Protective Effects of Pear Extract on Skin from In Vitro and In Vivo UVA-Induced Damage.

The ancient Chinese medical book "Compendium of Materia Medica" records that pears can relieve symptoms of respiratory-related diseases. Previous research has shown that pear Pyrus Pyrifolia (Burm.f.) Nakai has antioxidant and anti-inflammatory properties. However, the anti-inflammatory, antioxidant, and anti-photoaging protective effects of Pyrus pyrifolia (Burm.f.) Nakai seed components have not been studied. Ultraviolet light (UV) causes skin inflammation, damages the skin barrier, and is an important cause of skin photoaging. Therefore, UV light with a wavelength of 365 nm was used to irradiate HaCaT and mice. Western blot, real-time quantitative polymerase chain reaction, and fluorescence imaging system were used to explore its anti-UVA mechanism. Dialysis membrane and nuclear magnetic resonance were used for the chemical constituent analysis of pear seed water extract (PSWE). We found that PSWE can significantly reduce UVA-induced skin cell death and mitogen-activated protein kinase phosphorylation and can inhibit the mRNA expression of UVA-induced cytokines (including IL-1ß, IL-6, and TNF-α). In addition, PSWE can also reduce the generation of oxidative stress within skin cells. In vivo experimental studies found that PSWE pretreatment effectively reduced transepidermal water loss, inflammation, redness, and dryness in hairless mice. The molecular weight of the active part of pear water extract is approximately 384. Based on the above results, we first found that pear seeds can effectively inhibit oxidative stress and damage caused by UVA. It is a natural extract with antioxidant properties and anti-aging activity that protects skin cells and strengthens the skin barrier.

Active Constituents with Tyrosinase Inhibitory Activities from Waste Tobacco Leaves.

One novel compound, (R)-3, 6-diethoxy-4-hydroxycyclohex-3-en-1-one (1) and thirteen known compounds were isolated from the waste tobacco leaves. The structures of two compounds (1-2) were confirmed and attributed firstly by the extensive spectroscopic data, including 1D/2D NMR, IR, HR-ESI-MS, CD, and ECD spectra. Notably, seven compounds (2, 3, 9, 10, 11, 12, and 13) exhibited better tyrosinase inhibitory activity than the positive control kojic acid. The binding modes of these compounds revealed that their structure formed strong hydrogen bonds and van der Waals forces with the active sites of tyrosinase. These results indicated that waste tobacco leaves are good resources for developing tyrosinase inhibitors.

1D Cu(I)-based chiral organic-inorganic hybrid material with second harmonic generation and circular polarized luminescence.

In recent years, organic-inorganic hybrid materials have demonstrated exceptional performance in nonlinear optics, attracting widespread attention. However, there are relatively few examples of coordination compounds synthesized with Cu as the metal center that exhibit excellent nonlinear optical properties. In this study, we successfully synthesized a pair of enantiomers named R/S-Cu2I2 by reacting chiral ligands with CuI. The crystal structure reveals a one-dimensional copper-iodide chain structure built by Cu2I2 clusters, and its ordered arrangement in space provides not only a strong second harmonic generation (SHG) signal (1.24 × KDP) but also a large birefringence (0.15@1064 nm). Under excitation at 395 nm, the crystals exhibit red fluorescence peaked at 675 nm. The CD spectra of R/S-Cu2I2 show a distinct mirror-symmetric Cotton effect, and their CPL signals are corresponding and opposite in the emission range, with a maximum glum of approximately ±2.5 × 10-3. Theoretical calculations using density functional theory were also carried out to enhance our understanding of the correlation between their structures and optical properties.

Diterpenoids and Their Glycosides from the Stems of Tinospora crispa with Beta-Cell Protective Activity.

Seven previously undescribed diterpenoids, tinocrisposides A-D (1-4) and borapetic acids A (5), B (6), and C (7), together with 16 known compounds, were isolated from the stem of Tinospora crispa (Menispermaceae). The structures of the new isolates were elucidated by spectroscopic and chemical methods. The ß-cell protective effect of the tested compounds was examined on insulin-secreting BRIN-BD11 cells under dexamethasone treatment. Diterpene glycosides 12, 14-16, and 18 presented a substantial protective effect on BRIN-BD11 cells treated with dexamethasone in a dose-dependent manner. Compounds 4 and 17 with two sugar moieties exhibited clear protective effects on ß-cells.

