GRAS transcription factor PINNATE-LIKE PENTAFOLIATA2 controls compound leaf morphogenesis in Medicago truncatula.

The milestone of compound leaf development is the generation of separate leaflet primordia during the early stages, which involves two linked but distinct morphogenetic events: leaflet initiation and boundary establishment for leaflet separation. Although some progress in understanding the regulatory pathways for each event have been made, it is unclear how they are intrinsically coordinated. Here, we identify the PINNATE-LIKE PENTAFOLIATA2 (PINNA2) gene encoding a newly identified GRAS transcription factor in Medicago truncatula. PINNA2 transcripts are preferentially detected at organ boundaries. Its loss-of-function mutations convert trifoliate leaves into a pinnate pentafoliate pattern. PINNA2 directly binds to the promoter region of the LEAFY orthologue SINGLE LEAFLET1 (SGL1), which encodes a key positive regulator of leaflet initiation, and downregulates its expression. Further analysis revealed that PINNA2 synergizes with two other repressors of SGL1 expression, the BEL1-like homeodomain protein PINNA1 and the C2H2 zinc finger protein PALMATE-LIKE PENTAFOLIATA1 (PALM1), to precisely define the spatiotemporal expression of SGL1 in compound leaf primordia, thereby maintaining a proper pattern of leaflet initiation. Moreover, we showed that the enriched expression of PINNA2 at the leaflet-to-leaflet boundaries is positively regulated by the boundary-specific gene MtNAM, which is essential for leaflet boundary formation. Together, these results unveil a pivotal role of the boundary-expressed transcription factor PINNA2 in regulating leaflet initiation, providing molecular insights into the coordination of intricate developmental processes underlying compound leaf pattern formation.

Opinion Mining by Convolutional Neural Networks for Maximizing Discoverability of Nanomaterials.

The scientific literature contains valuable information that can be used for future applications, but manual analysis presents challenges due to its size and disciplinary boundaries. The prevailing solution involves natural language processing (NLP) techniques such as information retrieval. Nonetheless, existing automated systems primarily provide either statistically based shallow information or deep information without traceability, thereby falling short of delivering high-quality and reliable insights. To address this, we propose an innovative approach of leveraging sentiment information embedded within the literature to track the opinions toward materials. In this study, we integrated material knowledge into text representation and constructed opinion data sets to hierarchically train deep learning models, named as Scientific Sentiment Network (SSNet). SSNet can effectively extract knowledge from the energy material literature and accurately categorize expert opinions into challenges and opportunities (94% and 92% accuracy, respectively). By incorporating sentiment features determined by SSNet, we can predict the ranking of emerging thermoelectric materials with a 70% correlation to experimental outcomes. Furthermore, our model achieves a commendable 68% accuracy in predicting suitable nanomaterials for atomic layer deposition (ALD) over time. These promising results offer a practical framework to extract and synthesize knowledge from the scientific literature, thereby accelerating research in the field of nanomaterials.

Phase State Regulates Photochemical HONO Production from NaNO3/Dicarboxylic Acid Mixtures.

Field observations of daytime HONO source strengths have not been well explained by laboratory measurements and model predictions up until now. More efforts are urgently needed to fill the knowledge gaps concerning how environmental factors, especially relative humidity (RH), affect particulate nitrate photolysis. In this work, two critical attributes for atmospheric particles, i.e., phase state and bulk-phase acidity, both influenced by ambient RH, were focused to illuminate the key regulators for reactive nitrogen production from typical internally mixed systems, i.e., NaNO3 and dicarboxylic acid (DCA) mixtures. The dissolution of only few oxalic acid (OA) crystals resulted in a remarkable 50-fold increase in HONO production compared to pure nitrate photolysis at 85% RH. Furthermore, the HONO production rates (PHONO) increased by about 1 order of magnitude as RH rose from <5% to 95%, initially exhibiting an almost linear dependence on the amount of surface absorbed water and subsequently showing a substantial increase in PHONO once nitrate deliquescence occurred at approximately 75% RH. NaNO3/malonic acid (MA) and NaNO3/succinic acid (SA) mixtures exhibited similar phase state effects on the photochemical HONO production. These results offer a new perspective on how aerosol physicochemical properties influence particulate nitrate photolysis in the atmosphere.

