A dedicate sensorimotor circuit enables fine texture discrimination by active touch.

Active touch facilitates environments exploration by voluntary, self-generated movements. However, the neural mechanisms underlying sensorimotor control for active touch are poorly understood. During foraging and feeding, Drosophila gather information on the properties of food (texture, hardness, taste) by constant probing with their proboscis. Here we identify a group of neurons (sd-L neurons) on the fly labellum that are mechanosensitive to labellum displacement and synapse onto the sugar-sensing neurons via axo-axonal synapses to induce preference to harder food. These neurons also feed onto the motor circuits that control proboscis extension and labellum spreading to provide on-line sensory feedback critical for controlling the probing processes, thus facilitating ingestion of less liquified food. Intriguingly, this preference was eliminated in mated female flies, reflecting an elevated need for softer food. Our results propose a sensorimotor circuit composed of mechanosensory, gustatory and motor neurons that enables the flies to select ripe yet not over-rotten food by active touch.

Phytoavailability of cadmium in rice amended with organic materials and lime: Effects of rhizosphere chemical changes and cadmium sequestration in iron plaque.

Excessive Cd in rice grains produced with acidic paddy soil is receiving increasingly widespread attention because it endangers human health. Applying organic materials (OM) and lime (L) is a common technique used to reduce Cd concentration in grains (CdG). Nevertheless, the mechanism by which their simultaneous application affects the Cd phytoavailability in soilrice systems remains ambiguous. In the current study, we adopted a rhizobag pot culture test to explore the influences of single application of OM [rice straw (RS), milk vetch (MV)], L, and their co-utilization on Cd phytoavailability and the associated mechanisms. The results showed that the application of RS, MV, L, L + RS (LRS), and L + MV (LMV) significantly decreased CdG by 26.9%, 38.2%, 48.6%, 50.0%, and 53.0%, respectively. Fe plaque (IP) formation was not affected by these treatments; however, Cd sequestration in IP (CdIP) was significantly reduced. CdIP was significantly reduced by 18.3%, 23.6%, 43.8%, 33.1%, and 41.4%, after RS, MV, L, LRS, and LMV treatments, respectively. Additionally, available Cd concentrations in rhizospheric soil (RHS) were significantly reduced by 11.5%, 14.8%, 15.1%, and 18.4%, after MV, L, LRS, and LMV treatments, respectively. Cd availability in RHS was significantly influenced by pH, dissolved organic carbon concentration, and Zn, Fe, and Mn availability. The results of the structure equation mode showed that CdG was mainly affected by CdIP, followed by Cd availability and the pH of RHS. In conclusion, the reduction of CdG by OM, L, and their co-utilization was the results of their combined effects of reducing Cd availability in RHS, CdIP, and Cd uptake by the roots. This study emphasizes that the reduction of CdG is a result of the dual effects of reducing Cd availability in RHS and CdIP after amendments application. L application alone or in conjunction with OM is an efficient practice to reduce CdG in acidic Cd-contaminated paddy fields.

[Effects of post-traumatic stress disorder on the excitability of glutamatergic and GABAergic neurons in dorsal and ventral hippocampus in mice].

The purpose of this study was to investigate the effects of post-traumatic stress disorder (PTSD) on electrophysiological characteristics of glutamatergic and GABAergic neurons in dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) in mice, and to elucidate the mechanisms underlying the plasticity of hippocampal neurons and memory regulation after PTSD. Male C57Thy1-YFP/GAD67-GFP mice were randomly divided into PTSD group and control group. Unavoidable foot shock (FS) was applied to establish PTSD model. The spatial learning ability was explored by water maze test, and the changes in electrophysiological characteristics of glutamatergic and GABAergic neurons in dHPC and vHPC were examined using whole-cell recording method. The results showed that FS significantly reduced the movement speed, and enhanced the number and percentage of freezing. PTSD significantly prolonged the escape latency in localization avoidance training, shortened the swimming time in the original quadrant, extended the swimming time in the contralateral quadrant, and increased absolute refractory period, energy barrier and inter-spike interval of glutamatergic neurons in dHPC and GABAergic neurons in vHPC, while decreased absolute refractory period, energy barrier and inter-spike interval of GABAergic neurons in dHPC and glutamatergic neurons in vHPC. These results suggest that PTSD can damage spatial perception of mice, down-regulate the excitability of dHPC and up-regulate the excitability of vHPC, and the underlying mechanism may involve the regulation of spatial memory by the plasticity of neurons in dHPC and vHPC.