Preparation of Polyethylene/α-Zirconium Phosphate Nanocomposites via a Well-Controlled Polyethylene-Grafted Interface.

It is a daunting task to prepare polyolefin nanocomposites that contain well-exfoliated nanoplatelets due to the nonpolar and high crystallinity nature of polyolefins. In this research, a robust approach was developed to prepare polyethylene (PE) nanocomposites by grafting maleated polyethylene (MPE) onto pre-exfoliated α-zirconium phosphate (ZrP) nanoplatelets via a simple amine-anhydride reaction to form ZrP-g-MPE. Several variables, including maleic anhydride (MA) content, MPE graft density, MPE molecular weight, and PE matrix crystallinity, were investigated to determine how they influence ZrP-g-MPE dispersion in PE. It was found that grafted PE has a different morphology and that the long PE brushes with medium graft density on ZrP can achieve sufficient chain entanglement and cocrystallization with PE matrix to stabilize and maintain ZrP-g-MPE dispersion after solution or melt mixing. This leads to enhanced Young's modulus, yield stress, and ductility. The structure-property relationship of PE/ZrP-g-MPE nanocomposites and usefulness of this study for the preparation of high-performance polyolefin nanocomposites are discussed.

Pneumocystis jiroveci pneumonia after total hip arthroplasty in a dermatomyositis patient: A case report.

BACKGROUND: Pneumocystis jiroveci pneumonia (PJP) is a serious opportunistic infection that occurs mostly in patients with immunodeficiency and long-term immunosuppressive therapy. In non-human immunodeficiency virus-infected patients, the most important risk factor for PJP is the use of glucocorticoids in combination with other immunosuppressive treatments. The management of glucocorticoids during the perioperative period in patients with dermatomyositis requires special care. CASE SUMMARY: We report a case of PJP in the perioperative period. A 61-year-old woman with a history of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis and interstitial pneumonia was administered with long-term oral methylprednisolone and cyclosporine. The patient underwent right total hip arthroplasty in the orthopaedic department for bilateral osteonecrosis of the femoral head. She was given intravenous drip hydrocortisone before anesthesia and on the first day after surgery and resumed oral methylprednisolone on the second postoperative day. On the fifth day after surgery, the patient suddenly developed dyspnea. The computed tomography scan showed diffuse grid shadows and ground glass shadows in both lungs. Polymerase chain reaction testing of bronchoalveolar lavage fluid was positive for Pneumocystis jiroveci. The patient was eventually diagnosed with PJP and was administered with oral trimethoprim-sulfamethoxazole. At the 6-mo review, there was no recurrence or progression. CONCLUSION: Continued perioperative glucocorticoid use in patients with anti-MDA5-positive dermatomyositis may increase the risk of PJP.

White-Light Emission and Circularly Polarized Luminescence from a Chiral Copper(I) Coordination Polymer through Symmetry-Breaking Crystallization.

Achieving white-light emission, especially white circularly polarized luminescence (CPL) from a single-phase material is challenging. Herein, a pair of chiral CuI coordination polymers (1-M and 1-P) have been prepared by the asymmetrical assembly of achiral ligands and Cu2 I2 clusters. The compounds display dual emission bands and can be used as single-phase white-light phosphors, achieving a "warm"-white-light-emitting diode with an ultra-high color rendering index (CRI) of 93.4 and an appropriate correlated color temperature (CCT) of 3632 K. Meanwhile, corresponding CPL signals with maximum dissymmetry factor |glum |=8×10-3 have been observed. Hence, intrinsic white-light emission and CPL have been realized simultaneously in coordination polymers for the first time. This work gains insight into the nature of chiral assembly from achiral units and offers a prospect for the development of single-phase white-CPL materials.

Structural insights into the substrate selectivity of α-oxoamine synthases from marine Vibrio sp. QWI-06.

