An immune-related adverse event of Behcet's-like syndrome following pembrolizumab treatment.

BACKGROUND: In recent years, the emergence of immunotherapy has renewed therapeutic modality. Different from traditional anti-tumor therapy, immune-related adverse events of skin, gastrointestinal tract, liver, lung, endocrine glands commonly occurred. At present, only one case of immune-related adverse event of Behcet's-like syndrome following pembrolizumab treatment was reported in USA, and no one is reported in China. CASE PRESENTATION: Here, we report a rare case of Behcet's-like symptom following pembrolizumab treatment. A 43-year-old female was diagnosed as lymph node and bone metastasis of adenocarcinoma with unknown primary lesion, probably being of pulmonary origin. She was treated with pembrolizumab 200 mg every three weeks in combination with chemotherapy for 6 cycles, followed by pembrolizumab monotherapy maintenance. However, she developed Behcet's-like syndrome with oral ulcer, genital uler, phlebitis, and vision loss after 9 cycles of pembrolizumab treatment. She was treated with prednisone 5 mg orally three times a day. Two weeks later, dose of glucocorticoid gaven to the patient gradually decreased with improved symptoms. After a treatment-free withdrawal period, the patient requested to continue pembrolizumab treatment. Unfortunately, the above symptoms recurred on the second day following pembrolizumab treatment, and glucocorticoid was taken once again. The symptoms improved and the condition was under control. CONCLUSIONS: In view of the exponential growth of immunocheckpoint inhibitors (ICIs) in a variety of tumors, we should be alert to related adverse events, especially the rare rheumatic manifestations.

Nanoheterostructure by Liquid Metal Sandwich-Based Interfacial Galvanic Replacement for Cancer Targeted Theranostics.

Nanoheterostructures with exquisite interface and heterostructure design find numerous applications in catalysis, plasmonics, electronics, and biomedicine. In the current study, series core-shell metal or metal oxide-based heterogeneous nanocomposite have been successfully fabricated by employing sandwiched liquid metal (LM) layer (i.e., LM oxide/LM/LM oxide) as interfacial galvanic replacement reaction environment. A self-limiting thin oxide layer, which would naturally occur at the metal-air interface under ambient conditions, could be readily delaminated onto the surface of core metal (Fe, Bi, carbonyl iron, Zn, Mo) or metal oxide (Fe3 O4 , Fe2 O3 , MoO3 , ZrO2 , TiO2 ) nano- or micro-particles by van der Waals (vdW) exfoliation. Further on, the sandwiched LM layer could be formed immediately and acted as the reaction site of galvanic replacement where metals (Au, Ag, and Cu) or metal oxide (MnO2 ) with higher reduction potential could be deposited as shell structure. Such strategy provides facile and versatile approaches to design and fabricate nanoheterostructures. As a model, nanocomposite of Fe@Sandwiched-GaIn-Au (Fe@SW-GaIn-Au) is constructed and their application in targeted magnetic resonance imaging (MRI) guided photothermal tumor ablation and chemodynamic therapy (CDT), as well as the enhanced radiotherapy (RT) against tumors, have been systematically investigated.

Efficacy and safety of fluzoparib combined with anlotinib in extensive stage small cell lung cancer after first-line platinum-based chemotherapy: a multi-center, single-arm prospective phase II clinical study (STAMP study).

BACKGROUND: Small-cell lung cancer (SCLC) is a highly aggressive and lethal malignancy that accounts for 10-15% of lung cancers, and it is generally divided into limited and extensive stage. The standard of care for patients with newly diagnosed extensive-stage SCLC (ES-SCLC) is still platinum-based chemotherapy and as maintenance therapy scheme. Although most parts of patients experience a significant tumor response to first-line therapy, the disease recurs invariably. Anlotinib hydrochloride, a novel oral multitarget tyrosine kinase inhibitor, has significant inhibitory activity against angiogenesis-related kinases, such as VEGFR, FGFR, PDGFR, and c-Kit kinase associated with tumor cell proliferation. Fluzoparib is a type of inhibitor of poly ADP ribose polymerase (PARP, including PARPl, PARP2 and PARP3). Previous studies have shown that Fluzoparib has a strong inhibitory effect on PARP1 activity at the molecular and cellular levels. METHODS: This is a multi-center, prospective, single-arm phase II clinical study. A total of 50 ES-SCLC patients who experienced disease progression after first-line standard platinum-based chemotherapy with/without immune checkpoint inhibitors scheme, or within 6 months after the completion of treatment will be recruited. Those who had prior treatment with any PARP inhibitor or antiangiogenic agent includes anlotinib, bevacizumab, sorafenib, and thalidomide are excluded. Eligible patients will receive oral anlotinib 8 mg once daily and oral fluzoparib 150 mg twice daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR). DISCUSSION: The addition of fluzoparib to anlotinib is expected to increase the clinical benefit in ES-SCLC patients after platinum-based chemotherapy. TRIAL REGISTRATION: This study protocol was prospectively registered on June 17, 2021. CLINICALTRIALS: gov Identifier: NCT04933175 .