Image reconstruction algorithm based on frequency-wavenumber decoupling for three-dimensional MIMO-SAR imaging.

In this paper, a frequency-wavenumber decoupling algorithm with high-efficiency and high-precise for three-dimensional (3-D) multiple-input-multiple-output synthetic aperture radar (MIMO-SAR) imaging is proposed. Based on one-dimensional (1-D) MIMO array combined with synthetic aperture scan along another dimension, MIMO-SAR imaging scheme allows the number of array elements to be greatly reduced compared with the two-dimensional (2-D) MIMO arrays. By multi-dimensional Fourier transforming and Method of Stationary Phase (MSP), analytical expression of the object function in the frequency-wavenumber domain was derived. By further expanding the range Fourier transform factor to its Taylor series form, the range compression can be realized by a simple fast Fourier transform (FFT) without multi-dimensional interpolation. After that, a decoupling factor was multiplied to compensate for the cross-range and range coupling in frequency domain. Finally, 2-D IFFT is carried out after rearrangement in the MIMO spatial frequency to get a fully focused 3-D image. Simulation and experimental results demonstrated that the algorithm can obtain the same high-precision images as back projection (BP) algorithm, and has the same high efficiency as range migration algorithm (RMA) while avoiding cumbersome multi-dimensional interpolation. A bistatic prototype imaging system in 0.1 THz band was designed for the proof-of-principle experiments. The 3-D reconstruction results of different targets were presented to verify the theoretical results and effectiveness of the proposed algorithm for MIMO-SAR imaging.

Realizing frequency controlled wide-angle beam scanning with an artificial electromagnetic structure in the terahertz band.

In this paper, an approach to achieve wide-angle beam scanning in the terahertz (THz) band with frequency sweeping was proposed based on a metasurface structure. To widen the scanning angular scope, a coherent enhancement mechanism for improving the mode competition efficiency of the high-order diffraction mode was first implemented. A systematic method was firstly developed for the design of practical frequency-controlled beam scanning quasi-optics in THz band, in which the optimization of scanning range, linearity, and the avoidance of beam blocking are comprehensively considered. The proposed concept and approach was verified by the measured wide-angle beam scanning at the 0.18-0.22THz frequency band, with a diffraction efficiency of the main lobe as high as 88 percent. The good performance of the device paves the way for potential applications in THz imaging, moving target detection, and communication.

Costs of breast cancer recurrence after initial treatment for HR+, HER2-, high-risk early breast cancer: estimates from SEER-Medicare linked data.

OBJECTIVE: To assess the costs of treated recurrence and survival in elderly patients with early breast cancer (EBC) at high risk of recurrence using Surveillance Epidemiology and End Results (SEER) registry-Medicare linked claims data. METHODS: This retrospective study included patients aged ≥65 years with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive EBC at high risk of recurrence. Treated recurrences were defined based on treatment events/procedure codes from claims. Primary outcomes were monthly total extra costs and cumulative extra costs of treated recurrence relative to patients with non/untreated recurrence. Costs were calculated using a Kaplan-Meier sampling average estimator method and inflated to 2021 US$. Secondary outcomes included analysis by recurrence type and overall survival (OS) after recurrence. Subgroup analysis evaluated costs in patients with Medicare Part D coverage. RESULTS: Among 3,081 eligible patients [mean (SD) age at diagnosis was 74.5 (7.1) years], the majority were females (97.4%) and white (87.8%). Treated recurrence was observed in 964 patients (31.3%). The monthly extra cost of treated recurrence was highest at the beginning of the first treated recurrence episode, with 6-year cumulative cost of $117,926. Six-year cumulative extra costs were higher for patients with distant recurrences ($168,656) than for patients with locoregional recurrences ($96,465). Median OS was 4.34 years for all treated recurrences, 1.92 years for distant recurrence, and 6.78 years for locoregional recurrence. Similar cumulative extra cost trends were observed in the subgroup with Part D coverage as in the overall population. LIMITATIONS: This study utilizes claims data to identify treated recurrence. Due to age constraints of the dataset, results may not extrapolate to a younger population where EBC is commonly diagnosed. CONCLUSION: EBC recurrence in this elderly population has substantial costs, particularly in patients with distant recurrences. Therapies that delay or prevent recurrence may reduce long-term costs significantly.