Pyridoxal phosphate (PLP)-dependent α-oxoamine synthases are generally believed to be responsible for offloading and elongating polyketides or catalyzing the condensation of amino acids and acyl-CoA thioester substrates, such as serine into sphingolipids and cysteate into sulfonolipids. Previously, we discovered vitroprocines, which are tyrosine- and phenylalanine-polyketide derivatives, as potential new antibiotics from the genus Vibrio. Using bioinformatics analysis, we identified putative genes of PLP-dependent enzyme from marine Vibrio sp. QWI-06, implying a capability to produce amino-polyketide derivatives. One of these genes was cloned, and the recombinant protein, termed Vibrio sp. QWI-06 α-oxoamine synthases-1 (VsAOS1), was overexpressed for structural and biochemical characterization. The crystal structure of the dimeric VsAOS1 was determined at 1.8-Å resolution in the presence of L-glycine. The electron density map indicated a glycine molecule occupying the pyridoxal binding site in one monomer, suggesting a snapshot of the initiation process upon the loading of amino acid substrate. In mass spectrometry analysis, VsAOS1 strictly acted to condense L-glycine with C12 or C16 acyl-CoA, including unsaturated acyl analog. Furthermore, a single residue replacement of VsAOS1 (G243S) allowed the enzyme to generate sphingoid derivative when L-serine and lauroyl-CoA were used as substrates. Our data elucidate the mechanism of substrate binding and selectivity by the VsAOS1 and provide a thorough understanding of the molecular basis for the amino acid preference of AOS members.

NLRC4 inflammasome-dependent cell death occurs by a complementary series of three death pathways and determines lethality in mice.

Inflammasome is an innate immune defense mechanism, but its overactivation can lead to host death. Here, we show that cell death dictates mouse death caused by NLRC4 inflammasome overactivation. To execute NLRC4-dependent cell death, three death pathways complement each other in a specific order: Pyroptosis pathway requiring caspase-1 and GSDMD is the default path; impairment of it initiates ASC-mediated caspase-8­dependent apoptosis; when these two pathways are blocked, caspase-1 triggers intrinsic apoptotic pathway. Blocking one or two of these death pathways inhibits induction of various cytokines and lipid mediators, but mice still succumb, and only genetic deletions that block all death paths prevent NLRC4-mediated cell death, tissue damage, and mice death. In addition, infection of nonpropagative Salmonella-caused mice death is attenuated by blocking these death pathways. Thus, to reduce the lethality of infection-related diseases, preventing cell death might be necessary when propagation of infected pathogen was controlled by other means.

Efficacy and Safety of Intra-Articular Platelet-Rich Plasma in Osteoarthritis Knee: A Systematic Review and Meta-Analysis.

BACKGROUND: Knee osteoarthritis (KOA) is a common disease in aged adults. Intra-articular (IA) injection of platelet-rich plasma (PRP) therapy is an effective minimally invasive treatment for KOA. We aimed to compare the efficacy and safety of platelet-rich plasma (PRP) with placebo or other conservative treatments. METHODS: We conducted a meta-analysis to identify relevant articles from online register databases such as PubMed, Medline, Embase, and the Cochrane Library. The primary outcomes were the visual analogue scale (VAS) score, Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and International Knee Documentation Committee (IKDC) subjective score. The secondary outcome was the adverse event rate. RESULTS: A total of 895 articles were identified, of which 23 randomized controlled trials that met the inclusion criteria were determined as eligible. Compared with placebo, PRP had a lower VAS score and higher IKDC subjective score at the 6th month after treatment and significantly less WOMAC score during the follow-up period. Compared with oral NSAIDs, PRP gained a lower WOMAC score at the 6th month after treatment. The VAS score decreased after treatment when reaching PRP and CS. As compared to the HA, the VAS score, WOMAC score, and IKDC subjective score all revealed better PRP results. There were no significant differences in adverse event rates comparing PRP versus placebo or HA. Different PRP applications did not show significant differences in VAS score in the 1st month and WOMAC score in the 3rd month after treatment. CONCLUSION: To compare with the conservative treatments mentioned above, PRP is more effective in relieving symptoms. There were no significant differences between triple PRP application and single PRP application in short-term curative effect.