The Relationship Between Ureaplasma Species and Male Infertility: Pathogenicity, Biology, Diagnosis, and Treatment.

Objective: Ureaplasma spp. comprise a group of mycoplasmas containing two human-associated species, namely, Ureaplasma urealyticum (UUR) and Ureaplasma parvum (UPA). The characterization of Ureaplasma species as pathogens contributing to male infertility remains a subject of considerable controversy. While numerous authors have proposed a relationship between UUR and changes in fertility, there is limited evidence supporting the involvement of UPA in this context. There has been an increased focus on Ureaplasma spp. and its potential role in the development of male infertility, especially over the past few years. The review aims to clarify the relationship between Ureaplasma species and male infertility. Methods: Firstly, we introduce a background of the appropriate biology including growth characteristics, the divided biovars, and the transmission pathways. Secondly, we examine the studies that support a causal role for Ureaplasma spp. in the development of infertility in the last 30 years. Finally, the diagnosed method, antimicrobial susceptibility, and potential therapeutic considerations are evaluated. Results: UPA and UUR can impair semen motility. The species of Ureaplasma spp., the sexual history of the patient, the number of sexual partners, the load of Ureaplasma, and antimicrobial resistance are expected to constitute key risk factors in the development of male infertility. In terms of treatment, Doxycycline remains the drug of first choice for ureaplasmal infections. Conclusion: Ureaplasma spp. are not simply "innocent bystanders" in infertility and may indeed be an "underestimated enemy of human reproduction". Ureaplasma spp. can be considered an etiological agent in unexplained infertility and a useful marker.

Genome-wide mapping of GlnR-binding sites reveals the global regulatory role of GlnR in controlling the metabolism of nitrogen and carbon in Paenibacillus polymyxa WLY78.

BACKGROUND: Paenibacillus polymyxa WLY78 is a Gram-positive, endospore-forming and N2-fixing bacterium. Our previous study has demonstrated that GlnR acts as both an activator and a repressor to regulate the transcription of the nif (nitrogen fixation) operon (nifBHDKENXhesAnifV) according to nitrogen availability, which is achieved by binding to the two GlnR-binding sites located in the nif promoter region. However, further study on the GlnR-mediated global regulation in this bacterium is still needed. RESULTS: In this study, global identification of the genes directly under GlnR control is determined by using chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) and electrophoretic mobility shift assays (EMSA). Our results reveal that GlnR directly regulates the transcription of 17 genes/operons, including a nif operon, 14 nitrogen metabolism genes/operons (glnRA, amtBglnK, glnA1, glnK1, glnQHMP, nasA, nasD1, nasD2EF, gcvH, ansZ, pucR, oppABC, appABCDF and dppABC) and 2 carbon metabolism genes (ldh3 and maeA1). Except for the glnRA and nif operon, the other 15 genes/operons are newly identified targets of GlnR. Furthermore, genome-wide transcription analyses reveal that GlnR not only directly regulates the expression of these 17 genes/operons, but also indirectly controls the expression of some other genes/operons involved in nitrogen fixation and the metabolisms of nitrogen and carbon. CONCLUSION: This study provides a GlnR-mediated regulation network of nitrogen fixation and the metabolisms of nitrogen and carbon.

ABPP-CoDEL: Activity-Based Proteome Profiling-Guided Discovery of Tyrosine-Targeting Covalent Inhibitors from DNA-Encoded Libraries.