Long-term exposure to dietary emulsifier Tween 80 promotes liver lipid accumulation and induces different-grade inflammation in young and aged mice.

With the advent of industrialization, there has been a substantial increase in the production and consumption of ultra-processed foods (UPFs). These processed foods often contain artificially synthesized additives, such as emulsifiers. Emulsifiers constitute approximately half of the total amount of food additives, with Tween 80 being a commonly used emulsifier in the food industry. Concurrently, China is undergoing significant demographic changes, transitioning into an aging society. Despite this demographic shift, there is insufficient research on the health implications of food emulsifiers, particularly on the elderly population. In this study, we present novel findings indicating that even at low concentrations, Tween 80 suppressed the viability of multiple cell types. Prolonged in vivo exposure to 1 % Tween 80 in drinking water induced liver lipid accumulation and insulin resistance in young adult mice under a regular chow diet. Intriguingly, in mice with high-fat diet (HFD) induced metabolic dysfunction-associated steatotic liver disease (MASLD), this inductive effect was masked. In aged mice, liver lipid accumulation was replicated under prolonged Tween 80 exposure. We further revealed that Tween 80 induced inflammation in both adult and aged mice, with a more pronounced inflammation in aged mice. In conclusion, our study provides compelling evidence that Tween 80 could contribute to a low-grade inflammation and liver lipid accumulation. These findings underscore the need for increasing attention regarding the consumption of UPFs with Tween 80 as the emulsifier, particularly in the elderly consumers.

Real-World Molecular Biomarker Testing Patterns and Results for Advanced Gastroesophageal Cancers in the United States.

The decision to treat advanced gastroesophageal cancers (GECs) with targeted therapy and immunotherapy is based on key biomarker expression (human epidermal growth factor receptor 2 (HER2), programmed cell death-ligand 1 (PD-L1), microsatellite instability (MSI), and/or mismatch repair (MMR)). Real-world data on testing, results, and treatment patterns are limited. This retrospective observational study used a nationwide electronic health record-derived de-identified database of patients from the United States. The analysis included adult patients with advanced GECs who initiated systemic treatment between 2017 and 2020. Biomarker testing patterns, timing, assays, tissue collection site, results, and treatment sequences were assessed. Of 1142 eligible patients, adenocarcinoma was the most prevalent histology (83% of patients). Overall, 571 (50%) patients were tested for PD-L1, 582 (51%) were tested for MMR/MSI, and 857 (75%) were tested for HER2. Between 2017 and 2020, the PD-L1 testing rate increased from 39% to 58%, and the MMR/MSI testing rate increased from 41% to 58%; the median time from initial diagnosis to first test decreased for both biomarkers. Programmed cell death receptor-1 inhibitor use was observed among patients with positive PD-L1 or MMR-deficient/MSI-High results. These results supplement data reported in key clinical trials and may inform decision-making as treatment options for advanced GECs evolve.

Anaerobic co-digestion of three commercial bio-plastic bags with food waste: Effects on methane production and microbial community structure.

The emergence of bioplastic bags as a replacement for traditional petroleum-based plastic bags is promising for their simultaneous anaerobic digestion with food waste. In this study, the degradation of three bioplastic bags is evaluated during anaerobic co-digestion with food waste under mesophilic/thermophilic conditions, and the results indicated PBAT/PLA/starch > PLA > PBAT for methane production rate. The PBAT/PLA/starch mixture produced 23.4 ml/g of methane at 55 °C, and the cumulative methane production increased by 28.4 % compared to the control. In addition, the lag time before methane production was reduced by one to four days when anaerobic co-digestion was performed under thermophilic conditions, and the conversion of the bioplastics improved by 9.11-11.2 %. Microscopy further showed obvious physical degradation of the PBAT/PLA/starch material. The FTIR analysis showed that the characteristic peaks of the material at 3320, 2957, and 934 cm-1 decreased significantly after anaerobic fermentation. The biodegradability of the polymer decreased with an increase in the content of the crystalline area in the structure. The addition of a comonomer reduced the crystallinity of the polymer. In addition, the biodegradability was increased by adjusting the hydrolysis reaction and microbial activity of the polymer surface. An analysis of the structural features of the microbial communities revealed that Archaea exhibited different biodiversity at distinct temperatures. In particular, under thermophilic conditions, the relative abundance of Methanothermobacter was 56.0 %, and it plays an important role in the anaerobic degradation of PBAT/PLA/starch materials, while bacterial communities showed smaller differences. Overall, the bioplastic was able to be co-digested anaerobically with food waste to produce renewable energy. This study provides a plan for the practical application of biodegradable plastic bag collection for the combined treatment of food waste in anaerobic digesters. It provides a theoretical basis for modifications of bioplastic and domestication of anaerobic microorganisms.