Evaluation of the effect of 3D-bioprinted gingival fibroblast-encapsulated ADM scaffolds on keratinized gingival augmentation.

BACKGROUND AND OBJECTIVES: The keratinized gingiva plays an important role in maintaining healthy periodontal and peri-implant tissue. Acellular dermal matrix (ADM), as a substitute biomaterial, has a porous structure and good biocompatibility. 3D-bioprinting has the potential for tissue engineering because it enables precise loading of cells layer-by-layer. Herein, we bioprinted ADM scaffold encapsulating gingival fibroblasts (GFs) and evaluated its efficacy in keratinized gingiva augmentation in vivo to assess its potential for clinical periodontal tissue regeneration. METHODS: GFs were extracted from the gingiva of beagles and transfected with a green fluorescent protein (GFP). The ADM scaffold (ADM cell-free group) was constructed using ADM, gelatin, and sodium alginate mixed at an appropriate ratio via 3D-bioprinting. The ADM cell scaffold (ADM cell group) was established by adding extra GFs in the same manner. Six beagles were divided into blank control, ADM cell-free, and ADM cell groups; and implant surgery was performed. The keratinized gingiva was clinically and histologically evaluated at baseline and after 2 months. RESULTS: GFs transfected with GFPs expressed green fluorescence and were present in new tissue in the ADM cell group and not observed in the ADM cell-free group. At 2 months after surgery, the keratinized gingival augmentation in the ADM cell group was significantly more than that in the ADM cell-free group. Attached gingival augmentation was also observed more in the ADM cell group than that in the ADM cell-free group. Histological staining showed that the tissue in the ADM cell group displayed a more integrated structure and higher expression of COL I, COL III, and VEGF-A than those in the ADM cell-free group. CONCLUSION: 3D-bioprinted GF-encapsulated ADM scaffolds increased the amount of keratinized gingiva in vivo, suggesting that 3D-bioprinting has great potential for oral soft tissue regeneration.

Development and characterization of anti-HPV16 monoclonal antibodies for assembly of an HPV16 detection kit.

Quality control is very important during the development of 3-valent (16/18/58), 9-valent (6/11/16/18/31/33/45/52/58), and 15-valent human papillomavirus (HPV) vaccines (6/11/16/18/31/33/35/39/45/52/56/58/59/68). All 3-valent, 9-valent, and 15-valent HPV vaccines contain the HPV16 antigen; therefore, a detection method that can specifically identify HPV16 in vaccines is urgently required. This study aimed to develop and characterize monoclonal antibodies to assemble a highly specific HPV16 detection kit. The HPV16 L1 pentameric protein developed as an immunogen was used to prepare monoclonal antibodies. From the pool of prepared monoclonal antibodies, we selected 4G12 and 5A6 to screen and evaluate their subtypes, specificity, neutralizing activity, serum competition, binding affinity, and gene sequencing. After these characterizations, an enzyme-linked immunosorbent assay kit for these monoclonal antibodies was developed, and excellent quality was demonstrated in the assessment of linearity, repeatability, and specificity. The developed detection kit has great potential for wide use in clinical testing and quality control in vaccine production processes.

Preparation of SERS base membrane with cellulose compound dopamine and determination of hypochlorite.