DNA-encoded chemical library (DEL) has been extensively used for lead compound discovery for decades in academia and industry. Incorporating an electrophile warhead into DNA-encoded compounds recently permitted the discovery of covalent ligands that selectively react with a particular cysteine residue. However, noncysteine residues remain underexplored as modification sites of covalent DELs. Herein, we report the design and utility of tyrosine-targeting DELs of 67 million compounds. Proteome-wide reactivity analysis of tyrosine-reactive sulfonyl fluoride (SF) covalent probes suggested three enzymes (phosphoglycerate mutase 1, glutathione s-transferase 1, and dipeptidyl peptidase 3) as models of tyrosine-targetable proteins. Enrichment with SF-functionalized DELs led to the identification of a series of tyrosine-targeting covalent inhibitors of the model enzymes. In-depth mechanistic investigation revealed their novel modes of action and reactive ligand-accessible hotspots of the enzymes. Our strategy of combining activity-based proteome profiling and covalent DEL enrichment (ABPP-CoDEL), which generated selective covalent binders against a variety of target proteins, illustrates the potential use of this methodology in further covalent drug discovery.

The MIO1-MtKIX8 module regulates the organ size in Medicago truncatula.

Plant organ size is an important agronomic trait tightly related to crop yield. However, the molecular mechanisms underlying organ size regulation remain largely unexplored in legumes. We previously characterized a key regulator F-box protein MINI ORGAN1 (MIO1)/SMALL LEAF AND BUSHY1 (SLB1), which controls plant organ size in the model legume Medicago truncatula. In order to further dissect the molecular mechanism, MIO1 was used as the bait to screen its interacting proteins from a yeast library. Subsequently, a KIX protein, designated MtKIX8, was identified from the candidate list. The interaction between MIO1 and MtKIX8 was confirmed further by Y2H, BiFC, split-luciferase complementation and pull-down assays. Phylogenetic analyses indicated that MtKIX8 is highly homologous to Arabidopsis KIX8, which negatively regulates organ size. Moreover, loss-of-function of MtKIX8 led to enlarged leaves and seeds, while ectopic expression of MtKIX8 in Arabidopsis resulted in decreased cotyledon area and seed weight. Quantitative reverse-transcription PCR and in situ hybridization showed that MtKIX8 is expressed in most developing organs. We also found that MtKIX8 serves as a crucial molecular adaptor, facilitating interactions with BIG SEEDS1 (BS1) and MtTOPLESS (MtTPL) proteins in M. truncatula. Overall, our results suggest that the MIO1-MtKIX8 module plays a significant and conserved role in the regulation of plant organ size. This module could be a good target for molecular breeding in legume crops and forages.

YAP is critical to inflammation, endothelial-mesenchymal transition and subretinal fibrosis in experimental choroidal neovascularization.

Subretinal fibrosis causes local damage to the retina and irreversible vision loss, as the final stage of neovascular age-related macular degeneration (nAMD). More recently, the endothelial-to-mesenchymal transition (EndoMT) has been considered one of the most significant sources of myofibroblasts in subretinal fibrosis, though the underpinning molecular mechanisms remain unclear. In this study, a series of experiments were performed to test the hypothesis that Yes-associated protein (YAP) may be involved in EndoMT and subretinal fibrosis. We demonstrated that transforming growth factor (TGF)-ß2 stimulation induces YAP dephosphorylation (activated) and nuclear transcription in human umbilical vein endothelial cells (HUVECs) by increasing reactive oxygen species (ROS) levels. Moreover, TGF-ß2-mediated EndoMT and proinflammatory cytokine production in HUVECs were reduced by ROS clearance or YAP knockdown. Furthermore, the severity of subretinal fibrosis was markedly relieved by intravitreal administration of a small interfering RNA targeting YAP in the mouse laser-induced choroidal neovascularization (CNV) model. Our findings provide novel insights into a previously unknown effect of YAP on the EndoMT process and reveal YAP as a potential target for suppressing CNV-related subretinal fibrosis and protect vision.

