Divergent Construction of Azaheterocycles via Alkoxyl Radical-Triggered C-C Bond Cleavage/Cyclization of N-Functionalized Acrylamides.

An array of redox-neutral alkylation/cyclization cascade reactions of N-functionalized acrylamides with cycloalkyl hydroperoxides were achieved via the alkoxyl radical-triggered C-C bond cleavage. Through adjusting the radical acceptors on the N atom, a variety of keto-alkylated chain-containing azaheterocycles, including indolo[2,1-a]isoquinolin-6(5H)-ones, quinoline-2,4-diones, and pyrido[4,3,2-gh]phenanthridines were constructed by a one-pot procedure with good yields and excellent functional group tolerance.

A journey through the lectin pathway of complement-MBL and beyond.

Mannose-binding lectin (MBL), collectin-10, collectin-11, and the ficolins (ficolin-1, ficolin-2, and ficolin-3) are soluble pattern recognition molecules in the lectin complement pathway. These proteins act as mediators of host defense and participate in maintenance of tissue homeostasis. They bind to conserved pathogen-specific structures and altered self-antigens and form complexes with the pentraxins to modulate innate immune functions. All molecules exhibit distinct expression in different tissue compartments, but all are found to a varying degree in the circulation. A common feature of these molecules is their ability to interact with a set of serine proteases named MASPs (MASP-1, MASP-2, and MASP-3). MASP-1 and -2 trigger the activation of the lectin pathway and MASP-3 may be involved in the activation of the alternative pathway of complement. Furthermore, MASPs mediate processes related to coagulation, bradykinin release, and endothelial and platelet activation. Variant alleles affecting expression and structure of the proteins have been associated with a variety of infectious and non-infectious diseases, most commonly as disease modifiers. Notably, the severe 3MC (Malpuech, Michels, Mingarelli, and Carnevale) embryonic development syndrome originates from rare mutations affecting either collectin-11 or MASP-3, indicating a broader functionality of the complement system than previously anticipated. This review summarizes the characteristics of the molecules in the lectin pathway.

IGA-rule 17 for performance estimation of wavelength-extended InGaAs photodetectors: validity and limitations.

A rule of thumb, denoted as IGA-rule 17, has been developed to describe the temperature and cutoff wavelength-dependent dark currents of wavelength-extended InGaAs photodetectors in a 2-3 µm band. The validity and limitations of the rule are discussed. This rule is intended as an index for device developers to evaluate their technologies in processing, a simple tool for device users to estimate reachable performance at various conditions in their design, and an effective bridge between the two.

Soluble Collectin-12 (CL-12) Is a Pattern Recognition Molecule Initiating Complement Activation via the Alternative Pathway.

Soluble defense collagens including the collectins play important roles in innate immunity. Recently, a new member of the collectin family named collectin-12 (CL-12 or CL-P1) has been identified. CL-12 is highly expressed in umbilical cord vascular endothelial cells as a transmembrane receptor and may recognize certain bacteria and fungi, leading to opsonophagocytosis. However, based on its structural and functional similarities with soluble collectins, we hypothesized the existence of a fluid-phase analog of CL-12 released from cells, which may function as a soluble pattern-recognition molecule. Using recombinant CL-12 full length or CL-12 extracellular domain, we determined the occurrence of soluble CL-12 shed from in vitro cultured cells. Western blot showed that soluble recombinant CL-12 migrated with a band corresponding to ∼ 120 kDa under reducing conditions, whereas under nonreducing conditions it presented multimeric assembly forms. Immunoprecipitation and Western blot analysis of human umbilical cord plasma enabled identification of a natural soluble form of CL-12 having an electrophoretic mobility pattern close to that of shed soluble recombinant CL-12. Soluble CL-12 could recognize Aspergillus fumigatus partially through the carbohydrate-recognition domain in a Ca(2+)-independent manner. This led to activation of the alternative pathway of complement exclusively via association with properdin on A. fumigatus as validated by detection of C3b deposition and formation of the terminal complement complex. These results demonstrate the existence of CL-12 in a soluble form and indicate a novel mechanism by which the alternative pathway of complement may be triggered directly by a soluble pattern-recognition molecule.

