Miracle-dz/UniFAR-FTUs huggingface dataset:
Natural Voltage‐Gated Sodium Channel Ligands: Biosynthesis and Biology

Natural product biosynthetic pathways are composed of enzymes that use powerful chemistry to assemble complex molecules. Small molecule neurotoxins are examples of natural products with intricate scaffolds which often have high affinities for their biological targets. The focus of this Minireview is small molecule neurotoxins targeting voltage‐gated sodium channels (VGSCs) and the state of knowledge on their associated biosynthetic pathways. There are three small molecule neurotoxin receptor sites on VGSCs associated with three different classes of molecules: guanidinium toxins, alkaloid toxins, and ladder polyethers. Each of these types of toxins have unique structural features which are assembled by biosynthetic enzymes and the extent of information known about these enzymes varies among each class. The biosynthetic enzymes involved in the formation of these toxins have the potential to become useful tools in the efficient synthesis of VGSC probes.
Continuum of Host-Gut Microbial Co-metabolism: Host CYP3A4/3A7 are Responsible for Tertiary Oxidations of Deoxycholate Species

The gut microbiota modifies endogenous primary bile acids (BAs) to produce exogenous secondary BAs, which may be further metabolized by cytochrome P450 enzymes (P450s). Our primary aim was to examine how the host adapts to the stress of microbe-derived secondary BAs by P450-mediated oxidative modifications on the steroid nucleus. Five unconjugated tri-hydroxyl BAs that were structurally and/or biologically associated with deoxycholate (DCA) were determined in human biologic samples by liquid chromatography-tandem mass spectrometry in combination with enzyme-digestion techniques. They were identified as DCA-19-ol, DCA-6β-ol, DCA-5β-ol, DCA-6α-ol, DCA-1β-ol, and DCA-4β-ol based on matching in-laboratory synthesized standards. Metabolic inhibition assays in human liver microsomes and recombinant P450 assays revealed that CYP3A4 and CYP3A7 were responsible for the regioselective oxidations of both DCA and its conjugated forms, glycodeoxycholate (GDCA) and taurodeoxycholate (TDCA). The modification of secondary BAs to tertiary BAs defines a host liver (primary BAs)-gut microbiota (secondary BAs)-host liver (tertiary BAs) axis. The regioselective oxidations of DCA, GDCA, and TDCA by CYP3A4 and CYP3A7 may help eliminate host-toxic DCA species. The 19- and 4β-hydroxylation of DCA species demonstrated outstanding CYP3A7 selectivity and may be useful as indicators of CYP3A7 activity.
Colloidal Synthesis and Charge-Carrier Dynamics of Cs2 AgSb1-y Biy X6 (X: Br, Cl; 0 ≤y ≤1) Double Perovskite Nanocrystals.

A series of lead-free double perovskite nanocrystals (NCs) Cs2 AgSb1-y Biy X6 (X: Br, Cl; 0≤y≤1) is synthesized. In particular, the Cs2 AgSbBr6 NCs is a new double perovskite material that has not been reported for the bulk form. Mixed Ag-Sb/Bi NCs exhibit enhanced stability in colloidal solution compared to Ag-Bi or Ag-Sb NCs. Femtosecond transient absorption studies indicate the presence of two prominent fast trapping processes in the charge-carrier relaxation. The two fast trapping processes are dominated by intrinsic self-trapping (ca. 1-2 ps) arising from giant exciton-phonon coupling and surface-defect trapping (ca. 50-100 ps). Slow hot-carrier relaxation is observed at high pump fluence, and the possible mechanisms for the slow hot-carrier relaxation are also discussed.
Novel pipeline identifies new upstream ORFs and non-AUG initiating main ORFs with conserved amino acid sequences in the 5′ leader of mRNAs in Arabidopsis thaliana