Flexible silver substrates were made by in situ reduction of silver nanoparticles in bacterial cellulose membranes using the unique advantage of dopamine. Subsequently, we modified the substrate with 4-mercaptophenol (4-MP), a molecule capable of specifically recognizing ClO-, and its corresponding SERS signal changes with the concentration of hypochlorite, thus allowing the quantitative detection of ClO- content. The method showed a negative linear correlation (R2 = 0.9567) with the SERS intensity at 1077 cm-1 over the concentration range 0.5-100 µM, and the detection limit was 0.15 µM. The RSD of the SERS intensity at 1077 cm-1 under five batches was 4.2%, which proved the good reproducibility of P-BCM-Ag NP-MP. Finally, the P-BCM-Ag NPs were used for the detection of hypochlorite in cell contents, artificial urine, and clinical serum samples, utilizing spike experiments in all three environments. The recoveries were in the range 90-110% indicating the accuracy of the method for the detection of hypochlorite and validating the promising application of this assay for practical detection in intricate biological samples.

Development of HPV58 type-specific antibodies and detection kit.

Currently, human papillomavirus (HPV) vaccines are in short supply, so the development of HPV vaccines has a broad market prospect. The 3-, 9-, and 15-valent HPV vaccines developed by ourselves all contain HPV58-derived antigen components. It is important to detect HPV 58 during vaccine production. Here, we introduced a development process of HPV58 type-specific antibodies and a detection kit. Briefly, HPV58 L1-Virus Like Particles (VLPs) were used as antigens to immunize mice, followed by extraction of the ascites to prepare hybridoma cells. After culturing, the supernatants containing secreted antibodies were harvested, purified, and screened to obtain monoclonal antibodies (mAbs). In the pool of attained monoclonal antibodies, we selected 2F7 and 2G7 to evaluate their subtypes, specificity, neutralizing activity, serum competition, binding affinity and gene sequencing. Finally, an enzyme-linked immunosorbent assay (ELISA) detection kit was assembled with 2F7 and 2G7 mAbs which possessed high specificity to HPV58 L1-VLPs. The detection kit developed by 2F7 and 2G7 could be adopted to specifically detect HPV58 L1 protein with good linearity and detection range, which could be widely used in clinical testing and quality control in the production of HPV vaccines.Abbreviations: BSA: Bovine serum albumin; CDRs: Complementarity-determining regions; CV: Coefficient of variation; DTT: Dithiothreitol; ELISA: Enzyme-linked immunosorbent assay; HAT: Hypoxanthine-aminopterin-thymidine; HPV: Human Papillomavirus; IC50: 50% inhibition rate; IC90: 90% inhibition rate; mAbs: Monoclonal antibodies; VLP: Virus-like particle.

Preventive effect of swim bladder hydrolysates on cyclophosphamide-induced ovarian injury in mice.

AIMS: This study aimed to prepare swim bladder hydrolysate (SBH) with Mn  < 4000 Da, and investigate its effects on cyclophosphamide (CTX)-mediated ovarian injury in mice. METHODS: Hydrolysates were prepared by heating extraction, enzymatic hydrolysis and ultrafiltration. Mn and distribution of SBH were analyzed via gel filtration chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Changes in the mouse oestrus cycle were determined by cytological examination. The number of follicles was examined using histopathology. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum sex hormone levels. RESULTS: The Mn of SBH, prepared by heating extraction, enzymatic hydrolysis, ultrafiltration, and from different batches, was below 4000 Da, and the preparation process was stable. Compared with the control group, the low-, middle-, and high-dose SBH treatment groups showed different trends in oestrus duration, serum sex hormone levels, and the number of primordial and secondary follicles. The oestrus cycle duration of the high-dose SBH group was longer than that of the model group. The serum luteinizing hormone, follicle-stimulating hormone, and anti-Müllerian hormone levels in the middle-dose group were the closest to those of control group. The number of primordial and secondary follicles in the medium-dose group was significantly higher than that in the model group and closest to those of control group. CONCLUSION: After heating extraction, trypsin/Flavourzyme hydrolysis and ultrafiltration, a hydrolysate with Mn below 4000 Da could be prepared. We found that a moderate (400 mg/kg) SBH dose resulted in the greatest effect on ovarian injury remission in mice.

Circ-ACAP2 facilitates the progression of colorectal cancer through mediating miR-143-3p/FZD4 axis.