Perioperative ω-3 Polyunsaturated Fatty Acid Nutritional Support in Gastrointestinal Cancer Surgical Patients: A Systematic Evaluation.

This study was a systematic evaluation of the beneficial effects of n-3 polyunsaturated fatty acid (PUFA) in abdominal cancer surgical patients. A literature search of the databases PubMed, Medline, Cochrane, and EMBASE was conducted for studies published up to November 2014 in English language journals. Randomized controlled trials (RCTs) examining the effects of n-3 PUFA intake relative to conventional nutrition in surgical patients were included. The main outcomes were the duration of systemic inflammatory response syndrome (SIRS), length of hospital stay (LOS), serum C-reactive protein (CRP) levels, and postoperative complications. We identified 15 RCTs among 158 relevant trials. The results indicated the associations between n-3 PUFA intake and reduced LOS [mean differences (MDs), -2.47 d; 95% confidence intervals (CIs), -3.25 to -1.69], duration of SIRS (MD, -0.57 d; 95% CI, -0.92 to -0.22), and serum CRP levels (MD, -3.97 mg/l; 95% CI, -7.88 to -0.07) compared with consumption of conventional nutrition, as well as reduced incidence of postoperative infectious complications (risk ratio, 0.66; 95% CI, 0.49-0.87). This systematic evaluation suggests that n-3 PUFA significantly reduces the postoperative infectious complication rate, and shortens hospitalization and SIRS duration, particularly in malnourished gastrointestinal cancer patients.

[Study on the High Speed and Precision Gaussian Function Fitting Algorithm for Nuclear Single Spectral Peak].

In nuclear spectrum, Gaussian function least square fitting is a commonly used method. Usually the method has high precision, but it is very much sensitive to noise, which causes that the residual vector is larger near the peak in the Gaussian function. To solve the problem, Gaussian function least square fitting was deduced particularly, and the causes are analyzed. As a result, Gaussian function weighted least square fitting is proposed, i.e., a weight factor, which had an opposite tendency to the data weight reduction tendency after taking logarithm, or it had the same tendency to the origin data. This was introduced based on Gaussian function least square fitting to reduce noise sensitivity. In the process of solving Gaussian parameter, to improve the real-time performance, the solution process of inverse matrix was transferred to the solution process of simple equations because the computation of inverse matrix was time consuming. Gaussian function parameter, amplitude, center value and variance, were given with the fast calculation formulas. By applying these two methods to the practical fitting of 55Fe characteristic X-ray single spectrum peak, respectively, the results show that Gaussian function weighted least square fitting is more satisfactory. It indicates the proposed method can decrease the noise sensitivity and reduce the residual vector near the peak; in addition, the fitting precision is also improved. What's more, the real-time performance is improved by applying fast calculation formulas, which makes it possible to apply the proposed method to portable equipment efficiently.

Study on Heavy Metal Detection in Soil with Improved EDXRF.

Due to the low precision and accuracy of trace heavy metals detection wiith traditional energy dispersive X-ray fluorescence (EDXRF) system, an improved EDXRF system is proposed. In order to reduce the influence of reflected rays, the sample is irradiated with the incident X-rays vertically, and the detector is placed in parallel with the sample's section. The sample is connected with detector through collimator. With improved EDXRF measures certified reference materials, the results show that the detection limit of the improved EDXRF system for Mo，Zn，Cu，Pb，Zr，Nb is 0.4，6.68，1.97，6.84，1.60，7.59 mg·kg-1 respectively and the logarithm deviation of each element in the standard samples is between 0 and 0.05. The RSD%(GBW) is less than 7 as the element content is more than three times of the detection limit, and it is below 15 when the element content is less than three times of the detection limit. The soil samples collected from Da Xing'an Ling region are applied to verify the improved EDXRF system. The proposed EDXRF system can improve the measurement accuracy of trace heavy metal detection in soil, satisfying the requirements of geologic exploration.