Genome-wide identification of the NRAMP gene family in Populus trichocarpa and their function as heavy metal transporters.

The natural resistance-associated macrophage protein (NRAMP) gene family plays a key role in essential mineral nutrient homeostasis, as well as toxic metal accumulation, translocation, and detoxification. Although the NRAMP family genes have been widely identified in various species, they still require to be analyzed comprehensively in tree species. In this study, a total of 11 NRAMP members (PtNRAMP1-11) were identified in Populus trichocarpa, a woody model plant, and further subdivided into three groups based on phylogenetic analysis. Chromosomal location analysis indicated that the PtNRAMP genes were unevenly distributed on six of the 19 Populus chromosomes. Gene expression analysis indicated that the PtNRAMP genes were differentially responsive to metal stress, including iron (Fe) and manganese (Mn) deficiency, as well as Fe, Mn, zinc (Zn), and cadmium (Cd) toxicity. Furthermore, the PtNRAMP gene functions were characterized using a heterologous yeast expression system. The results showed that PtNRAMP1, PtNRAMP2, PtNRAMP4, PtNRAMP9, PtNRAMP10, and PtNRAMP11 displayed the ability to transport Cd into yeast cells. In addition, PtNRAMP1, PtNRAMP6, and PtNRAMP7 complemented the Mn uptake mutant, while PtNRAMP1, PtNRAMP6, PtNRAMP7, and PtNRAMP9 complemented the Fe uptake mutant. In conclusion, our findings revealed the respective functions of PtNRAMPs during metal transport as well as their potential role in micronutrient biofortification and phytoremediation.

Secondary Metabolite Analysis of Phomopsis sp. LGT-5 Based on the Dual Guidance of Whole-Genome Sequencing and HPLC-Q-ToF-MS/MS.

Microorganisms produce a wealth of structurally diverse specialized metabolites with a remarkable range of biological activities. The Phomopsis sp. LGT-5 was obtained through tissue block and repeatedly crossed methods from Tripterygium wilfordii Hook. F. The antibacterial experiments of LGT-5 showed that it has high inhibitory activity against Staphylococcus aureus and Pseudomonas aeruginosa, and moderate inhibitory activity against Candida albicans. To research the generation of the antibacterial phenomenon of LGT-5 and provide support for further research and application, the whole genome sequencing (WGS) of LGT-5 was obtained by single-molecule real-time DNA sequencing platform Pacific Biosciences (PacBio) sequencing and Illumina paired-end sequencing. The final assembled LGT-5 genome is 54.79 Mb with a contig N50 of 290.07 kb; in addition, its secondary metabolites were detected through HPLC-Q-ToF-MS/MS. By comparing its MS/MS data, the secondary metabolites were analyzed based on visual network maps obtained on the Global Natural Products Social Molecular Networking (GNPS). The analysis results showed that the secondary metabolites of LGT-5 were triterpenes and various cyclic dipeptides.

Quantitative Validation and Application of the Photo-Cross-Linking Selection for Double-Stranded DNA-Encoded Libraries.

The DNA-encoded compound library (DEL) technology has accelerated the target hits discovery in new drug development. While affinity-based DEL selection can distinguish high-affinity ligands, moderate-affinity ligands are also potential drug candidates with further modifications. Herein, we designed a photo-cross-linking selection method for DELs with double-stranded DNA (dsDELs) to screen moderate-affinity ligands. We constructed two photo-cross-linking libraries with linkers of different lengths that connect a diazirine group to the DNA encoded compound. The diazirine group can be activated by UV irradiation and thus bond with the target protein in a reachable distance. In the model selection, the feasibility of the photo-cross-linking screening system was verified by qPCR and NGS technology. Both high-affinity and moderate-affinity ligands were successfully selected from the libraries.

Highly Active La(III)-Based Metal-Organic Framework as a Heterogeneous Lewis Acid Catalyst for Friedel-Crafts Alkylation.