BACKGROUND: Circular RNAs (circRNAs) play crucial roles in multiple cancers, including colorectal cancer (CRC). Here, we explored the role of circRNA ArfGAP with coiled-coil, ankyrin repeat and PH domains 2 (circ-ACAP2) in the progression and radioresistance of CRC. METHODS: Quantitative real-time polymerase chain reaction (qPCR) and Western blot assay were used to detect RNA and protein expression, respectively. The proliferation, apoptosis, migration, invasion and radioresistance of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, transwell migration assay, transwell invasion assay and colony formation assay. The target interaction between microRNA-143-3p (miR-143-3p) and circ-ACAP2 or frizzled class receptor 4 (FZD4) was verified by dual-luciferase reporter assay. Murine xenograft model was established to explore the role of circ-ACAP2 in vivo. RESULTS: The expression of circ-ACAP2 was prominently enhanced in CRC tissues and cell lines. Circ-ACAP2 facilitated the proliferation, migration, invasion and radioresistance whereas inhibited the apoptosis of CRC cells. MiR-143-3p was a direct target of circ-ACAP2 in CRC cells. Circ-ACAP2 promoted the progression and radioresistance of CRC partly by sponging miR-143-3p. MiR-143-3p interacted with the 3' untranslated region (3'UTR) of FZD4 in CRC cells, and FZD4 overexpression partly reversed miR-143-3p-mediated effects in CRC cells. Wnt/ß-catenin signalling was modulated by circ-ACAP2/miR-143-3p/FZD4 axis in CRC cells. CONCLUSION: Circ-ACAP2 contributed to the development and radioresistance of CRC partly through targeting miR-143-3p/FZD4 axis, which provided novel potential diagnostic and therapeutic targets for CRC.

Near-Earth space balloon-based multi-band airglow imager optic design.

As a common tracer in the atmosphere, airglow can be used as an important means to study the interaction between the lower atmosphere, near space, and ionosphere. In the near-Earth space, the high-altitude balloon can realize long time flight, which makes the airglow detection realize both high range resolution and time resolution. In this paper, a balloon-based multi-band airglow imager is designed, which can observe OI (557.7 nm), Na (589.3 nm), OI (630.0 nm), and OH (720-910 nm) with annular field of view (30° inner ring and 80° outer ring), and its resolution is 500 m at 250 km. The multi-band airglow imager designed in this paper is equipped in the payload cabin and raised to above 30 km for flat flying for more than 6 h. The experimental results show that the imager worked normally, and airglow images were photographed and stored; the optical system can stand the harsh environment in the near space. The multi-band airglow imager designed in this paper will take part in other near-space exploration tasks in the future and obtain corresponding results.

DHRS12 inhibits the proliferation and metastasis of osteosarcoma via Wnt3a/ß-catenin pathway.

Aim: This experimental design was based on DHRS12 to explore its biological effects on osteosarcoma (OS). Materials & methods: The expression level of endogenous DHRS12 was analyzed by immunohistochemical analysis. DHRS12 was overexpressed in MG-63 and HOS cells by plasmid transfection. Cell proliferation, invasion, migration, apoptosis and western blot were used in the experiment. Results: The expression of DHRS12 was significantly reduced in OS. Overexpression of DHRS12 inhibited the proliferation, migration and invasion of MG-63 and HOS cells and induced apoptosis of OS cells. Overexpression of DHRS12 upregulated Bax, Caspase 9 and Caspase 3. Overexpression of DHRS12 resulted in inactivation of the Wnt3a/ß-catenin signaling pathway. Conclusion: Overexpression of DHRS12 inhibited the progression of OS via the Wnt3a/ß-catenin pathway.

Non-Magnetic Injectable Implant for Magnetic Field-Driven Thermochemotherapy and Dual Stimuli-Responsive Drug Delivery: Transformable Liquid Metal Hybrid Platform for Cancer Theranostics.