The consumption of omega-3 polyunsaturated fatty acids improves clinical outcomes and prognosis in pancreatic cancer patients: a systematic evaluation.

This study was aimed to systematically evaluate results of trials examining the effects of omega-3 polyunsaturated fatty acid (n-3 PUFA) consumption on body weight, lean body mass, resting energy expenditure, and overall survival in pancreatic cancer patients. We searched Medline, Pubmed, Embase, and Cochrane databases. We selected randomized controlled trials of n-3 PUFA vs. conventional nutrition in unresectable pancreatic cancer patients. We analyzed our data using the Cochrane statistical package RevMan 5.1. Eleven trials met our inclusion criteria. There was a significant increase in body weight [weighted mean difference (WMD) = 0.62; 95% confidence interval (CI), 0.54-0.69, P < 0.00001) and lean body mass (WMD = 0.96; 95% CI, 0.86-1.06, P < 0.00001), a significant decrease in resting energy expenditure (WMD = -29.74; 95% CI, -55.89-3.59, P = 0.03), and an increase in overall survival (130-259 days vs. 63-130 days) in unresectable pancreatic cancer patients who consumed an oral nutrition supplement enriched with n-3 PUFAs compared to those who consumed conventional nutrition. This preliminary study suggests that n-3 PUFAs are safe and have a positive effect on clinical outcomes and survival in pancreatic cancer patients.

Ficolin-1-PTX3 complex formation promotes clearance of altered self-cells and modulates IL-8 production.

The long pentraxin 3 (PTX3) has been shown to be important in maintaining internal tissue homeostasis and in protecting against fungal Aspergillus fumigatus infection. However, the molecular mechanisms of how these functions are elicited are poorly delineated. Ficolin-1 is a soluble pattern recognition molecule that interacts with PTX3. We hypothesized that heterocomplexes between ficolin-1 and PTX3 might mediate the signals necessary for sequestration of altered self-cells and A. fumigatus. We were able to show that ficolin-1 interacts with PTX3 via its fibrinogen-like domain. The interaction was affected in a pH- and divalent cation-sensitive manner. The primary binding site for ficolin-1 on PTX3 was located in the N-terminal domain portion of PTX3. Ficolin-1 and PTX3 heterocomplex formation occurred on dying host cells, but not on A. fumigatus. The heterocomplex formation was a prerequisite for enhancement of phagocytosis by human monocyte-derived macrophages and downregulation of IL-8 production during phagocytosis. On A. fumigatus, PTX3 exposed the C-terminal portion of the molecule, probably resulting in steric hindrance of ficolin-1 interaction with PTX3. These results demonstrate that ficolin-1 and PTX3 heterocomplex formation acts as a noninflammatory "find me and eat me" signal to sequester altered-host cells. The fact that the ficolin-1-PTX3 complex formation did not occur on A. fumigatus shows that PTX3 uses different molecular effector mechanisms, depending on which domains it exposes during ligand interaction.

WGCNA reveals a biomarker for cancer-associated fibroblasts to predict prognosis in cervical cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are crucial components of the cervical cancer tumor microenvironment, playing a significant role in cervical cancer progression, treatment resistance, and immune evasion, but whether the expression of CAF-related genes can predict clinical outcomes in cervical cancer is still unknown. In this study, we sought to analyze genes associated with CAFs through weighted gene co-expression network analysis (WGCNA) and to create a predictive model for CAFs in cervical cancer. METHODS: We acquired transcriptome sequencing data and clinical information on cervical cancer patients from the TCGA and GEO databases. Weighted gene co-expression network analysis was conducted to identify genes related to CAFs. We developed a prognostic model based on CAF genes in cervical cancer using LASSO Cox regression analysis. Single-cell sequencing data analysis and in vivo experiments for validation of hub genes in CAFs. RESULTS: A prognostic model for cervical cancer was developed based on CAF genes including COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1. Cervical cancer patients were divided into low and high risk groups based on the optimal cutoff value. Patients in the high risk group had significantly worse prognosis. Single-cell RNA sequencing data revealed that hub genes in the CAFs risk model were expressed mainly in fibroblasts. The real-time fluorescence quantitative PCR results revealed a significant difference in the expression levels of COL4A1, LAMC1, POSTN, and SERPINF1 between the cancer group and the normal group (p < 0.05). Consistently, the results of the immunohistochemical tests exhibited notable variations in COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1 expression between the cancer and normal groups (p < 0.001). CONCLUSION: The CAF risk model for cervical cancer constructed in this study can be used to predict prognosis, while the CAF hub genes can be utilized as crucial markers for cervical cancer prognosis.