Foliar zinc reduced Cd accumulation in grains by inhibiting Cd mobility in the xylem and increasing Cd retention ability in roots1.

Cadmium (Cd) pollution endangers the safe utilization of paddy soils, and foliar zinc (Zn) can reduce the toxic effects of Cd. However, little is known about the effects of foliar Zn application on the transport and immobilization of Cd in key rice tissues and the physiological state of rice plants. A pot experiment was conducted to explore the effects of spraying 0.2% and 0.4% Zn (ZnSO4) during the early grain-filling stage on Cd transport in rice, photosynthesis, glutathione (GSH) levels, Cd concentrations in xylem sap, and the expression of Zn transporter genes. The results showed that grain Cd concentrations in the 0.2% Zn and 0.4% Zn treatments were 24% and 31% lower, respectively, than those of the control treatments at maturity. Compared with the control treatments, the 0.4% Zn treatment increased Cd by 60%, 69%, 23%, and 22% in husks, rachises, first internodes, and roots, respectively. Application of Zn reduced xylem Cd content by up to 26% and downregulated transporter genes (OSZIP12, OSZIP4, and OSZIP7a) in flag leaves. Foliar Zn increased Cd bioaccumulation in roots while decreasing Cd bioaccumulation in grains. Zn reduced GSH concentration in flag leaves and stems, inhibiting photosynthesis (intercellular CO2 concentration, transpiration rate). Taken together, foliar Zn can reduce the expression of Zn transporter genes and the mobility of Cd in the xylem, promoting the fixation of Cd in husks, rachises, first internodes, and roots, ultimately reducing Cd concentration in rice grains.

Therapeutic role of growth factors in treating diabetic wound.

Wounds in diabetic patients, especially diabetic foot ulcers, are more difficult to heal compared with normal wounds and can easily deteriorate, leading to amputation. Common treatments cannot heal diabetic wounds or control their many complications. Growth factors are found to play important roles in regulating complex diabetic wound healing. Different growth factors such as transforming growth factor beta 1, insulin-like growth factor, and vascular endothelial growth factor play different roles in diabetic wound healing. This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds. Further, some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors. The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.

Dihydroartemisinin represses oral squamous cell carcinoma progression through downregulating mitochondrial calcium uniporter.

Dysregulation of mitochondrial calcium uniporter (MCU) exerts a carcinogenic effect in several cancers. Nevertheless, the roles of MCU in oral squamous cell carcinoma (OSCC) remain elusive. It has been reported that dihydroartemisinin (DHA) may suppress the progression of OSCC but its associated mechanisms have not been investigated. The purpose of our research was to observe the biological function of MCU on OSCC and its regulatory relationship with DHA. MCU, MICU1, MICU2, N-cadherin, TGF-ß and vimentin expression was detected in OSCC and peritumoral tissues by immunohistochemistry and Western blot. Following DHA treatment, the expression of the aforementioned proteins was detected in CAL-27 cells transfected with shMCU or pcDNA3.1-MCU by Western blot or immunofluorescence. Furthermore, clone formation, mitochondrial membrane potential (MMP), wound healing and transwell assays were presented in CAL-27 cells treated with DHA, shMCU or pcDNA3.1-MCU. Our results showed that the members of MCU complex (MCU, MICU1 and MICU2) were overexpressed in OSCC than peritumoral tissues. Furthermore, TGF-ß and epithelial to mesenchymal transition (EMT) proteins (N-cadherin and vimentin) exhibited higher expression in OSCC. DHA treatment significantly lowered the expression of MCU in CAL-27 cells. MCU overexpression reversed the inhibitory effects of DHA on MICU1, MICU2, N-cadherin, TGF-ß and vimentin. MCU knockdown or DHA suppressed proliferation, MMP and migration of CAL-27 cells. DHA treatment could reverse the effects of MCU overexpression. Collectively, our study demonstrated that MCU was an oncogene of OSCC and DHA exerted a suppressive role on proliferation and migration of OSCC cells by suppressing MCU expression.

