Evaluation of pancreatic iodine uptake and related influential factors in multiphase dual-energy CT.

OBJECTIVES: To establish normative values and identify potential factors influencing pancreatic iodine uptake using dual-energy CT (DECT). MATERIALS AND METHODS: This retrospective study included participants without pancreatic diseases undergoing DECT at two institutions with different platforms. Their protocols both included arterial phase (AP), portal venous phase (PP), and equilibrium phase (EP), defined as 35 s-40 s, 60 s-70 s, and 150 s-180 s after injection of contrast agent, respectively. Both iodine concentration (IC) and normalised IC (NIC) were measured. Demographic features, local measurements of the pancreas and visceral fat area (VFA) were considered as potential factors influencing iodine uptake using multivariate linear regression analyses. RESULTS: A total of 562 participants (median age 58 years [interquartile range: 47-67], with 282 men) were evaluated. The mean IC differed significantly between two institutions (all p < 0.001) across three contrast-enhanced phases, while the mean NIC showed no significant differences (all p > 0.05). The mean values of NIC were 0.22 at AP, 0.43 at PP and 0.45 at EP. NICAP was independently affected by VFA (ß = 0.362, p < 0.001), smoking (ß = -0.240, p = 0.001), and type-II diabetes (ß = -0.449, p < 0.001); NICPP by VFA (ß = -0.301, p = 0.017) and smoking (ß = -0.291, p < 0.001); and NICEP by smoking (ß = -0.154, p = 0.10) and alcohol consumption (ß = -0.350, p < 0.001) with statistical power values over 0.81. CONCLUSION: NIC values were consistent across institutions. Abdominal obesity, smoking, alcohol consumption, and diabetes are independent factors influencing pancreatic iodine uptake. CLINICAL RELEVANCE STATEMENT: This study has provided reference normative values, influential factors and effective normalisation methods of pancreatic iodine uptake in multiphase dual-energy CT for future studies in this area as a new biological marker. KEY POINTS: Evaluation of pancreatic iodine uptake measured by dual-energy CT is a promising method for future studies. Abdominal obesity, smoking, alcohol consumption, diabetes, and sex are independent factors influencing pancreatic iodine uptake. Utility of normalised iodine concentration is necessary to ensure the consistency across different institutions.

Thermal and (Thermo-Reversible) Photochemical Cycloisomerization of 1H-2-Benzo[c]oxocins: From Synthetic Applications to the Development of a New T-Type Molecular Photoswitch.

A novel T-type molecular photoswitch based on the reversible cyclization of 1H-2-benzo[c]oxocins to dihydro-4H-cyclobuta[c]isochromenes has been developed. The switching mechanism involves a light-triggered ring-contraction of 8-membered 1H-2-benzo[c]oxocins to 4,6-fused O-heterocyclic dihydro-4H-cyclobuta[c]isochromene ring systems, with reversion back to the 1H-2-benzo[c]oxocin state accessible through heating. Both processes are unidirectional and proceed with good efficiency, with switching properties─including reversibility and half-life time─easily adjusted via structural functionalization. Our new molecular-switching platform exhibits independence from solvent polarity, originating from its neutral-charge switching mechanism, a property highly sought-after for biological applications. The photoinduced ring-contraction involves a [2+2] conjugated-diene cyclization that obeys the Woodward-Hoffmann rules. In contrast, the reverse process initiates via a thermal ring-opening (T > 60 °C) to produce the original 8-membered 1H-2-benzo[c]oxocins, which is thermally forbidden according to the Woodward-Hoffmann rules. The thermal ring-opening is likely to proceed via an ortho-quinodimethane (o-QDM) intermediate, and the corresponding switching mechanisms are supported by experimental observations and density functional theory calculations. Other transformations of 1H-2-benzo[c]oxocins were found upon altering reaction conditions: prolonged heating of the 1H-2-benzo[c]oxocins at a significantly elevated temperature (72 h at 120 °C), with the resulting dihydronaphthalenes formed via the o-QDM intermediate. These reactions also proceed with good chemoselectivities, providing new synthetic protocols for motifs found in several bioactive molecules, but are otherwise difficult to access.

PoDPBT, a BAHD acyltransferase, catalyses the benzoylation in paeoniflorin biosynthesis in Paeonia ostii.