In this study, a novel La(III)-based two-dimensional (2D) metal-organic framework, [La2/3 (qptca)1/2 ] (referred to as SLX-2), from LaCl3 and 1,1' : 4',1'' : 4'',1''' : 4''',1''''-quinquephenyl]-2,2'',2'''',5''-tetracarboxylic acid (H4 qptca) was synthesized by conventional solvothermal method and thoroughly characterized by using X-ray single-crystal diffraction, powder X-ray diffraction, and thermogravimetric analyses. The 2D SLX-2 features a unique lanthanum center exposed to the skeleton and was used as an efficient Lewis acid catalyst for the Friedel-Crafts alkylation of indole and pyrrole with ß-nitrostyrene along with a wide substrate scope, giving the desired products in good-to-high yields under the optimal reaction conditions. Furthermore, the catalyst was used for twenty cycles, with nearly no effect on its activity, and the reaction was heterogeneous in nature. Moreover, compared to the previous hydrogen-bond-donating MOF catalysts for such alkylation reactions, SLX-2 showed an excellent stability toward harsh acidic and basic environment, and gave comparable catalytic activities.

Real-Time Ultrasound-Guided Versus Ultrasound-Assisted Spinal Anesthesia in Elderly Patients With Hip Fractures: A Randomized Controlled Trial.

BACKGROUND: Traditional landmark-guided spinal anesthesia can be challenging in elderly patients with hip fractures. Ultrasound assistance (USAS) and real-time ultrasound guidance (USRTG) techniques can facilitate lumbar neuraxial blocks. However, it remains undetermined which method is optimal for use in elderly patients. This study aimed to evaluate which technique was associated with a higher success rate of spinal anesthesia in elderly patients with hip fractures: USAS or USRTG technique. METHODS: A total of 114 elderly patients (≥70 years of age) with hip fractures were randomly assigned to receive spinal anesthesia using either the USAS or USRTG technique. The primary outcome was the first-attempt success rate, analyzed using the χ2 test. Secondary outcomes included first-pass success rate, the number of needle attempts and passes, locating time, procedure time, total time, adverse reactions and complications, patient satisfaction, and procedural difficulty score. RESULTS: The first-attempt success rate (80.7% vs 52.6%; 95% confidence interval [CI], for the difference, 11.6-44.6) and first-pass success rate (63.2% vs 31.6%; 95% CI for the difference, 14.2-49) were both significantly higher in the USAS compared with the USRTG group (both P = .001). The number of attempts (1 [1-1] vs 1 [1-3]; P = .001) and median passes (1 vs 3; P < .001) were both significantly lower in the USAS group than in the USRTG group. The USRTG group had a shorter locating time (175 seconds [129-234 seconds] vs 315 seconds [250-390 seconds]; P < .001) but a longer procedure time (488 seconds [260-972 seconds] vs 200 seconds [127-328 seconds]; P < .001) and total time (694 seconds [421-1133 seconds] vs 540 seconds [432-641 seconds]; P = .036). There were no significant differences between the 2 groups with regard to the adverse reactions and complications. More patients in the USAS group had a high satisfaction score of 3 to 5 (P = .008). Overall, anesthesiologists rated the USRTG group procedure as "more difficult" (P = .008). CONCLUSIONS: In elderly patients with hip fractures, spinal anesthesia with the USRTG technique is not superior to the USAS technique since it has a lower success rate, longer procedure time, lower satisfaction score, and is more difficult to perform. So USAS technique may be more suitable for elderly patients.

Changes in retinal vascular bifurcation in eyes with myopia.