Eukaryotic mRNAs contain a 5′ leader sequence preceding the main open reading frame (mORF) and, depending on the species, 20%–50% of eukaryotic mRNAs harbor an upstream ORF (uORF) in the 5′ leader. An unknown fraction of these uORFs encode sequence conserved peptides (conserved peptide uORFs, CPuORFs). Experimentally validated CPuORFs demonstrated to regulate the translation of downstream mORFs often do so in a metabolite concentration-dependent manner. Previous research has shown that most CPuORFs possess a start codon context suboptimal for translation initiation, which turns out to be favorable for translational regulation. The suboptimal initiation context may even include non-AUG start codons, which makes CPuORFs hard to predict. For this reason, we developed a novel pipeline to identify CPuORFs unbiased of start codon using well-annotated sequence data from 31 eudicot plant species and rice. Our new pipeline was able to identify 29 novel Arabidopsis thaliana (Arabidopsis) CPuORFs, conserved across a wide variety of eudicot species of which 15 do not initiate with an AUG start codon. In addition to CPuORFs, the pipeline was able to find 14 conserved coding regions directly upstream and in frame with the mORF, which likely initiate translation on a non-AUG start codon. Altogether, our pipeline identified highly conserved coding regions in the 5′ leaders of Arabidopsis transcripts, including in genes with proven functional importance such as LHY, a key regulator of the circadian clock, and the RAPTOR1 subunit of the target of rapamycin (TOR) kinase.
The afterglow thermoluminescence band as an indicator of changes in the photorespiratory metabolism of the model legume Lotus japonicus.

The afterglow (AG) luminescence is a delayed chlorophyll fluorescence emitted by the photosystem II that seems to reflect the level of assimilatory potential (NADPH+ATP) in chloroplast. In this work, the thermoluminescence (TL) emissions corresponding to the AG band were investigated in plants of the WT and the Ljgln2-2 photorespiratory mutant from Lotus japonicus grown under either photorespiratory (air) or non-photorespiratory (high concentration of CO2 ) conditions. TL glow curves obtained after two flashes induced the strongest overall TL emissions, which could be decomposed in two components: B band (tmax = 27-29°C) and AG band (tmax = 44-45°C). Under photorespiratory conditions, WT plants showed a ratio of 1.17 between the intensity of the AG and B bands (IAG /IB ). This ratio increased considerably under non-photorespiratory conditions (2.12). In contrast, mutant Ljgln2-2 plants grown under both conditions showed a high IAG /IB ratio, similar to that of WT plants grown under non-photorespiratory conditions. In addition, high temperature thermoluminescence (HTL) emissions associated to lipid peroxidation were also recorded. WT and Ljgln2-2 mutant plants grown under photorespiratory conditions showed both a significant HTL band, which increased significantly under non-photorespiratory conditions. The results of this work indicate that changes in the amplitude of IAG /IB ratio could be used as an in vivo indicator of alteration in the level of photorespiratory metabolism in L. japonicus chloroplasts. Moreover, the HTL results suggest that photorespiration plays some role in the protection of the chloroplast against lipid peroxidation.
The clinical application value of MR diffusion-weighted imaging in the diagnosis of rectal cancer

Abstract The present study evaluated the clinical potential of magnetic resonance (MR) diffusion-weighted imaging (DWI) in the diagnosis of rectal cancer. A total of 84 patients confirmed with rectal cancer were used as study subjects in the present study. All patients received conventional sequence MR T1WI, T2WI, and DWI examination as well as operative pathological examination. The differences between the MRI results and operative pathological results were analyzed. The diagnosis accordance rates of conventional sequence examination in stage T1, T2, T3, and T4 were 60.00%, 82.75%, 62.85%, and 80.00%, respectively. The diagnosis accordance rates of conventional sequence combined with DWI examination in stages T1, T2, T3, and T4 were 100.00%, 100.00%, 82.85%, and 100.00% respectively. The total diagnosis accordance rates in the T staging of rectal cancer with conventional (Routinely or generally applied) sequence examination and conventional sequence combined with DWI examination were 71.42% and 92.85%, respectively. The analysis on consistency of MR conventional sequence examination suggested that the conventional sequence combined with DWI examination is more consistent with pathological staging when compared with the convention sequence examination alone. MR DWI combined with conventional sequences reveals quite good accuracy in the T staging of rectal cancer.
Targeting the pattern‐triggered immunity pathway to enhance resistance to Fusarium graminearum