Effect of Flexible Half-Dose Gonadotropin-Releasing Hormone Antagonist Protocol on in vitro Fertilization Outcome in Predicted Normal Responder: A Study Protocol for a Multicentered, Randomized, Non-Inferiority, Parallel Controlled Trial.

Background: Gonadotropin-releasing hormone antagonists (GnRH-ant) are widely used in current in vitro fertilization-embryo transfer (IVF-ET), however, whether the lowest daily dose of GnRH-ant is individualized remains unknown. Due to the negative effect of GnRH-ant on endometrial receptivity, lessening the amount of GnRH-antagonists used during controlled ovarian stimulation may be helpful for embryo implantation. As such, a randomized controlled study is essential to validate the feasibility and efficacy of daily GnRH-ant dose reduction to 0.125 mg geared towards providing scientific evidence for guidance in clinical practice. Methods: In total, 620 infertile women undergoing in vitro fertilization will be enrolled in the multicentered, randomized, parallel controlled trial. Based on a computer-generated random list, they will be randomly and equally subdivided into half-dose GnRH-ant group or conventional-dose GnRH-ant group. The primary outcome is ongoing pregnancy ie, intrauterine pregnancy diagnosed by pelvic ultrasonography at more than 12 weeks of gestation accompanied by normal fetal heartbeats. Secondary outcomes include cycle cancellation, premature luteinizing hormone surge, positive pregnancy, embryo implantation rate, clinical pregnancy, early spontaneous abortion, and live birth. The intention-to-treat and per protocol analyses will be used to initially analyze the difference in ongoing pregnancy rate between the two groups, while the multiple imputation method was used to handle missing values in the data. Discussion: At present, no randomized controlled trials (RCTs) have been performed on the use of the half-dose GnRH-ant protocol (0.125mg/d) to improve reproductive outcomes of IVF-ET in predicted normal responder, compared to conventional-dose GnRH-ant protocol (0.25mg/d). Half-dose GnRH-ant protocol might provide a suitable clinical solution for predicted normal responder undergoing IVF treatment. Thus, it is critical to conduct a well-designed RCT to evaluate the impact of a half-dose GnRH-ant protocol on the reproductive outcomes of IVF-ET in predicted normal responder. Trial Registration: This study was registered in the Chinese Clinical Trials Registry Platform on August 29, 2020. (chictr.org.cn; identifier: ChiCTR2000037629). This trial is version 1.3.

Application of Human Menopausal Gonadotropins in the Treatment of Idiopathic Hypogonadotropic Hypogonadism (IHH)-Based Infertility in Females: A Case Report.