Investigation of the association between ten pathogens causing sexually transmitted diseases and high-risk human papilloma virus infection in Shanghai.

Cervical cancer, one of the high-incidence female malignant tumors, has predominated in recent years. Persistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer. Studies have shown that infection with certain sexually transmitted disease (STD) pathogens increases the risk of persistent infection with HR-HPV and is a high-risk factor for cervical cancer. In the present study, cervical specimens were collected for Thinprep cytology test detection, while DNA of cervical cells was extracted for HPV genotyping and detection of 10 STD pathogens, including Neisseria gonorrhoeae, Chlamydia trachomatis (CT), Ureaplasma urealyticum, Ureaplasma urealyticum parvum (Uup)1, Uup3, Uup6, Uup14, Mycoplasma hominis (Mh), Mycoplasma genitalium (Mg) and herpes simplex virus II. Significant differences were observed between CT, Mh and Mg infections and HR-HPV infection (P<0.05). In addition, CT, Uup3, Uup6 and Mh infections were associated with HR-HPV infection (odds ratio >1; P<0.05). In the comparison of Uup3, Uup6 and Mg infections between the cervical intraepithelial neoplasia (CIN) group and the control group, statistically significant differences were observed (P<0.05). In conclusion, the incidences of CT, Mh and Mg infections were similar with HR-HPV infection. CT, Uup6, Mh and Mg infections were risk factors for HR-HPV infection. Finally, Uup3, Uup6 and Mg were risk factors of CIN.

Preparation of Well-Exfoliated Poly(ethylene-co-vinyl acetate)/α-Zirconium Phosphate Nanocomposites.

Poly(ethylene-co-vinyl acetate) (PEVAc) nanocomposites containing exfoliated α-zirconium phosphate (ZrP) have been prepared using a simple solution mixing method to improve their barrier and mechanical properties. ZrP was pre-exfoliated with a surfactant, followed by additional targeted surface functionalization and surfactant exchange to allow for hydrogen bonding of ZrP with the acetate functionality on PEVAc and to improve ZrP surface hydrophobicity. The solvent is found to play an important role in stabilizing ZrP exfoliation in the presence of PEVAc to retain full exfoliation and homogeneous dispersion upon the removal of the solvent. The PEVAc/ZrP nanocomposite exhibits greatly improved oxygen barrier, melt strength, and mechanical properties. The usefulness of the present study for the preparation of olefinic polymer nanocomposites is discussed.

Tailoring of a visible-light-absorbing biaxial ferroelectric towards broadband self-driven photodetection.

In terms of strong light-polarization coupling, ferroelectric materials with bulk photovoltaic effects afford a promising avenue for optoelectronic devices. However, due to severe polarization deterioration caused by leakage current of photoexcited carriers, most of ferroelectrics are merely capable of absorbing 8-20% of visible-light spectra. Ferroelectrics with the narrow bandgap (<2.0 eV) are still scarce, hindering their practical applications. Here, we present a lead-iodide hybrid biaxial ferroelectric, (isopentylammonium)2(ethylammonium)2Pb3I10, which shows large spontaneous polarization (~5.2 µC/cm2) and a narrow direct bandgap (~1.80 eV). Particularly, the symmetry breaking of 4/mmmFmm2 species results in its biaxial attributes, which has four equivalent polar directions. Accordingly, exceptional in-plane photovoltaic effects are exploited along the crystallographic [001] and [010] axes directions inside the crystallographic bc-plane. The coupling between ferroelectricity and photovoltaic effects endows great possibility toward self-driven photodetection. This study sheds light on future optoelectronic device applications.

Does new instrument for Oxford unicompartmental knee arthroplasty improve short-term clinical outcome and component alignment? A meta-analysis.