Summary Fusarium head blight (FHB) is a disease of the floral tissues of wheat and barley for which highly resistant varieties are not available. Thus, there is a need to identify genes/mechanisms that can be targeted for the control of this devastating disease. Fusarium graminearum is the primary causal agent of FHB in North America. In addition, it also causes Fusarium seedling blight. Fusarium graminearum can also cause disease in the model plant Arabidopsis thaliana. The Arabidopsis–F. graminearum pathosystem has facilitated the identification of targets for the control of disease caused by this fungus. Here, we show that resistance against F. graminearum can be enhanced by flg22, a bacterial microbe‐associated molecular pattern (MAMP). flg22‐induced resistance in Arabidopsis requires its cognate pattern recognition receptor (PRR) FLS2, and is accompanied by the up‐regulation of WRKY29. The expression of WRKY29, which is associated with pattern‐triggered immunity (PTI), is also induced in response to F. graminearum infection. Furthermore, WRKY29 is required for basal resistance as well as flg22‐induced resistance to F. graminearum. Moreover, constitutive expression of WRKY29 in Arabidopsis enhances disease resistance. The PTI pathway is also activated in response to F. graminearum infection of wheat. Furthermore, flg22 application and ectopic expression of WRKY29 enhance FHB resistance in wheat. Thus, we conclude that the PTI pathway provides a target for the control of FHB in wheat. We further show that the ectopic expression of WRKY29 in wheat results in shorter stature and early heading time, traits that are important to wheat breeding.
Low fecal calprotectin predicts clinical remission in Crohn's disease patients: the simple answer to a challenging question

Abstract Background and aim: Fecal calprotectin (FC) is a noninvasive marker of intestinal inflammation. Predicting relapses in Crohn’s disease (CD) patients can allow earlier changes in therapy. The aim of this study was to evaluate the role of FC in predicting relapse in CD patients in clinical remission within six months follow-up. Methods: Patients with CD who were in clinical remission at least ≥3 months were included in this study. The first FC sample during the remission period was evaluated and was used as the baseline value. Relapse was defined as an unexpected escalation in therapy, hospitalization or need for surgery for active CD. The accuracy and optimal cutoff FC values for predicting clinical relapse at six months were assessed by the area under the ROC curve (AUC). Results: One hundred and forty-four patients were evaluated, with mean age of 38.4 years. Of these, 13 (9%) had a relapse during the follow-up period. The mean FC value was significantly lower for non-relapsers (203.2 μg/g) than for relapsers (871.3 μg/g), p < . 001. The AUC for predicting relapse by using FC values was 0.924. The optimal cutoff FC value to predict relapse was 327 μg/g; with values of sensitivity, specificity, negative predictive value and positive predictive value were 92.3%, 82.4%, 99.1% and 34.3%, respectively. Conclusions: FC is more useful in predicting remission maintenance than relapse in patients with CD in clinical remission. Values of FC ≤327 μg/g can exclude relapse at least at six months follow-up period.
Pre‐operative cardiac optimisation: a directed review

Cardiac events remain the leading cause of peri‐operative morbidity and mortality, and patients undergoing major surgery are exposed to significant risks which may be preventable and modifiable. Proper assessment and management of various cardiac conditions in the peri‐operative period by anaesthetists can markedly improve patient safety, especially in high‐risk patient populations. This involves understanding and applying current evidence‐based practice and international guidelines on the main aspects of cardiac optimisation, including management of patients with hypertension, chronic heart failure, valvular heart diseases and cardiac implantable electronic devices. Peri‐operative management of antihypertensive drugs in keeping with the current best evidence is discussed. Pre‐operative cardiac risk assessment and cardiac biomarkers can be used to help predict and quantify peri‐operative adverse cardiac events. There is an increasing need for anaesthetist‐led services, including focused transthoracic echocardiography and management of implantable cardiac electronic devices. Anaesthetists should be encouraged to play a proactive role in pre‐operative risk stratification and make timely multidisciplinary referrals if necessary. A personalised approach to pre‐operative cardiac optimisation enables a safer peri‐operative journey for at‐risk patients undergoing major surgery.
Video Monitoring Application of CMOS 4T-PPD-APS Under γ-ray Radiation