OBJECTIVE: To evaluate the effect of myopia on retinal vascular bifurcation. METHODS: A cross-sectional study that retrospectively analyzed the fundus photographs and clinical data of 493 people who participated in routine physical examinations in Huadong Sanatorium. One eye of each subject was included in the analysis. Retinal vascular bifurcation measurements were extracted by using a validated computer program. One-way ANOVA and analysis of covariance were performed to compare the measurements across high myopia, low to moderate myopia, and non-myopia groups. RESULTS: The mean age was 41.83 ± 10.43 years and 63.49% were women. The mean spherical equivalent refraction (SER) was - 4.59 ± 3.07 D. Ninety-nine (20.08%) eyes met the definition of high myopia (SER ≤ -6.0 D), along with 234 (47.46%) low to moderate myopia (-6.0 D < SER <-0.5 D), and 160 (32.45%) non-myopia (SER ≥ -0.5 D). The differences in the arteriolar branching angle, venular branching coefficient, venular asymmetry ratio, venular angular asymmetry, and venular junctional exponent among the three groups remained significant (p < 0.05) after multivariate adjustment. Pairwise comparisons showed arteriolar branching angle and venular angular asymmetry in high myopia were significantly lower than low to moderate myopia (p < 0.001, p = 0.014 respectively) and non-myopia (p = 0.007, p = 0.048 respectively). Venular asymmetry ratio and venular branching coefficient in high myopia were significantly higher than low to moderate myopia (p = 0.029, p = 0.001 respectively) and non-myopia (p = 0.041, p = 0.043 respectively). There was a significant difference in venular junctional exponent between high myopia and low to moderate myopia (p = 0.031). CONCLUSION: The vascular bifurcation differs in dependence on the myopic refractive error and a significant increase in the difference can be observed in high myopic eyes.

Perioperative transcutaneous electrical acupoint stimulation (pTEAS) in pain management in major spinal surgery patients.

BACKGROUND: Lumbar disc herniation is seen in 5-15% of patients with lumbar back pain and is the most common spine disorder demanding surgical correction. Spinal surgery is one of the most effective management for these patients. However, current surgical techniques still present complications such as chronic pain in 10-40% of all patients who underwent lumbar surgery, which has a significant impact on patients' quality of life. Research studies have shown that transcutaneous electrical acupoint stimulation (TEAS) may reduce the cumulative dosage of intraoperative anesthetics as well as postoperative pain medications in these patients. OBJECTIVE: To investigate the effect of pTEAS on pain management and clinical outcome in major spinal surgery patients. METHODS: We conducted a prospective, randomized, double-blind study to verify the effect of pTEAS in improving pain management and clinical outcome after major spinal surgery. Patients (n = 90) who underwent posterior lumbar fusion surgery were randomized into two groups: pTEAS, (n = 45) and Control (n = 45). The pTEAS group received stimulation on acupoints Zusanli (ST.36), Sanyinjiao (SP.6), Taichong (LR.3), and Neiguan (PC.6). The Control group received the same electrode placement but with no electrical output. Postoperative pain scores, intraoperative outcome, perioperative hemodynamics, postoperative nausea and vomiting (PONV), and dizziness were recorded. RESULTS: Intraoperative outcomes of pTEAS group compared with Control: consumption of remifentanil was significantly lower (P < 0.05); heart rate was significantly lower at the end of the operation and after tracheal extubation (P < 0.05); and there was lesser blood loss (P < 0.05). Postoperative outcomes: lower pain visual analogue scale (VAS) score during the first two days after surgery (P < 0.05); and a significantly lower rate of PONV (on postoperative Day-5) and dizziness (on postoperative Day-1 and Day-5) (P < 0.05). CONCLUSION: pTEAS could manage pain effectively and improve clinical outcomes. It could be used as a complementary technique for short-term pain management, especially in patients undergoing major surgeries. TRIAL REGISTRATION: ChiCTR1800014634, retrospectively registered on 25/01/2018. http://medresman.org/uc/projectsh/projectedit.aspx?proj=183.

Regulation of indoleamine 2, 3-dioxygenase in hippocampal microglia by NLRP3 inflammasome in lipopolysaccharide-induced depressive-like behaviors.