PoDPBT, an O-benzoyltransferase belonging to the BAHD family, can catalyze the benzoylation of 8-debenzoylpaeoniflorin to paeoniflorin. PoDPBT is the first enzyme demonstrated to be involved in the modification stage of paeoniflorin biosynthesis. DFGGG, a new DFGWG-like motif, was revealed in the BAHD family. The transcriptome database provides a resource for further investigation of other enzyme genes involved in paeoniflorin biosynthesis.

Natural variation of MS2 confers male fertility and drives hybrid breeding in soybean.

A complete and genetically stable male sterile line with high outcrossing rate is a prerequisite for the development of commercial hybrid soybean. It was reported in the last century that the soybean male sterile ms2 mutant has the highest record with seed set. Here we report the cloning and characterization of the MS2 gene in soybean, which encodes a protein that is specifically expressed in the anther. MS2 functions in the tapetum and microspore by directly regulating genes involved in the biosynthesis of secondary metabolites and the lipid metabolism, which is essential for the formation of microspore cell wall. Through comparison of the field performance with the widely used male sterile mutants in the same genetic background, we demonstrated that the ms2 mutant conducts the best in outcrossing rate and makes it an ideal tool in building a cost-effective hybrid system for soybean.

Kinetin inhibits hepatic stellate cell activation and induces apoptosis via interactions with the TGF-ß1/Smad signaling pathway.

Hepatic fibrosis is the pathological repair response of the liver to chronic injury; hepatic stellate cell (HSC) activation is the central link in the pathogenesis of hepatic fibrosis. Previously, we showed that kinetin, a plant cytokinin hormone, has a protective effect on CCl4-induced liver injury in mice. However, the role of kinetin in liver fibrosis remains unclear. We aimed to study these protective effects and to determine the mechanisms by which kinetin mediates HSC activation and apoptosis. For this purpose, the human HSC line LX-2 was treated with 10 ng/ml transforming growth factor-ß1 (TGF-ß1) for 24 h to stimulate activation. We found that treatment with kinetin at the sub-cytotoxic dose of 40 µg/ml for 48 h reduced the expression of the HSC activation marker α-SMA and inhibited the secretion of extracellular matrix proteins. In addition, kinetin was found to inhibit the proliferation and migration of LX-2 cells. We found that kinetin induced apoptosis in LX-2 cells by increasing the level of cleaved-caspase 3 and the Bax-to-Bcl-2 ratio. Interestingly, these effect were not observed in quiescent HSCs, suggesting that they are activation-dependent. Further study showed that kinetin attenuates activation and promotes apoptosis of LX-2 cells in vitro in part by suppressing the TGF-ß1/Smad signaling pathway.

Understanding Off-Cycle and Deactivation Pathways in Radical-Type Carbene Transfer Catalysis.

Transition metal radical-type carbene transfer catalysis is a sustainable and atom-efficient method to generate C-C bonds, especially to produce fine chemicals and pharmaceuticals. A significant amount of research has therefore been devoted to applying this methodology, which resulted in innovative routes toward otherwise synthetically challenging products and a detailed mechanistic understanding of the catalytic systems. Furthermore, combined experimental and theoretical efforts elucidated the reactivity of carbene radical complexes and their off-cycle pathways. The latter can imply the formation of N-enolate and bridging carbenes, and undesired hydrogen atom transfer by the carbene radical species from the reaction medium which can lead to catalyst deactivation. In this concept paper, we demonstrate that understanding off-cycle and deactivation pathways not only affords solutions to circumvent them, but can also uncover novel reactivity for new applications. In particular, considering off-cycle species involved in metalloradical catalysis can stimulate further development of radical-type carbene transfer reactions.

Rational design of HJH antimicrobial peptides to improve antimicrobial activity.

Antimicrobial peptides (AMPs) have attracted considerable interest in the past decade due to their advantages for tackling antibiotic resistance. They exhibit potential antimicrobial activity through unique cell membrane destruction mechanism based on their net charge, hydrophobic properties, and α-helix. In this work, a series of HJH peptides was rationally designed and synthesized. The antimicrobial activity and cytotoxicity assays indicated that HJH-5 and HJH-6 containing hydrophobic residues and helices displayed prominent antimicrobial activity and mild cytotoxicity, respectively. These peptides may be developed for combatting microbial infections.

PABPN1 functions as a predictive biomarker in colorectal carcinoma.