Rationale: Idiopathic hypogonadotropic hypogonadism (IHH) is a prevalent congenital genetic disorder with multiple inheritance patterns. IHH can manifest as normal hypogonadotrophic sexual hypofunction (nIHH) or with an abnormal sense of smell, known as Kallmann. It primarily affects the production and effectiveness of gonadotropin-releasing-hormone (GnRh), leading to reduced follicle-stimulating hormone and luteinizing hormone levels. This results in infertility and underdeveloped secondary sexual characteristics. Patient Concerns: A 29-year-old female presented with infertility. Diagnosis: IHH diagnosis was confirmed through magnetic resonance (MR) scan, endocrine tests, physical examination, and B ultrasonic inspection. Additionally, genetic studies, including chromosome analysis, were conducted for the patient. The results confirmed no genetic abnormalities or concerns. Interventions: The patient underwent multiple ovulation induction programs. Outcome: After several ovulation induction cycles, the patient conceived and delivered a live baby. Lessons: For IHH patients, a tailored human menopausal gonadotropin (HMG) dose is recommended. High-dose HMG can benefit those with poor follicular response. The addition of letrozole (5-7.5mg) may enhance follicular response during stimulation. Our approach, which emphasizes the combined use of high-dose HMG, letrozole, and the adjustment of FSH and LH ratios, offers a unique perspective compared to traditional treatments. If HMG treatment is ineffective, alternative ovulation induction methods, such as r-fsh combined with r-lh or HMG combined with rLH, can be considered. Adjusting the FSH and LH ratio and varying rFSH and rLH additions might help achieve dominant follicles and live birth in resistant cases. This case report underscores the potential benefits of our regimen, suggesting its consideration for future research and clinical applications.

Complement-pentraxins synergy: Navigating the immune battlefield and beyond.

The complement is a crucial immune defense system that triggers rapid immune responses and offers efficient protection against foreign invaders and unwanted host elements, acting as a sentinel. Activation of the complement system occurs upon the recognition of pathogenic microorganisms or altered self-cells by pattern-recognition molecules (PRMs) such as C1q, collectins, ficolins, and pentraxins. Recent accumulating evidence shows that pentraxins establish a cooperative network with different classes of effector PRMs, resulting in synergistic effects in complement activation. This review describes the complex interaction of pentraxins with the complement system and the implications of this cooperative network for effective host defense during pathogen invasion.

Alleviation effect of GR24, a strigolactone analogue, on low-nitrogen stress in Malus baccata seedlings.

To investigate the efficacy of foliar application of GR24, a strigolactone analogue, in alleviating low-nitrogen stress in Malus baccata, we applied GR24 with different concentrations (0, 1, 5, 10, and 20 µmol·L-1) to leaves of plants under low nitrogen stress. We evaluated the changes in photosynthetic characteristics of leaves, reactive oxygen metabolism, and nitrogen assimilation in roots. The results showed that shoot biomass of seedling significantly decreased and root-shoot ratio increased under low-nitrogen stress. The chlorophyll contents decreased, the carotenoid content increased, and the photosynthetic activity decreased. The activities of superoxide dismutase and catalase enzymes in roots changed little, while the activities of peroxidase and ascorbic acid peroxidase enzymes, along with the levels of soluble sugar, free proline, and reactive oxygen species showed a significant increase, and the soluble protein content decreased. The NO3- content in roots decreased, the NH4+ content increased, while activities of nitrate reductase and glutamine synthase decreased. Compared to the control group without GR24 application, foliar sprays of 10 and 20 µmol·L-1 GR24 under both normal and low-nitrogen increased biomass and root-shoot ratio to varying degrees. Additionally, GR24 application increased chlorophyll content, photosynthesis indices (net photosynthetic rate, transpiration rate and stomatal conductance), and fluorescence (maximum photochemical efficiency of PSⅡ and quantum yield of electron transfer per unit area) performance parameters, as well as the contents of osmotic regulation substances (soluble protein, soluble sugar, and free proline) and glutamine synthase activity. Application of 10 and 20 µmol·L-1 GR24 under low-nitrogen stress decreased carotenoid, reactive oxygen species, and NH4+ contents, while increased the activities of antioxidases and key enzymes in nitrogen metabolism (nitrate reductase and glutamine synthase) and NO3- content. The 10 µmol·L-1 GR24 treatment was the most effective in alleviating low nitrogen stress, which has potential for application in apple orchards with low nitrogen soil.

Identifying priority protection areas of key food resources of the giant panda.