In the brain, NLRP3 (Nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin-domain-containing 3) inflammasome is mainly expressed in microglia located in the hippocampus and other mood-regulated regions, which are particularly susceptible to stress. The activation of NLRP3 inflammasome and production of the activation products may contribute to the development of depressive disorder and memory deficits. Indoleamine 2, 3-dioxygenase (IDO) is a key factor mediating inflammation and major depressive disorder (MDD). We here generated NLRP3 and apoptosis-associated speck-like protein containing caspase recruitment domain (ASC)-knockout mice, respectively, to verify the effects of NLRP3 or ASC deficiency on lipopolysaccharide (LPS)-induced depressive-like behaviors, neuroinflammation, and regulation of IDO expression. Furthermore, we treated these mice with the antidepressant clomipramine (CLO) to observe its effect on depressive-like behaviors and the expression of the NLRP3 inflammasome and LPS-induced IDO. We found that intraperitoneal LPS administration led to marked depressive-like behavior and neuroinflammation. NLRP3 or ASC deficiency attenuated LPS-induced depressive-like symptoms and increased IDO gene expression, which was accompanied by inhibition of LPS-induced microglial activation, suggesting that IDO may be a downstream mediator of the NLRP3 inflammasome in inflammation-mediated depressive-like behaviors. Clomipramine administration ameliorated depressive-like behavior in LPS-treated mice by regulating the expression of ASC and IDO. In conclusion, NLRP3 inflammasome is involved in LPS-induced depressive-like behaviors, and that NLRP3 and ASC may play roles in regulating IDO expression in microglia. This may be a potential mechanism for its involvement in MDD. The antidepressant effect of clomipramine may be exerted through the regulation of ASC-mediated expression of IDO.

Rapamycin Protects Skin Fibroblasts from Ultraviolet B-Induced Photoaging by Suppressing the Production of Reactive Oxygen Species.

BACKGROUND/AIMS: Ultraviolet B (UVB) irradiation alters multiple molecular pathways in the skin, thereby inducing skin photoaging. Murine dermal fibroblasts (MDFs) were subjected to a series of 4 sub-cytotoxic UVB doses (120 mJ/cm2), resulting in changes in cell shape, DNA damage, cell cycle arrest, extracellular matrix variations, reactive oxygen species (ROS) generation, and alterations in major intracellular antioxidant and cellular autophagy levels. Rapamycin (RAPA) is a new macrolide immunosuppressive agent that is primarily used in oncology, cardiology, and transplantation medicine and has been found to extend the lifespan of genetically heterogeneous mice. Several studies have shown that RAPA may have anti-aging effects in cells and organisms. Thus, in this study, we explored the effects and mechanisms of RAPA against the photoaging process using a well-established cellular photoaging model. METHODS: We developed a stress-induced premature senescence (SIPS) model through repeated exposure of MDFs to ultraviolet B (UVB) irradiation. The cells were cultured in the absence or presence of RAPA for 48 h. Senescent phenotypes were assessed by examining cell viability, cell morphology, senescence-associated ß-galactosidase (SA-ß-gal) expression, cell cycle progression, intracellular ROS production, matrix metalloproteinase (MMP) synthesis and degradation, extracellular matrix (ECM) component protein expression, alterations in major intracellular antioxidant levels, and the cellular autophagy level. RESULTS: Compared with the UVB group, pretreatment with RAPA (5 µM) significantly decreased the staining intensity and percentage of SA-ß-gal-positive cells and preserved the elongated cell shape. Moreover, cells pretreated with RAPA showed inhibition of the reduction in the type I collagen content by blocking the UVB-induced upregulation of MMP expression. RAPA also decreased photoaging cell cycle arrest and downregulated p53 and p21 expression. RAPA application significantly attenuated irradiation-induced ROS release by modulating intracellular antioxidants and increasing the autophagy level. CONCLUSIONS: Our study demonstrated that RAPA elicited oxidative damage in vitro by reducing ROS accumulation in photoaged fibroblasts. The anti-aging effect can be attributed to the maintenance of normal antioxidant and cellular autophagy levels. However, determination of the definitive mechanism requires further study.