Transformable liquid metal (LM)-based materials have attracted considerable research interest in biomedicine. However, the potential biomedical applications of LMs have not yet been fully explored. Herein, for the first trial, the inductive heating property of gallium-indium eutectic alloy (EGaIn) under alterative magnetic field is systematically investigated. By virtue of its inherent metallic nature, LM possesses excellent magnetic heating property as compared to the conventional magnetite nanoparticles, therefore enabling its unique application as non-magnetic agents in magnetic hyperthermia. Moreover, the extremely high surface tension of LM could be dramatically lowered by a rather facile PEGylation approach, making LM an ideal carrier for other theranostic cargos. By incorporating doxorubicin (DOX)-loaded mesoporous silica (DOX-MS) within PEGylated LM, a magnetic field-driven transformable LM hybrid platform capable of pH/AFM dual stimuli-responsive drug release and magnetic thermochemotherapy are successfully fabricated. The potential application for breast cancer treatment is demonstrated. Furthermore, the large X-ray attenuation ability of LM endows the hybrid with the promising ability for CT imaging. This work explores a new biomedical use of LM and a promising cancer treatment protocol based on LM hybrid for magnetic hyperthermia combined with dual stimuli-responsive chemotherapy and CT imaging.

Identification of Ophiocordyceps sinensis and Its Artificially Cultured Ophiocordyceps Mycelia by Ultra-Performance Liquid Chromatography/Orbitrap Fusion Mass Spectrometry and Chemometrics.

Since the cost of Ophiocordyceps sinensis, an important fungal drug used in Chinese medicine, has increased dramatically, and the counterfeits may have adverse health effects, a rapid and precise marker using the peptide mass spectrometry identification system could significantly enhance the regulatory capacity. In this study, we determined the marker peptides in the digested mixtures of fungal proteins in wild O. sinensis fruiting bodies and various commercially available mycelium fermented powders using ultra-performance liquid chromatography/Orbitrap Fusion mass spectrometry coupled with chemometrics. The results indicated the following marker peptides: TLLEAIDSIEPPK (m/z 713.39) was identified in the wild O. sinensis fruiting body, AVLSDAITLVR (m/z 579.34) was detected in the fermented O. sinensis mycelium powder, FAELLEK (m/z 849.47) was found in the fermented Ophiocordyceps mycelium powder, LESVVTSFTK (m/z 555.80) was discovered in the artificial Ophiocordyceps mycelium powder, and VPSSAVLR (m/z 414.75) was observed in O. mortierella mycelium powder. In order to verify the specificity and applicability of the method, the five marker peptides were synthesized and tested on all samples. All in all, to the best of our knowledge, this is the first time that mass spectrometry has been employed to detect the marker peptides of O.sinensis and its related products.

Interaction of arginine with protein during refolding process probed by amide H/D exchange mass spectrometry and isothermal titration calorimetry.

Arginine has been widely used as low molecular weight additive to promote protein refolding by suppressing aggregate formation. However, methods to investigate the role of arginine in protein refolding are often limited on protein's global conformational properties. Here, hydrogen/deuterium exchange mass spectrometry (HDX-MS) was used to study the effects of arginine on recombinant human granulocyte colony-stimulating factor (rhG-CSF) refolding at the scale of peptide mapping. It was found that deuteration levels of rhG-CSF refolded with arginine was higher than that without arginine during the whole refolding process, but they became almost the same when the refolding reached equilibrium. This phenomenon indicated that arginine could protect some amide deuterium atoms from being exchanged with hydrogen, but the protection diminished gradually along with refolding proceeding. Enzymatic digestion revealed six particular peptides of 16-47, 72-84, 84-93, 114-124, 145-153 and 154-162 were mainly responsible for the deuteration, and all of them dominantly located in protein's α-helix domain. Furthermore, thermodynamics analysis by isothermal titration calorimetry provided direct evidence that arginine could only react with denatured and partially refolded rhG-CSF. Taking all of the results together, we suggest that arginine suppresses protein aggregation by a reversible combination. At the initial refolding stage, arginine could combine with the denatured protein mainly through hydrogen bonding. Subsequently, arginine is gradually excluded from protein with protein's native conformation recovering.

Metabolic reprogramming in cancer cells: glycolysis, glutaminolysis, and Bcl-2 proteins as novel therapeutic targets for cancer.