PURPOSE: PABPN1 acts as a modulator of poly(A) tail length and alternative polyadenylation. This research was aimed to explore the role of PABPN1 in colorectal cancer (CRC). METHODS: Public databases were performed to analyze expression, location, roles of prognosis and tumor immunity and interaction with RNAs and proteins of PABPN1. To investigate PABPN1 expression in tissues, 78 CRC specimens were collected to conduct IHC, and 30 pairs of frozen CRC and corresponding adjacent normal tissues were used to conduct qRT-PCR and WB. In addition, in vitro experiments were then carried out to identify the role of PABPN1 in CRC. RESULTS: Compared with normal tissues, PABPN1 expression was significant higher in CRC. Its high level predicted poor outcome of CRC. Th1 and Treg had significant negative relationships not only with PABPN1 expression, but also with six molecules interacting with PABPN1, including IFT172, KIAA0895L, RECQL4, WDR6, PABPC1 and NCBP1. In addition, PABPN1 had negative relationships with quite a few immune markers, such as CSF1R, IL-10, CCL2 and so on. In cellular experiments, silencing PABPN1 inhibited proliferation and promoted apoptosis in HCT-116 CRC cells. CONCLUSION: In summary, PABPN1 might become a novel biomarker and correlate with tumor immunity in CRC.

Optimization of the decolorization conditions of Rose Bengal by using Aspergillus niger TF05 and a decolorization mechanism.

Aspergillus niger TF05 was applied to decolorize Rose Bengal dye. The effects of carbon source, nitrogen source, metal ion and spore concentration on Rose Bengal treatment with A. niger TF05 were studied. A Plackett-Burman design (PBD) and a uniform design (UD) were used to optimize the decolorization conditions of A. niger TF05 and enhance its decolorization effect. The mechanism of Rose Bengal decolorization by A. niger TF05 was examined by analysing degradation products via UV-visible light spectroscopy, IR spectroscopy and GC-MS. The best decolorization effect was achieved in the single factor test with glucose and ammonium chloride as carbon and nitrogen sources, respectively. Mg2+ was an essential ion that could improve the mould ball state and adsorption efficiency if the spore concentration was maintained at 106 spores ml-1. The optimal decolorization conditions obtained using the PBD and UD methods were 11.5 g l-1 glucose, 6.5 g l-1 ammonium chloride, 0.4 g l-1 magnesium sulphate, pH 5.8, 28 °C, 140 r.p.m. rotational speed, 0.18 g l-1 dye concentration, 0.5 ml of inocula and 120 h decolorization time. Under these conditions, the maximum decolorization rate was 106%. Spectral analysis suggested that the absorption peak of the product changed clearly after decolorization; GC-MS analysis revealed that the intermediate product tetrachlorophthalic anhydride formed after decolorization. The combined use of the PBD and UD methods can optimize multi-factor experiments. A. niger TF05 decolorized Rose Bengal during intracellular enzymatic degradation after adsorption.

Sortase A-mediated cyclization of novel polycyclic RGD peptides for ανß3 integrin targeting.

Cyclic arginine-glycine-aspartic (RGD) peptides that specifically bind to integrin ανß3 have been developed for drug delivery, tracers, and imaging for tumor diagnosis and treatment. Herein, a series of polycyclic RGD peptides containing dual, tri, and tetra rings were designed and synthesized through sortase A-mediated ligation. An in vitro test on cell adhesion inhibition indicated that the RGD peptide containing tricylic structure exhibited outstanding potency and selectivity for ανß3 integrin.

Rapid, Simultaneous, and Automatic Determination of Lead and Cadmium in Cereals with a New High Performance Composite Hollow Cathode Lamp Coupled to Graphite Furnace Atomic Absorption Spectrometry.

A simple, rapid, sensitive, accurate, and automatic graphite furnace atomic absorption spectrometry (GFAAS) method for detecting Cd and Pb in cereals is presented. This method enables the simultaneous determination of Cd and Pb in cereals with a pre-treatment method of diluted acid extraction and a high-performance lead-cadmium composite hollow-cathode lamp (LCC-HCL), and it realizes automatic determination from sample weighing to result output through an automatic diluted acid extraction system. Under the optimization, Pb and Cd in cereals were simultaneously and automatically detected in up to 240 measurements in 8 h. The LOD and LOQ of this method were 0.012 and 0.040 mg·kg-1 for Pb, and 0.0014 and 0.0047 mg·kg-1 for Cd, respectively. The results of the four certified reference materials were satisfied; there was no significant difference compared with the ICP-MS method according to a t-test, and the RSDs were less than 5% for Cd and Pb. The recoveries of naturally contaminated samples compared with the ICP-MS method were favorable, with 80-110% in eight laboratories. The developed method is rapid, low-cost, and highly automated and may be a good choice for grain quality discrimination and rapid analysis of Cd and Pb in different institutions.