Reference values for skin microanatomy: A systematic review and meta-analysis of ex vivo studies.

BACKGROUND: Few studies have characterized reference values of normal human skin microanatomy parameters. OBJECTIVE: To quantify histologic measurements of epidermal thickness, melanocyte density, hair follicle density, and eccrine gland density as a function of age and anatomic site. METHOD: We searched the PubMed, Embase, Web of Science, and Cochrane databases for articles published through May 25, 2017. Two reviewers independently screened 2016 articles; 327 relevant articles and 151 additional articles found via forward or reference citations underwent full-text review by 1 of 4 reviewers for relevance, data extraction, and critical appraisal. Weighted averages, meta-analysis, and meta-regression were used in statistical analysis. RESULTS: A total of 56 articles were included; when all anatomic locations were used, the overall estimates for epidermal thickness, melanocyte density, hair follicle density, and eccrine gland density were 99.75 µm (95% confidence interval [CI], 83.25-116.25), 955.05 cells/mm2 (95% CI. 880.89-1029.21), 1.40 hairs/mm2 (95% CI. 0.91-1.89), and 1.28 glands/mm2 (95% CI. 0.91-1.64), respectively. LIMITATIONS: There was significant data heterogeneity across studies, possibly because of differences in histological techniques and absence of standardized microanatomy definitions. CONCLUSIONS: We established summary estimates for normal human skin microanatomy parameters.

A New Anti-Inflammatory Alkaloid from Roots of Heracleum dissectum.

Using various chromatographic methods, a new piperidinone alkaloid, (3S)-3-{4-[(1E)-3-hydroxyprop-1-en-1-yl]-2-methoxyphenoxy}piperidin-2-one (1), together with 10 known compounds, bergapten (2), xanthotoxol (3), isopimpinellin (4), isobergapten (5), heratomol-6-O-ß-d-glucopyranoside (6), scopoletin (7), apterin (8), 3-methoxy-4-ß-d-glucopyranosyloxypropiophenone, (praeroside; 9), tachioside (10) and coniferin (11), were isolated from roots of Heracleum dissectum Ledeb. Their structures were elucidated on the basis of physicochemical properties and the detailed interpretation of various spectroscopic data. All the isolated compounds were screened for anti-inflammatory activity in vitro. As the results, compound 1 and 8 showed significantly inhibitory activity on nitric oxide production in RAW264.7 cells.

Synthesis of Unsupported d(1)-d(x) Oxido-Bridged Heterobimetallic Complexes Containing V(IV): A New Direction for Metal-to-Metal Charge Transfer.

Heterobimetallic complexes composed only of first-row transition metals [(TMTAA)V(IV)═O→M(II)Py5Me2](OTf)2 (TMTAA = 7,16-dihydro-6,8,15,17-tetramethyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecine; Py5Me2 = 2,6-bis(1,1-bis(2-pyridyl)ethyl)pyridine; M = Mn(II), Fe(II), Co(II), Ni(II), Cu(II); OTf = trifluoromethanesulfonate) have been synthesized through a dative interaction between a terminal oxido and M(II) metal centers. This is the first series of V(IV)═O→M(II) heterobimetallic complexes containing an unsupported oxido bridge. Among these five complexes, only V(IV)═O→Fe(II) (3b) has a clear new absorption band upon formation of the dinuclear species (502 nm, ε = 1700 M(-1) cm(-1)). This feature is assigned to a metal-to-metal charge transfer (MMCT) transition from V(IV) to Fe(II), which forms a V(V)-O-Fe(I) excited state. This assignment is supported by electrochemical data, electronic absorption profiles, and resonance Raman spectroscopy and represents the first report of visible-light induced MMCT in a heterobimetallic oxido-bridged molecule where the electron originates on a d(1) metal center.