Nitrogen application practices to reduce cadmium concentration in rice (Oryza sativa L.) grains.

Cadmium (Cd) pollution in paddy soils creates challenges in rice grain production, thereby threatening food security. The effectiveness of different base-tillering-panicle urea application ratios and the combined basal application of urea and Chinese milk vetch (CMV, Astragalus sinicus L.) in minimizing Cd accumulation in rice grains was explored in a Cd-contaminated acidic soil via a field experiment. The results indicated that under similar nitrogen (N) application rates, an appropriate amount of urea applied at the panicle stage or the combined basal application of urea and CMV decreased Cd absorption by rice roots and its accumulation in rice grains, as compared with that of conventional N application (control). Furthermore, under a 3:4:3 base-tillering-panicle urea application ratio or under a high basal application of CMV (37,500 kg hm-2), Cd concentrations in brown rice were significantly lower (40.7% and 34.1%, respectively) than that of control. Cadmium transport coefficient from root to straw was significantly higher than that of control when an appropriate amount of urea was applied at the panicle stage or when urea and CMV were applied basally, whereas the Cd transport coefficient from straw to brown rice was relatively lower. Moreover, soil pH, or the CEC and CaCl2-Cd concentrations under different N fertilizer treatment was not significantly different. However, the rice grain yield increased by 29.4% with basal application of a high CMV amount compared with that of control. An appropriate amount of urea applied at the panicle stage or the combined basal application of urea and CMV decreased Cd absorption by rice roots and inhibited its transport from straw to brown rice, thus reducing Cd concentration in brown rice. Therefore, combined with the key phase of Cd accumulation in rice, a reasonable urea application ratio or a basal application of high CMV amounts could effectively reduce Cd concentration in brown rice.

Milk vetch returning reduces rice grain Cd concentration in paddy fields: Roles of iron plaque and soil reducing-bacteria.

Milk vetch (MV, Astragalus sinicus L.) is used in agricultural production as a green manure; however, its impact on accumulation levels of heavy metals (e.g., Cd) in rice remains poorly understood. This study investigated the effects of MV on Cd accumulation in rice, iron plaque formation, soil properties, and the soil microbial community structure through field experiments. The results showed that MV reduced Cd concentration in the roots, stem, leaves, and grains by 33%, 60%, 71%, and 49%, respectively. Chemical fertilizer and MV treatment promoted iron plaque formation, and MV considerably increased the Fe/Mn ratio in the iron plaque. More importantly, MV inhibited Cd transportation from the root iron plaque to the root by 74%. The concentrations of CaCl2-extractable Cd, available phosphorus, and available potassium, as well as the cation exchange capacity and urease activity, were significantly reduced in the MV treatment. Furthermore, 16 S rDNA high-throughput sequencing results of the soil microbial community structure showed that compared with the control, MV increased the soil microbial richness, increased the relative abundance of anaerobic microorganisms, and significantly increased the relative abundance of Thermodesulfovibrio and Geobacter at the genus level. The increase in anaerobic microbial abundance was closely related to the decrease in CaCl2-extractable Cd concentration. The application of MV promoted the formation of iron plaque, inhibited the transport of Cd, increased the abundance of anaerobic microorganisms, decreased the CaCl2-extractable Cd concentration, and reduced the Cd concentration in rice grain.

[Effects of Iron Intensity-regulated Root Microbial Community Structure and Function on Cadmium Accumulation in Rice].