Animals that live in seasonal environments adjust their reproduction cycle to optimize seasonal forage quality. Giant pandas ( Ailuropoda melanoleuca) are seasonal altitudinal migrants that feed on bamboo shoots and leaves with different nutritional quality. However, the importance of bamboo shoots to giant pandas, especially small and isolated populations, is not fully appreciated. Here, we explored whether mating time of giant pandas is shaped by bamboo shoot phenology. We also assessed the intensity of ongoing bamboo shoot harvesting by local communities in 42 giant panda reserves based on questionnaire surveys. Varying intensity and protection levels of bamboo shoot harvesting were found. From these data, we developed a priority ranking scheme of protection areas for this key food resource. Our study showed that pandas time their mating behavior to coincide with bamboo shoot phenology due to the high nutritional demands associated with mating and pregnancy. We also found that bamboo shoots were not well protected in many places. Liangshan, Daxiangling, and Xiaoxiangling, containing the most isolated panda populations, were identified as the areas with the most urgent need of protection. Furthermore, equal attention should be paid to the QiongL-B population, as this region holds considerable potential to serve as a corridor between the Minshan and Qionglai populations. To address the challenges posed by bamboo shoot harvesting, we recommend establishing more practical bamboo shoot management policies, increasing public awareness of bamboo shoot protection, and providing alternative sources of income for local communities.

Heterocomplexes of mannose-binding lectin and the pentraxins PTX3 or serum amyloid P component trigger cross-activation of the complement system.

The long pentraxin 3 (PTX3), serum amyloid P component (SAP), and C-reactive protein belong to the pentraxin family of pattern recognition molecules involved in tissue homeostasis and innate immunity. They interact with C1q from the classical complement pathway. Whether this also occurs via the analogous mannose-binding lectin (MBL) from the lectin complement pathway is unknown. Thus, we investigated the possible interaction between MBL and the pentraxins. We report that MBL bound PTX3 and SAP partly via its collagen-like domain but not C-reactive protein. MBL-PTX3 complex formation resulted in recruitment of C1q, but this was not seen for the MBL-SAP complex. However, both MBL-PTX3 and MBL-SAP complexes enhanced C4 and C3 deposition and opsonophagocytosis of Candida albicans by polymorphonuclear leukocytes. Interaction between MBL and PTX3 led to communication between the lectin and classical complement pathways via recruitment of C1q, whereas SAP-enhanced complement activation occurs via a hitherto unknown mechanism. Taken together, MBL-pentraxin heterocomplexes trigger cross-activation of the complement system.

Comparison of Hantaan and Seoul viral infections among patients with hemorrhagic fever with renal syndrome (HFRS) in Heilongjiang, China.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a serious public health problem in China, and is primarily caused by either the Hantaan virus (HTNV) or Seoul virus (SEOV) strains. However, the causative hantavirus has only been definitively identified in a few HFRS cases, and detailed comparisons of patient data for the 2 strains are limited. METHODS: We conducted a 1-y prospective study in Heilongjiang Province, China. A total of 152 patients from 3 hospitals met the HFRS diagnostic criteria used in China. The diagnosis was further confirmed by specific immunoglobulin M to HTNV or SEOV. In addition, serum samples were tested for the presence of HTNV or SEOV using a reverse transcription-polymerase chain reaction (RT-PCR). Clinical manifestations and laboratory findings in patients with the 2 hantaviruses were subsequently compared. RESULTS: Eighty (61.1%) HTNV and 51 (38.9%) SEOV infections were identified. Fever and proteinuria, key to the diagnosis of HFRS, were observed in all patients. The clinical manifestations of hemorrhage and renal injury from SEOV infection were milder than those of HTNV infection. Interestingly, compared to patients with HTNV infection, patients with SEOV presented with a significantly longer febrile period, more normal white blood cell counts or even transient leukocytopenia, a higher incidence of liver injury related to disease severity, and a lower occurrence of the 5 typical phases of HFRS. The mortality was 6.3% in HTNV infections and 0% in SEOV infections. CONCLUSIONS: Clinical manifestations of SEOV infection appear to be milder and less typical than HTNV. This information may help us to improve the diagnosis of SEOV-infected patients.

Auricular cartilage versus donor sclera as a wrapping of hydroxyapatite orbital implants.