Catalytic Synthesis of 1H-2-Benzoxocins: Cobalt(III)-Carbene Radical Approach to 8-Membered Heterocyclic Enol Ethers.

The metallo-radical activation of ortho-allylcarbonyl-aryl N-arylsulfonylhydrazones with the paramagnetic cobalt(II) porphyrin catalyst [CoII(TPP)] (TPP = tetraphenylporphyrin) provides an efficient and powerful method for the synthesis of novel 8-membered heterocyclic enol ethers. The synthetic protocol is versatile and practical and enables the synthesis of a wide range of unique 1H-2-benzoxocins in high yields. The catalytic cyclization reactions proceed with excellent chemoselectivities, have a high functional group tolerance, and provide several opportunities for the synthesis of new bioactive compounds. The reactions are shown to proceed via cobalt(III)-carbene radical intermediates, which are involved in intramolecular hydrogen transfer (HAT) from the allylic position to the carbene radical, followed by a near-barrierless radical rebound step in the coordination sphere of cobalt. The proposed mechanism is supported by experimental observations, density functional theory (DFT) calculations, and spin trapping experiments.

Simultaneous AC and DC measurement based on an FBG-magnetostrictive fiber sensor.

Simultaneous alternating current (AC) and direct current (DC) measurement is demonstrated with a new fiber sensor that combines fiber Bragg gratings (FBGs) with giant magnetostrictive materials (GMMs). Deformation of GMMs, proportional to the central wavelength shift of FBGs, is different when applying DC and AC to a solenoid where the whole sensing structure is located. DC introduces a constant deformation while AC causes a periodic variation. Therefore, the central wavelength of FBG has a periodic harmonic variation, which makes it possible to demodulate the values of DC and AC at the same time. In addition, the proposed method has potential significance for reducing temperature cross talk caused by the thermal sensitivity of FBGs. The experimental results show that the sensitivity of the AC current can reach up to 0.090576 nm/A in the range of 0 to 1 A, and in different AC environments, the sensitivity of the DC current can reach up to 0.2378 nm/A.

Roles of eIF3m in the tumorigenesis of triple negative breast cancer.

BACKGROUND: Without targets, triple negative breast cancer (TNBC) has the worst prognosis in all subtypes of breast cancer (BC). Recently, eukaryotic translation initiation factor 3 m (eIF3m) has been declared to be involved in the malignant progression of various neoplasms. The aim of this study is to explore biological functions of eIF3m in TNBC. METHODS: Multiple databases, including Oncomine, KM-plotter and so on, were performed to analyze prognosis and function of eIF3m in TNBC. After transfection of eIF3m-shRNA lentivirus, CCK-8, colony formation assay, cell cycle analysis, wound healing assay, transwell assays, mitochondrial membrane potential assay and cell apoptosis analysis were performed to explore the roles of eIF3m in TNBC cell bio-behaviors. In addition, western blotting was conducted to analyze the potential molecular mechanisms of eIF3m. RESULTS: In multiple databases, up-regulated eIF3m had lower overall survival, relapse-free survival and post progression survival in BC. EIF3m expression in TNBC was obviously higher than in non-TNBC or normal breast tissues. Its expression in TNBC was positively related to differentiation, lymph node invasion and distant metastasis. After knockdown of eIF3m, cell proliferation, migration, invasion and levels of mitochondrial membrane potential of MDA-MB-231 and MDA-MB-436 were all significantly suppressed, while apoptosis rates of them were obviously increased. In addition, eIF3m could regulate cell-cycle, epithelial-mesenchymal transition and apoptosis-related proteins. Combined with public databases and RT-qPCR, 14 genes were identified to be modulated by eIF3m in the development of TNBC. CONCLUSIONS: eIF3m is an unfavorable indicator of TNBC, and plays a vital role in the process of TNBC tumorigenesis.

Hybrid plasmonic grating slot waveguide with high field enhancement for an on-chip surface-enhanced Raman scattering sensor.