In this paper, we discuss the potential use of four transistor active pixel sensor (4T-APS) as a video monitor at a nuclear accident site with a high level of γ radiation. The resistance and radiation responses to γ radiation were investigated by radiation experiments using 137Cs and 60Co γ-ray sources. The radiation resistance of 4T-APS was studied by testing the mean and the maximum dark current of the sensors after irradiation. A random spatial distribution of radiation response events was observed upon analyzing these events on the video images in a given time during irradiation. The background dependence of the 4T-APS was also studied by comparing the grayscale incremental value of the images with different color and grayscale backgrounds: the radiation response events were obvious on the images with a background having a smaller grayscale value or a deeper color. Finally, the color saturation and resolution of the images were tested using a vector oscilloscope and a test card. When the total ionizing dose was less than or equal to the damage threshold, no significant performance deterioration of 4T-APS was observed in an environment with sufficient light.
The equity paradox: older patients' participation in patient portal development.

Purpose This paper reflects on ethical concerns to patient portals design and evaluation approaches and provides a comprehensive overview of methodological considerations to advance patient participation of older patients to patient portal research and development. Reflection Barriers to the use of current patient portals experienced by older patients are concentrated on access issues and difficulties with interpretation of medical content. As patient portals' functionalities are being expanded by means of co-creation and user-testing such barriers often remain unrecognized. A main challenge of these patient participation efforts is namely to include a variety of older patients; foremost autonomous patients seem to participate. By selecting autonomous participants in co-creation or user-testing, design solutions are proposed that specifically benefit the autonomy of that patient, whereas it does not do justice to values and interests of patients who are less independent and are confronted with a wider variety of use barriers. Consequently, there is a risk of widening the gap between those who can use and benefit from patient portals and those who cannot. To prevent this from happening, we propose three main methodological aspects to consider in co-creation and user-testing activities that aim to optimize patient portal functionalities. Implications We encourage policy makers and patient portal developers to use present-day's momentum to include older patients' abilities, needs and context in the decision-making and investments in further advancing patient portals. We further stimulate future research that aims to improve methods to overcome challenges of older patients' participation regarding design and evaluation of eHealth systems.
Ginsenoside Rd Inhibits the Metastasis of Colorectal Cancer via Epidermal Growth Factor Receptor Signaling Axis

Ginsenoside Rd is a saponin from ginseng and has been reported to have various biological activities. However, the effect of ginsenoside Rd on the metastasis of colorectal cancer (CRC) remains unknown. Here, we found that ginsenoside Rd decreased the colony‐forming ability, migration, invasion, and wound‐healing abilities of CRC cells, although it did not affect cell proliferation. In addition, using an inverse‐docking assay, we found that ginsenoside Rd bound to epidermal growth factor receptor (EGFR) with a high binding affinity, inducing the downregulation of stemness‐ and epithelial‐mesenchymal transition‐related genes; these were partially rescued by either exogenous EGF treatment or ectopic expression of SOX2. Furthermore, ginsenoside Rd significantly decreased the number and size of tumor metastasis nodules in the livers, lungs, and kidneys of mouse model of metastasis. © 2018 IUBMB Life, 71(5):601–610, 2019
POTENSI DAN NILAI MANFAAT JASA LINGKUNGAN HUTAN MANGROVE DI KABUPATEN SINJAI SULAWESI SELATAN