AIM: To retrospectively compare postoperative outcomes after primary enucleation and placement of a hydroxyapatite (HA) implant without wrapping, wrapped with auricular cartilage or donor sclera. METHODS: Medical records of patients presented as intraocular tumor or severe ocular injury were identified from the electronic medical record system. Cases underwent enucleation and HA orbital implantation were enrolled in this study and were divided into 3 groups according to the wrapping material of HA implant. Cases with autogenous cartilage caps were enrolled in group A (n=11), with donor sclera caps in group B (n=12), and without any wrapping material in group C (n=9). Follow-ups were set at 1, 2wk, 1, 3, 6, and 12mo after surgery. RESULTS: Altogether 32 cases finished the follow-up and were enrolled in this study. Three cases (27.27%) in group A, 4 cases (33.33%) in group B, and 4 cases (44.44%) in group C developed one complication each after surgery. In group A, no HA exposure occurred, but conjunctival inclusion cyst occurred in one and severe conjunctive chemosis in two cases. In group B, one HA exposure occurred, conjunctive inclusion cysts occurred in one, severe conjunctive chemosis occurred in one, and conjunctival granuloma occurred in one case. In group C, one HA exposure occurred, severe conjunctive chemosis occurred in two cases, and conjunctival granuloma occurred in one case. The case of exposure of none-wrapped implant was noted in the first 6mo after placement of the orbital implant. The case of exposure of donor sclera-wrapped implant was noted at the 12mo after placement of the orbital implant. Both exposure cases were treated successfully with conservative treatment. CONCLUSION: With low incidence of implant exposure and mild complications, auricular cartilage can be a good choice of alternative wrapping material of orbit implant with satisfied outcome.

Artesunate: A natural product-based immunomodulator involved in human complement.

Complement is an important innate immune defence machinery. Once dysregulated, it is often linked to pathogenesis of diverse autoimmune diseases. Artesunate (ART) is a well-known anti-malarial compound. Recently, ART has been highlighted by its potential therapeutic effects on certain complement-related autoimmune diseases. However, the underlying mechanisms are hitherto unknown. In the present study, we found that ART mediated complement interception as validated by analysis of complement haemolytic assay. In cell-based setup using dying Jurkat cells, ART-mediated complement interception was also confirmed. Further, we newly established an ELISA system selectively allowing complement activation via the classical pathway, the lectin pathway and the alternative pathway, respectively. ELISA analysis revealed that ART dose-dependently inhibited C4 activation, C3 activation and terminal complement complex assembly via the effector pathways. ART was found to blockade C1q, C3 and C5 with a lesser extent to properdin. The interaction of ART with C1q was determined to be mediated via C1q globular head region. FACS analysis using ART-conjugated mesoporous silica particles revealed that ART specifically bound the key therapeutic targets of C1q, C3 and C5 on microparticles. In conclusion, we for the first time report the anti-complement bioactivities of ART and suggest a potential therapeutic benefit of ART in the complement-related human diseases.

Two new phenolic glycosides with anti-complementary activity from the roots of Sanguisorba officinalis L.

Sanguisorba officinalis L. is a traditional herbal plant that belongs to the genus Sanguisorba and the family Rosaceae. Two new phenolic glycosides (1-2), ten known phenolics (3-12), and six known monoterpenoid glycosides (13-18) were isolated from the roots of S. officinalis using silica gel column and preparative middle pressure liquid chromatography (MPLC). The chemical structures were elucidated based on extensive spectroscopic experiments, including 1D and 2D NMR as well as HR-ESI-MS, and comparison with those reported in the literature. Compounds 3-5, and 13 were isolated from the Rosaceae family and compound 7 was obtained from the genus Sanguisorba for the first time. Additionally, all compounds were evaluated for their anti-complementary activities against the classical pathway. Furthermore, compounds 1, 5, 9, and 14 showed significant anti-complementary activities with the 50% haemolytic inhibition concentrations (CH50) values of 0.40 ± 0.03, 0.57 ± 0.01, 0.51 ± 0.07, and 0.53 ± 0.05 mM, respectively.