We design and theoretically investigate a surface-enhanced Raman scattering (SERS) sensor based on the hybrid plasmonic grating slot waveguide. The sensor is formed by combining a dielectric deep slot waveguide and a metallic grating slot waveguide. The proposed sensor exhibits a high field enhancement with a maximum enhancement factor of 7580.9 at the wavelength of 785 nm, revealing that the electric field in such hybrid plasmonic grating slot waveguide can be extremely strengthened. To better characterize the performance of the sensor in the SERS application, the total normalized volumetric enhancement factor (TNVEF) is proposed, which is determined by both the |E|4-approximation-based volumetric field enhancement and Raman scattered light collection efficiency. The TNVEF is utilized to characterize the influences of the structural parameters on the sensor and further optimize the sensing structure. Such on-chip SERS sensor can be integrated with a micro-laser and a micro-multiplexer on a photonic platform to realize an all-integrated on-chip SERS detection system.

Pandemic programming: How COVID-19 affects software developers and how their organizations can help.

CONTEXT: As a novel coronavirus swept the world in early 2020, thousands of software developers began working from home. Many did so on short notice, under difficult and stressful conditions. OBJECTIVE: This study investigates the effects of the pandemic on developers' wellbeing and productivity. METHOD: A questionnaire survey was created mainly from existing, validated scales and translated into 12 languages. The data was analyzed using non-parametric inferential statistics and structural equation modeling. RESULTS: The questionnaire received 2225 usable responses from 53 countries. Factor analysis supported the validity of the scales and the structural model achieved a good fit (CFI = 0.961, RMSEA = 0.051, SRMR = 0.067). Confirmatory results include: (1) the pandemic has had a negative effect on developers' wellbeing and productivity; (2) productivity and wellbeing are closely related; (3) disaster preparedness, fear related to the pandemic and home office ergonomics all affect wellbeing or productivity. Exploratory analysis suggests that: (1) women, parents and people with disabilities may be disproportionately affected; (2) different people need different kinds of support. CONCLUSIONS: To improve employee productivity, software companies should focus on maximizing employee wellbeing and improving the ergonomics of employees' home offices. Women, parents and disabled persons may require extra support.

Catalytic Synthesis of 8-Membered Ring Compounds via Cobalt(III)-Carbene Radicals.

The metalloradical activation of o-aryl aldehydes with tosylhydrazide and a cobalt(II) porphyrin catalyst produces cobalt(III)-carbene radical intermediates, providing a new and powerful strategy for the synthesis of medium-sized ring structures. Herein we make use of the intrinsic radical-type reactivity of cobalt(III)-carbene radical intermediates in the [CoII (TPP)]-catalyzed (TPP=tetraphenylporphyrin) synthesis of two types of 8-membered ring compounds; novel dibenzocyclooctenes and unprecedented monobenzocyclooctadienes. The method was successfully applied to afford a variety of 8-membered ring compounds in good yields and with excellent substituent tolerance. Density functional theory (DFT) calculations and experimental results suggest that the reactions proceed via hydrogen atom transfer from the bis-allylic/benzallylic C-H bond to the carbene radical, followed by two divergent processes for ring-closure to the two different types of 8-membered ring products. While the dibenzocyclooctenes are most likely formed by dissociation of o-quinodimethanes (o-QDMs) which undergo a non-catalyzed 8π-cyclization, DFT calculations suggest that ring-closure to the monobenzocyclooctadienes involves a radical-rebound step in the coordination sphere of cobalt. The latter mechanism implies that unprecedented enantioselective ring-closure reactions to chiral monobenzocyclooctadienes should be possible, as was confirmed for reactions mediated by a chiral cobalt-porphyrin catalyst.

An asymmetric Mannich reaction of α-diazocarbonyl compounds and N-sulfonyl cyclic ketimines catalyzed by complexes generated from chiral and achiral phosphines with gold(i).

An unprecedented Lewis acidic gold(i)-complex generated from chiral and achiral phosphines has been developed for the Mannich reaction of α-diazocarbonyl compounds and N-sulfonyl cyclic ketimines. A series of chiral ß-amino-α-diazoesters bearing a quaternary stereocenter were obtained in high yields with good enantioselectivities. In addition, the products could be converted to promising bioactive spirosuccinimide. Furthermore, operando IR, NMR and control experiments were carried out to gain insight into the mechanism.

[3 + 2] Cycloaddition of Azaoxyallyl Cations with Cyclic Ketones: Access to Spiro-4-oxazolidinones.

The first formal [3 + 2] cycloaddition reaction of in situ generated azaoxyallyl cation with cyclic ketones has been developed using mild reaction conditions. A variety of spiro-4-oxazolidinones was obtained in excellent yields (up to 99%). The high efficiency of this process, coupled with the operational simplicity, makes it an attractive method for the synthesis of spiro-4-oxazolidinones.