Nearly a century ago, Otto Warburg made the ground-breaking observation that cancer cells, unlike normal cells, prefer a seemingly inefficient mechanism of glucose metabolism: aerobic glycolysis, a phenomenon now referred to as the Warburg effect. The finding that rapidly proliferating cancer cells favors incomplete metabolism of glucose, producing large amounts of lactate as opposed to synthesizing ATP to sustain cell growth, has confounded scientists for years. Further investigation into the metabolic phenotype of cancer has expanded our understanding of this puzzling conundrum, and has opened new avenues for the development of anti-cancer therapies. Enhanced glycolytic flux is now known to allow for increased synthesis of intermediates for sustaining anabolic pathways critical for cancer cell growth. Alongside the increase in glycolysis, cancer cells transform their mitochondria into synthesis machines supported by augmented glutaminolysis, supplying lipid production, amino acid synthesis, and the pentose phosphate pathways. Inhibition of several of the key enzymes involved in these pathways has been demonstrated to effectively obstruct cancer cell growth and multiplication, sensitizing them to apoptosis. The modulation of various regulatory proteins involved in metabolic processes is central to cancerous reprogramming of metabolism. The finding that members of one of the major protein families involved in cell death regulation also aberrantly regulated in cancers, the Bcl-2 family of proteins, are also critical mediators of metabolic pathways, provides strong evidence for the importance of the metabolic shift to cancer cell survival. Targeting the anti-apoptotic members of the Bcl-2 family of proteins is proving to be a successful way to selectively target cancer cells and induce apoptosis. Further understanding of how cancer cells modify metabolic regulation to increase channeling of substrates into biosynthesis will allow for the discovery of novel drug targets to treat cancer. In the present review, we focused on the recent developments in therapeutic targeting of different steps in glycolysis, glutaminolysis and on the metabolic regulatory role of Bcl-2 family proteins.

Acupuncture at KI3 in healthy volunteers induces specific cortical functional activity: an fMRI study.

BACKGROUND: Using functional magnetic resonance imaging (fMRI), we determined brain regions that were activated/deactivated more by acupuncture at Taixi (KI3) than by non-acupoint or sham acupuncture. METHODS: A total of 30 healthy volunteers were randomly divided into a KI3 group (15 subjects) and non-acupoint group (15 subjects). Subjects in KI3 group received a sham acupuncture and then a real acupuncture, fMRI was performed before and after sham acupuncture as well as after ture acupuncture. Subjects in non-acupoint group received a ture acupuncture and the fMRI was performed before and after ture acupuncture. The fMRI data obtained were successively analyzed using DPARSF2.3 and REST1.8 software, yielding regional homogeneity (ReHo) and amplitude of low frequency fluctuations (ALFF) values. RESULTS: Compared with sham acupuncture, ALFF values were higher in Brodmann area (BA) 10 and lower in BA7 and BA18. ReHo values after real acupuncture at KI3 were higher in the right sub-lobar region and BA10 and were lower in BA31. Compared with the changes before and after real acupuncture at non-acupoint, the changes at KI3 showed higher ALFF valued in the left cerebellum posterior lobe, BA10, BA39, BA31 and decreased ALFF was observed in the BA18, BA19 and BA40; and higher ReHo values were shown in left cerebellum posterior lobe pyramis, left cerebellum anterior lobe. BA37, BA10, BA39, BA31 and lower ReHo values were shown in BA18 and BA31. CONCLUSION: Acupuncture at KI3 has a specific effect on certain brain regions associated with perception, body movement, spirit, and association. Additionally, visual and auditory cortices were affected, which may be related to the clinical applications of KI3 acupuncture in auditory and cognitive disorders, hypomnesis, loss of concentration, and the loss of ability to work and learn. TRIAL REGISTRATION: The research ethics committee was achieved at 01/08/2012, the NO. was ChiECRCT-2012011. Website for Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=7123 . This study was registered at www.chictr.org, the Clinical Trial Registration Number was ChiCTR-TRC-12002427, and the registration number was achieved at 18/08/2012. The name of IRB that provided approval for the study and clearly state is Chinese Clinical Trail Registry.

[Study of Spectral Property and Measurement of Linear Variable Filters].

Linear variable filters (LVF) are widely used in a variety of small rapid spectrometric detecting devices. In the present paper, the splitting property of LVF was studied, and the spectral-property expression in Gaussian form was given, and the relationship between indexes of expression and LVF center transmission, width of spectrum, and linear dispersion was specified. Measurement based on monochromator for imaging spectrometers calibration was introduced, the sensitivity for detection system was discussed, and the tolerance was analyzed. It was shown that the slit displacement of monochromator relative to the optical axle and the slope of LVF affect the detecting accuracy most, and the tolerance can be reduced by adjustment of optical path and structure to reach requirement. System was built and the detection for spectral property of sample LVF was made. The result of data processing indicates that MSE for center transmission detection was lower than 0.05%, and the accuracy of this method was proved. Reference-parameters of relevant system designing and calibrating based on the LVF can be provided by this method.