Exploring the effects of exogenous iron (Fe) on cadmium (Cd) in rice is of great significance for ensuring food security. The accumulation of Cd and the changes in the microbial community structure in rice roots under three Fe concentrations (5, 50, and 500 µmol·L-1 EDTA-Na2Fe) were studied through a hydroponic experiment. The results showed that the increase in the environmental Fe concentration promoted the formation of iron plaque on the rice roots, and both Fe-deficiency and Fe-sufficiency would enhance the adsorption and fixation of Cd on the root surface. Compared with that of normal Fe levels (50 µmol·L-1), Fe deficiency increased Cd accumulation in rice roots and shoots by 49.76% and 15.68%, respectively. Although Fe sufficiency also increased Cd accumulation in the roots by 18.39%, the Cd concentration in shoots was significantly reduced by 35.95% compared with that of the normal Fe. 16S rRNA high-throughput sequencing was used to determine the root microbial community structure, and through PCA, LEfSe, and RDA analysis, it was found that compared with normal Fe, an Fe-deficient environment reduced the abundance and uniformity of root microbes. Proteobacteria and Bacteroidetes at the phylum level were the dominant flora, Fe deficiency inhibited the increase in the relative abundance of Bacteroidetes, and high-concentration Fe reduced the relative abundance of Proteobacteria. At the genus level, the relative abundance of functional microorganisms Ensifer, Rhodopila, Bdellovibrio, and Dyella were different under different Fe environments, which may have affected the absorption and accumulation of Cd by rice by affecting the formation of Fe plaque on the root and other biochemical processes. In addition, the effect of an Fe-deficient environment on microbial functions was higher than that of the Fe sufficient environment. This study investigated the changes in the rice root microbial community structure and the ability of rice to absorb and transport Cd under different Fe environments, which provided a theoretical basis and an important reference for the inhibition of Fe on Cd accumulation in rice in Cd-polluted paddy soil in southern China.

Potential roles of gut microbiota and microbial metabolites in Parkinson's disease.

Parkinson's disease (PD) is a complicated neurodegenerative disease attributed to multifactorial changes. However, its pathological mechanism remains undetermined. Accumulating evidence has revealed the emerging functions of gut microbiota and microbial metabolites, which can affect both the enteric nervous system and the central nervous system via the microbiota-gut-brain axis. Accordingly, intestinal dysbiosis might be closely associated with PD. This review explores alterations to gut microbiota, correlations with clinical manifestations of PD, and briefly probes the underlying mechanisms. Next, the highly controversial roles of microbial metabolites including short-chain fatty acids (SCFAs), H2 and H2S are discussed. Finally, the pros and cons of the current treatments for PD, including those targeting microbiota, are assessed. Advancements in research techniques, further studies on levels of specific strains and longitudinal prospective clinical trials are urgently needed for the identification of early diagnostic markers and the development of novel therapeutic approaches for PD.

Data-Driven Patient Clustering and Differential Clinical Outcomes in the Brigham and Women's Rheumatoid Arthritis Sequential Study Registry.

OBJECTIVE: To use unbiased, data-driven, principal component (PC) and cluster analysis to identify patient phenotypes of rheumatoid arthritis (RA) that might exhibit distinct trajectories of disease progression, response to treatment, and risk for adverse events. METHODS: Patient demographic, socioeconomic, health, and disease characteristics recorded at entry into a large, single-center, prospective observational registry cohort, the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS), were harmonized using PC analysis to reduce dimensionality and collinearity. The number of PCs was established by eigenvalue >1, cumulative variance, and interpretability. The resulting PCs were used to cluster patients using a K-means approach. Longitudinal clinical outcomes were compared between the clusters over 2 years. RESULTS: Analysis of 142 variables from 1,443 patients identified 41 PCs that accounted for 77% of the cumulative variance in the data set. Cluster analysis distinguished 5 patient clusters: 1) less RA disease activity/multimorbidity, shorter RA duration, lower incidence of comorbidities; 2) less RA disease activity/multimorbidity, longer RA duration, more infections, psychiatric comorbidities, health care utilization; 3) moderate RA disease activity/multimorbidity, more neurologic comorbidity; 4) more RA disease activity/multimorbidity, shorter RA duration, more metabolic comorbidity, higher body mass index; 5) more RA disease activity/multimorbidity, longer RA duration, more hepatic, orthopedic comorbidity and RA-related surgeries. The clusters exhibited differences in clinical outcomes over 2 years of follow-up. CONCLUSION: Data-driven analysis of the BRASS registry identified 5 distinct phenotypes of RA. These results illustrate the potential of data-driven patient profiling as a tool to support personalized medicine in RA. Validation in an independent data set is ongoing.