BACKGROUND: The Microplasty (MP) instrumentation designed for the Phase III Oxford mobile-bearing unicompartmental knee arthroplasty (UKA) system is considered a better option to achieve more accurate component positioning and alignment. In the present study, we focused on short-term clinical and radiological outcomes to determine whether the MP instrumentation can reduce the short-term revision rate and occurrence of outliers of metallic components. METHODS: The literature in PubMed, Embase, the Cochrane Library, and Web of Science was searched up to May 2020. Studies were scrutinized by two independent authors, and the revision rate, complication spectrum, and radiological assessment with outlier rates were specifically analyzed. RevMan 5.3 was used for the statistical analysis. RESULTS: Seven studies were included in the meta-analysis. Four studies reported both clinical and radiological outcomes, two reported only radiological outcomes, and one reported only clinical outcomes. The pooled analysis showed that the revision rate in the MP instrumentation group was 0.866 per 100 component years, while that in the control group was 1.124 (odds ratio, 0.77; p < 0.05). The subgroup analysis of the bearing dislocation rate showed a significantly greater reduction in the Korean population than in the populations of other countries (p < 0.05). The radiological assessment showed that the alignment of the femoral component was significantly improved (p < 0.05), while that of the tibial component was not (p > 0.05). CONCLUSION: The newly developed MP instrumentation for Oxford UKA significantly reduced the revision rate of this treatment. The positioning of the femoral component was also proven to be better by radiological assessments.

Asymmetric Synthesis of Chiral Spiroketal Bisphosphine Ligands and Their Application in Enantioselective Olefin Hydrogenation.

A series of chiral spiroketal bisphosphine ligands containing 1,1'-spirobi(3 H,3' H)isobenzofuran backbones was accessed through asymmetric synthesis and subsequently tested in enantioselective Rh-catalyzed hydrogenation of α-dehydroamino acid esters. The ligand providing the highest enantioselectivity (up to 99.5%) was obtained in seven steps in an overall 38% yield. The synthesis could be performed on a gram scale, and no kinetic resolution of enantiomers is required. Overall, the developed ligand provides an easily accessible alternative to SDP ligands as well as other chiral bisphosphine ligands.

Carnosic acid protects mice from high-fat diet-induced NAFLD by regulating MARCKS.

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver damage characterized by abnormal hepatic fat accumulation and inflammatory response. Although the molecular mechanisms responsible for the disease are not yet fully understood, the pathogenesis of NAFLD likely involves multiple signals. The identification of effective therapeutic strategies to target these signals is of utmost importance. Carnosic acid (CA), as a phenolic diterpene with anticancer, anti-bacterial, anti-diabetic and neuroprotective properties, is produced by many species of the Lamiaceae family. Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major protein kinase C (PKC) substrate in many different cell types. In the present study, wild-type C57BL/6 and MARCKS-deficient mice were randomly divided into the normal chow- or high-fat (HF) diet-fed groups. The HF diet increased the fasting glucose and insulin levels, and promoted glucose intolerance in the wild-type mice. MARCKS deficiency further upregulated intolerance, fasting glucose and insulin. The HF diet also promoted hepatic steatosis, serum alanine transaminase (ALT) and aspartate transaminase (AST) activity, inflammation and lipid accumulation in the wild-type mice. These responses were accelerated in the MARCKS-deficient mice. Importantly, increased inflammation and lipid accumulation were associated with phosphoinositide 3-kinase (PI3K)/AKT, NLR family pyrin domain containing 3 (NLRP3)/nuclear factor-κB (NF-κB) and sterol regulatory element binding protein-1c (SREBP-1c) signaling pathway activation. The mice treated with CA exhibited a significantly improved glucose and insulin tolerance. The production of pro-inflammatory cytokines and lipid accumulation were suppressed by CA. Significantly, MARCKS was reduced in mice fed the HF diet. CA treatment upregulated MARCKS expression compared to the HF group. Furthermore, the activation of the PI3K/AKT, NLRP3/NF-κB and SREBP-1c signaling pathways was inhibited by CA. Taken together, our data suggest that CA suppresses inflammation and lipogenesis in mice fed a HF diet through MARCKS regulation. Thus, CA may be prove to be a useful anti-NAFLD agent.

Selective CO2 Capture and High Proton Conductivity of a Functional Star-of-David Catenane Metal-Organic Framework.

Network structures based on Star-of-David catenanes with multiple superior functionalities have been so far elusive, although numerous topologically interesting networks are synthesized. Here, a metal-organic framework featuring fused Star-of-David catenanes is reported. Two triangular metallacycles with opposite handedness are triply intertwined forming a Star-of-David catenane. Each catenane fuses with its six neighbors to generate a porous twofold intercatenated gyroid framework. The compound possesses exceptional stability and exhibits multiple functionalities including highly selective CO2 capture, high proton conductivity, and coexistence of slow magnetic relaxation and long-range ordering.

