starting materials is achieved with the integration of the Co-catalyzed intramolecular Pauson-Khand reaction for the stereoselective construction of cyclopentanone bearing an all-carbon quaternary stereogenic center at the bridge-head position and the light-initiated photocatalysis for convergent and asymmetric cross-coupling of the unstabilized C(sp3)-radical with an enone. The developed chemistry paves the way to synthesizing structurally diverse analogs of haperforin G (6).

The kite flap for reconstructing tumour excision wounds in the middle and lower face: a retrospective study.

OBJECTIVE: The aim of this study was to present our experience with a kite flap in reconstruction of facial wounds after malignant tumour excision. METHOD: From October 2008 to September 2017, patients with facial malignant tumour were treated in the Xinjiang Uygur Autonomous Region Bazhou People's Hospital with kite flaps after complete excision. The survival rate, colour, cicatrix of the flap and patient satisfaction were recorded after surgery. RESULTS: A total of 95 patients were included in the study. During follow-up, from six months to 8 years, all the kite flaps achieved primary closure and survived well, and the colour and texture were similar to the surrounding skin with no obvious scar. Dysfunction, complications and recurrence had not been reported. CONCLUSION: The kite flap may be a good option in reconstructing facial wounds after malignant tumour excision (diameters 1-5cm). It is a simple surgical method with sufficient blood supply and extensive adaptability. For patients in this study, no obvious scars were formed and the recipient site matched well with the donor site.

[Quality evaluation of Gastrodiae Rhizoma standard decoction based on UPLC fingerprint and quantitative analysis multi-components method].

To establish the quantitative analysis multi-components with a single-marker(QAMS) method for six components and fingerprint of standard decoction of Gastrodiae Rhizoma, verify the accuracy and feasibility of the method, and evaluate the quality of standard decoction. Based on UPLC with gastrodin as the internal standard, relative correction factors of p-hydroxybenzyl alcohol, parishin E, parishin B, parishin C, parishin A and gastrodin were determined by investigating the column temperature, flow rate, chromatographic columns and multi-point concentration correction. The total contents in 18 batches of standard decoction of Gastrodiae Rhizoma and the similarity were determined to calculate the similarity. The results of standard curve method, external standard one-point method and quantitative analysis multi-components with a single-marker(QAMS) were compared, and the results showed that there was no significant difference among these three methods. By analyzing the results of standard decoctions from different origins, it can be seen that the quality of Gastrodia standard decoctions derived from Anhui and Yunnan was better, followed by Shaanxi and Hubei, and relatively poor in Gansu, with similarities all above 0.90 in the fingerprints. Therefore, the QAMS method that can measure the contents of gastrodin, p-hydroxybenzyl alcohol, parishin E, parishin B, parishin C and parishin A in standard decoction of Gastrodiae Rhizoma combined with fingerprint is accurate, feasible and fast, which can be used to evaluate the quality of standard decoction of Gastrodiae Rhizoma, and also provide a reference for the research on the quality standards of raw materials for Gastrodiae Rhizoma prepared slices and alike.

Targeting Trim69 alleviates high fat diet (HFD)-induced hippocampal injury in mice by inhibiting apoptosis and inflammation through ASK1 inactivation.

The prevalence of obesity is growing, and high fat diet (HFD)-induced obesity can alter the brain and cognition. However, the link between HFD, hippocampal function, and inflammation is still not fully understood. Tripartite motif (TRIM) family has been implicated in various cellular processes, such as apoptosis, neurogenesis, and innate immune responses. Trim69, a member of TRIM family, was investigated in the present study to determine its role in HFD-induced hippocampal damage. Here, we first found that hippocampal Trim69 expression was markedly down-regulated in wild-type (WT) mice challenged with HFD. Trim69 knockout (KO) mice exhibited an exaggerated version of the metabolic disorder after HFD challenge, as evidenced by their increased body weight and elevated insulin resistance. HFD-induced hippocampal injury was further aggravated by Trim69 deletion, as confirmed by the reduced survival of neurons and increased level of apoptotic cell death. In addition, the inflammatory response triggered by HFD was more pronounced in the hippocampi of Trim69-KO mice after blockage of the activation of the nuclear factor kappa B (NF-κB) signaling pathway. Phosphorylation of mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), MKK7, and c-Jun N-terminal kinase (JNK) in the hippocampi of HFD-challenged mice was intensified by the loss of Trim69. Hippocampal-apoptosis-signal-regulating kinase 1 (ASK1) phosphorylation was also found to be up-regulated by HFD, especially in mice with Trim69 deletion. Of note, we found that Trim69 directly interacted with and deubiquitinated ASK1 in microglial cells. Microglial cell-specific suppression of Trim69 exacerbated inflammation and apoptosis in response to lipopolysaccharide (LPS). Trim69 over-expression markedly alleviated LPS-induced inflammatory response and apoptotic cell death in microglial cells. Together, these results indicated that Trim69 might be a functionally essential inhibitor of ASK1 activation during the pathogenesis of hippocampal inflammation and apoptosis, and it could serve as a novel molecular target for obesity-associated brain damage.