[Isolation, structural identification of secondary metabolites from Pseudomonas aeruginosa HBD-12 with antibacterial and antitumor activities].

To screen strains with antibacterial and antitumor activity, pregnenolone was used as the sole carbon source for screening bacteria from soil. Based on bacteriostatic activity assay, Pseudomonas aeruginosa HBD-12 was found to be effectively inhibiting the growth of Escherichia coli, Bacillus thuringiensis, Penicillium digitatum and Penicillium italicum, and its fermentation broth was separated and purified using column chromatography. Then, structure of the obtained monomeric compounds was analyzed by spectrum analysis, and their antitumor activity was measured using HTRF kinase detection kit. The isolated monomeric compounds 1-hydroxy-9,10-phenanthroline and 3-hydroxy-9,10-dihydrophenanthroline had significant antitumor activity. At 20 µg/mL, 1-hydroxy-9,10-phenanthroline and 3-hydroxy-9,10-dihydrophenanthroline inhibited 78.39±2.29% and 60.34±8.35% Aurora kinase A, respectively. Therefore, the secondary metabolites of Pseudomonas aeruginosa HBD-12 have the potential to develop antibacterial and antitumor drugs.

Wheat TabZIP8, 9, 13 participate in ABA biosynthesis in NaCl-stressed roots regulated by TaCDPK9-1.

In plants, basic leucine zipper (bZIP) transcription factors (TFs) participate in various biological processes such as development and stress responses. But the molecular mechanism of wheat bZIP TFs modulating abscisic acid (ABA) biosynthesis is unknown. In this study, we demonstrated the expressions of three bZIP TF genes TabZIP8, 9, 13, were regulated by Triticum aestivum calcium (Ca2+)-dependent protein kinase 9-1 (TaCDPK9-1) and they took part in ABA biosynthesis in wheat roots under salt stress. We first isolated TabZIP8, 9, 13 and TaCDPK9-1 from wheat. TabZIP8, 9, 13 genes transcripts were strongly induced by salt stress, but salt-induced TabZIP8, 9, 13 transcriptions were drastically impaired by Ca2+ channel blocker LaCl3. TaCDPK9-1 kinase could interact with TabZIP8, 9, 13 TFs through yeast two-hybrid assay. Next, the expression levels of salt-induced wheat 9-cis-epoxycarotenoid dioxygenase1, 2 (TaNCED1,2) encoding a key enzyme controlling ABA production and salt-induced ABA content were found to be decreased under LaCl3 treatment, and yeast one-hybrid experiment revealed TabZIP8, 9, 13 could bind to the ABA-responsive elements (ABREs) and the promoter sequence of TaNCED2 gene. Together, our results suggest that salt stress-induced ABA accumulation is mediated by TabZIP8, 9, 13, which are adjusted by TaCDPK9-1 in wheat roots.

Development of a colorimetric PNGase activity assay.

PNGases are crucial targets and valuable tools in analyzing asparagine-linked carbohydrate moieties (N-glycans) of glycoproteins. Activity tests of PNGases have been little improved since their discovery four decades ago, and still rely on observing deglycosylation patterns of glycoproteins or glycopeptides using SDS-PAGE or HPLC analysis. These techniques cannot be easily adapted for automated sampling and high-throughput procedures. Herein, we describe a PNGase activity assay which relies on the conversion of WST-1, a yellowish, water-soluble tetrazolium dye (sodium 2-(4-Iodophenyl)-3-(4-nitro-phenyl)-5-(2,4-disulfophenyl)-2H-tetrazolate), into a blue formazan dye. In this work, we showed that WST-1 could be reduced by N-glycans, which were enzymatically released from glycoprotein substrates. After optimization of the assay conditions, the robustness of the method was challenged by quantifying the activity of various PNGase isoforms at different purification stages using a microwell plate reader. Furthermore, the assay could be used to obtain steady-state kinetics of PNGase H+ wild-type and mutant variants, which showed significant differences in their enzymatic reaction rates. The simplicity and robustness of this method might be of benefit for the detection of PNGase activity in routine applications of large amounts of samples.