Elevated microRNA-520g in pre-eclampsia inhibits migration and invasion of trophoblasts.

INTRODUCTION: Pre-eclampsia (PE) is a common and severe obstetric complication. MicroRNAs (miRs) have emerged as molecules that are associated with the disease. METHODS: Quantitative reverse transcription PCR (RT-qPCR) was used for serum miR-520g characterization from 19 severe pre-eclamptic and 19 normal pregnancies. In situ hybridation was adopted to localize microRNA-520g (miR-520g). Migration and invasion of HTR-8/SVneo cells were evaluated after miR-520g mimic treatment with transwell system. MiR-520g target gene was verified in luciferase reporter system. RESULTS: The expression of serum miR-520g displayed an upward trend as pregnancies progress. At first-trimester, miR-520g in pre-eclampsia was significantly higher than that in the control, but no significant differences were found in the second and last trimesters. MiR-520g localized in cytoplasm of early trimester placental trophoblasts. The migration and invasion of HTR8/SVneo were inhibited by miR-520g mimic treatment. Matrix metalloproteinase 2 (MMP2) was verified as a direct target of miR-520g. CONCLUSIONS: Elevated maternal serum level of miR-520g level in first trimester was detected in patients with severe PE. By suppressing the migration and invasion of trophoblast via at least partial inhibition of MMP2 translation inhibition, miR-520g might play a role in the defective spiral artery remodeling, and thus contribute to pre-eclampsia pathophysiology.

Cisplatin-induced necroptosis in TNFα dependent and independent pathways.

Cisplatin is a chemotherapeutic drug for treatment of many solid tumors. It has been shown to induce apoptosis and/or necrosis in different types of cancer cells. However, the underlying mechanisms remain elusive. In this study, we provide evidences that cisplatin induces necroptosis in receptor-interacting protein 3 (RIP3)-expressing cell lines, but not in cell lines lacking RIP3 protein expression. Deficiency of core components of necroptotic pathway, RIP1, RIP3, or mixed lineage kinase domain-like protein (MLKL) blocked cisplatin-induced cell death in L929 cells. This phenomenon is dependent on RIP1/RIP3/MLKL necrosome formation and translocation to mitochondria-associated membrane (MAM), but only partially via autocrine production of tumor necrosis factor α (TNFα). Moreover, we demonstrate that the mitochondrial permeability transition pore opening (mPTP) opening and reactive oxygen species (ROS) generation is a critical downstream event of the formation of necrosome in cisplatin-induced necroptosis, which is TNFα independent. Deficiency of cyclophilin-D (CypD) partially reduced cisplatin-induced cell death, indicating CypD mediated-mPTP opening plays an important role during cisplatin-induced necroptosis. Both deletion of CypD and TNFα completely blocked cisplatin-induced cell death, suggesting that cisplatin could induce necroptosis through TNFα dependent and independent pathway. These findings provide new insight into the molecular mechanisms underlying cisplatin-induced necroptosis.

Superior thermoelasticity and shape-memory nanopores in a porous supramolecular organic framework.

Flexible porous materials generally switch their structures in response to guest removal or incorporation. However, the design of porous materials with empty shape-switchable pores remains a formidable challenge. Here, we demonstrate that the structural transition between an empty orthorhombic phase and an empty tetragonal phase in a flexible porous dodecatuple intercatenated supramolecular organic framework can be controlled cooperatively through guest incorporation and thermal treatment, thus inducing empty shape-memory nanopores. Moreover, the empty orthorhombic phase was observed to exhibit superior thermoelasticity, and the molecular-scale structural mobility could be transmitted to a macroscopic crystal shape change. The driving force of the shape-memory behaviour was elucidated in terms of potential energy. These two interconvertible empty phases with different pore shapes, that is, the orthorhombic phase with rectangular pores and the tetragonal phase with square pores, completely reject or weakly adsorb N2 at 77 K, respectively.