Discovery of novel N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides as potent RORγt inhibitors.

Novel series of N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides were discovered as potent retinoic acid receptor-related orphan receptor-gamma-t (RORγt) inhibitors. SAR studies of the RORγt HTS hit 6a led to identification of thiazole ketone amide 8h and thiophene ketone amide 9g with high binding affinity and inhibitory activity of Th17 cell differentiation. Compound 8h showed in vivo efficacy in both mouse experimental autoimmune encephalomyelitis (EAE) and collagen induced arthritis (CIA) models via oral administration.

Effect of experimental methodology on fasting heat production and the net energy content of corn and soybean meal fed to growing pigs.

The aim of the three experiments was to evaluated methods to predict fasting heat production (FHP) and to compare methods to determine the net energy (NE) of corn and soybean meal (SBM) fed to growing pigs. To estimate heat production (HP), pigs were housed in respiratory chambers for all experiments. In Experiment 1, six barrows (43.0 ± 1.4 kg body weight [BW]) were fed a Corn-SBM diet for 20 d. The experimental design consisted of following periods: 7 d adaptation, 5 d ad libitum feeding, 3 d feeding at 2 × metabolisable energy (ME) for maintenance (MEm), 3 d feeding at 1 × MEm and 2 d fasting. The FHP was calculated by extrapolating HP measured at the different feeding levels to zero ME intake. The daily FHP [per kg BW(0)(.6)] determined directly after fasting for 24 h and using the regression method was 774 kJ and 694 kJ, respectively. In Experiment 2, 18 barrows (34.3 ± 1.1 kg BW) were randomly allotted to three diets: Diet 1 contained 97.5% corn (direct NE determination of corn); diets 2 and 3 contained 25 % and 15% SBM at the expense of corn, respectively, and were used to calculate the NE of corn by difference. The NE of corn determined directly (13.21 MJ/kg DM) and by difference (13.69 MJ/kg DM) was not different. In Experiment 3, 24 barrows (36.2 ± 1.4 kg BW) were randomly allotted to four diets to determine the effects of different basal diets on the NE content of SBM. The diets were: Basal diet 1 (97.5% corn), Test diet 1 (15% SBM at the expense of corn), Basal diet 2 (contained 72.5% corn and 25% SBM) and Test diet 2 (58% corn and 39.5% SBM). These diets were used to determine the NE of SBM using the Corn-basal diet or the Corn-SBM-basal diet, respectively. It was shown that the estimated NE of SBM did not depend on the used diet (10.04 MJ/kg and 10.62 MJ/kg DM for Basal diet 1 and 2, respectively). In summary, using the regression method to determine FHP results in lower FHP than the fasting method. There was no difference observed in the NE of corn determined directly or by difference, and different basal diets did not affect the NE of SBM.

[Multi-DSP parallel processing technique of hyperspectral RX anomaly detection].

To satisfy the requirement of high speed, real-time and mass data storage etc. for RX anomaly detection of hyperspectral image data, the present paper proposes a solution of multi-DSP parallel processing system for hyperspectral image based on CPCI Express standard bus architecture. Hardware topological architecture of the system combines the tight coupling of four DSPs sharing data bus and memory unit with the interconnection of Link ports. On this hardware platform, by assigning parallel processing task for each DSP in consideration of the spectrum RX anomaly detection algorithm and the feature of 3D data in the spectral image, a 4DSP parallel processing technique which computes and solves the mean matrix and covariance matrix of the whole image by spatially partitioning the image is proposed. The experiment result shows that, in the case of equivalent detective effect, it can reach the time efficiency 4 times higher than single DSP process with the 4-DSP parallel processing technique of RX anomaly detection algorithm proposed by this paper, which makes a breakthrough in the constraints to the huge data image processing of DSP's internal storage capacity, meanwhile well meeting the demands of the spectral data in real-time processing.