Hutan mangrove merupakan ekosistem utama pendukung kehidupan yang penting di wilayah pesisir dan lautan. Mempunyai fungsi ekonomi yang penting seperti, penyedia kayu, daun-daunan sebagai bahan baku obat-obatan dan lain-lain. Penelitian ini bertujuan untuk mengetahui potensi dan nilai manfaat langsung dari hutan tanaman mangrove. Pengamatan terhadap potensi tegakan dilakukan dengan metode observasi lapangan melalui pembuatan petak ukur berukuran 10 m x 10 m untuk setiap tipe strata tegakan. Pengamatan pada masyarakat dilakukan melalui wawancara terhadap 30 responden. Hasil penelitian menunjukkan bahwa masyarakat pesisir Sinjai Timur telah memanfaatkan hutan mangrove secara langsung berupa kayu, buah dan daun bakau masing-masing sebanyak 67%, 20% dan 13%. kuantifikasi dan penilaian ekonomi dari pemanfaatan fungsi sumberdayahutan mangrove berupa manfaat kayu senilai Rp 7,85 juta/ha/th, buah bakau senilai Rp 2,04 juta/ha/th dan daun bakau senilai Rp 1,72 juta/ha/th secara keseluruhan sejumlah Rp 11,61 juta/ha/th. Perkiraan perolehan total nilai ekonomi manfaat langsung sumberdayahutan mangrove paling besar didapat dari produk kayu untuk bahan bangunan yaitu senilai Rp 847,27 juta/th, selanjutnya produk buah bakau sebagai sumber benih senilai Rp 779,28 juta/th, produk kayu bakar senilai Rp 584,80 juta/th dan paling kecil diperoleh dari daun bakau sebagai produk pakan ternak senilai Rp 292,40 juta/th.
Molecular Mechanisms of pre-mRNA Splicing through Structural Biology of the Spliceosome.

SUMMARYPrecursor messenger RNA (pre-mRNA) splicing is executed by the spliceosome. In the past 3 years, cryoelectron microscopy (cryo-EM) structures have been elucidated for a majority of the yeast spliceosomal complexes and for a few human spliceosomes. During the splicing reaction, the dynamic spliceosome has an immobile core of about 20 protein and RNA components, which are organized around a conserved splicing active site. The divalent metal ions, coordinated by U6 small nuclear RNA (snRNA), catalyze the branching reaction and exon ligation. The spliceosome also contains a mobile but compositionally stable group of about 13 proteins and a portion of U2 snRNA, which facilitate substrate delivery into the splicing active site. The spliceosomal transitions are driven by the RNA-dependent ATPase/helicases, resulting in the recruitment and dissociation of specific splicing factors that enable the reaction. In summary, the spliceosome is a protein-directed metalloribozyme.
The therapeutic potential of novel kappa opioid receptor-based treatments.

INTRODUCTION Similarly to the µ opioid receptor, kappa opioid receptor (KOR), is present either in the central nervous system and peripherally. In the last years several molecules, able to interact with KOR, have been the focus of basic research for their therapeutic potential in the field of chronic pain, as well as in depression, autoimmune disorders and neurological diseases. Topic The role of KOR system and the consequent clinical effects derived by its activation or inhibition are discussed. Their potential therapeutic utilization in conditions of stress and drug relapse, besides chronic pain, is here presented, including the possible use of KOR-agonists in drug addiction. Moreover, the potential role of KOR-antagonists, KOR agonist-antagonists, and peripheral KOR agonists is proposed. CONCLUSION Other than pain, KORs have a role in regulating reward and mood. Due to its location, KORs seems to mediate interactions between psychiatric disorders, addiction, and depression. Experimental studies in animal models have identified brain mechanisms that may contribute to clarify specific pathophysiological processes.
Endoscopic Management of Combined Biliary and Duodenal Obstruction

Combined obstruction of the bile duct and duodenum is a common occurrence in periampullary malignancies. The obstruction of gastric outlet or duodenum can follow, occur simultaneously, or precede biliary obstruction. The prognosis in patients with combined obstruction is particularly poor. Therefore, minimally invasive palliation is preferred in these patients to avoid morbidity associated with surgery. Endoscopic palliation is preferred to surgical bypass due to similar efficacy, less morbidity, and shorter hospital stay. The success of endoscopic palliation depends on the type of bilioduodenal stenosis and the presence of previously placed duodenal metal stents. Biliary cannulation is difficult in type II bilioduodenal strictures where the duodenal stenosis is located at the level of the papilla. Consequentially, technical and clinical success is lower in these patients than in those with type I and III bilioduodenal strictures. However, in cases with failure of endoscopic retrograde cholangiopancreatography, with the introduction of endoscopic ultrasound for biliary drainage, the success of endoscopic bilioduodenal bypass is likely to increase further. The safety and efficacy of endoscopic ultrasound-guided drainage has been documented in multiple studies. With the development of dedicated accessories and standardization of drainage techniques, the role of endoscopic ultrasound is likely to expand further in cases with double obstruction.